intensive_care_nursery_2003

Copyright © 2004 The Regents of the University of California

The William H. Tooley Intensive Care Nursery

HOUSE STAFF MANUAL

Eighth Edition July, 2003


Intensive Care Nursery House Staff Manual

This manual, now in its eighth edition, is designed for use by the pediatric residents, interns and medical students who work in the William H. Tooley Intensive Care Nursery at UCSF Medical Center. Therefore, the recommendations in this manual are specific for the practices in that unit. If this manual is used in other intensive care nurseries, it must be revised and adapted to suit the circumstances in those units. This is not a mini-textbook or outline of neonatology. The purpose of this manual is to assist pediatric house officers by providing:

• Guidelines for the initiate management of patients with conditions that require immediate attention

• Reminders to help them in their daily work • Detailed instructions for performing procedures

There is little discussion of pathophysiology, which is covered in textbooks. Certain important and common problems are not covered at all. This particularly applies to most chronic problems, as they can be discussed on attending rounds.



Contributors

Thomas Bartman, M.D., Ph.D. Michael D. Becker, D. Pharm. Carlos M. Botas, M.D. William A. Carey, M.D. Annette M. Carley, M.S., N.N.P., P.N.P. Ronald I. Clyman, M.D. George A. Gregory, M.D. Nalin Gupta, M.D., Ph.D. Shannon E. G. Hamrick, M.D. Sam Hawgood, M.B., B.S. Maria Hetherton, R.D., C.S.P. Debra Hummel, R.N.C., N.N.P. Priya Jegatheesan, M.D. Susan B. Johnson, R.N.C., N.N.P. Erna Josiah, R.N., M.S. A. Javier Kattan, M.D. Roberta L. Keller, M.D. Joseph A. Kitterman, M.D. Michael W. Kuzniewicz, M.D., M.P.H. Hanmin Lee, M.D. Stacey M. Levitt, M.D.

Vedang A. Londhe, M.D. Alma M. Martinez, M.D. Claire W. McLean, M.D. Carol A. Miller, M.D. Steven P. Miller, M.D. Seymour Packman, M.D. J. Colin Partridge, M.D. Roderic H. Phibbs, M.D. Robert E. Piecuch, M.D. Dolores Quinn, R.N., M.S. Kay Ramsdell, N.N.P., M.S.N. Christopher T. Retajczyk, M.D. Sally A. Sehring, M.D. Jan Sherman, R.N., Ph.D. Beverly Shoemaker, R.N., M.S. Susan H. Sniderman, M.D. Dongli Song, M.D., Ph.D. George Van Hare, M.D. Diane W. Wara, M.D. Peggy S. Weintrub, M.D.

Joseph A. Kitterman, M.D., edited this Manual with the assistance of Shannon E. G. Hamrick, M.D., and Roberta L. Keller, M.D.

Cory Fergus prepared the manuscript.



Table of Contents Section I: Procedures Page Resuscitation of High Risk Infants (S. Johnson, R. Phibbs) 1

Meconium in Amniotic Fluid (P. Jegatheesan) 8

Respiratory Support (G. Gregory) 10 Intravascular Catheters: 25

-Catheterization of Umbilical Vessels (J. Kitterman) -Peripheral Arterial Catheterization (J. Kitterman)

-Percutaneous Venous Catheterization (D. Hummel) Blood Pressures (J. Kitterman) 35 Administration of Blood Products (B. Shoemaker) 40 Exchange Transfusion (R. Phibbs) 42 ECMO (J. Kattan, R. Keller) 44

Section II: General Care ICN Nursing Routines (D. Quinn) 46 Health Care Maintenance (R. Phibbs) 48 Feeding of Preterm Infants (C. McLean) 50 Content of Formulas (M. Hetherton) 54 Vitamins (M. Hetherton) 55 Fluids and Electrolytes (S. Sniderman) 56 Acid Base Balance (S. Sniderman) 62 Very Low Birth Weight Infants (J. Partridge) 65 Intrauterine Growth Retardation (A. Martinez, E. Josiah) 69 Immunizations (M. Becker) 71 Discharge Planning (J. Kitterman) 73 Well Baby Nursery (C. Miller) 74


Section III: Specific Conditions PULMONARY

Respiratory Distress Syndrome (M. Kuzniewicz, S. Hawgood) 79 Pulmonary Hypoplasia and Diaphragmatic Hernia (J. Kitterman) 85 Persistent Pulmonary Hypertension (R. Keller) 87 Nitric Oxide (R. Keller) 89 Pulmonary Hemorrhage (J. Kattan) 90 Apnea (R. Clyman) 91 Chronic Lung Disease (P. Jegatheesan) 93

CARDIOVASCULAR

Congenital Heart Disease (T. Bartman, D. Teitel) 95 Patent Ductus Arteriosus (R. Clyman) 99 Shock (V. Londhe) 101 Hypertension (T. Bartman) 103 Cardiac Arrhythmias (J. Kattan, G. Van Hare) 105

HEMATOLOGIC

Anemia (A. Carley, B. Shoemaker) 108 Guidelines for Use of Erythropoietin (R. Phibbs) 111 Polycythemia/Hyperviscosity (C. Retajczyk, C. Miller) 112 Neonatal Coagulation Disorders (A. Carley, B. Shoemaker) 115 Jaundice (C. Botas) 118 Hemolytic Disease of the Newborn (S. Hamrick, R. Phibbs) 121

INFECTIOUS DISEASES

Bacterial Infections (W. Carey) 125 Candidiasis (J. Sherman) 128 Other Congenital & Perinatal Infections 130 (R. Keller, D. Wara, P. Weintrub)

GASTROINTESTINAL

Necrotizing Enterocolitis (K. Ramsdell) 133 Parenteral Nutrition (S. Sniderman, M. Hetherton) 136

NEUROLOGICAL

Neonatal Seizures (S. Miller) 140 Intraventricular Hemorrhage (S. Miller, R. Piecuch) 144 Pain Management and Sedation (J. Partridge) 147


METABOLIC Infants of Diabetic Mothers (S. Sehring) 151 Hypoglycemia (S. Sehring) 153 Inborn Errors of Metabolism (S. Hamrick, S. Packman) 155

SURGICAL PATIENTS

Neonatal Surgical Conditions (S. Sniderman, H. Lee) 160 Meningomyelocele (N. Gupta) 166 Fetal Therapy (S. Levitt) 168

OTHER

Hydrops Fetalis (R. Phibbs, V. Londhe) 170 Multiple Births (D. Song) 172 Perinatal Substance Abuse (A. Martinez, J. Partridge) 174 Renal Disease (J. Sherman) 178 Neonatal Clinical Physiology Laboratory (J. Kitterman) 181


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Resuscitation of Newborn Infants BASIC RESUSCITATION OF ALL HIGH-RISK INFANTS: 1. Preparation of Resuscitation Room (“Set-Up Room”)

A. Notify Charge Nurse, Neonatology Fellow, Respiratory Therapy (RT), and Neonatal Laboratory of impending delivery.

B. Check equipment for proper functioning: •Oxygen & air sources and blender: for most cases, set blender to deliver 40% O2 •Bag system: check pop-off for maximal pressure (25 cmH2O) •Suction pressure and catheters •Face masks for bag and mask ventilation •Endotracheal tubes & laryngoscope (#1 blade for term infant, #0 for preterm)

C. With Nurse, “wet down” UAC tray. D. Have blood in room for known fetal anemia (e.g., Hemolytic Disease of Newborn).

2. Duties of Team Members A. Member A - Physician or Neonatal Nurse Practitioner (NNP)

•Assess infant •Manage airway and intubate trachea •Perform assisted ventilation •Stabilize ET tube while RT secures it

B. Member B - MD, NNP or RN •Assess heart rate; give compressions PRN (unable to↑ heart rate with ventilation). •Auscultate chest and abdomen for proper position of ET tube. •Insert umbilical catheter(s) under sterile technique (MD or NNP only). •Assess perfusion, draw blood for culture and pH and blood gas tensions. •Administer fluids and drugs.

C. Member C - RN, MD or NNP •Dry infant, apply ECG leads and attach SpO2 and CO2 monitors. •Assist with ET tube suctioning and adjust FIO2. •Assist Member B by providing medications in sterile syringes. •Monitor temperature and capillary blood glucose. •Record resuscitation, including vital signs, Apgar scores, procedures, all infusions

and medications, and lab results, and times of each.

3. Goals of resuscitation are to assist adaptation to extra-uterine life by: •Inflating lungs, establishing oxygenation and ventilation to •Establish adequate pulmonary blood flow •Support cardiovascular function.

4. Sequential steps in resuscitation: •Maintain body temperature (dry infant and put under radiant warmer). •Clear airway and initiate ventilation. •Cardiac compressions, if needed. •Attach ECG leads, pulse oximeter and CO2 monitor and insert OG tube. •Catheterize umbilical artery/vein and measure blood pressures. •Give resuscitation drugs as needed. •Assign Apgar scores at 1 and 5 min and q5 min until score is ≥7.

Resuscitation of High Risk Infants

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RESUSCITATION OF THE ASYPHYXIATED INFANT:

1. Definition: Asphyxia (from the Greek, asphuxia, stopping of the pulse) produces hypoxia and respiratory and metabolic acidosis that, in turn, cause peripheral and pulmonary vasoconstriction with hypertension and bradycardia. If allowed to persist, asphyxia leads to myocardial failure, hypotension, bradycardia and elevated CVP.

2. Conditions that place newborn infants at ↑ risk for asphyxia:

A. Maternal conditions: •Diabetes Mellitus •Pre-eclampsia, hypertension, chronic renal disease •Anemia •Blood type incompatibilities •Antepartum hemorrhage •Drug or alcohol ingestion •Previous neonatal death •PROM with evidence of amnionitis •Systemic Lupus •Maternal cardiac disease

B. Labor and delivery conditions: •Forceps or vacuum extraction •Breech or abnormal presentation •Cesarean section •Cephalo-pelvic disproportion •Cord prolapse/compression •Maternal hypotension or hemorrhage

C. Fetal conditions: •Premature/postmature birth •Meconium in amniotic fluid •Abnormal heart rate pattern •Fetal cardiac dysrhythmia •Oligo- or polyhydramnios •Fetal growth retardation •Macrosomia •Fetal malformations •Hydrops fetalis •Low biophysical profile •Multiple births, especially: •Sepsis

-Discordant twins -Twin-twin transfusion syndrome with stuck twin -Mono-amniotic twins

3. Phases of resuscitation: Follow sequence above in Basic Resuscitation, Part 4.

A. Phase I: Clinical assessment of severity of asphyxia and treatment •Use Apgar scoring as an assessment tool: the length of time it takes to reach a

score of 7 is a rough indication of the severity of asphyxia. •With mild asphyxia, ventilate using bag-mask with 40% O2 to establish FRC in

the following manner: -Slowly apply opening pressures of 20 cmH2O for term and maintain pressure

for 1-2 sec -Follow with a rate of 40-60/min with Ti of 0.25 to 0.4 sec -Insert NG tube to decompress stomach

•Intubation: With severe asphyxia (or if there is not a prompt increase in heart rate with bag-mask ventilation) immediately intubate the trachea and begin assisted ventilation.

•Naloxone: If infant does not subsequently make respiratory efforts and if mother has received narcotics within 1h of delivery, give naloxone hydrochloride (0.1 mg/kg IV, IM or SC) with the following precautions:

-Do not give naloxone if there is persistent bradycardia. This will delay appropriate resuscitative measures.


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-If naloxone is given, remember that the duration of action is shorter than narcotics and, therefore, an additional dose of naloxone may be necessary.

•Treat persistent bradycardia in the following sequence -Ventilate and increase FIO2 if baby does not respond quickly. -Cardiac compressions using NRP guidelines -Epinephrine -NaHCO3 or THAM™ to treat severe metabolic acidosis (pH <7.05 or base

deficit of 15 mEq/L or more) with aims of (1) reversing myocardial failure and low cardiac output and (2) relieving pulmonary vasoconstriction.

i) Calculation of dose: Buffer (mEq) = 0.3 x BW (kg) x Base Deficit (mEq/L)

ii) Use NaHCO3 only when infant is receiving adequate assisted ventilation. With inadequate ventilation, NaHCO3 will worsen respiratory acidosis (NaHCO3 + H2 → Na+ + H2CO3 → H2O + CO2)

iii) Tham™ is for mixed acidosis as it buffers metabolic acid and lowers PaCO2. However, it can cause apnea and hypoglycemia.

iv) Infuse buffer at rate of 1 mEq/kg/min. -Atropine and CaCl2. -Catheterize an umbilical artery (or vein if unable to get into an artery) for

assessment of pH and PCO2. (See section on Intravascular Catheters, P. 25). -Drug doses are on placard mounted on wall of Resuscitation Room.

B. Phase II: Evaluation after stabilization: Perform careful physical examination

to detect: -Major anomalies -Neural tube defect is easy to miss in a supine infant -Scaphoid abdomen and respiratory distress should alert one to possibility of

a diaphragmatic hernia -Dysmorphic features -Assessment of intrauterine growth -Signs of infection

•Re-evaluate assisted ventilation -Be alert for complications of tracheal intubation: dislodgment of tube into

esophagus, inadvertent advancement into right mainstem bronchus. -Continually assess for changes in pulmonary function

i) Hyperoxia can occur as ventilation and perfusion are better matched. Manage by decreasing the inspired O2 concentration.

ii) Hypocarbia, due to improved ventilation, can decrease cerebral and myocardial blood flow. Manage by reducing ventilator rate or PIP.

iii) Hypotension: As lung compliance improves, ventilatory pressures may become excessive and impede venous return causing hypotension. Test for this by briefly disconnecting the patient from positive pressure ventilation; if arterial pressure rises (usually within 5-10 sec), then reduce airway pressures.

iv) Tension pneumothorax may occur spontaneously or with assisted ventilation. It leads to hypoxia, hypercarbia, and, if large, it will obstruct cardiac return and lead to shock.


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•Assess circulatory status: In most asphyxiated infants, blood volume is ≥ normal and hypovolemic shock does not develop. However, it will develop in some asphyxiated infants. It is important to assess this carefully and accurately since giving volume to an asphyxiated baby who is not in shock can be harmful.

-Signs of hypovolemia ٠Hypotension, narrow pulse pressure ٠Falling hematocrit (Hct) ٠Prolonged capillary filling time ٠Persistent metabolic acidosis ٠Cold extremities ٠Low PvO2 with normal PaO2

-Treatment of hypovolemic shock: See section on Neonatal Shock, P. 101. Use great caution when giving volume expanders in an asphyxiated infant. Dopamine is more appropriate for treating hypotension in an asphyxiated infant (starting dose: 5 mcg/kg/min).

-Conditions that can be mistaken for hypovolemic shock ٠Vasoconstriction of asphyxia

Findings: ↓ pH, ↑ blood pressure (BP), peripheral pallor Action: Correct acidosis Response: BP ↓ to normal, perfusion ↑

٠Asphyxial cardiomyopathy Findings: ↓ pH, ↓ BP, ↑ central venous pressure (CVP) Action: Correct acidosis, hypoxia, and hypocalcemia, if present Response: BP ↑, CVP ↓, perfusion improves

٠Obstruction of venous return Findings: ↓ BP, ↑ CVP, pallor Action: Relieve pneumothorax or decrease airway pressures Response: BP ↑, perfusion improves

٠Hypocarbia Findings: ↓ BP Action: Reduce ventilation so PaCO2 >30-35 mmHg. Response: BP ↑

C. Phase III: General management. This is the period of time where the mildly

affected infant will begin to improve rapidly and the severely affected infant will start showing signs of end organ damage. •Ventilation: Adjust to meet changes in pulmonary function. Give surfactant if

RDS is suspected; RDS, congenital pneumonia and post-asphyxial respiratory distress may be indistinguishable.

•Use Dopamine to treat post-asphyxial cardiomyopathy. Hypotension may persist for 1 -2 d and may be distinguished from hypovolemia by ↑ CVP.

•Persistent Pulmonary Hypertension of the Newborn may coexist with asphyxial cardiomyopathy. Avoid treating PPHN with hypocarbia, as it will ↓ myocardial (and cerebral) blood flow.

•Coagulopathy is almost always transient. Administer platelets and clotting factors as needed (see section on Administration of Blood Products, P. 40).

•Hypoglycemia may occur after resuscitation. Treat with continuous glucose infusion to maintain normal serum glucose; monitor for hypoglycemia and hyperglycemia

•Fluids and electrolytes


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-Carefully monitor renal function with measurements of intake, urine output, creatinine, proteinuria, and hematuria.

-Monitor electrolytes (serum and urine). Replace Na+, K+, Cl- and Ca++ as needed, as electrolyte losses may be high in diuretic recovery phase.

-Gastrointestinal: Delay feeds to prevent NEC secondary to reduced blood flow to the gut during asphyxia.

-Observe for hypoxic-ischemic encephalopathy. RESUSCITATION OF INFANT WITH MECONIUM ASPIRATION: See section on Management of Infants Born through Meconium Stained Amniotic Fluid (P. 8). RESUSCITATION OF THE VERY LOW BIRTHWEIGHT INFANT: See section on Very Low Birthweight Infant (P. 65). Factors to be considered when resuscitating a VLBW or ELBW infant: 1. Respiratory Care: The majority of ELBW infants (i.e., <1,000 g) will require

intubation at birth (to assist in their cardiopulmonary adaptation to extra-uterine life) and assisted ventilation for a prolonged period. They require close attention with frequent measurements of pH and blood gas tensions. In addition to surfactant deficiency, they are at risk for respiratory failure because of:

•Weak chest wall •Smaller alveoli (↑ tendency to atelectasis) •Weak muscles of respiration •Decreased central respiratory drive

Indications for endotracheal intubation at birth include any of the following for infants ≤27 weeks gestation:

•Apnea •Need to maintain airway •Need for FIO2 ≥0.4 •PaCO2 ≥60 mmHg •Arterial pH ≤7.25

Surfactant is to be given immediately after birth to preterm infants as indicated in Table 1 of the section on RDS (P. 79). Provide adequate PEEP or CPAP to prevent atelectasis after FRC has been established and lung compliance improves. It is rare that these infants will do well with PEEP or CPAP <5 cmH2O.

2. Oxygenation: Maintain oxygen saturation (SpO2) in the range 85-92% to limit the damaging effects of hyperoxia

3. Insensible water loss and temperature maintenance: See section on VLBW and ELBW Infants (P. 65).

RESUSCITATION OF MULTIPLE BIRTHS

A. Complications of multiple births include: increased incidence of preterm labor and delivery, intrapartum asphyxia, congenital anomalies in monozygotic twins, IUGR, twin-twin transfusion and stuck twin syndrome (see section on Multiple Births, P. 170).

B. Special situations:

•Twin-to-Twin Transfusion Syndrome (TTTS). Delivery room management will vary with the clinical picture. Management is based on measurements of their hemoglobin/hematocrits and arterial and venous pressures.


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-If blood transfusion between twins has been recent, the donor twin will be anemic and will require volume as with any hypovolemic infant. The recipient twin will be polycythemic and will require a partial exchange transfusion to reduce the hematocrit (see section on Polycythemia-Hyperviscosity, P. 112).

-If blood transfusion between twins has been chronic, the donor twin is usually SGA and anemic, is likely to need partial exchange transfusion with PRBCs to treat the anemia because of low tolerance to blood volume expansion (which occurs with simple transfusion). If the donor twin dies there is danger of damage to the brain, kidneys and GI tract of the recipient, either from hypoperfusion or emboli. The recipient twin is usually AGA and may or may not be polycythemic. Hydrops fetalis may develop in either twin.

•Stuck Twin Syndrome occurs in discordant, monochorionic twins with TTTS.

There is oligohydramnios in the SGA fetus and polyhydramnios in the AGA fetus. The SGA fetus becomes compacted into a small volume within the uterus leading to lung growth restriction and pulmonary hypoplasia.

RESUSCITATION OF AN INFANT WITH BIRTH TRAUMA may be complicated by management of significant blood loss requiring blood volume and coagulation factors. Bleeding may be:

•Intra-abdominal: Abdominal distension and discoloration may indicate ruptured liver, spleen, subcapsular liver hematoma or adrenal hemorrhage. These are more common with breech deliveries.

•Intracranial: If bleeding is sufficient to cause hypovolemia, it will manifest in a bulging fontanel.

•Subgaleal: Earliest sign of an expanding hemorrhage is pushing of the ears laterally and forward. Treatment is difficult and may require vigorous therapy.

RESUSCITATION OF AN INFANT WITH HYDROPS FETALIS: For causes, see section on Hydrops Fetalis (P. 168). 1. Problems that may complicate resuscitation of hydropic infant:

•Restriction of ventilation by pleural effusions and ascites •Pulmonary edema •Anemia (with some causes) resulting in reduced O2 carrying capacity •Hypoplastic lungs •Circulatory abnormalities including:

-Hypovolemia -Hypervolemia -Myocardial failure -Pulmonary vasoconstriction

2. Delivery room preparation: •Discuss patient with Obstetrical staff (and, if possible, meet with parents) ante-

natally to learn as much as possible about possible causes of the hydrops. •Have extra delivery room personnel assigned to do thoracentesis and

paracentesis.


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•Have 2 umbilical catheters prepared and already connected to transducers for measurement of arterial and venous pressures.

•Have PRBCs available since many infants with non-immune hydrops are anemic. •Be cognizant of the latest fetal ultrasound results and size of any pleural

effusions. •Designate someone to obtain an umbilical cord blood and measure Hct

immediately after birth. 3. Post-natal management:

•Intubate immediately and begin assisted ventilation. Respiratory failure and pulmonary vasoconstriction are common.

•Perform paracentesis if abdomen is distended and interfering with ventilation. -Insert needle/cannula in lower left abdomen lateral to rectus muscle to avoid

puncturing possibly enlarged spleen. -Remove enough fluid to decompress abdomen thus allowing the diaphragm to

move easily. Do not attempt to remove all of the ascitic fluid as this may lead to circulatory instability.

-Perform thoracentesis if there are pleural effusions that are interfering with ventilation.

-Insert umbilical arterial and venous catheters and measure vascular pressures. Be certain that UVC is in right atrium before diagnosing elevated CVP. Remember, pressure in the portal circulation is higher than CVP by a variable amount.

-Transfuse PRBCs if cord Hct shows anemia. Raise Hct to >30-35%. Resuscitation may not be effective until transfusion increases Hct to that level.

-Obtain appropriate diagnostic laboratory tests. In an infant with non-immune hydrops who is not expected to live, obtain the following to help establish a diagnosis to provide counseling to the parents regarding future pregnancies:

٠Blood samples for karyotyping, TORCH infections, parvovirus B-19 and hemoglobin electrophoresis

٠Full body radiographic examination ٠Send placenta to Pathology ٠Obtain consent for autopsy and for post-mortem skin biopsy for

karyotyping.

RESUSCITATION OF INFANT WITH PULMONARY HYPOPLASIA & CONGENITAL DIAPHRAGMATIC HERNIA: See section on Pulmonary Hypoplasia (P. 85).


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Management of Infants Born through Meconium

Stained Amniotic Fluid BACKGROUND: In 10-20% of deliveries, there is meconium in the amniotic fluid. Aspiration of meconium results in respiratory distress that, in severe cases, can be life threatening. There is strong suggestive evidence that prevention of meconium aspiration, by its removal from the respiratory tract, can ameliorate or prevent the vast majority of cases of severe meconium aspiration syndrome (MAS). Recently reported data indicate that infants who are vigorous immediately after birth do not benefit from routine endotracheal intubation and suctioning to remove the meconium. The following are in accord with the “International Guidelines for Neonatal Resuscitation” (Pediatrics 106: E29, 2000). A. For all infants born with meconium in the amniotic fluid:

1. All infants with meconium in the amniotic fluid, should have their nose, mouth and pharynx suctioned as soon as the head is delivered (intrapartum suctioning) regardless of whether the meconium is thin or thick.

2. If the amniotic fluid is merely colored or stained with meconium but there is no particulate meconium in the fluid, no further special intervention for meconium is indicated and the infant should receive routine resuscitation as indicated by the infant’s condition.

B. For infants born with any particulate meconium in the amniotic fluid:

1. Assess the infant immediately after birth (in the first 15 sec after birth), before any drying or stimulation.

2. If the infant is depressed (i.e., absent or depressed respirations, or heart rate <100/min, or decreased muscle tone in the first 15 sec after birth):

•Immediately perform direct laryngoscopy, before drying or stimulating the infant. •Suction any meconium that is in the hypopharynx. •Then intubate the infant’s trachea, apply suction directly to the endotracheal tube

as it is withdrawn from the trachea. •If meconium is obtained, repeat the intubation and suctioning until little meconium

is recovered or the heart is <60. Do not intubate and suction more than three times. Then proceed with routine resuscitation.

•With a markedly depressed infant, it may be necessary to give positive pressure ventilation and proceed with resuscitation despite the presence of some meconium in the airway. In such an infant, intubate the trachea and suction only one time before giving positive pressure ventilation.

•Suction catheters inserted through the endotracheal tube may be too small to accomplish initial removal of particulate meconium; subsequent use of suction

catheters inserted through a tracheal tube may be adequate to continue removal of meconium.

Meconium in Amniotic Fluid

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3. If the infant is vigorous (i.e., spontaneous respirations, and heart rate >100/min and good muscle tone in the first 15 sec after birth), use routine resuscitation procedures as indicated by the infant’s condition. There is no evidence that routine intubation and tracheal suctioning of vigorous infants is beneficial.

4. Meconium stained infants, who develop apnea or respiratory distress at any time during resuscitation, should receive tracheal suctioning before positive-pressure ventilation, even if they had been vigorous initially.

5. There is no evidence that lavage of the trachea is beneficial. Conversely, it may facilitate movement of the meconium into the distal airways and worsen the infant’s respiratory status.

C. If respiratory distress develops in an infant born through meconium, that infant

requires close observation and early intervention: •Provide liberal amounts of humidified oxygen to maintain adequate systemic and

alveolar oxygenation and correct acidosis, if present, to avoid development of Persistent Pulmonary Hypertension (See P. 87).

•Obtain chest radiograph immediately. •Consider early insertion of an umbilical arterial catheter to monitor arterial

oxygenation and acid-base status. Many infants who go on to have severe MAS appear relatively mildly affected for the first few hours of life.

•If the infant requires assisted ventilation, avoid high inspiratory pressures in an attempt to prevent pneumothorax.

•Tension pneumothorax is common with meconium aspiration syndrome and may occur with spontaneous breathing or assisted ventilation.


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Respiratory Support ABBREVIATIONS FIO2 Fractional concentration of O2 in inspired gas PaO2 Partial pressure of arterial oxygen PAO2 Partial pressure of alveolar oxygen PaCO2 Partial pressure of arterial carbon dioxide PACO2 Partial pressure of alveolar carbon dioxide tcPCO2 Transcutaneous PCO2 PBAR Barometric pressure PH2O Partial pressure of water RQ Respiratory quotient (CO2 production/oxygen consumption) SaO2 Arterial blood hemoglobin oxygen saturation SpO2 Arterial oxygen saturation measured by pulse oximetry PIP Peak inspiratory pressure PEEP Positive end-expiratory pressure CPAP Continuous positive airway pressure PAW Mean airway pressure FRC Functional residual capacity Ti Inspiratory time Te Expiratory time IMV Intermittent mandatory ventilation SIMV Synchronized intermittent mandatory ventilation HFV High frequency ventilation OXYGEN (Oxygen is a drug!): A. Most infants require only enough O2 to maintain SpO2 between 87% to 92%, usually

achieved with PaO2 of 40 to 60 mmHg, if pH is normal. Patients with pulmonary hypertension may require a much higher PaO2.

B. With tracheal suctioning, it may be necessary to raise the inspired O2 temporarily. This should not be ordered routinely but only when the infant needs it. These orders are good for only 24h.

OXYGEN DELIVERY and MEASUREMENT: A. Oxygen blenders allow O2 concentration to be adjusted between 21% and 100%. B. Head Hoods permit non-intubated infants to breathe high concentrations of

humidified oxygen. Without a silencer they can be very noisy. C. Nasal Cannulae allow non-intubated infants to breathe high O2 concentrations and to

be less encumbered than with a head hood. O2 flows of 0.25-0.5 L/min are usually sufficient to meet oxygen needs. O2 concentrations >50% may be delivered via nasal cannulae, depending on the size of the patient. The actual alveolar O2 depends both

Respiratory Support

11


on FIO2 and flow rate and varies with respiratory rate, tidal volume and the amount of room air entrained with each breath.

D. FIO2 is measured by portable O2 analyzers, calibrated to display % inspired O2. ALVEOLAR GAS EQUATION, used to calculate PAO2 (the maximal arterial oxygen tension that theoretically can be achieved at any given FIO2), is defined as:

PAO2 = FIO2 (PBAR – PH2O) – PACO2/RQ This can be simplified by the following considerations:

-PH2O at 37º C = 47 mmHg. -PBAR at sea level varies from 745 to 765 mmHg, and can be assumed for this

calculation to be 747 mmHg. -Assume that PACO2 = PaCO2. -Assume that RQ = 1.

Then, the Alveolar Gas Equation can be simplified to:

PAO2 = FIO2 (700) – PaCO2 Example: Using this simplified version, we can calculate that an infant, who is breathing 30% O2 (FIO2 = 0.3), has an arterial CO2 of 40 mmHg and has perfect matching of ventilation and perfusion, would have an alveolar oxygen tension of:

PAO2 = 0.3(700) – 40 = 170 mmHg

IMPORTANT TECHNIQUES MASK and BAG VENTILATION: A. The gas flow rate should be ~5-6 L/min. B. Place the infant’s head in neutral position facing straight forward. C. Ensure that the mask fits closely to the face and covers the mouth and nose without

compressing the eyes or nares. Do not allow the mask to slide down from bridge of nose and occlude the nares.

D. Do not apply pressure with your fingers to the submental triangle, as you may push the tongue back and obstruct the airway. Keep your fingers on the mandible.

E. Place the small finger of one hand at the angle of the jaw and pull forward. F. Apply sufficient pressure to the bag to move the chest gently with each inflation.

Over-inflation of the lung, even for brief periods, can initiate lung damage that may persist for months to years.

G. Allow sufficient time between each breath for complete exhalation. H. If the infant is making spontaneous breathing efforts, attempt to inflate the lungs as

the infant inhales. I. Generate sufficient PEEP to maintain FRC (~5 cmH2O) and increase PaO2 without

compromising intravascular pressures. J. Insert an orogastric tube and leave it open to atmospheric pressure to avoid gastric

distention that may prevent descent of the diaphragm and interfere with ventilation.

Respiratory Support

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Et T

ube

Size

Lip

To

Tip

Dis

tanc

e (C

m)

1 2 3 4

7

8

9

10

Body Weight (kg)

Gestational Age (Weeks) and Body Weight (kg)

2.5

3.0

3.5

4.0

< 30 Weeks

2 3 4131-35 Weeks 36-40 Weeks > 40 Weeks

Figure 1: Top: Solid bars, usual size of tube to be used for infants of the corresponding birth weight and gestational age; shaded bars, range of bigger and smaller infants in which that size of tube may be needed on occasion. Bottom: Distance from the infant's lip to the tip of the tube when the tip is in the midtrachea. Most endotracheal tubes have numbered centimeter mrks on the sides indicating the distance to the tip. The appropriate number should be even with the infant's lip. These are guidelines. There will be some variation among infants.

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TRACHEAL INTUBATION: (Many patients die from lack of oxygen, but few die from lack of an endotracheal tube.) A. Before attempting tracheal intubation, ventilate the patient’s lungs by mask and and

bag with sufficient O2 to raise PaO2 or SpO2 to normal. B. With elective or semi-elective intubation and if the baby is hemodynamically stable,

give morphine (0.1 mg/kg) and/or lorazepam (0.05 mg/kg) IV to facilitate intubation, to prevent increases in intracranial pressure, and decrease stress responses due to intubation. Monitor blood pressure; even these low drug dosages can produce hypotension if the infant is hypovolemic.

C. Muscle relaxants are almost never necessary. Do not administer them unless (1) the infant resists vigorously after sedation has been given and (2) you can effectively ventilate the patient’s lungs with mask and bag before administering the muscle relaxant. Succinylcholine may cause cardiac arrest when the serum K+ concentration is elevated or when there is CNS or muscle injury.

D. See Figure 1 for appropriate size of endotracheal (ET) tube. Tube size is determined by infant’s weight and also by gestational age. Always use an ET tube with an internal diameter (I.D.) <1/10 of the infant’s gestational age (i.e., if gestational age is 35 weeks, use a 3.0 I.D. tube, not a 3.5 tube).

E. Use an ET tube that has only an end hole. Do not use tubes with a side hole (Murphy Eye) close to its tip, as they are prone to occlusion by secretions and are associated with subglottic stenosis.

F. Laryngoscope: Use Miller #1 blade for term infants and Miller #0 for smaller infants. G. Empty the stomach to reduce the risk of vomiting and aspiration. H. Position the patient’s head close to the end of the bed with the head in the “sniffing

position.” Avoid hyperextension or flexion of the neck, since either may occlude the larynx and make intubation more difficult.

I. During tracheal intubation, place head in neutral position facing straight forward, insert laryngoscope along right side of the tongue, and move tongue towards the left side of the mouth. Advance tip of the laryngoscope blade into the vallecula and pull upward and caudad at a 45° angle. About 90% of the laryngoscope blade should be within the mouth when the blade is appropriately positioned. This puts the light where needed and allows for maximal control of the blade. Do not apply pressure on the gums with the laryngoscope blade, as this may permanently injure the teeth.

J. Hold laryngoscope with thumb and index finger of left hand. Hold chin with ring and middle fingers, and push on the hyoid bone with small finger of the left hand. This allows head, hand, and laryngoscope to move as a unit if patient’s head moves, and prevents pharyngeal injury by the laryngoscope blade. Pushing on the hyoid bone moves the larynx posteriorly and improves visualization of the larynx.

K. Insert the ET tube under direct vision. While visualizing the larynx, insert the ET tube through right side of the mouth to the right of the laryngoscope; watch the ET tube tip pass between the vocal cords. Do not insert ET tube through the laryngoscope. This blocks your vision and increases the likelihood of esophageal intubation and injury to the vocal cords. Advance the ET tube until the heavy black line is at the vocal cords.

L. BE GENTLE! DO NOT USE FORCE!

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M. If intubation is difficult and bradycardia +/or cyanosis occur, stop the procedure. Ventilate the patient’s lungs with mask and bag until color and heart rate return to normal.

N. Reflex bradycardia is common during tracheal intubation, but heart rate should return to normal quickly with adequate ventilation of the lungs with oxygen.

O. Figure 2 is a guide for proper positioning of the ET tube. Carefully monitor tube position until it is securely taped in place. Immediately obtain a chest x-ray to confirm proper position of ET tube (i.e., tip of ET tube 1 cm above carina). Important points regarding proper ET tube placement are:

1) Position of infant’s head: Neck flexion advances tube down airway; neck extension withdraws tube. Try to take x-ray with head in neutral position.

2) Tension on ET tube (With loose tape, tube can move up to 1 cm in or out. 3) Principal focus of x-ray beam. 4) Position and alignment of the clavicles on x-ray. 5) Tip of ET tube should be between T1 and T2 (except with congenital

diaphragmatic hernia, when carina may be more cephalad than normal). P. The bevel on the ET tube tip must face ventrally, or the tube may obstruct. If the blue

line running lengthwise on the tube is to the left, the bevel will face ventrally. Complications of Tracheal Intubation: A. With the most common complication, intubation of the esophagus, SpO2 and heart

rate do not increase with bag and tube ventilation, the abdomen rapidly distends, and breath sounds are louder over the stomach than axillae. Withdraw the ET tube and ventilate with a bag, mask and oxygen.

B. Advancing the ET tube too far, so that its tip is in the right mainstem bronchus, is a common and serious complication. As soon as the ET tube is in place and with head in the neutral position, begin gentle bag and tube ventilation. Observe the upper chest for chest movement. Another person should auscultate the chest to ensure that heart rate returns to normal quickly and that breath sounds are equal (not just present) bilaterally. If breath sounds are unequal (usually the left is decreased), the tube is in too far (or there is a pneumothorax). While continuing to ventilate the lungs and to auscultate the chest, withdraw the ET tube slowly until breath sounds are equal bilaterally. When the tube is in appropriate position, note a mark (letter, number) on the tube that is even with the upper lip. Fix the tube in place keeping the tube in the same position.

C. Bleeding, especially if the patient has a coagulopathy. Bleeding can be avoided by using gentle, appropriate techniques for tracheal intubation.

D. Bradycardia and hypoxemia (See above under Tracheal Intubation) E. Subglottic stenosis, a late complication occurs from a tight fitting tube that occludes

blood flow to adjacent soft tissues. This infrequent, but serious, complication can usually be prevented by ensuring that there is a small gas leak between endotracheal tube and trachea when ventilatory pressures are 15-30 cmH20.

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Figure 2. Diagram of proper position of tip of endotracheal tube.

Suctioning of Endotracheal Tube: -ET tube obstruction is a constant threat; signs of occlusion include an increase in

PaCO2 or tcPCO2, decreased breath sounds, inability to pass suction catheter through ET tube, and increase in the pressure required to ventilate the lungs.

-Endotracheal suctioning is necessary because the ET tube reduces mucus transport in airways. However, suctioning decreases lung volume and causes atelectasis. After suctioning, the lungs must be re-expanded using gentle pressure.

-Patients with Respiratory Distress Syndrome may need no suctioning in the first 24h. Suctioning may be required 2-3 times/day on the 2nd day and q4-12h after that.

-See section on Respiratory Distress Syndrome (P. 79) for suctioning after surfactant administration.

-Infants with aspiration syndromes will need more frequent suctioning (at least q12h). -Suctioning is a two-person procedure, and must be performed gently. -Many infants tolerate the suctioning procedure and require no changes in ventilation or

oxygenation. However, some infants may require increased respirator settings (PIP, rate and FIO2) during and after the procedure, because suctioning often reduces FRC, which recovers very slowly unless the lungs are re-expanded. Judge the need for hand ventilation after the suctioning procedure on an individual basis. Some infants may be managed more effectively by adjusting the ventilator.

-Orders for needed changes in FIO2 during suctioning must be written daily. If transient ventilator changes are needed for the infant to tolerate suctioning, the settings should be returned to baseline as soon as possible.

-For infants who do not tolerate the suctioning well (e.g., SpO2 decreases significantly, recovery takes a long time), discuss the case with Attending Physician or Neonatology Fellow and then write orders appropriate for the infant’s care.

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Extubation of the Trachea: A. Empty stomach before extubating the trachea. Do not feed patient for at least 4 h

after extubation, especially if trachea has been intubated for more than 24 h. B. Remove ET tube when it is clear that the infant no longer needs tracheal intubation

(i.e., PIP <20 cmH2O, ventilator rate <10, and PEEP ≤4 cmH2O). C. Suction the trachea and re-expand the lungs. D. Remove ET tube with lungs in full inspiration and with positive pressure applied to

the lungs to prevent aspiration of secretions when ET tube is removed. E. With extubation, increase inspired O2 concentration ~5%; then decrease it based

on SpO2. F. After tracheal extubation, monitor the infant carefully for early signs of respiratory

distress and hypoventilation (that may be immediate or progressive) including: •Grunting •Nasal Flaring •Stridor •Restlessness •Retractions •Cyanosis •Irritability •Tachycardia •Hypertension •Tachypnea •CO2 retention •Need for increased O2

G. For stridor (usually due to laryngeal edema), give inhalations of the vasoconstrictor,

racemic epinephrine 2.25% (0.2-0.25 mL). For bronchospasm, give inhalations of a bronchodilator, either metaproterenol (Alupent) 5% (0.1-0.2 mL) or albuterol (Ventolin) 0.5% (0.1-0.4 mL).

H. When there is progressive or severe respiratory worsening after extubation, reintubate the trachea early. Do not wait for respiratory failure. After reintubation, it is often necessary for a time to use higher ventilator pressures (to re-expand areas of atelectasis) than were needed just prior to extubation. Later, the pressures can be reduced. It may be useful to obtain a chest x-ray to rule out post-extubation atelectasis (4-8 h after extubation).

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METHODS of RESPIRATORY SUPPORT

General Principles: A. The aims of ventilatory support are to maintain adequate oxygenation and

ventilation, to reduce respiratory work and to prevent lung injury. B. With mechanical ventilation, use small or normal tidal volumes and the

lowest effective ventilator pressures. Both large tidal volumes and high pressures cause lung injury and inflammation, especially in preterm infants.

C. PEEP is critical for maintenance of FRC. PEEP is the main factor that influences PAW, a major determinant of oxygenation.

D. Minute ventilation (the amount of gas moved in and out of the lung per minute) is the product of respiratory rate and tidal volume.

Continuous Positive Airway Pressure (CPAP): A. CPAP, used during spontaneous breathing, increases FRC, lowers airways resistance,

and has variable effects on respiratory rate, minute ventilation and compliance. B. Application of CPAP by ET tube is the best way to ensure that the desired pressure is

applied to the lungs. C. Application of CPAP by mask or nasal prongs avoids the need for an ET tube, but

does not ensure that the desired pressure is applied. These forms of CPAP are useful to prevent re-intubation of the trachea in infants recovering from lung disease. In some cases, NCPAP is applied in the delivery room shortly after birth to reduce the need for tracheal intubation; the efficacy of this is unproven.

D. Gastric distention by nasal or mask CPAP may interfere with ventilation. E. The amount of pressure applied to the airway by NCPAP is not constant. The

pressure is decreased (even to atmospheric) when the mouth is open or the nasal prongs become dislodged.

F. NCPAP usually is not effective if >8 cmH2O pressure is required. G. Flow rates of 6 L/min are used during the application of CPAP. H. In some cases of apnea, CPAP is useful as a respiratory stimulant. Positive Pressure Ventilation (PPV): A. PPV by mask and bag is useful to stabilize the patient’s condition until the trachea

can be intubated and the lungs mechanically ventilated. B. In infants, PPV is usually pressure-limited (not volume-limited as in older patients)

and time cycled. This means that no more than the preset pressure can be generated and that respiratory rate is set by adjusting inspiratory (Ti) and expiratory (Te) times.

C. With each breath there is a PIP, a PEEP, and a PAW . D. Raising PEEP increases FRC (in most cases) and reduces/prevents atelectasis. If PIP

is not changed, raising PEEP reduces tidal volume and lowering PEEP increases tidal volume, when ventilation is pressure-limited.

E. Prolonging Ti allows more time for expansion of the lungs and is useful to treat widespread atelectasis. With localized atelectasis, a long Ti may worsen the infant’s condition by over-expanding non-atelectatic areas of lung and reducing venous return and pulmonary blood flow.

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F. High inspiratory flows may injure the lungs. Consequently, it is seldom necessary to use gas flows >10 L/min. Flows of 6 to 8 L/min are usual; some very small babies with mild lung disease can be ventilated with 4 L/min. Assess flow rates at start of PPV, with changes in respirator settings, and if the patient is not improving.

G. Ventilation pressures should be monitored continuously. Guides to adequate ventilation are normal chest movement and blood gas tensions.

H. Tidal volume is generated by the difference between PIP and PEEP. Changing PIP or PEEP independently of the other may increase or decrease tidal volume.

I. Oxygenation is primarily a function of FIO2 and PAW , “the area under the curve.” Figure 3 shows the effects on PAW during a single breath of changing each of the following: (1) inspiratory flow, (2) PIP, (3) Ti, and (4) PEEP. Note that when inspiratory flow is increased, PIP is reached earlier and the pressure wave becomes more “square,” but the durations of Ti and Te do not change. Also, (not shown in Figure 3) PAW increases when the respiratory rate is increased, because Te decreases.

J. Respiratory rate is altered by adjusting Ti and Te. A very short Te leads to gas trapping within the lung. The minimal required Te varies with the disease state of the lungs but usually should not be <0.6 sec with standard mechanical ventilation.

K. Ti is usually set at 0.3 to 0.4 sec (almost always <0.5 sec). Te will then be related to the respiratory rate. For example, if Ti = 0.4 sec and respiratory rate is 60/min, then each respiratory cycle lasts 1.0 sec; therefore, Te will be 0.6 sec. If respiratory rate is 30/min with the same Ti (0.3 sec), each respiratory cycle lasts 2 sec and Te will be 1.6 sec. (Note: the “I to E ratio” is calculated from the above. In the first example I:E = 1:1.5; in the second example I:E = 1:4. Do not manage ventilation by the I:E ratio. The actual Ti (to facilitate lung inflation), the actual Te (to avoid gas trapping) and the respiratory rate should guide ventilator management.

L. The time constant (TC) of the lung is a measure of the time necessary for the alveolar pressure to reach 63% of the change in applied airway pressure. For example, if Ti = one TC, only 63% of the pressure difference applied by the ventilator will be equilibrated at the alveolar level, and the delivered tidal volume will be proportional to the equilibrated pressure. TC is a function of lung compliance and airways resistance. When lung disease is not uniform throughout the lung, TC will vary in different parts of the lung. The longer the duration allowed for pressure equilibration (i.e., during Ti and Te), the greater the equilibration that will occur. Equilibration of pressures will be 86% complete when Ti (or Te) = 2TC and 95% complete when Ti (or Te) = 3TC. Further prolongation has little effect. If Ti or Te as set on the ventilator is not ≥3TC, there may be incomplete delivery of tidal volume (leading to hypoxemia and/or hypercarbia) or incomplete exhalation (leading to gas trapping, increased FRC, inadvertent PEEP and hypercarbia). TC varies with the state of the lung (i.e., type of lung disease). Examples include:

Lung Condition TC (sec) Normal newborn 0.12 Hyaline membrane disease (HMD) 0.025* Meconium aspiration syndrome 0.28

*TC increases markedly with recovery from HMD and with surfactant treatment. Ventilators also have a TC; for most ventilators, complete exhalation requires 0.3 sec.

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1.00.500

5

10

15

20

25

30

PAW

PEEP

Time (Seconds)

Airw

ay P

ress

ure

(cm

H2O

)

T i T e

PIP

Increased Flow

1.00.500

5

10

15

20

25

30

PAW

PEEP

Ti Te

Time (Seconds)

Airw

ay P

ress

ure

(cm

H2O

) PIP

Increased T i

1.00.500

5

10

15

20

25

30

PAW

PEEP

Time (Seconds)

Airw

ay P

ress

ure

(cm

H2O

)

T i Te

PIP

Original Respiratory Settings

Time (Seconds)

PEEP

PAW

1.00.500

5

10

15

20

25

30

PIP

Decreased PEEP

Airw

ay P

ress

ure

(cm

H2O

)

1.00.500

5

10

15

20

25

30

PAW

PEEP

Time (Seconds)

PIP

Increased PIP

Airw

ay P

ress

ure

(cm

H2O

)

Figure 3. Effects of changing different variables on the ventilator. Please see text for discussion.

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M. Common adjustments in respirator management: Condition Management Strategies High PaCO2 (>55 mmHg) Increase ventilator rate, if Ti & Te are not too short

Increase PIP Consider decreasing PEEP, if >5 cmH2O

Low or normal PaCO2 Decrease PIP, decrease rate

Low PaO2 Increase FIO2 (see Table 1)

Increase PAW by raising PEEP (or Ti, PIP and/or flow)

High PaO2 Decrease FIO2 Decrease PEEP (see Table 1).

The interrelationship between ventilator controls, pulmonary mechanics and ventilation in a newborn with a pressure ventilator are illustrated in Figure 4.

With pressure-limited ventilation, tidal volume depends on PIP – PEEP, lung compliance, and the pressure gradient between airway and alveolar pressures. A short Ti, in relation to the TC, will reduce tidal volume at a given pressure gradient. Lowering flow (L/min) may also decrease tidal volume, depending on Ti and TC.

FIGURE 4

PIP - PEEP

Ti

Minute Ventilation

Flow

Te

Rate

Oxygenation Alveolar Ventilation

PaO2 a nd Pa CO 2

PAW

Tidal Volume

R

CL

TC

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Raising PEEP to >6-7 cmH2O will rarely increase oxygenation. In fact high PEEP (and PAW ) may over-distend the lung, leading to increased dead space (hypercarbia) and right-to-left shunting (hypoxemia) and impair venous return and cardiac output. In this last case, PaO2 may be normal, but O2 transport and O2 delivery to the tissues will be reduced.

An additional variable is the compression volume of the ventilator circuit, the amount of gas compressed in the circuit with each breath (i.e., a compression volume of 5, a common value, means that for every cmH2O pressure generated, 5 mL of gas will be compressed in the circuit). Compression volume is not important in pressure-limited ventilation, but is a critical variable for volume ventilation.

N. As lung disease improves (especially after surfactant administration), reduce ventilator pressures to prevent lung injury. Table 1 gives guidelines to the relationship between FIO2 and PAW . In general, an infant in lower O2 should be able to tolerate lower airway pressures.

Table 1: A guide to the relationship between FIO2 and mean airway pressure.

FIO2 Mean Airway Pressure <0.25 5

0.25-0.30 6-7 0.31-0.40 7-9 0.41-0.50 8-10 0.50-0.60 9-11

>0.6 >10

O. Sedation is usually used to prevent “fighting the ventilator” and to facilitate mechanical ventilation. Initially, use morphine (0.05 - 0.1 mg/kg q3-4h). Other forms of sedation to consider include phenobarbital (2.5 mg/kg/day maintenance) and lorazepam (0.05-0.1 mg/kg q6-12h. Reserve use of muscle relaxants, or paralytic agents, (e.g., pancuronium 0.1 mg/kg IV) for those critically ill neonates who cannot be adequately ventilated. Following administration of sedatives or muscle relaxants, it is often necessary to alter the ventilator settings because oxygenation and carbon dioxide concentrations may change suddenly, in either direction.

P. With each change in ventilator settings, document the infant’s responses in tcPCO2, SpO2 and arterial blood gas tensions. Measurements of arterial pH and blood gas tensions should be made 15-30 min after each ventilator change during the acute phase of the disease, particularly when non-invasive monitors (i.e., SpO2 and tcPCO2) are not giving reliable results.

High Frequency Ventilation (HFV): including oscillator, flow-interruptor, and jet

ventilator: A. With these forms of ventilation, the lungs are ventilated at very high rates with tidal

volumes smaller than anatomic deadspace. B. Ventilation rates are very high, about 300 to 900 breaths/min.

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C. HFV is very effective in removing CO2. Thus, it is easy to hyperventilate the patient. However, because hypocarbia decreases cerebral blood flow and may cause brain damage, care must be taken to avoid respiratory alkalosis (i.e., pH>7.5).

D. HFV is less effective at increasing oxygenation. Therefore, compared to conventional ventilation, a higher PAW is required to achieve equivalent oxygenation.

E. HFV is most commonly used for patients who have air leaks (i.e., pneumothorax or pulmonary interstitial emphysema), pulmonary hypoplasia or severe pulmonary hypertension.

F. The oscillator (SensorMedics) pushes gas into the lung during inspiratory phase and pulls it out during the expiratory phase. This active exhalation may help prevent gas trapping. This ventilator is effective in large infants. Settings that can be adjusted are: Rate Usually between 6 and 12 Hz (360 to 720 breaths/min) Amplitude Similar to tidal volume

PAW Affects oxygenation Flow Affects inspiratory flow rate

G. The flow interruptor (Infant Star Ventilator) allows a rapid inflow of gas for a brief period, and then exhalation is passive. HFV can be used with or without a back-up rate of conventional ventilation. This ventilator is most useful in preterm infants, but is not usually effective in larger infants.

H. The jet ventilator injects a small volume of gas into the airway through a small tube connected to the endotracheal tube and entrains gas from the endotracheal tube. Gas can easily be trapped within the lung. Currently, jet ventilation is not used in the UCSF ICN.

I. Early studies suggested a higher rate of intracranial hemorrhage in very low birth weight infants treated with oscillatory ventilation, a finding not seen in later studies.

J. Because of the noise associated with HFV, it can be difficult to detect air leaks or other lung changes by physical examination and other monitors. Therefore, obtain a chest radiograph at least daily.

Synchronized Intermittent Mandatory Ventilation (SIMV): Conventional intermittent mandatory ventilation (IMV) produces mechanical breaths at preset intervals. In a spontaneously breathing infant, many ventilator breaths will be out of phase with the infant’s breaths. Consequently, the infant may struggle against the ventilator resulting in decreased oxygenation and ventilation and an increased risk of air leaks, unless the infant is heavily sedated or paralyzed.

SIMV provides mechanical breaths at a preset rate, but the exact timing of the ventilator breath occurs together with spontaneous breaths. SIMV synchronizes the ventilator breaths by sensing spontaneous inspiration efforts of the patient, using the “time frame window” concept: if the patient does not breath, the ventilator will deliver a mechanical breath; if the patient breathes too quickly, only a preset number of breaths will trigger the ventilator. The sensing of the spontaneous breath by the ventilator is accomplished either by (a) an abdominal sensor that detects respiratory movement or (b) a pressure sensor attached to a flow transducer on the adapter of the ET tube. With a properly functioning sensor, more than 90% of the ventilator breaths will be synchronized with the infant’s breaths, leading to increased oxygenation and ventilation, less need for sedation and less barotrauma to the lungs.

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With the current generation of infant ventilators, a variety of ventilatory techniques are possible, including SIMV, pressure support, and volume ventilation. The use and the details of management with these techniques should be discussed with the Neonatology Fellow or the Attending Physician for each individual patient. Complications of Assisted Ventilation: A. Ventilator Failure due to

(1) Accidental disconnection of the ventilator from the ET tube (which can rapidly lead to asphyxia) activates the low-pressure alarm of the ventilator.

(2) Obstruction of the ventilator tubing activates the high-pressure alarm. Ventilate the lungs by bag and tube. If no improvement, suspect obstruction of the ET tube. Remove ET tube and ventilate lungs with mask and bag. Reintubate the trachea when the infant’s condition is stable.

(3) Accidental tracheal extubation is usually accompanied by decreasing oxygenation and/or abdominal distension. Remove ET tube and ventilate by mask and bag. Because abdominal distension may prevent effective ventilation, insert an oro-gastric tube to remove gas from the stomach.

B. Pulmonary Tamponade occurs when lungs become over-expanded by gas trapped within the lung. Causes include: excessive PIP or PEEP, Te that is too short, air leak or a partially blocked ET tube. Effects of pulmonary tamponade include decreased chest movement, hypercarbia and hypoxemia. Severe tamponade impedes venous return and decreases cardiac output, causing blood pressure to decrease. If you suspect pulmonary tamponade and there is an indwelling arterial catheter, disconnect ventilator from ET tube for ~5 sec while carefully observing the blood pressure tracing. If tamponade is the problem and is due to maladjustment of the ventilator, the blood pressure will increase within a few heartbeats. Correct the problem by ventilator adjustment (e.g., lengthen Te, lower PIP and/or PEEP, shorten Ti).

C. Air Leaks (1) Pneumothorax

-A tension pneumothorax is an emergency heralded by a fall in SpO2 and a rise in PaCO2. Arterial pressure increases with a small pneumothorax, but with a large tension pneumothorax arterial pressure falls, pulse pressure narrows and central venous pressure increases.

-The ipsilateral hemithorax is hyperinflated (expanded), moves poorly with ventilation and may have decreased breath sounds. Heart sounds and maximal cardiac impulse may be shifted to the contralateral side.

-Increased transillumination on the affected side, but is not a constant finding. -If pneumothorax is suspected, order stat chest x-ray (AP & cross-table lateral) -If the patient’s condition rapidly worsens, insert a 22 gauge angiocath between

3rd and 4th ribs (midclavicular line over the superior aspect of the 4th rib) into the pleural space. Attach syringe and 3-way stopcock; then aspirate with the syringe. If gas is obtained, continue to remove gas from the chest, emptying the syringe through the 3-way stopcock.

-For long-term removal of air, insert an 8-10 Fr thoracostomy tube through the 5th interspace in the mid axillary line, directing the tube anteriorly. Remember that the intercostal neurovascular bundle is on the inferior surface of the ribs, so pass the tube over the top of the 6th rib. If the patient’s condition

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allows it, give 0.1 mg/kg of morphine IV and local anesthesia with 1% lidocaine (Do not give >5 mg/kg.). Once inserted, connect the chest tube to suction of 5-10 cmH20 in the suction chamber. In some cases of rapid air leak, it is necessary to place an anterior chest tube in the midclavicular line. Avoid inserting this catheter through the breast bud, nipple or areola.

-Suture the chest tube in place and apply a gas-tight dressing. -When there has been no gas leak for 24 h, turn off the suction on the chest tube.

Do not clamp the tube; leave it to underwater seal. If no gas accumulates in the pleural space after several hours, rapidly remove the chest tube at end-inspiration to prevent air from being sucked into the pleural space as the catheter is removed. Cover the wound immediately with a 2x2 gauze with bacitracin ointment on it to provide a seal, then close the chest tube hole with sutures or a clip, and obtain a repeat chest x-ray.

(2) Pneumopericardium -A pneumopericardium seldom causes problems for an infant. -Rarely, a tension pneumopericardium causes cardiac tamponade, obstructing

venous return and decreasing cardiac output. When this emergency occurs, immediately call the Neonatology Fellow or Attending and Cardiology. If the infant is rapidly worsening, insert a 22 gauge angiocath beneath the sternum just lateral to the xiphoid aiming towards the left shoulder. Apply negative pressure as the angiocath is advanced. As soon as air is obtained, stop advancing the needle or you risk injuring the heart. Withdraw the needle and leave the angiocath in place connected to a stopcock to allow evacuation of the gas. If there is time, insert the catheter into the pericardium under echocardiographic guidance.

-It is rarely necessary to insert a larger tube into the pericardium to remove air. (3) Pneumomediastinum seldom causes distress or requires treatment in infants. If

it does, have the surgeons insert a mediastinal tube. (4) Pneumoperitoneum results from perforation of a hollow viscus or from

dissection of air from the mediastinum into the abdomen. Differentiation between these may be difficult, but can usually be resolved by the following:

-Patients with bowel perforation often appear toxic with discoloration of the abdomen, leukocytosis and a left shift of the white blood cell count.

-Chest x-ray: A patient with dissection of gas from the mediastinum will almost always have lung disease with a pneumomediastinum or air seen in the inferior pleural ligament (“behind the heart”).

-Abdominal paracentesis: With bowel perforation, stool-like material can usually be aspirated. When pneumoperitoneum results from dissection of gas from the thorax, only gas can be aspirated.

-Measure PO2 of the aspirated gas. If infant is breathing >30% O2, the PO2 of the gas will usually be >150 mmHg if the gas is from the thorax. With bowel perforation, PO2 of the aspirated gas is almost always <100 mmHg.

Occasionally, enough gas dissects into the abdomen to restrict ventilation. If this occurs, insert a catheter or tube into the peritoneal cavity to drain the gas.

D. Chronic Lung Disease most commonly occurs in very preterm infants or after ventilation with very high pressures and FIO2 (See Chronic Lung Disease, P. 93)


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Intravascular Catheters ARTERIAL CATHETERS: Most infants admitted to the ICN will need an arterial catheter for measurement of blood pressure, pH and blood gas tensions. Usually, an umbilical arterial catheter (UAC) is used. Peripheral arterial catheters are indicated when:

•Catheterization of umbilical artery was unsuccessful. •It is desirable to measure pre-ductal PaO2 (i.e., from the right radial a.) •The UAC has been in place several days or was removed due to thrombus formation. •The infant is too old to catheterize an umbilical artery.

UMBILICAL ARTERIAL CATHETERS have the following advantages:

•Rapid and easy insertion •Accurate measurement of arterial blood pressure •Useful for administration of fluids, glucose and medications as well as blood sampling

1. Anatomy: The umbilical arteries are extensions of the internal iliac (hypogastric) arteries and extend from the pelvis to umbilicus in the anterior abdominal wall deep to the rectus muscle and fascia (Figure 1).

Figure 1A. Diagram of neonatal arterial system including umbilical artery. (Ao, aorta; DA, ductus arteriosus; IMA, inferior mesenteric a.; LCCA, left common carotid a.; LCIA, left common iliac a.; LRA, left renal a.; MPA, main pulmonary a.; REIA, right external iliac a.; RHA, right hypogastric a.; RUA, right umbilical a.) Figure 1B. Diagram of the umbilical venous system in a newborn infant. (DV, ductus venosus; FO, foramen ovale; IVC, inferior vena cava; PS, portal sinus; PV, portal vein; SVC, superior vena cava; UV, umbilical v.)

Intravascular Catheters

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B. Insertion of UAC:

1. Preparation. Use UAC Insertion tray and appropriate sterile technique including cap, mask and gloves. Restrain the infant’s limbs. For infants >1500g, use a 5 Fr catheter; for those ≤1500g, use a 3.5 Fr catheter. Attach a stopcock to the catheter and fill the system with sterile heparinized flush solution (usually 0.9% NaCl). Cleanse umbilical cord and adjacent abdomen with iodine solution. Drape the area so that only the umbilical cord is exposed. Place a cord tie around base of the umbilical cord and tie loosely. Cut the cord about 0.5 cm above the skin line. If bleeding occurs, tighten the tie.

2. Insertion of catheter. Hold cord stump gently upright. The umbilical vein is the single large, thin-walled vessel. The two arteries are smaller, thick-walled, and often tightly constricted. Gently insert the closed tips of the thin curved forceps into the lumen of an artery; allow the spring of the forceps to spread the forceps tips apart to dilate the artery (In extremely LBW infants, it may be necessary to insert only one tip of the forceps to begin the dilatation). Repeat the process several times until the lumen is well dilated and the forceps can be inserted into the lumen up to the bend in the forceps; this is exceedingly important. The most common cause of failure to catheterize an umbilical artery is inadequate dilatation of the artery. After the artery is well dilated, insert catheter tip into the lumen and advance the catheter while directing it towards the pelvis. The catheter may encounter obstruction at either the level of the abdominal wall or about 5 cm farther, approximately the level of the bladder. The obstruction can usually be overcome by gentle, steady pressure for 30-60 sec. Avoid excessive pressure or repeated probing of the artery, as these may cause arterial perforation. If the obstruction persists, leave the catheter in place and insert a catheter in the other artery; in most cases, you will be able to successfully catheterize one of the arteries. When the catheter has passed the point of obstruction, advance it the appropriate distance for the infant’s size (Table 1). Then, obtain blood sample for hematocrit, pH and blood gas tensions. Flush the catheter with heparinized saline and use care to avoid infusing bubbles. Measure arterial blood pressure. Then secure the catheter.

________________________________________________________________________ Table 1. Guide for distance to insert an umbilical arterial catheter.

Distance to insert umbilical Birth Weight (g) arterial catheter (cm)*

1,000 7 1,500 8 2,000 9 2,500 10

________________________________________________________________________ *Note that this guide cannot be used for umbilical venous catheters. 3. Securing the catheter: Use a round (non-cutting) needle with 4-0 silk, place one

suture through the wall of the cord and tie a firm knot. Wrap each end of the suture around the catheter only one time and tie the catheter tightly using a surgeon’s knot; tie


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firmly but do not occlude the catheter lumen. Be sure catheter cannot slip through the suture. Apply antibiotic ointment to umbilicus, cover with a dry 2x2 dressing and secure dressing and catheter with tape.

4. Location of catheter tip. Always verify location of the UAC tip radiographically; it should be in the abdominal aorta below the 3rd lumbar vertebra (L-3) and above the aortic bifurcation (usually, bottom of L-4). This will ensure that the tip is below the origin of the inferior mesenteric and renal arteries but still in an area of relatively high blood flow. If the UAC is advanced farther into the aorta and into the thorax, the tip will almost always pass through the ductus arteriosus into the pulmonary artery. This will lead to errors in treatment, because PaO2 and blood pressure in the pulmonary artery are almost always lower than in the aorta. After completing the catheterization, examine the infant’s legs for evidence of decreased femoral arterial blood flow (blanching, mottling, decreased or absent femoral pulse). If femoral flow is decreased, remove the catheter.

5. Catheter maintenance. Maintain a constant infusion of heparinized fluid through the UAC. Heparin concentration should be 1 unit/mL. Examine the legs daily and remove UAC if there is evidence of decreased femoral blood flow. Also, remove the UAC if there is damping of the arterial wave form (See below under Blood Pressure).

C. Complications of umbilical arterial catheters are listed below and can cause

serious, and sometimes fatal, consequences: -Ischemia due to obstruction of blood flow to the legs (see above). When UAC tip is

above L-3, there may be occlusion of the inferior mesenteric a. leading to bowel ischemia resulting in necrotizing enterocolitis (NEC). Do not feed an infant with a UAC. If abdominal distension or other signs of NEC occur, remove the UAC.

-Thrombosis, the most common complication of a UAC, may cause damping of the arterial tracing, NEC, renal insufficiency, hypertension (renovascular or secondary to aortic obstruction) or decreased blood flow to the legs. If there are signs of thrombosis, remove the UAC.

-Emboli occur from small bubbles inadvertently infused into the UAC (e.g., with flushing) or particulate matter from a thrombus on the UAC. If signs of emboli occur, remove UAC. Because packed RBCs infused into a UAC have caused infarcts of the spinal cord with resultant paralysis, do not give packed RBCs through a UAC.

-Vasospasm: If the leg blanches, warm the other leg to induce reflex vasodilatation. If improvement does not occur, remove the UAC.

-Hemorrhage will occur if UAC is accidentally disconnected from stopcock or tubing. -Vascular perforation may occur if excessive pressure is used to insert the UAC.

Massive intra-abdominal hemorrhage may result. -Hypoglycemia can occur if the UAC tip is above the recommended site. The infusion

of glucose may stream into the pancreatic a. via the celiac axis, causing hyperinsulinemia and resultant hypoglycemia.

-Infection is rare with arterial catheters and can usually be prevented by keeping the cord covered with antibiotic ointment and a dry dressing.


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PERIPHERAL ARTERIAL CATHETERS are useful in infants in whom UACs cannot be used. Peripheral arterial catheters can often be used for several days; complications have been minor and infrequent. The most commonly used site is the radial a.; the ulnar, dorsalis pedis, posterior tibial and, rarely, the axillary arteries can also be cannulated. Do not use temporal arteries because of possible CNS damage from retrograde emboli. Do not use brachial artery because of poor collateral circulation and risk of ischemia to hand and forearm. A. Radial Artery Catheterization: 1. Technique.

(a) Before cannulating or doing a single arterial puncture on a radial a., ensure that the ulnar a. is present by palpation or by the Allen Test. To perform the Allen Test, compress both the radial and ulnar arteries. Then, compress the hand to drain blood from the hand. Carefully release the ulnar artery while still compressing the radial. The hand should flush as blood flows through the ulnar artery to the hand. If the ulnar artery cannot be palpated and the Allen Test is negative, do not use the radial artery in that arm as ischemia of the hand may result.

(b) Extend the wrist to about 45o over a gauze pad; secure the hand and arm to a board. Apply tape so that the tips of all 5 fingers are visible. Cleanse the wrist with iodine preparation and wipe with alcohol.

(c) Palpate the point of maximal pulsation of the radial a. over the distal radius. Insert a #22 catheter (Angiocath™ or similar device) at an angle of 30º to 45o with the skin; use a #24 for very small infants. Advance the needle tip so that it enters the artery.

(d) When blood return is seen, advance the catheter over the needle into the artery and withdraw the needle.

(e) If the catheter cannot be advanced, it is not in the arterial lumen. Remove the catheter and apply firm pressure over the artery for several minutes to prevent formation of a hematoma. If a hematoma does form, it will probably not be possible to catheterize that artery.

(f) After advancing the catheter, attach it to a T-connector filled with heparinized saline for fluid infusion and measurement of blood pressure.

(g) Carefully secure the catheter to the skin with tape. Examine the tips of all fingers. If blood flow is inadequate, loosen the tape. If no improvement, remove the catheter.

2. Complications of Radial Arterial Catheters include: •Hemorrhage •Ischemia of hand •Retrograde emboli to CNS (if catheter is vigorously flushed)

B. Catheterization of Other Peripheral Arteries. Technique is similar to that used for the radial a. Before cannulating a peripheral artery, be sure you are familiar with the anatomy, including adjacent nerves and alternate routes of blood supply. Do not attempt to cannulate an axillary a. without discussion with Neonatology Fellow or Attending. C. Fluid Infusion in Peripheral Arteries. In most cases, use 0.9% or 0.45% NaCl. In some cases, 5% glucose can be used in a peripheral artery, but it must be infused at slow rate (i.e., 0.5 to 1.0 mL/h). To prevent vasospasm, lidocaine can be added to the infusion fluid at a concentration of 40 mcg/mL.


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VENOUS CATHETERS UMBILICAL VENOUS CATHETERS: In most circumstances, arterial catheters are safer and more useful than venous catheters. However, in some cases, an umbilical venous catheter (UVC) is desirable (e.g., for exchange transfusion, measurement of central venous pressure). A. Insertion of UVC: Preparations are similar to those for UAC. The vein is the large, thin-walled vessel in the cord.

•Remove any visible clots in vein with forceps. •Connect catheter to pressure transducer, before inserting it into the vein. •Insert catheter using only gentle pressure. •Never open UVC to atmospheric pressure as this may result in air embolism. •While continuously measuring pressure, insert catheter into umbilical vein.

B. Location of UVC Tip. Figure 1B shows the relevant anatomy. Note the several possible locations for the UVC tip, including umbilical vein, portal vein, portal sinus, right atrium, left atrium, left ventricle, pulmonary vein and SVC (rare). 1. The preferred location is beyond the ductus venosus in IVC or low right atrium. 2. Placement of UVC tip in the portal system is undesirable for the following reasons:

•Portal venous pressure is higher than central venous pressure, but by a variable amount and thus gives no useful information about the cardiovascular system.

•Infusion of hypertonic solutions (e.g., 10% glucose, NaHCO3) into the portal system may thrombose the portal vein.

•Exchange transfusion with the UVC tip in the portal system may cause necrotizing enterocolitis.

3. If the UVC tip is advanced farther into the right atrium, it almost always passes through the foramen ovale into left atrium. If advanced farther, the UVC tip will enter either the left ventricle or a pulmonary vein. Because of the risk of systemic emboli, do not allow the UVC tip to remain in the left side of the heart.

4. It is very unusual for a UVC to advance up into the SVC and into a jugular vein. C. Placement of UVC. The location of the UVC tip cannot be determined by the distance the catheter has been inserted. It must be localized using pressure measurements, measurements of PO2, and by radiograph: 1. Advance UVC while continuously measuring pressure. As the tip passes through the

ductus venosus, the pressure will decrease and the wave form will resemble an atrial pressure tracing (See Figure 2). If you are unsure if the tip is in the thorax stimulate the infant to take a deep inspiration or cry. If the UVC tip is in the thorax, there will be a negative pressure during spontaneous inspiration (Figure 2A). Note that the pressure never goes below atmospheric when the UVC tip is in the portal system (Figure 2B).

2. When the UVC tip has entered the thorax, take a blood sample to measure PO2; If PO2 is >50 mmHG, it is likely that the UVC tip is in left atrium, pulmonary vein or left ventricle. If it has been advanced into LV, a ventricular pressure wave will be seen. Withdraw UVC until tip is in right atrium (Blood will appear less pink and pressure tracing will have a dominant “a” wave; see below).


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Figure 2. Venous pressures measured through an umbilical venous catheter with tip

in the right atrium (A) and in the portal sinus (B). A. With the catheter tip in the right atrium, there are negative pressure deflections (I) during spontaneous inspiration. When the infant takes a deep inspiration or sigh (S), the pressure goes well below atmospheric pressure to about 10 mmHg. B. With the catheter tip below the diaphragm in the portal venous system, the mean pressure is higher than central venous pressure, the pressure goes slightly positive during inspiration (I) and never goes below zero (atmospheric pressure).

3. When catheter has been localized to right atrium by measurements of pressure and

PO2, secure catheter and obtain a chest radiograph to confirm the position. D. Complications of umbilical venous catheters include:

-Infection -Hemorrhage is unusual because of the low pressure in the umbilical venous system. -Air embolism is a potentially catastrophic event and may occur if bubbles are infused

or if the catheter system is opened to the atmosphere when the infant makes a strong inspiratory effort thus decreasing intrathoracic pressure below atmospheric. With the UVC tip in right atrium near the foramen ovale (or in left atrium), emboli will cross the foramen and be distributed in the systemic arterial circulation. Because both the coronary and cerebral circulations have high flows, it is likely that emboli will be distributed there.

-Portal venous thrombosis, especially if hypertonic fluids are infused with the UVC tip in the portal circulation.

-Necrotizing enterocolitis may occur from obstruction of portal venous flow if the tip of the UVC is in the portal circulation during exchange transfusion.

SURGICALLY INSERTED VENOUS CATHETERS: Other central venous catheters (e.g., subclavian, internal or external jugular) are usually inserted for parenteral alimentation. In most cases, these are inserted by a Pediatric or Cardiothoracic surgeon. Catheters used for intravenous alimentation should not be used for routine blood sampling but can be used for measurement of central venous pressure.


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PERIPHERALLY INSERTED CENTRAL CATHETERS (PICC) provide extended vascular access. They are very small silicone or polyurethane radiopaque catheters inserted into a peripheral vein via a needle or sheath introducer and advanced to a central location. These are not adequate for measurement of central venous pressure because they are soft and have a high resistance to flow. 1. Patient selection: Infants with the following needs are candidates for PICC placement:

•Predicted need for 5 to 7 d of continuous IV infusion •Greater than 7 d of IV antibiotics

Early placement, within 24 to 72 h after birth, is preferred, particularly in preterm infants. With known or suspected sepsis, defer PICC placement until the infant has received at least 24 h of IV antibiotic therapy.

2. Insertion procedure: (a) Preparation: Use prepackaged percutaneous catheter tray. Wash hands and clean

work surface with Cavicide™ or alcohol. Ensure supportive care as needed (analgesia, oxygen, assisted ventilation).

(b) Select appropriate site: •Use lower extremities as 1st choice, right arm next and left arm last. A PICC can

also be inserted centrally from a scalp vein. •Medial antecubital v. is usually easier than cephalic v. to thread to central location •If using upper extremity, turn patient’s head toward selected extremity •As a general rule, use only one extremity per insertion attempt •Restrain infant appropriately •Measure distance for catheter insertion:

-Upper extremity: measure from entry site to head of right clavicle, then down to 3rd intercostal space.

-Lower extremity: measure from entry site to the xiphoid process of sternum. -Scalp: measure from entry site to head of right clavicle, then down to 3rd

intercostal space and add 3 cm. (c) Insertion technique:

•Open tray, don mask and cap, scrub, and put on sterile gown and gloves. Rinse gloves with sterile water or use powder-free gloves. Prep and drape patient.

•Prepare catheter and needle; measure silastic catheter. Flush with heparinized sterile normal saline. The silicone catheters may be trimmed. Document final length of catheter in procedure note.

•Place catheter and introducer needle, gauze and forceps in sterile work area. Always use forceps to handle catheter. Apply sterile tourniquet.

•Insert introducer needle at 30-degree angle into desired vessel, advancing slowly until flashback of blood is evident.

•After flashback is seen: -Peel-Away Technique: After flashback, reduce the angle and advance introducer sheath to ensure that the introducer tip is within the vein. Never reinsert the needle into the introducer sheath if the venipuncture is unsuccessful. This could result in a sheared or severed introducer sheath. Withdraw the needle from the sheath, supporting the introducer sheath to


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avoid displacement. Apply digital pressure on the vessel above the insertion site to minimize bleeding. -Breakaway Technique: Ensure stability of introducer needle while advancing catheter into vein.

•Insert catheter into sheath/introducer needle and advance slowly to desired depth using forceps. Loosen tourniquet after catheter is advanced beyond tip of introducer. Flush intermittently to facilitate catheter advancement. Do not withdraw catheter while needle is in the vein, as this may shear off catheter. During insertion, observe ECG for dysrhythmia or bradycardia.

•Once catheter has been advanced to proper position, withdraw sheath/introducer needle while maintaining pressure on vein just beyond the needle tip to prevent inadvertent withdrawal of the catheter. Continue to apply pressure over the needle insertion site after the needle/sheath has been removed, as bleeding is common and often lasts for a few minutes.

•After with drawing needle or sheath: -Peel-Away technique: Split the introducer sheath and peel it away from the catheter, using care to maintain catheter position. -Breakaway technique: With the wings of needle facing downward, grasp each wing between thumb and index finger. Snap the wings upward until the plastic portion is completely separated. Peel away from the catheter allowing the catheter to fall down. The needle is not designed to break completely.

•Measure length of the catheter remaining outside of the skin. Subtract this measurement from total length of catheter. The remaining is the length of catheter in the patient and should approximate the previously calculated desired catheter insertion length. Make adjustments in catheter position as necessary.

•To ensure catheter patency, aspirate the catheter with a heparinized saline filled syringe to visualize blood return and then gently flush.

•Apply steri-strips over puncture site to secure catheter. Refer to nursing procedure for dressing guidelines.

(d) Documentation: Write a procedure note describing site, catheter type and length, tip location, patient response, and complications (if any). This information should be recorded on the PICC documentation form.

(e) Radiographic confirmation of catheter tip location: Use radio-contrast material (e.g., Omnipaque 180™) to visualize the catheter. Use 0.1 mL of contrast for Vygon™ 27 gauge, and NeoPICC™ 1.9 and 2.8 Fr catheters . Immediately before the x-ray cassette is exposed, instill the contrast at the hub of the catheter, injecting slowly with a 3cc syringe. Prior to exposing the x-ray, place the involved upper extremity in a position of maximal abduction, or the involved lower extremity in a fully flexed position. After radiograph has been taken, withdraw the contrast and gently flush the catheter with saline (0.9%) before reconnecting IV tubing. If the tip of the catheter is still difficult to visualize, repeat the film with a slightly oblique view with the side of catheter placement elevated. Monitor catheter tip placement with weekly (q Monday) radiographs.

(f) Proper location of catheter tip: For catheters inserted through arm or scalp vein, tip should be in SVC just above right atrium. For catheters inserted through a leg


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vein, catheter tip should be in IVC, just below right atrium. The tip of a PICC should never be in the heart, because of the risk of perforation and cardiac tamponade.

3. Guidelines for use:

•Appropriate infusates include crystalloids, alimentation fluid, lipids, continuous drug infusions, and albumin. Other blood products should not be infused because of clotting and hemolysis.

•All infusates must have heparin added at a concentration of 1 unit/cc. Minimal infusion rate is 1cc/hr.

•PICCs 1.9 Fr and larger may be placed to heparin lock for short periods but are at increased risk of occlusion by clot. The dose is 0.6 cc heparin (10 u/mL) q4hr.

•Blood sampling from PICCs is not recommended •For flushing, use a 3 or 5cc syringe for 1.9 Fr catheters, 3cc only for 27gauge. •In event of fungal line infection, the catheter should be removed and replacement

deferred until a negative blood culture has been obtained. Mild bacterial infections (i.e., Staph epidermidis) may be treated with a PICC in situ. If a repeat blood culture is positive or the infant’s condition worsens, the catheter should be removed.

4. Complications include:

•Infection, local or systemic •Vascular perforation •Atrial perforation with cardiac tamponade •Thrombophlebitis • Catheter leakage, breakage or perforation by needle; splitting or cracking at the hub •Embolism of broken catheter •Pleural effusion (chylous or IV fluid)

5. Catheter removal: There is a nursing procedure for catheter removal. The Resident or

NNP will be contacted for catheter damage or a stuck catheter (i.e., one that cannot be withdrawn). If a portion of a catheter is missing, obtain a stat “babygram” to locate the catheter embolus and notify the Attending or Fellow. For a stuck catheter, apply gentle tension and tape the catheter to the skin. Repeat hourly until the catheter is removed. Apply a warm compress to the affected extremity while removing the catheter.


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CARE OF INDWELLING CATHETERS 1. Keep catheters filled with fluid and free of blood except when obtaining blood samples. As soon as possible after inserting the catheter, begin infusion of heparinized fluid (1unit/mL) through the catheter. 2. Cover catheter insertion site with antibiotic ointment on a dry gauze pad. The dressing should be changed daily and the site inspected for signs of infection. Catheter sites, umbilical or other, should neither be left exposed nor covered with an occlusive dressing, which may cause maceration. 3. A guide to the types of fluids to be used in UVCs, UACs and peripheral arterial catheters is given in Table 2. Table 2. Guide for use of fluids in intravascular catheters.1

________________________________________________________________________ Peripheral Infusion Fluid UVC2 UAC3 Arterial Catheter 0.9% NaCl + + + 0.45% NaCl + + + 5% Glucose + + + 6 to 12.5% Glucose + + 0 Ringer's Lactate + + 0 Calcium + +4 0 Antibiotics and + + 0 Other Medications ________________________________________________________________________ (+ = acceptable; 0 = unacceptable) 1 Do not give intravenous alimentation with lipids and/or amino acids via UVC or UAC. 2 This guide assumes that it is known that the tip of the UVC is in IVC or right atrium and not in the portal system or the left side of the heart. 3 This assumes that it is known that the tip of the UAC is in proper position. 4 Give calcium into UAC as a push only in emergency situations.


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Blood Pressures Measure intravascular pressure continuously in all infants who have:

•Arterial catheters (umbilical or peripheral) •Umbilical venous catheters •Central venous catheters (Unless the infant's cardiorespiratory status is stable and

catheter was inserted only for intravenous alimentation.)

Figure 1. Diagram of system used for measuring intravascular pressures.

A, umbilical catheter; B, stopcock; C, pressure transducer. TECHNIQUE: Figure 1 shows the system for continuous direct measurement of intravascular pressures. Calibration of the system is done electronically. To apply zero pressure to the transducer, turn the stopcock (B in Figure 1) off to the baby and remove the syringe. This allows the transducer to read atmospheric (or zero) pressure. For this measurement, the stopcock must be at the level of the infant's midthorax.

(Never turn the stopcock so that the catheter is open to the atmosphere; serious hemorrhage can occur!)

ARTERIAL BLOOD PRESSURE varies directly with birth weight. Normal values for mean, systolic, diastolic and pulse pressures are shown in Figure 2. Before treating an infant for an abnormal blood pressure (arterial or venous), be certain that the calibration is accurate and that the zero pressure measurement has been checked. A. Causes of abnormal blood pressure:

1. Abnormal mean arterial blood pressure (a) Hypotension may be caused by:

•Hypovolemia •Shock (from any cause) •Tension pneumothorax or other severe air leak •Improper catheter position (e.g., pointing down femoral a. or through ductus arteriosus into pulmonary a.)

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•Excessive ventilatory pressures that impede venous return to the heart. To test for this, briefly disconnect the ventilator from the endotracheal tube. If ventilatory pressures are

excessive, arterial pressure will rise in <10 sec. •Marked alkalosis and hypocarbia •Myocardial failure due to:

-Asphyxia -Cardiomyopathy -Hypocalcemia -Cardiac arrhythmias -Congenital heart disease (left sided obstructive lesions)

•Drugs (e.g., PGE1, nitroprusside, isoproterenol, vancomycin [if infused rapidly])

(b) Hypertension may be caused by: •Hypercarbia, moderate asphyxia •Polycythemia •Renovascular disease •Drugs (e.g., dopamine, epinephrine, phenylephrine) •Hypervolemia usually does not cause systemic hypertension, but may cause

pulmonary hypertension. •Pain

2. Abnormal arterial pulse pressures (a) Narrow pulse pressure may be caused by:

•Damping of pulse wave (See below) •Tension pneumothorax or other severe air leak •Improper catheter position •Congenital heart disease (e.g., coarctation of aorta, aortic stenosis) •Myocardial failure •Shock

(b) Wide pulse pressure may be caused by: •Patent ductus arteriosus •Arterio-venous malformation •Truncus arteriosus •Vasodilator drugs

B. Damping of the blood pressure tracing is due to decreased frequency response of the system. It abnormally narrows the pulse pressure and should be suspected when the dicrotic notch is not visible on the blood pressure tracing. An example of damping of an arterial pressure tracing is shown in Figure 3. Damping can be caused by:

•Air bubbles in the catheter system or transducer •Blood in the catheter system •Clot in the catheter •Thrombosis of the artery •Kinking of the catheter (with peripheral arterial catheters) •Abnormal position of catheter tip (e.g., UAC pointed down a femoral a.) •Damping of venous blood pressure also can occur (e.g., when UVC tip is against the

atrial wall or wedged in the liver or a pulmonary vein)

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Damped Normal

Figure 3. Damped blood pressure tracing measured through an umbilical arterial catheter in a newborn infant. The damping was caused by an air bubble in the catheter system. When the bubble was removed, the fidelity of the tracing improved and both the anacrotic and dicrotic notches could be detected.

Damping will affect systolic, diastolic and pulse pressures. However, in most cases, the mean pressure will be accurate. 1. If there is damping of an umbilical arterial or venous pressure wave form and the

damping cannot be corrected by removing blood and/or bubbles from the system, remove the catheter. Do not flush a damped catheter. This may cause embolism with disastrous consequences.

2. Damping of the pressure wave from a peripheral arterial catheter is less serious and can be tolerated if the catheter samples well. Do not vigorously flush a damped peripheral arterial catheter because of the risk of retrograde emboli.

INDIRECT MEASUREMENT OF ARTERIAL BLOOD PRESSURE can be done with a cuff and an electronic monitor. In stable infants, indirect blood pressure is usually accurate. However, in some cases, indirect blood pressure is inaccurate and may be misleading (e.g., shock, marked vasoconstriction, extremely LBW infants).

When indirect blood pressure does not agree with directly measured arterial blood pressure, the direct measurement is more accurate if the calibration is correct and the zero pressure has been adjusted accurately.

CENTRAL VENOUS PRESSURE (CVP): In most cases, the trend in CVP (over several minutes to hours) is more helpful than the absolute value of the CVP. CVP may be difficult to interpret because it is affected by several factors.

A. Increased CVP may be caused by: •Hypervolemia •Myocardial failure (from any cause) •Excessive ventilatory pressures •Grunting respirations •Tension pneumothorax •Pleural effusion •UVC tip in portal system (i.e., not central venous)

B. Decreased CVP may be caused by: •Hypovolemia •Deep inspiratory retractions

80

40

0 Time (seconds)

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C. Location of UVC Tip. It may be difficult to know if the UVC tip is in right or left atrium even with radiographs and measurements of PO2. Comparison of the CVP tracing with the ECG tracing can be helpful. In right atrium, the “a” wave is dominant; in left atrium and pulmonary veins, the “v” wave is dominant (Figure 4).

______________________________________________________________________ Right Atrium Left Atrium or Pulmonary Vein ECG a v a v Pv Figure 4. Relationships of right and left atrial pressures to ECG in newborn infants. a, atrial “a” wave; v, atrial “v” wave; ECG, electrocardiogram; Pv, venous pressure

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Intensive Care Nursery House staff Manual

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Administration of Blood Products INTRODUCTION: Most infants admitted to the ICN will require transfusion of blood or blood products. Because of the unique characteristics of ICN patients, special precautions and procedures are necessary when administering blood products to them. It is important to remember that, except in an emergency, parental consent must be obtained before an infant is given a blood transfusion. TYPE AND CROSS-MATCH:

1. Packed red blood cells (PRBCs) should be type and Rh specific and, for untransfused newborn, cross-matched against the mother’s blood.

2. Platelets should be type and Rh specific. IRRADIATION of all blood products is routine for ICN patients. This is to prevent graft versus host disease in immuno-compromised patients. Because some patients require transfusion before their immune status is known, all blood products are irradiated. CMV NEGATIVE whole blood, PRBCs, platelet and white blood cells should be given to immuno-compromised patients to prevent tranfusion acquired CMV infection. However, because of the limited availability of CMV blood products, CMV negative products are given only to infants with birth weight <1.5 kg (and <4 months of age) and infants at high risk of being immune-deficient (e.g., congenital heart disease). SPECIFIC BLOOD PRODUCTS: Note: Whole blood is almost never available from the Blood Bank. Transfusion therapy is done by administration of PRBCs and other specific blood products 1. PRBC transfusion: The main reason for PRBC transfusions in the first week of life in low birth weight infants is anemia from phlebotomies for laboratory studies. Preterm infants recover from anemia at 34-36 weeks of gestation. Endogenous erythropoietin (EPO) is released when hematocrit (Hct) decreases to low 20s; reticulocytes increase 1 week later. Transfusion of infants at this point suppresses EPO and delays recovery. Indications for PRBC transfusions:

A. Clinical hypovolemia and Hct <40% (see section on Neonatal Shock, P. 101). In an emergency CMV negative, irradiated O negative blood may be given without type and cross match by Attending order. B. Anemia without evidence of hypovolemia

(1) Infant with cardiopulmonary disease: •Severe (e.g., RDS with PAW ≥10cm H2O and >50% O2, cyanotic heart disease,

pulmonary hypoplasia on assisted ventilation and in >40% O2): transfuse for Hct <40%

•Moderate (e.g., RDS with lower ventilator settings, PDA, Chronic Lung Disease): transfuse for Hct <35%

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•Mild (e.g., nasal CPAP, head hood O2): transfuse for Hct <30% •Apnea of Prematurity: transfuse for Hct <30% and worsening apnea (see section

on Apnea, P. 91). (2) Stable, growing preterm infant: Consider transfusion

•If Hct <20% and reticulocyte count <100 x 109/L. •If no weight gain for several days with adequate caloric intake, Hct <28% and

other signs consistent with anemia (e.g., tachycardia, tachypnea) (3) Infant with sepsis if Hct <30% (4) Infants with symptomatic heart disease: transfuse to keep Hct 40-45%. With large

left-to-right shunt, maintain Hct in 50-55% range. Except in emergency, discuss with Cardiology before transfusing any infant with heart disease.

Transfusion volume: PRBCs must be infused within 4h of their release from Blood bank. Therefore,

A. Infuse 15 mL/kg over 1-3h or B. Infuse 10mL/kg over 1-3h, check Hct 1h later and, if needed, give another 10 mL/kg

from same quadpack (same donor). C. Special Considerations

•For an infant unlikely to tolerate volume overload (e.g., symptomatic PDA, Chronic Lung Disease), use B (above) and give furosemide (1mg/kg IV) after 1st transfusion.

•For all transfusions, check Hct 1-4 h after completion of the transfusion. •If PRBCs are being given for volume resuscitation, give transfusion more rapidly,

over 15-30 min. 2. Platelet transfusion: See section on Bleeding Disorders (P. 115) for causes of thrombocytopenia

•¼ unit of platelets/kg will raise the platelet count more that 50,000 •give dried platelets for infants with concern for volume overload

Indications for platelet transfusion:

•Stable infant with platelets <20 x 109/L •Active bleeding with platelets <50 x 109/L •Platelets <50 x 109/L in a “sick” infant (e.g., preterm infant on mechanical ventilation)

Transfusion volume varies with condition. Usual starting volume is 10 mL/kg of platelets. For a term infant with birth weight >2.5 kg, transfuse 1 unit of platelets. 3. Plasma components are usually given for specific clotting deficiencies. See section on Bleeding Disorders (P. 115) for indications. Note: Fresh frozen plasma is to be used only for hemostasis. Treatment of hypovolemia is discussed in the section on Neonatal Shock (P. 101).


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Exchange Transfusion (ExTx) INTRODUCTION: This procedure, used most commonly to treat severe unconjugated hyperbilirubinemia, removes the infant’s circulating blood and replaces it with donor blood. The amount of blood exchanged is expressed as multiples of the infant’s blood volume. The standard “two volume” ExTx uses a volume twice the infant’s blood volume (i.e., 170 mL/kg). The procedure is done in small increments. As the procedure progresses, relatively more of the donor blood (infused earlier) and less of the patient’s own blood is removed. The washout of the infant’s blood is a simple exponential function: Volume exchanged Patient’s blood removed (of patient’s total blood volume) (% of total blood volume) 0.5 volume 39 % 1.0 volume 63 % 2.0 volume 86 % 4.0 volume 98 % These values are for washout of the vascular compartment. However, an ExTx will remove more bilirubin than shown above. This is because unconjugated bilirubin is distributed in both the intra-vascular and extra-vascular spaces, and will move rapidly into the intra-vascualr space as the concentration decreases during the ExTx. Thus, a 2 volume ExTx will remove twice as much bilirubin as was in the circulating plasma at the start of the procedure. However, because of continued movement of bilirubin into the vascular space, the plasma bilirubin concentration at the end of the ExTx will be reduced by only ½ of the pre-exchange level. PROCEDURE: There are several possible methods. Before proceeding with an ExTx, review the section on Intravascular Catheters (P. 25) paying particular attention to the sections on umbilical catheters. 1. Method and types of catheters: These methods are listed in decreasing order of preference (because of considerations of safety and effectiveness):

A. Continuous Exchange is performed by two operators, one infuses blood and the other simultaneously withdraws it. The best method is

•withdrawal from an umbilical arterial catheter (UAC) and infusion into an umbilical venous catheter (UVC) with tip in IVC or right atrium. Flush withdrawal catheter with heparinized saline every 10-15 min to prevent clotting.

Alternatives are: •withdrawal from a peripheral arterial catheter and infusion into a central

venous catheter. However, this is slow and the arterial catheter frequently clots. •withdrawal from a central venous catheter and infusion into a peripheral vein.

Flush the central catheter frequently to prevent clotting. B. Push-Pull Method can be done through:

•a single UVC with tip in IVC or right atrium. •a single UAC with tip in lower aorta (below 3rd lumbar vertebra)

Caution: Do not perform ExTx through a UVC if the tip is in the portal circulation. This may cause necrotizing enterocolitis by markedly decreasing bowel blood flow.

Exchange Transfusion

43


2. Technique: With the push-pull method, use increments of 5 mL/kg. Small increments are safer and just as efficient as larger ones, provided that you clear the donor blood from the dead-space of the catheter. Do this at the end of each infusion increment by withdrawing 2 mL of blood from the catheter into the syringe and then reinfusing it.

During the procedure, the operator(s) must call out the volume in and out with each infusion and withdrawal (e.g., “ten in - ten out”). A 3rd person must keep a written timed, running record of each infusion and withdrawal and of cumulative volumes to be sure that the volumes infused and withdrawn are equal.

Take 45-60 min to perform a 2 volume ExTx in a vigorous baby and longer in a sick one. If the infant is receiving O2 or assisted ventilation, measure pH, PaCO2 and PaO2 frequently (e.g., q 100 mL). You often will need to increase FIO2 during the ExTx.

3. Important reminders: •Monitor ECG, blood pressure, O2 saturation, transcutaneous CO2 and temperature

during ExTx. •Measure pH at mid-point and at end of ExTx (more frequently in a “sick” baby. •Measure glucose and electrolytes at end of ExTx, and glucose at 10, 30, 60 min later. •Warm blood to 34-35º C. Warming blood to >37º C causes hemolysis. •Agitate the unit of donor blood q 10-15 min so that cells do not settle. •ExTx does not significantly ↓ plasma gentamicin level; do not give an extra dose.

4. Complications of ExTx: Problem with Effect on Donor Blood Infant Prevention or Treatment

Blood is cold Hypothermia Warm donor blood to 34 - 35o C

High K+ Hyperkalemia, Use fresh blood, monitor ECG Arrhythmia Low pH (e.g., 6.9) Acidosis Consider buffering blood with THAM if infant is unstable. This will also ↓ [K+].

No platelets (old Thrombocytopenia Consider platelet Tx at end of ExTx. If ↑ risk blood or PRBC+FFP) of bleeding, also Tx platelets at mid-point.

Citrate anticoagulant Low Ca++ & Mg++ Give 30 mg/kg of dilute Ca gluconate, over 5 min at ¼, ½, ¾ and at end of a 2 volume ExTx, and if unexplained tachycardia or arrhythmia occurs.

High glucose Reactive Start IV glucose at 5mg/kg/min 10-15 min Hypoglycemia after end of ExTx; monitor blood glucose. Partial ExTx: •To raise hematocrit in severe anemia: see section on Anemia (P. 108) and Hemolyic

Disease of newborn (P. 121). •To correct polycythemia: see section on Polycythemia/Hyperviscosity (P. 112).


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Extracorporeal Membrane Oxygenation (ECMO) DEFINITION: ECMO is temporary support of heart and lung function by partial cardio-pulmonary bypass (up to 75% of cardiac output). It is used for patients who have reversible cardiopulmonary failure from pulmonary, cardiac or other disease. PHYSIOLOGY: Blood is drained from the patient to an external pump which pushes the blood through a membrane gas exchanger (for oxygenation and CO2 removal) and warmer and returns the blood to the patient’s circulation. The method requires heparin anticoagulation of the patient, that is managed by frequent measurements of activated clotting time (ACT). Various devices monitor pressures, flow, and temperature of the ECMO blood and gas circuits, as well as physiological variables in the patient. ECMO can be either:

(a) Veno-arterial (VA), in which blood is drained from right atrium (via a right internal jugular venous catheter) and is returned to the thoracic aorta (via a right carotid arterial catheter). VA-ECMO provides cardiac as well as pulmonary support.

(b) Veno-venous (VV), in which blood is drained from right atrium (via side holes of a double lumen catheter) and returned to the right atrium through the end hole of the catheter which is directed towards the tricuspid valve. VV-ECMO requires good cardiac function and avoids cannulation of the carotid artery.

Cannulation for ECMO is done by a Pediatric Surgeon and patient management is by Neonatology. With both forms of ECMO, the ventilator settings are decreased to allow recovery of lungs, but generally PEEP is maintained at higher pressure (e.g., 8 cm H2O) to prevent atelectasis. PATIENT SELECTION CRITERIA: Because of the potential risks of ECMO, criteria are designed to select patients with a high predicted mortality with conventional therapy. Selection criteria include:

-Gestational age ≥34 weeks -Mechanical ventilation for ≤14 d -Weight ≥1.8 kg -Failure of maximal medical management -Reversible disease -Predicted mortality ≥80% by historical criteria

Exclusion criteria include: -Major intracranial hemorrhage -Uncontrollable coagulopathy -Lethal malformation -Syndrome with poor prognosis -Severe neurologic injury

Clinical indications for ECMO include: -Oxygen index (OI) >40 on 2 or more arterial blood gas measurements [OI = (MAP x FIO2 x 100) ÷ PaO2] -PaO2 <40 mmHg for 4 h in 100% O2 -Intractable metabolic acidosis -Intractable shock -Progressive, intractable pulmonary or cardiac failure -Inability to come off cardiopulmonary bypass at operation

ECMO

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PRE-ECMO ASSESSMENT includes, in addition to chest x-ray and arterial pH and blood gas measurements:

-Physical examination with careful neurological examination -PT, PTT, fibrinogen, CBC with platelets, electrolytes, Ca, BUN, Creatinine -Cranial ultrasound -Echocardiogram -If patient is dysmorphic, consider emergency Genetics Consult

MANAGEMENT: Initial settings are aimed at bypass of ≥50% of cardiac output and are adjusted to maintain adequate oxygenation, blood pressure and acid-base status. With cardiac failure, VA ECMO is the preferred method. Because of recirculation, VV ECMO cannot usually support >50% of cardiac output, which may limit the ability to adequately oxygenate the patient. Patients on ECMO require frequent measurements of pH and blood gas tensions and various laboratory tests, as well as frequent transfusions with packed RBCs and platelets. Meticulous attention to all aspects of a patient’s condition is essential. The infants are sedated, but usually do not require paralysis while on ECMO.* Allowing the patient to move facilitates neurological assessment. As patient improves, ECMO support is gradually reduced. Patient is decannulated when able to tolerate minimal ECMO support on low to moderate ventilator settings. The duration of ECMO treatment is usually limited to 7-10 d for neonatal respiratory diseases, but longer treatment may be needed for newborns with diaphragmatic hernia and cardiac disease and in older children. *One exception includes patients with congenital diaphragmatic hernia prior to operative repair. They are usually kept paralyzed to prevent air swallowing which dilates the bowel, complicates the operation and interferes with pulmonary function.

COMPLICATIONS: -Hemorrhage (pulmonary, GI, surgical site) -Cardiac dysrhythmia -CNS damage (bleeding or infarction) -Renal failure -Seizures (metabolic or CNS causes) -Hyperbilirubinemia -Fluid retention and severe edema -Sepsis OUTCOME: Survival in neonatal patients varies with underlying disease. Disease Category Survival Aspiration syndromes >90% Persistent pulmonary hypertension 80% Infection 65% Congenital diaphragmatic hernia 50% Congenital heart disease 40% Cardiomyopathy 50% Note: The above comments apply primarily to neonatal patients. Occasionally, older infants and children, and even some adult patients, benefit from ECMO treatment.


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Routine ICN Nursing Procedures INTRODUCTION: For each infant admitted to the ICN, there are routine nursing procedures that are designed to assist in rapid evaluation of the infant’s status and to monitor the infant appropriately for his/her medical condition. These procedures are performed in addition to any physicians’ orders and vary according to the status of the patient. These routine procedures assist the House Officer by providing important patient data shortly after the infant has been admitted to the ICN and in preparing an infant for discharge from the ICN. I. ADMISSION PROCEDURES: A. Outborn infant transported from another facility:

1. Arterial pH and blood gas tensions while infant is in transport incubator 2. Weigh infant and transfer to ICN radiant warmer bed. 3. Apply monitors:

-Leads for cardio-respiratory and temperature monitors -Probe for Pulse Oximeter (oxygen saturation) -Skin electrode for continuous measurement of transcutaneous CO2

4. Measure and record vital signs and do physical assessment. 5. Connect IV fluids. 6. Obtain blood for the following:

-Hematocrit, CBC with differential, platelet count, and type, Rh & antibody screen

-If infant’s age >12h, blood is also sent for electrolytes, calcium, BUN, creatinine, and bilirubin (total and direct)

B. Inborn infant admitted from Resuscitation Room (Set-up Room) 1. Plug warmer bed into electrical outlet 2.Apply monitors:

-Leads for cardio-respiratory and temperature monitors -Probe for Pulse Oximeter (oxygen saturation) -Skin electrode for continuous measurement of transcutaneous CO2

3. Measure and record vital signs 4. Connect IV fluids 5. Unless obtained during resuscitation, send blood for Hematocrit, CBC with

differential, platelet count, and type, Rh & antibody screen. C. Infant with known or suspected cardiac disease: In addition to above, obtain:

1. 12 lead ECG 2. 4 limb blood pressures 3. Pre- and post-ductal saturation monitors (right upper limb and a lower limb)

II. DAILY ROUTINES: A. AM shift:

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1. 7:00 to 7:15 AM: Shift change and nursing bedside report 2. 8:00 to 9:00 AM: X-rays and ultrasounds done (Requisitions are to be filled out

by the Resident or NNP and posted near the Secretary’s Desk before 7:00 AM.) 3. Vital signs either q2h or q3h according to feeding schedule; if unstable, q1h 4. Bed meeting 8:30 AM daily: Charge nurse discusses planned admissions,

discharges and off-unit procedures as well as status of patients in Labor/Delivery 5. IV fluids changed in afternoon (i.e., intra-venous alimentation and lipids)

B. PM shift: 1. 7:00 to 7:15 PM: Shift change and nursing bedside report 2. Baths and weight done between 8:00 and 11:00 PM 3. Dressing changes for central catheters (Broviac q72h; femoral q48h) 4. Midnight: 24h intake and output totals calculated (based on current weight) 5. ~4:00 AM: routine labs are sent

III. DISCHARGE PROCEDURES: A. Complete “bumble bee” sheets (Discharge forms) B. Discharge physical exam (may be done ≤24h prior to discharge) C. Discharge medications: Complete prescription form ≈24h prior to discharge. These

are to include: 1. Vitamins with iron for premature infants 2. Iron for infants with cardiac disease

C. Discharge feedings: 1. Be sure that, for 2-3d before discharge, the infant is on the feeding routine

(volume, strength, frequency) which he/she will receive at home. 2. For growing VLBW infants (i.e., birthweight ≤1500 g):

-If formula fed, change to 22 calorie/oz Neosure Advance™. -If breast fed, fortify supplemental breast milk to 22 calorie/oz with Neosure

Advance™ powder. 3. The bedside Nurse or Discharge Coordinator will provide formula mixing

instructions and discharge education materials. D. Cardiac patients need chest radiograph and 12 lead ECG ≈24h prior to discharge E. Goal is to discharge patient by 11 AM.


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Health Care Maintenance

STANDARD MEASUREMENTS: You will need the following measurements and calculations to plan health care maintenance. Begin collecting these data as soon as the infant is admitted to the ICN.

•Body temperature and ambient temperature, if in an incubator •Daily weight and weight change over the previous 24h. Plot the daily weights on

postnatal growth chart •Head circumference measured weekly and plotted on growth chart •Fluid intake for the previous 24h •Total caloric intake for the previous 24h •Urine output for previous 24h, calculated both as mL/kg/hr and as total volume •Blood glucose screening and blood chemistries (see below for frequency of these

measurements) •Hematocrit, at least weekly

TEMPERATURE AND ENVIRONMENT: Both hypo- and hyperthermia ↑ oxygen consumption and caloric utilization. The less mature the infant, the greater the risk of hypothermia because of the higher surface area relative to body mass and the limited capacity for thermogenesis. Most episodes of hyperthermia result from misuse of incubators or radiant heaters. Heat loss occurs by: •Radiation to the surrounding cooler surfaces •Conduction to cooler surfaces in direct skin contact •Convection to cooler ambient air •Evaporative heat loss through skin as trans-epidermal water loss An isolation incubator provides warm ambient air at about 50% humidity, thereby reducing convective, and to a lesser extent, evaporative and conductive losses. Its relatively warm double-walls reduce radiant losses. A clear plastic wrap over the whole body reduces convective and evaporative losses but could obstruct the nose and mouth. Use this only in intubated infants. Clothing, particularly a hat, further reduces heat loss. Radiant heaters provide effective heating but create high evaporative water losses. Infants <36 weeks gestation should be placed in an incubator or under a radiant warmer with temperature probe on the skin. Set the incubator temperature at neutral thermal environment for infant's weight and gestational age (i.e., that environmental temperature at which oxygen consumption and caloric utilization are lowest). If an infant <1,500 g must be under a radiant warmer to allow easier access, cover the infant with a plastic wrap (if intubated) and cover the head with a hat. Temperature control for newborn infants is important to avoid the excess stress which hypo- or hyperthermia imposes on a newborn. To provide a neutral thermal environment,

Health Care Maintenance

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the incubator temperature should be kept at the temperatures shown in the following tables. Incubator Air Temperatures for the First 24 Hours after Birth Temperatures (ºC) Birth Weight (g) Median ± Range 500 35.5 0.5 1,000 34.9 0.5 1,500 34.0 0.5 2,000 33.5 0.5 2,500 33.2 0.8 3,000 33.0 1.0 3,500 32.8 1.2 4,000 32.6 1.4

Neutral Thermal Environment Temperatures According to Age and Birth Weight

Weight (g): <1500 1,501-2,500 > 2,500 Age Temperature (ºC) Temperature (ºC) Temperature (ºC) Day Median ± Range Median ± Range Median ± Range 1 34.3 0.4 33.4 0.6 33.0 1.0 2 33.7 0.5 32.7 0.9 32.4 1.3 3 33.5 0.5 32.4 0.9 31.9 1.3 4 33.5 0.5 32.3 0.9 31.5 1.3 5 33.5 0.5 32.2 0.9 31.2 1.3 6 33.5 0.5 32.1 0.9 30.9 1.3 7 33.5 0.5 32.1 0.9 30.8 1.4 8 33.5 0.5 32.1 0.9 30.6 1.4 9 33.5 0.5 32.1 0.9 30.4 1.4 10 33.5 0.5 32.1 0.9 30.2 1.5 11 33.5 0.5 32.1 0.9 29.9 1.5 12 33.5 0.5 32.1 0.9 29.5 1.6 13 33.5 0.5 32.1 0.9 29.2 1.6 14 33.4 0.6 32.1 0.9 15 33.3 0.7 32.0 0.9 Week 4 32.9 0.8 31.7 1.1 5 32.1 0.7 31.1 1.1 6 31.8 0.6 30.6 1.1 7 31.1 0.6 30.1 1.1 When the incubator is opened for procedures, use a portable overhead warmer with temperature probe and/or a Portawarmer™ to prevent hypothermia.


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Feeding of Preterm Infants INTRODUCTION: Proper nutrition in infancy is essential for normal growth, resistance to infection, long term health and optimal neurologic and cognitive development. Providing adequate nutrition to preterm infants is challenging because of several problems, some of them unique to these small infants. These problems include immaturity of bowel function, inability to suck and swallow, high risk of necrotizing enterocolitis (NEC), illnesses that may interfere with adequate enteral feeding (e.g., RDS, patent ductus arteriosus) and medical interventions that preclude feeding (e.g., umbilical vessel catheters, exchange transfusion, indomethacin therapy). PHYSIOLOGY AND PATHOPHYSIOLOGY: The gut has formed and has completed its rotation back into the abdominal cavity by 10 weeks of gestation. By 16 weeks, the fetus can swallow amniotic fluid. GI motor activity is present before 24 weeks, but organized peristalsis is not established until 29-30 weeks and is facilitated by antenatal corticosteroid treatment. Coordinated sucking and swallowing develops at 32-34 weeks. By term, the fetus swallows about 150 cc/kg/day of amniotic fluid, which has 275 mOsm/L, contains carbohydrates, protein, fat, electrolytes, immunoglobulins and growth factors, and plays an important role in development of GI function. Preterm birth interrupts this development. Even if nutrients are provided parenterally, lack of enteric intake leads to decreased circulating gut peptides, slower enterocyte turnover and nutrient transport, decreased bile acid secretion, and increased susceptibility to infection due to impaired barrier function by intestinal epithelium, lack of colonization by normal commensal flora and colonization by pathogenic organisms. For fat digestion, the newborn depends on lingual lipase, which is stimulated by sucking and swallowing and by nutrients in the stomach but not the small bowel. The figure is a chronological representation of GI development during fetal life.

0 5 10 15 20 25 30 35 40

Gestation (weeks)

Figure. Chronology of gastrointestinal development in the fetus.

Feeding of Preterm Infants

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CONTRA-INDICATIONS TO FEEDING: Do not start feeds if the infant:

•is receiving indomethacin, or received it within the previous 48h •has a hemodynamically significant patent ductus arteriosus •has either an umbilical arterial or venous catheter. Do not start feedings until the

catheters have been removed for ≥8h. •is polycythemic. •has significant metabolic acidosis. •has severe respiratory instability or there is impending endotracheal intubation •has hemodynamic instability as evidenced by clinical signs of sepsis, hypotension,

is receiving dopamine (at a dose >3 mcg/kg/min) or other vasopressor drugs •received an exchange transfusion within the past 48h. •has abdominal distension or other signs of GI dysfunction. •has had an episode of severe asphyxia (perinatal or post-natal) in the previous 72h.

FEEDING PROTOCOL: The following are guidelines for the initiation and advance of enteral feedings in preterm infants: 1. Method of feeding: Because these infants usually have not yet developed coordinated sucking and swallowing, they must be fed by gavage:

-Orogastric tubes are usually used. Because infants are obligate nose breathers, it is best not to occlude the nares with a tube. In addition, repeated insertion of a nasal gastric tube can cause inflammation of the nose with subsequent obstruction.

-Estimate length of tube that must be inserted to reach the stomach. -Insert the tube and aspirate to see if gastric contents are returned. While listening

over stomach with stethoscope, inject ~5cc of air. If tube is in stomach, you should hear bubbling as you inject air. If you cannot hear any bubbling, tube may be in the trachea. Therefore, do not feed infant until you are certain that tube is in stomach.

-Do not use duodenal or jejunal tubes for gavage feedings as feedings are less well tolerated and do not stimulate secretion of lingual lipase. In addition, residuals are no longer useful in assessing tolerance of feedings.

-Nipple feedings can be considered as the infant matures. The best judge of when to start nipple feedings is an experienced Nurse.

2. Content of feeding: Begin with either: -Breast milk (preterm breast milk is 290 mOsm/L) or -Formula for preterm infants (e.g., Premature Enfamil™ or Similac Special

Care™, 260 mOsm/L). -Some physicians use half-strength feedings, but there is no evidence that this is

beneficial. In fact, hypo-osmolar solutions may slow gastric emptying, leading to increased incidence of residuals and feeding intolerance.

-Remember that fetuses swallow amniotic fluid, which is 275 mOsm/L, and this swallowing begins at 16 weeks gestation.

3. Guidelines for Feeding: Initiation of feedings, their volume and the rate of advance of feedings are related to birth weight, gestational age and how the infant has tolerated feeds to date. General guidelines include:

•Initial volume is 2 cc/kg per feeding with a minimal absolute volume of 2 cc


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•Do not advance feedings faster than 20 cc/kg/d. •Do not advance feedings if there are any signs that the baby is not tolerating

feeds. Aggressive advances of feedings increase the risk of NEC. •A small volume, even if not advanced, is much better than nothing at all. Even very

small volumes stimulate maturation of gut motility and production of enteric peptides.

•Bolus feedings are preferable to continuous feedings. •The goals for “full feedings” are:

-Volume: 150-160 cc/kg/d -Calories: 110-120 kcal/kg/d -Some SGA infants will require a higher caloric intake to achieve consistent

weight gain. Detailed recommendations for feeding are shown in the following table. Table. Recommendations for feeding of preterm infants. Volume of Gestational first feed Rate of feeding Age (weeks) (cc/kg) Frequency advance 24 to 26 2 or q6-8h None for 5-7d, then 2 cc total 10-15 cc/kg/d 26-28 2 q4-6h None for 3-5d, then 10-20 cc/kg/d 28-32 2 q4h As tolerated, but aim to reach

full feeds only after 7d

FORTIFYING FEEDINGS not only provides mores calories but also improved intake of calcium, phosphorus and protein. Fortify feedings (breast milk and formula) as follows:

-When infant is tolerating ≥100 cc/kg/d, feedings may be fortified to 22 cal/oz. -When infant has been tolerating ≥150 cc/kg/d for at least 2d, feedings may be

fortified to 24 cal/oz. INTOLERANCE TO FEEDINGS is common among very small preterm infants, and most such infants will have episodes that require either temporary discontinuation of feedings or a delay in advancing feedings. Although most episodes resolve spontaneously and without sequelae, any signs of feeding intolerance should be regarded as potentially serious because of the increased risk of NEC among these infants. Signs that indicate possible intolerance of feeding include:

-Gastric residuals or emesis -Abdominal distension -Blood in the stool (gross or occult) -“Loose stools” or diarrhea -Metabolic acidosis -Temperature instability -Onset of apneic episodes -Hyperglycemia


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MANAGEMENT OF FEEDING INTOLERANCE should be related to the type and severity of the presenting signs, as described below: 1. Gastric residuals:

•Non-bilious residuals: -If these are smaller than the volume of a feeding and are not increasing in

volume, and if the infant otherwise appears well, feeding can continue but the infant should be observed carefully for other signs of feeding intolerance. If the infant has any other worrisome findings, hold the feedings, consider obtaining an abdominal radiograph and observe the infant.

-If the residuals are greater than the volume of a feeding or are progressively increasing in volume, hold the feedings and observe closely.

•Bilious residuals are a serious sign. Hold feedings, evaluate infant closely, and consider further workup including abdominal radiograph, CBC and platelets.

2. Abdominal distension is a serious sign. Discontinue feedings, obtain abdominal radiograph, and consider further evaluation and treatment (see section on NEC, P. 133).

3. Blood in stools: Discontinue feedings, consider obtaining clotting studies and abdominal radiograph.

4. If metabolic acidosis occurs, hold feedings, evaluate closely for NEC, sepsis, hypotension and a patent ductus arteriosus. Metabolic acidosis in the presence of NEC is a grave prognostic sign.

5. Loose stools, temperature instability, apnea, hyperglycemia: Hold feedings and evaluate infant carefully.

If feedings have to be stopped for any of these reasons, notify the Neonatology Fellow and/or the Attending Physician, so that they can follow the infant’s condition with you. If there is any doubt about how well an infant is tolerating feedings, it is best to hold feedings, evaluate the infant and discuss the case with the other members of the team. Experienced ICN Nurses are experts at feeding small preterm infants and are valuable resources for advice on feeding problems.


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Formula Analysis* and Feeding Recommendations

Nutrient AAP-CON 19981 (per kg/d) Preterm

MBM 24 with HMF2: 150 ml/kg

PE 243 150 ml/kg

SSC 244 150 ml/kg

Similac Neosure Advance 150 ml/kg

Term MBM 150 ml/kg

Enfamil Lipil 150 ml/kg

Similac Advance 150 ml/kg

Dietary Reference Intakes5: Full Term

MVI with iron 1 ml/d

ADEK 1 ml/d

Kcal/kg 90-120 120 121 121 112 102 101 101 80-110/d -- -- Protein (g) 3.5-4.0 3.1 3.6 3.3 2.9 1.57 2.1 2.1 1.52 g/kg/d -- -- CHO (g) 10.8-15.6 11 13.4 12.8 11.5 10.7 11.1 11 60/d -- -- Fat (g) 5.4-7.2 7.2 6.2 6.6 6.1 5.9 5.4 5.5 n/a -- -- Vitamin A (IU) 90-270 1716 1512 1512 513 338 304 304 1333/d 1500 1500 Vitamin D (IU) 324 222 290 181 78 3 61 61 300/d 400 400 Vitamin E (IU) >1.3 7.3 7.6 4.8 4 0.6 2 1.5 4/d 5 40 Vitamin K (mcg) 4.8 6.7 9.7 14.5 12.3 0.3 8.1 8.1 2/d -- 100 Thiamine (mcg) >48 250 242 302 246 32 81 101 200/d 500 500 Riboflavin (mcg) >72 372 363 750 167 52 142 152 300/d 600 600 Vitamin B6 (mcg) >42 198 181 302 112 31 61 61 100/d 400 600 Vitamin B12 (mcg) >0.2 0.3 0.3 0.7 0.45 0.07 0.3 0.25 0.4/d -- 4 Niacin (mg) >3 4.6 4.8 6 2.2 0.2 1 1.1 2/d 8 6 Folic acid (mcg) 39.6 43.5 48.4 44.8 28 7.1 16.2 15.2 65/d -- -- Pantothenic acid (mcg) >360 1330 1452 2298 893 270 507 456 1700/d -- 3 Biotin (mcg) >1.8 4.6 4.8 44.8 10 0.6 3 4.5 5/d -- 15 Vitamin C (mg) 42 23.5 24.2 44.8 16.7 6.1 12.2 9.1 40/d 35 45 Calcium (mg) 210 172 200 218 117 42 79 79 210/d -- -- Phosphorus (mg) 110 94 100 121 69 21 54 43 100/d -- -- Iron (mg) 2-3 2.1 2.2 2.2 2. 0.04 1.8 1.8 0.27/d 10 -- Zinc (mg) >0.6 1.2 1.8 1.8 1.3 0.2 1 0.8 2/d -- 5 Sodium (mEq) 2.5-3.5 2.1 3 2.3 1.6 1.2 1.2 1 -- -- -- Potassium (mEq) 2.0-3.0 3 3.1 4 4.1 2.1 2.8 2.7 -- -- --

1. American Academy of Pediatrics, Committee on Nutrition 1998; based on recommendations per 100 kcal calculated for 120 kcal/kg/d 2. Term Maternal Breastmilk with Human Milk Fortifier (Mead Johnson), 24 kcal/oz 3. Enfamil Premature Lipil with iron, 24 kcal/oz 4. Similac Special Care with iron, 24 kcal/oz 5. Dietary Reference Intakes/Adequate Intake 1998/2000/2002

*Compiled from Neonova Nutrition Optimizer 4.55, 2002; Ross Products Division , Spring 2003


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UCSF ICN Vitamin Policy

Preterm infants: Feeding Vitamin Supplement q d Iron Supplement q d Unfortified breastmilk* Polyvisol 1 mL, folate 50 mcg 2-4 mg/kg/d MBM 24 with EHMFψ None 0-2 mg/kg/d‡ PE 24 or SSC 24 w/Fe None 0-2 mg/kg/d‡ Term Formula* with Iron Polyvisol 1 mL, folate 50 mcg 0-2 mg/kg/d‡ (MBM, maternal breast milk; EHMF, Enfamil Human Milk Fortifier; PE, Premature Enfamil; SSC, Similac Special Care)

Preterm infants being treated with Recombinant Erythropoietin: Feeding Vitamin Supplement q d Iron Supplement q d Unfortified breastmilk* Polyvisol 1 mL, folate 50 mcg,

vitamin E 15 IU♦ 6 mg/kg

MBM 24 with EHMFψ vitamin E 15 IU♦ 4 mg/kg‡ PE 24 or SSC 24 w/Fe vitamin E 15 IU♦ 4 mg/kg‡ Term Formula with Iron* Polyvisol 1 mL, folate 50 mcg,

vitamin E 15 IU♦ 4 mg/kg‡

♦vitamin E dosing: Aquasol E=15 IU/0.3 mL

Preterm infants preparing for discharge: Feeding Vitamin Supplement q d Iron Supplement q d Unfortified breastmilk Polyvisol with iron 1 mL none Similac Neosure Polyvisol 1 mL (until 500 ml/d) 0-2 mg/kg‡ Term Formula with Iron Polyvisol 1 mL (until 750 ml/d) 0-2 mg/kg‡

Term infants Feeding Vitamin Supplement q d Iron Supplement q d Maternal breastmilk Consider Vitamin D 200 IU by 4-6 months Term Formula with Iron none none

Infants with congenital heart disease Weight Fer-in-sol (15 mg elemental iron/0.6 cc) <2.3 kg 7.5 mg iron/0.3 ml q d 2.3-4.5 kg 7.5 mg iron/0.3 ml bid 5-6.8 kg 11.25 mg iron/0.45 ml bid 7.3-9.1kg 15 mg iron/0.6 ml bid >9 kg 15 mg iron/0.6 ml bid NOTE: Infants with congenital heart disease need additional iron supplementation. The dose will need to be increase as weight increases to maintain minimum intake of 3 mg/kg/d.

All infants A fluoride source is needed by 6 months of age (corrected GA for preterm infants). *Preterm infants on full feeds should be fed fortified breastmilk or preterm formula, unless there are clinical reasons to

use another formula or not to fortify breast milk. ψEnfamil Human Milk Fortifier (EHMF) contains iron ‡Assumes infant will receive iron 2 mg/kg/d in formula at volume to meet 120 kcal/kg/d.


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Fluids and Electrolytes INTRODUCTION: The requirements for fluids and electrolytes of the newborn infant are unique. At birth, there is an excess of extra-cellular water (ECW), and this decreases over the first few days after birth. Furthermore, ECW at birth and insensible water loss decrease as birth weight and gestational age increase. Several days after birth, fluid and electrolyte requirements increase as the infant starts to grow. Therefore, appropriate management of fluids and electrolytes in preterm infants must take into consideration the birth weight, gestational age and age after birth. Fluid and electrolyte requirements are also influenced by a variety of medical conditions that affect preterm infants (e.g., RDS, patent ductus arteriosus, necrotizing enterocolitis). BODY COMPOSITION at birth varies with gestational age and body weight. Examples are shown in the table below. (BW, body weight)

Gestation Body Total Body ECW Body (weeks) Weight (g) Water (%BW) (%BW) Fat (%BW) 24-27 <1,000 85-90 60-70 0.1-2.5 28-32 1,500 82-85 50-60 3.3-5.5 36-40 >2,500 71-76 ~40 9-16

After birth, infants lose weight due to loss of ECW, and this is proportionately greater in smaller, less mature infants. Weight loss after birth reflects this difference in ECW; term infants normally lose up to 5% of their body weight, whereas very immature infants may lose up to 10-15%. Thus, fluid replacement must be adjusted accordingly.

INSENSIBLE WATER LOSS (IWL) is greatest in the smallest and least mature infants due to high surface area to body mass ratio and to immature, water-permeable skin. Estimated IWL in the first few days of life are:

Body Insensible water loss (mL/kg/d) Weight (g) In Radiant Warmer In Incubator <1,000 100-150 75-100 1,000-1,500 75-100 50 1,500-2,000 50 25-50 >2,000 50 25-50

Phototherapy can increase IWL by 25-50%. IWL may exceed urinary output in smaller infants but, unlike urine output, IWL cannot be measured directly. However, IWL must be estimated in order to plan appropriate fluid management. IWL can be estimated by:

IWL = Fluid intake - Urine output + weight loss (or – weight gain) (e.g., 24-hour totals = intake 90 mL, urine output 60 mL, and weight loss 55 g. Therefore, IWL = 90 - 60 + 55 = 85 mL)

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Some SGA infants have increased IWL and, therefore, need increased fluid intake to compensate for this (see section on Intrauterine Growth Retardation, P. 69). INITIAL FLUID ADMINISTRATION: Guidelines for the first few days of life are: •For larger infants (i.e., >1,250 g) start at 60 mL/kg/d of D10W. If estimated ILW is

high (e.g., extreme prematurity, abdominal wall defect), start fluids at higher rate, 80-100 mL/kg/d.

•Normal glucose utilization rate in a newborn is 4-8 mg/kg/min. Initial glucose administration rate should be in that range.

•Extremely premature infants (23-26 weeks gestation) under radiant warmers may occasionally require more than 200 mL/kg/d during the first 2 to 3 days of life.

•Increase IV fluid rate if weight loss is >expected, urine output is low, urine specific gravity is rising, and/or serum sodium concentration [Na+] is rising.

•Conversely, decrease IV fluid rate if serum [Na+] is falling, weight did not decrease appropriately or actually increased.

•Proper fluid management requires accurate determination of urinary output in mL/kg/h. In the first 24h after birth, urine output may be very low (or even absent) in normal newborns. After the first day, urine output should be >1 mL/kg/h.

•If you make a major change in the rate of fluid infusion, you must also change the glucose concentration proportionately to maintain a constant rate of glucose delivery and prevent hyperglycemia (and osmotic diuresis) or hypoglycemia.

•Fluid requirements gradually decrease by day 5-6 as skin permeability decreases. INITIAL ELECTROLYTE MANAGEMENT:

1. General guidelines: •All infants receiving only IV fluids should have daily measurements of electrolytes for

the first few days of life. The frequency can be reduced as condition stabilizes. •For infants <750 g, measure electrolytes within 12h of birth to have a baseline, so that

adjustments in fluid intake can be made as serum sodium changes. In these extremely preterm infants, significant hyperkalemia may develop in the first 48-72h.

•Measure BUN and creatinine initially and at least every other day until stable, then weekly until feedings are well established.

•Measure magnesium in first few hours after birth if mother had received magnesium. Suggested frequency of measurements of electrolytes, including calcium for infants receiving only IV fluids:

<750 g q8-12 h x 3-4d, then daily 750-1,500 g q12 h x 3-4 days, then daily >1,500 g daily

2. Sodium:


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•Do not add Na+ to IV fluids on the first day; wait until day 3-4 when [Na+] begins to fall. Na+ is usually given as NaCl, but Na-acetate may be used to decrease metabolic acidosis from renal bicarbonate wasting in ELBW infants.

•Usual maintenance for Na+ is 2-4 mEq/kg/d. 3. Potassium (K+): •Do not add K+ to IV fluids for the first few days after birth, until urine output is well

established and serum K+ level starts to decline. K+ may be given as KCl or K-acetate. •Usual maintenance for K+ is 1-3 mEq/kg/d. 4. Calcium (Ca++): •Ca++ should be started on the first day after birth especially in infants who are preterm,

SGA, asphyxiated, septic, and post operative, and infants of a diabetic mother. •Ca++ may be added to the IV solution infusing through central catheters after the

location of the catheter tip has been verified radiographically to be in proper position. This includes umbilical arterial and venous catheters and central venous catheters (see section on Intravascular Catheters, P. 25).

•Ca++ should not be added to IV solutions infusing in peripheral veins because extravasation of Ca++ containing solutions may cause severe sloughing of skin. If peripheral IV access is being used, Ca++ should be given as an intermittent bolus over 5 to 15 minutes while watching the IV insertion site to ensure that fluid is not infiltrating into the tissues.

•Usual maintenance for Ca++ is calcium gluconate 200-400 mg/kg/d. •Usual intermittent dose is calcium gluconate 50-100 mg/kg IV q6h.

ELECTROLYTE ABNORMALITIES: 1. Hyponatremia is defined as serum [Na+] <130 mEq/L. Hyponatremia may cause hypotonia, apnea, and, if acute and severe, seizures. In the first few days after birth, hyponatremia usually indicates fluid overload (i.e., dilutional hyponatremia). After the first week, it may be either dilutional or indicate a true deficit of total body Na+.

A. Dilutional hyponatremia is usually accompanied by weight gain or absence of expected weight loss and may be secondary to:

•Renal dysfunction with ↓ urine output and usually a low urine specific gravity. •Excessive water intake, often with high urine output and low specific gravity. •Congestive heart failure with ↓ urine output and ↑ specific gravity. • ↑ extracellular fluid volume (e.g., water retention due to sepsis, prolonged use of

muscle relaxants). •Syndrome of inappropriate secretion of anti-diuretic hormone (SIADH) with low

urine output and high urine specific gravity. This condition is rare.

Dilutional hyponatremia should be treated primarily by fluid restriction. However, if serum [Na+] is <120 mEq/L, the baby may require additional Na+ as well.

B. Sodium deficiency may be accompanied by weight loss and may be caused by:

•Diuretic administration •Renal Na+ losses •Low Na+ intake •Osmotic diuresis from hyperglycemia •Gastrointestinal Na+ losses


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Treat Na+ deficiency by treating the underlying condition and increasing Na+ intake. If hyponatremia is caused by diuretic treatment for chronic lung disease, consider decreasing the diuretic dose or giving the diuretic every other day instead of daily, and consider tolerating lower serum [Na+] (e.g., 125-130 mEq/L). Total body deficit of Na+ can be calculated by: Na+ deficit (mEq) = (desired [Na+] - current [Na+]) x 0.8 x body weight (kg) (0.8 x body weight is the volume of distribution for Na+)

C. Symptomatic hyponatremia: (e.g., seizures or [Na+] <120 mEq/L). Calculate

Na+ deficit to raise [Na+] to 125 mEq/L and give as 3% NaCl (0.5 mEq/mL) over 3-6h. Correct remaining deficit over next 24h.

D. Asymptomatic hyponatremia: Calculate total deficit of Na+ and give ½ over 6-

8h and the rest over the next 24h, as Na+ added to IV fluids. 2. Hypernatremia (serum [Na+] >150 mEq/L) may cause hyperexcitability and hyperreflexia. Severe hypernatremia (serum [Na+] >160 mEq/L) may cause permanent CNS damage. Hypernatremia is usually secondary to excess Na+ intake or negative water balance. Usually in a newborn, excessive Na+ intake leads to excess total body water, and, thus, serum [Na+] is normal. When hypernatremia is due to excessive Na+ intake, restrict Na+ intake and consider administering diuretics. When due to water deficit, it is associated with weight loss and should be treated by increasing free water to correct negative water balance slowly. In babies with meningitis, hypoxic ischemic encephalopathy or severe intracranial hemorrhage, consider diabetes insipidus, which should be treated initially by increasing free water administration. Rapid correction of hypernatremia may cause seizures and permanent neurodevelopmental sequelae. Therefore, do not lower serum [Na+] more rapidly than 10 mEq/L q12h. 3. Hypokalemia (serum [K+] <3 mEq/L) may cause ileus, arrhythmia (unusual unless [K+] is <2.5 mEq/L), and altered renal function. Hypokalemia may be caused by:

•↑ K+ loss from diuretics, diarrhea, renal defect •Inadequate K+ intake •↓ extracellular K+ secondary to metabolic alkalosis.

If the hypokalemia is secondary to metabolic alkalosis, correct alkalosis before considering increasing K+ intake. For other causes of hypokalemia, increase K+ in daily maintenance fluids. K+ must never be given as a push or bolus infusion because of the risk of serious cardiac arrhythmias. In extreme emergencies, K+ can be given as a rapid infusion, but give no more than 0.3 mEq/kg over 20 min. 4. Hyperkalemia (serum [K+] >6 mEq/L) may cause lethal arrhythmias, especially ventricular fibrillation. Early EKG changes of hyperkalemia include peaked T waves and widening of the QRS complex. The most common cause of high serum [K+] is hemolysis of the specimen. When an abnormally elevated [K+] is reported by the Laboratory, send a repeat sample for stat [K+] measurement before starting treatment unless the EKG indicates hyperkalemia.


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Hyperkalemia is common in ELBW infants (i.e., <1,000 g), especially in the first few days after birth. Newborns are more resistant to cardiac arrhythmias secondary to hyperkalemia than older children. Treatment is usually indicated when serum [K+] is >7 mEq/L. If acidosis is present, it should be corrected to increase transfer of potassium from extracellular to the intracellular fluid compartment.

A. Causes of hyperkalemia include: •Oliguria and renal failure •Acidosis •“Sick cell” syndrome secondary to tissue hypoxia and marked prematurity •Excessive administration of K+ in IV fluid or in old or hemolyzed blood •Congenital adrenal hyperplasia •Hemolysis of blood sample or, more rarely, laboratory error.

B. Treatment of hyperkalemia:

•If [K+] >7.0 mEq/L, obtain twelve lead EKG. •Discontinue K+ administration •Increase pH with bicarbonate or THAM™ •Give calcium gluconate (200 mg/kg IV over several minutes) to reach high-normal

calcium range which stabilizes the myocardium but has no effect on serum [K+] •If [K+] >8, consider Kayexalate™, a cation exchange resin. Dose is 1 gm/kg q 4-6h

per rectum, but it may be given q2h if [K+] is rising. Kayexalate removes K+ by exchanging it for Na+; therefore, it will give the infant a Na+ load.

•↑ glucose administration rate IV and consider an insulin infusion. •Insulin infusion: add 2 units of soluble insulin to 60 mL of D12.5%, which gives a

concentration of 1 unit of insulin per 30 mL D12.5% (or about 3.3 units of insulin/100mL). This will give glucose/insulin ratio of 3.75 /1, which is safe. Start insulin infusion rate at 0.1 units/kg/h.

5. Hypocalcemia is defined as ionized calcium (iCa++) concentration <0.9 mmol/L. In preterm infants, total serum Ca may be low because serum albumin is low, but [iCa++] may be perfectly normal. True hypocalcemia may cause jitteriness, irritability, high-pitched cry, hypocalcemic seizures, stridor, tetany as well as decreased myocardial contractility with hypotension and decreased cardiac output. EKG may show prolonged QT interval and flat T-wave. Early onset hypocalcemia is common in:

•Preterm infants •SGA infants •Term infants with birth asphyxia •Infants of diabetic mothers

Late onset hypocalcemia may be associated with: •DiGeorge syndrome •Magnesium deficiency •Hyperphosphatemia •Renal failure •Hypoparathyroidism •Diuretic therapy

-Transient neonatal hypoparathyroidism -Secondary to maternal hyperparathyroidism

Treatment of hypocalcemia: Slow infusion (over 5 min) of calcium gluconate 10% at a dose of 200 mg/kg (2 cc/kg). Rapid infusion may cause bradyarrhythmias. The infusion may be repeated if necessary and maintenance calcium dose can be increased. In


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DiGeorge syndrome, may give oral calcium solution (Neo-Calglucon™). Calcium chloride infusion should be used only in emergencies. 6. Hypercalcemia is defined as total serum [Ca] >12 mg/dL or [ionized calcium] >1.5 mmol/L and is rare in newborns. Hypercalcemia may cause vomiting, hypotonia and encephalopathy. Causes of hypercalcemia include:

•Low serum phosphorus with bone demineralization •Congenital hyperparathyroidism (primary or secondary) • William’s syndrome • Hypervitaminosis D • Subcutaneous fat necrosis • Adrenal insufficiency • Thiazide diuretic therapy • Hypophosphatasia •Hyperthyroidism •Blue diaper syndrome (abnormal tryptophan transport ).

Treatment of hypercalcemia:

•Correct underlying cause, if possible •Adequate hydration •Obtain consult with Endocrine Service •Furosemide to increase calcium excretion •Glucocorticoids to inhibit intestinal absorption of calcium and ↓ bone resorption •Increase inorganic phosphate by giving oral phosphate solution (Neutra-Phos™

200 mg/mL) at a dose of 3-5 mg/kg. Avoid parenteral phosphate solution in severely hypercalcemic infants.

7. Hypomagnesemia is unusual and is associated with persistent hypocalcemia. Treatment is MgSO4 25-50 mg/kg/dose IV slowly over several minutes. This can be repeated. 8. Hypermagnesemia, defined as a serum magnesium concentration >3 mg/dL, usually occurs secondary to magnesium treatment of the mother as a tocolytic to stop preterm labor or in mothers with pre-eclampsia. Neonatal symptoms include hypotonia, hyporeflexia, hypotension and apnea, as well as vasodilatation with marked flushing. The treatment is usually symptomatic until magnesium level gradually falls secondary to renal excretion. With severe cases, administration of calcium IV (see above) may help. Infants with severe hypermagnesemia may require assisted ventilation and blood pressure support.


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Acid-Base Balance INTRODUCTION: The newborn infant is subject to numerous conditions that may disturb acid-base homeostasis. Management of ventilation, which controls the respiratory component of acid-base balance, is discussed in the section on Respiratory Support (P. 10). This section is a brief discussion of the metabolic aspects of acid-base balance. METABOLIC ACIDOSIS, defined as a base deficit >5 mEq/L on the first day and >4 mEq/L thereafter, occurs from:

•Loss of buffer (mainly bicarbonate) or •Excess production of acid or decreased excretion of acid

The anion gap is a useful calculation in assessing metabolic acidosis.

Anion gap = [Na+] – ([Cl-] + [HCO3-])

Loss of buffer has no effect on anion gap. Accumulation of organic acid (e.g., lactic acid) causes an increase in anion gap. Normal anion gap: <15 mEq/L Increased anion gap:

>15 mEq/L in LBW infants (<2,500 g) >18 mEq/L in ELBW infants (<1,000 g)

Newborn infants normally have a base deficit of 1 to 3 mEq/L. Common causes of metabolic acidosis:

•Bicarbonate loss, especially via immature kidney or from GI tract •Lactic acidosis from inadequate tissue perfusion and oxygenation (e.g., from asphyxia, shock,

severe anemia, hypoxemia, PDA, NEC, excessive ventilator pressures with ↓ cardiac output) •Hypothermia •Organic acidemia due to an inborn error of metabolism (see P. 155) •Excessive Cl in IV fluids •Renal failure •Excessive acid load from high protein formula in preterm (late metabolic acidosis of

prematurity ) •Excretion of HCO3

- as metabolic compensation for respiratory alkalosis Dilution acidosis is caused by excessive volume expansion (with saline, Ringer’s lactate or dextrose solutions). The extracellular space becomes “diluted” (relative decrease of HCO3-); carbonic acid dissociates more and liberates more H+. Therefore, pH falls. Effects of metabolic acidosis: Major physiological effects of metabolic acidosis include:

•Pulmonary vasoconstriction (with risk of persistent pulmonary hypertension) •↓ myocardial contractility •Shift of O2-Hgb dissociation curve to right (↓ saturation at a given PO2) •CNS damage with severe acidosis

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•↑ work of breathing as compensation for acidosis

Management of metabolic acidosis: •Treat underlying cause when possible •Do not treat metabolic acidosis by hyperventilation (other than briefly while

preparing to give alkali). This may correct pH but has deleterious effects on cardiac output and pulmonary blood flow.

•Volume expansion (i.e., bolus 10 mL/kg of 0.9% NaCl) should not be used to treat acidosis unless there are signs indicative of hypovolemia. A volume load is poorly tolerated in severe acidosis because of the ↓ myocardial contractility.

•Alkali treatment should be used only if significant metabolic acidosis is present (e.g., pH <7.30 with base deficit >7)

•Dose of alkali for treatment of metabolic acidosis can be calculated by: Dose of alkali (mEq) = base deficit x 0.3 x body weight (kg) •Administer alkali IV at a rate not exceeding 1 mEq/kg/min. •The usual alkali used in newborns is NaHCO3 and the concentration is 0.5 mEq/mL,

so it is hyperosmolar (900 mOsm/L) •Do not give NaHCO3 unless the infant is receiving assisted ventilation that is

adequate. With inadequate ventilation, NaHCO3 will worsen acidosis because of the liberation of CO2.

•With severe acidosis and CO2 retention despite vigorous assisted ventilation, consider use of the organic buffer, THAM™. This is provided as a 0.3 molar solution (i.e., 0.3 mEq/mL)

Risks of alkali administration include:

•Acute hyperosmolality with rapid shift of water from intracellular to extracellular space

•The intracellular dehydration increases the risk of intracranial hemorrhage •Acute expansion of intravascular volume

•↓ ionized Ca++ •Shift of O2-Hgb dissociation curve to left (↑ binding of O2 to Hgb) •Paradoxical CNS acidosis •With bicarbonate: sodium load and increased CO2 •With THAM™, risk of apnea and hypoglycemia

For correction of acidosis in an emergency, see section on Resuscitation (P. 1). For chronic mild metabolic acidosis in small premature infants on hyperalimentation, maximize acetate and minimize chloride in the solution.

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METABOLIC ALKALOSIS is usually iatrogenic in premature infants related to diuretic use or GI losses and occurs in combination with contracted intravascular and ECF volumes.

Cause of Metabolic Alkalosis Treatment Compensation for respiratory acidosis Correct ventilation Diuretic Rx (especially furosemide) Decrease diuretic dose, add (contraction alkalosis) spironolactone, replace K+ and Cl- deficit Loss of gastric fluid from vomiting or Replace deficit and give fluids and electrolytes diarrhea with Cl- loss to keep pace with continuing losses. Increased alkali load from feedings ↑ Cl- administration as KCl or Arginine Cl (alkalosis of prematurity) Excessive administration of alkali ↑ Cl- as KCl or Arginine Cl (Excess acetate in parenteral nutrition) Bartter syndrome (rare) Replace electrolyte losses


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Very Low and Extremely Low Birthweight Infants

INTRODUCTION and DEFINITIONS: Low birth weight infants are those born weighing less than 2500 g. These are further subdivided into:

•Very Low Birth Weight (VLBW): Birth weight <1,500 g •Extremely Low Birth Weight (ELBW): Birth weight <1,000 g

Obstetrical history (LMP, sonographic dating), newborn physical examination, and examination for maturational age (Ballard or Dubowitz) are critical data to differentiate premature LBW from more mature growth-retarded LBW infants. Survival statistics for ELBW infants correlate with gestational age. Morbidity statistics for growth-retarded VLBW infants correlate with the etiology and the severity of the growth-restriction. PREVALENCE: The rate of VLBW babies is increasing, due mainly to the increase in prematurely-born multiple gestations, in part related to assisted reproductive techniques. The distribution of LBW infants is shown in the Table: ________________________________________________________________________ Table. Prevalence by birth weight (BW) of LBW babies. Percentage of Percentage of Births

Birth Weight (g) Total Births with BW <2,500 g

<2,500 7.6% 100%

2,000-2,500 4.6% 61%

1,500-1,999 1.5% 20%

1,000-1,499 0.7% 9.5%

500-999 0.5% 7.5%

<500 0.1% 2.0% ________________________________________________________________________ CAUSES: The primary causes of VLBW are premature birth (born <37 weeks gestation, and often <30 weeks) and intrauterine growth restriction (IUGR), usually due to problems with placenta, maternal health, or to birth defects. Many VLBW babies with IUGR are preterm and thus are both physically small and physiologically immature. RISK FACTORS: Any baby born prematurely is more likely to be very small. However, other factors that can contribute to the risk of VLBW include:

•Race: African-American babies are twice as likely as Caucasian to be VLBW. Black infants (16% of US live births) account for 37% of ELBW infants.

•Age: Teen mothers (especially if <15 years old) have a much higher risk of having VLBW infant.

•Multiple birth babies are at increased risk of being VLBW because they often are premature. More than 50% of twins and other multiple gestations are VLBW.

•Maternal health: Women exposed to drugs, alcohol, and cigarettes during pregnancy are more likely to have LBW or VLBW babies. Mothers of lower socioeconomic

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status are also more likely to have poorer pregnancy nutrition, inadequate prenatal care, and complications of pregnancy. All are factors that can contribute to VLBW.

NEONATAL COMPLICATIONS are markedly increased in VLBW, and especially ELBW, infants. Because most VLBW infants are also premature, it may be difficult to differentiate problems due to prematurity from those due to very small size. In general, the lower a baby's birthweight, the greater are the risks for complications. However, some complications of prematurity (e.g., risk of RDS) are lessened by the stress of mild to moderate intrauterine growth restriction. Clinical problems associated with VLBW and ELBW include: 1. Hypothermia: LBW infants have higher body surface area:body weight ratios,

decreased stores of brown fat and glycogen, and may not be able to conserve or generate body heat. Clinical problems associated with hypothermia include hypoglycemia, apnea, increased O2 consumption and metabolic acidosis. Prevention of hypothermia increases survival of the infants. Methods of preventing heat loss include:

•Drying the infant at birth to prevent evaporative heat loss •Warmed blankets or plastic wrap to prevent convective and radiant heat loss during

transport •Swaddling to preserve body heat in larger infants, and radiant heater or a heated

incubator to maintain a neutral thermal environment for smaller infants. 2. Hypoglycemia due to decreased stores of glycogen and fat. Hypothermia and hypoxia

aggravate this due to increased metabolic demands and anaerobic glycolysis. 3. Perinatal asphyxia, especially among growth retarded infants because of

compromised O2 delivery in utero. 4. Respiratory problems:

•Respiratory Distress Syndrome, due to surfactant deficiency (see P. 79) •Apnea of prematurity (see section on Apnea, P. 91)

5. Fluid and electrolyte imbalances due to increased insensible water loss (due to ↑ surface area/body weight, thin skin), impaired renal function. They are at risk for dehydration, fluid overload, hypernatremia, hyponatremia, hyperkalemia (especially ELBW), hypocalcemia, hypermagnesemia (iatrogenic from maternal treatment). Compromised renal function may impair tolerance of free water, bicarbonate resorption, potassium secretion, or urinary concentrating capacity.

6. Hyperbilirubinemia (see section on Jaundice, P. 118) •Indirect (unconjugated) hyperbilirubinemia due to bruising or hemorrhage, ↓ RBC

survival, hepatic immaturity, delayed enteric feedings and ↓ gut motility. With IUGR, risk factors may include infection and/or polycythemia.

•Direct (conjugated) hyperbilirubinemia as a complication of parenteral nutrition. 7. Anemia due to:

•Phlebotomy for laboratory tests and small total blood volume •Anemia of prematurity

8. Impaired nutrition, feeding difficulties and slow rates of weight gain due to: •Gut immaturity with decreased motility, enzyme deficiencies and ↑ risk of

necrotizing enterocolitis (see P. 133) •Delayed enteric feeding due to respiratory disease, PDA, indomethacin treatment •Infants <32-34 weeks gestation are developmentally not ready to nipple feed •Increased caloric needs (↑surface area/body weight)

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9. Infection: Risks are increased because of immunologic immaturity, prolonged invasive treatments (e.g., endotracheal tube, intravascular catheters, parenteral nutrition and prolonged, recurrent treatment with antibiotics.

10. Neurological problems including: •Intraventricular hemorrhage (see P. 144) •Periventricular leukomalacia •Increased long term risks for cerebral palsy, developmental delay, learning

disabilities 11. Ophthalmologic complications including:

•Retinopathy of prematurity (ROP) •Strabismus and refractive errors 12. Hearing deficits due to:

•Prematurity itself •Hyperbilirubinemia •Meningitis •Hypotension •Ototoxic drugs (e.g., aminoglycosides, furosemide)

13. Sudden infant death syndrome (SIDS): Premature infants are at increased risk, but home monitoring has not been shown to be an effective preventive measure. Home monitoring is not recommended in absence of other risk factors (e.g.. twin sibling with SIDS, two siblings with SIDS, obstructive airway problems, or craniofacial anomalies posing risks for obstructed airways).

MANAGEMENT: Because of the increased risk for multiple problems, these infants require meticulous attention to all facets of their care. The following are but a brief summary of certain aspects of the care of these fragile infants: 1. Resuscitation: (see section on Resuscitation, P. 1) 2. Respiratory Care: The majority of ELBW (i.e., <1,000 g) will require intubation

at birth (to assist in their cardiopulmonary adaptation to extra-uterine life) and assisted ventilation for a prolonged period. They require close attention with frequent measurements of pH and blood gas tensions. In addition to surfactant deficiency, they are at risk for respiratory failure because of:

•Weak chest wall •Weak muscles of respiration •Smaller alveoli (↑ tendency to atelectasis) •Decreased central respiratory drive

3. Cardiovascular: Most VLBW and almost all ELBW infants will require an umbilical arterial catheter for blood sampling and blood pressure measurement. Hypotension is common. The most effective therapy is dopamine (usual starting dose is 5 mcg/kg/min). Do not automatically give fluid boluses for “decreased perfusion,” acidosis, or hypotension. Excess fluid will worsen pulmonary function and give excess Na+. Reserve volume expansion for situations where there are signs of hypovolemia (see sections on Shock, P. 101, and Blood Pressures, P. 35).

3. Oxygen therapy: Maintain SpO2 in range of 85-92%. If SpO2 is > 94%, arterial oxygen tension may be high (>100 mmHg) because of the inaccuracy of the pulse oximeter at high saturations. This puts the infants at ↑ risk for ROP. Do not write titration orders for oxygen.

4. Fluids: On the 1st day of life, preterm infants should receive restricted fluids (e.g., 60-80 mL/kg/d). However, for ELBW infants, fluid intake should be higher (e.g., 100-125 mL/kg/d. Follow intake and output closely, at least q12h for the first several days.

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5. Electrolytes: On the 1st day, do not give Na+ or K+. To avoid hypocalcemia, start Ca gluconate at 200 mg/kg/d. Follow serum electrolytes closely.

6. Nutrition: Feedings on the 1st day of life are unusual for VLBW infants. Do not start feeds on the 1st day of life in ELBW infants. (see section on Feeding, P. 50). Trophic (gut stimulation) feedings for several days facilitate later advance of feedings. Consider early institution of TPN. Do not give IV lipids for 3-5 d, especially if there is severe pulmonary disease. (see section on Parenteral Nutrition, P. 136).

7. Infection: Obtain CBC and blood culture at birth. If there are any risk factors, begin antibiotic therapy (48 h of treatment until culture results are known).

8. Glucose: Maintain blood glucose ≥45 mg/dL. (see section on Hypoglycemia, P. 153). Initial IV fluid should be D10W. Some ELBW infants may become hyperglycemic and require lower glucose intake and/or insulin.

9. Hyperbilirubinemia: (see section on Jaundice, P. 118) 10. Anemia: Assume all ELBW and many VLBW infants will need at least 1 transfusion.

Obtain parental consent in advance, discussing option for designated donor blood. Type and cross match packed cells in small volume aliquots to minimize number of donors. Start erythropoietin as described in Guidelines for Use of Erythropoietin (P. 107).

11. Intraventricular hemorrhage (see schedule for cranial sonograms on P. 146) 12. Ophthalmology examination for ROP commencing at age 1 mo for infants born <

32 weeks. OUTCOME: Survival of VLBW babies is directly related to birth weight. Survival data for infants born at UCSF from 1998-2002 (inclusive) are:

Birth Weight (g) Survival 500-750 74% 751-1,000 82% 1,001-1,250 92% 1,251-1,500 95%

Long-term outcome: VLBW and ELBW infants are at ↑ risk for cerebral palsy, developmental delay, mental retardation, visual problems (including blindness), hearing impairment, chronic lung disease and SIDS. Risk for these ↑ with decreasing BW and GA. Data for very preterm infants followed in the UCSF ICN Follow-Up Clinic are shown below: GA* No Deficits‡ One Deficit‡ Two or More‡ 24 28% 39% 33% 25 47% 23% 30% 26 63% 34% 3% *GA, completed gestational weeks; deficits include deficient cognitive development, cerebral palsy and visual and auditory deficits.


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Intrauterine Growth Retardation CLINICAL SIGNIFICANCE: Intrauterine growth retardation (IUGR) affects 3-10% of pregnancies; 20% of stillborn infants have IUGR. Perinatal mortality rates are 4-8 times higher for growth retarded infants, and morbidity is present in 50% of surviving infants. DEFINITIONS and CLASSIFICATION: -AGA, appropriate for gestational age: Birth weight is between 10th and 90th percentile

for infant’s gestational age (GA). -LGA, large for gestational age: Birth weight >90th percentile for GA. - SGA, small for gestational age: Birth weight <10th percentile for GA. Other definitions

are sometimes used for SGA, including <3rd percentile for GA or more than 2 S.D. below the mean.

-IUGR vs. SGA: IUGR refers to deviation and reduction in expected fetal growth pattern. Multiple adverse conditions inhibit normal fetal growth potential. Not all IUGR infants are SGA.

ASYMMETRIC vs. SYMMETRIC GROWTH RETARDATION: Most growth retarded infants have asymmetric growth restriction. First there is restriction of weight and then length, with a relative “head sparing” effect. This asymmetric growth is more commonly due to extrinsic influences that affect the fetus later in gestation, such as pre-eclampsia, chronic hypertension, and uterine anomalies. Postnatal growth after IUGR depends on cause of growth retardation, postnatal nutritional intake, and social environment. Symmetric growth retardation affects all growth parameters. In the human brain, most neurons develop prior to the 18th week of gestation. Early gestational growth retardation would be expected to affect the fetus in a symmetric manner, and thus have permanent neurologic consequences for the infant. Examples of etiologies for symmetric growth retardation include genetic or chromosomal causes, early gestational intrauterine infections (TORCH) and maternal alcohol use. CAUSAL FACTORS: A. Maternal

-Before pregnancy: • Prepregnancy weight influences fetal size • Periconceptual nutritional status can affect embryogenesis (e.g., folate deficiency).

-During pregnancy: Factors that may adversely affect fetal growth include: • Low pre-pregnancy weight and small maternal size • Recent pregnancy and/or high parity • Poor weight gain during pregnancy, especially in latter half • Chronic illness - such as malabsorption, diabetes, renal disease • Inadequate or poorly balanced intake associated with alcoholism, drug abuse,

poverty, adolescence, anorexia nervosa, food faddism • Maternal drug and alcohol use also influence maternal nutrition. • Decreased O2 availability to fetus (e.g., high altitude, severe maternal anemia)

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B. Uterine and placental factors that can adversely affect fetal growth include inadequate placental growth, uterine malformations, decreased utero-placental blood flow (e.g., toxemias of pregnancy, diabetic vasculopathy) and multiple gestations

C. Fetal causes are unusual, include familial genetic and chromosomal abnormalities and intrauterine infections (i.e., TORCH), and usually have a poor long term prognosis. PATHOPHYSIOLOGY: With maternal or placental causes of IUGR, there is decreased placental transfer of nutrient (including oxygen) resulting in reduced fetal body stores of lipids and glycogen resulting in neonatal hypoglycemia; chronic hypoxemia stimulates erythropoietin production leading to polycythemia. These infants are also at increased risk for perinatal asphyxia. Other associated problems include hypocalcemia, pulmonary hemorrhage, hypothermia and, with IUGR associated with toxemia, thrombocytopenia and leukopenia. With fetal causes, decreased growth is constitutive (due to genetic factors) or secondary to infection. ASSESSMENT and MANAGEMENT:

-Treat asphyxia if present. -Measure weight, head circumference and length to categorize the type of IUGR. -Careful physical examination for anomalies and dysmorphic features. -Blood glucose and hematocrit to detect hypoglycemia and polycythemia. See

sections on Hypoglycemia (P. 153) and on Polycythemia (P. 112). -Serum Ca++, WBC count with differential and platelet count. -Infants with IUGR due to placental factors have ↑ O2 consumption. This ↑ insensible

water loss to a variable degree (as much as 20-30%). Compensate for this by increasing IV fluid intake. These infants may also need greater intake (>150 mL/kg/d and >100 kcal/kg/d) to achieve adequate growth.

-Further workup and treatment depends on abnormalities identified on history and physical examination.

OUTCOME:

-Perinatal mortality for IUGR infants is 5-20 times greater than for AGA, mainly due to intrauterine death, perinatal asphyxia, and congenital anomalies.

-Neurologic morbidity is 5-10 times higher than for AGA infants, especially for infants with ↓ head circumference at birth. Intellectual and motor function (excluding those with congenital infections, chromosomal abnormalities) depends on adverse perinatal events and on the specific cause of growth restriction. Early identification and treatment of hypoglycemia and polycythemia improves outcome. Neurologic abnormalities are usual with genetic and infectious causes of IUGR.

-Retarded growth: With placental causes of IUGR, catch-up growth occurs after birth, but these patients usually remain smaller than expected.

-Fetal “programming” of cardiovascular disease: Recent studies implicate IUGR with adult onset of hypertension, coronary heart disease, hypercholesterolemia, and diabetes. These studies suggest that IUGR has long term affects on endocrine development and homeostasis.


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Immunizations: Policies and Procedures INTRODUCTION: All infants admitted to the ICN will receive immunizations according to their age after birth and consistent with CDC guidelines. DOCUMENTATION POLICY: •By law, all health care providers who administer vaccines shall provide a copy of the vaccine

information sheet (VIS) to the legal representative of an infant before the vaccine is given and for each dose of vaccine. The VIS should be supplemented with visual presentation or oral explanations as appropriate.

•VIS forms are kept at the ICN Secretary’s desk for the following: diphtheria, tetanus, pertussis, measles, mumps, rubella, polio, hepatitis B, hepatitis A, and Haemophilus influenzae B.

•It is not necessary to obtain a signature acknowledging receipt of the VIS, but a notation must be made in the medical record indicating that the VIS materials were provided.

•This policy applies to both inborn and outborn infants. •Documentation can be on the Physician’s Order Sheet (e.g., for 1 month immunization, write

”IPV 0.5 mL SQ, DTaP 0.5 mL IM now; VIS have been provided.”) •Although written consent for vaccine administration is not required, it is better to obtain it. •For each patient, a Vaccine Administration Record will be kept in the bedside chart. This

record shall include all immunizations as well as lot numbers and manufacturer (as required by the CDC). All immunizations shall also be documented on the yellow state immunization card that is given to the parents at the time of discharge.

•A detailed description of the vaccine documentation policy can be obtained from the Pharmacy. IMMUNIZING AGENTS: COMVAX, HBV and HIB combined HIB, Haemophilus influenzae B DTaP, Diphtheria, Tetanus, acellular Pertussis IPV, inactivated Polio vaccine HBIG, Hepatitis B Immune Globulin PCV7, Pneumococcal Conjugate vaccine HBV, Hepatitis B vaccine Dose for all of these agents is 0.5 mL IM, except IPV which is 0.5 mL SQ or IM.

ADMINISTRATION of VACCINES: •Each Monday, the ICN Pharmacy will generate a list of patients to be vaccinated the current

week, those eligible the next week and those past due. This list will be given to the Discharge Coordinators, who will give the information to the Residents, Fellows and NNPs.

•To minimize the number of injections, the HBV series will be initiated at birth only for infants born to mothers whose HbsAg status is either + or unknown. All others will be given COMVAX at 2, 4 and 12-15 months.

•The patient care team will review the list for contraindications. If none, infants will be immunized. For any patient for whom a decision is made not to give an immunization, notify the Pharmacy and the bedside Nurse and document the decision in the infant’s medical record.

•All vaccines are contraindicated in infants who have or who are being evaluated for active infection.

•The only other contraindication for HBV is allergic reaction to a prior dose of vaccine. •The only other contraindication for Pertussis vaccine is uncontrolled active seizures.

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• If a decision is made to never immunize an infant (e.g., if the parents do not want their infant immunized), the infant’s Nurse will document this on the immunization record in the medical record and the Pharmacy will not include this patient on future notification lists.

•Unless contraindicated, all patients should receive Acetaminophen (10 mg/kg PO) 1-2h prior to DTaP immunization and q4-6h after for 24 hours.

IMMUNIZATION SCHEDULE for ICN: Mother’s HbsAg Status Age Negative Positive Unknown Birth HBV #1 (by age 12 h) HBV #1 (by age 12 h) HBIG “ HBIG*

*Determine maternal HbsAg status after birth; if positive, give HBIG by age 7d for full term infants; for preterm, give HBIG within 12h after birth..

1 month HBV#2 2 months IPV #1 IPV #1 DTaP #1 DTaP #1 COMVAX #1 HIB #1 PCV7 #1 PCV7 #1 4 months IPV #2 IPV #2 DTaP #2 DTaP #2 COMVAX #2 HIB #2 PCV7 #2 PCV7 #2 6 months‡ DTaP #3 DTaP #3 PCV7 #3 PCV7 #3 HIB #3 HBV #3

‡Consider giving Influenza vaccine to infants with chronic lung disease or cardiac disease. 12-15 months IPV #3 IPV #3 COMVAX #3 IMMUNIZATION against RESPIRATORY SYNCITIAL VIRUS (RSV): RSV pneumonia is a major cause of serious pediatric respiratory disease from November through April, especially among infants who have chronic lung disease and those born prematurely. Palivizumab (Synagis™), a recombinant monoclonal antibody against RSV, is effective in decreasing the incidence of RSV pneumonia in high risk infants. Current recommendations are that infants at risk for RSV be given Synagis™ 15 mg/kg IM monthly from November through April after discharge from hospital. This treatment is started a few days before discharge (November to April). Patients who are to be given this treatment include:

•Gestational age (GA) ≤28 wks and <12 months postnatal age at start of RSV season •GA 29-32 wks and postnatal age ≤6 months at start of RSV season •GA 33-35 wks and additional risk factors as judged by the ID Service. •Patients up to age 24 months with chronic lung disease and requiring O2, steroids or

bronchodilators in the 6 months prior to start of RSV season •Consult with Cardiology regarding administration of Synagis™ to infants with congenital

heart disease. For any questions about immunizations not covered here, consult the Neonatology Fellow, the Discharge Coordinator or the Pharmacy.


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Discharge Planning INTRODUCTION: Preparing an ICN patient for discharge involves several individuals and careful planning. For most infants, discharge planning can begin at admission when the physician formulates the treatment plan. Below are guidelines to facilitate the discharge process, avoid delays and ensure continuing care after the baby leaves UCSF. SOCIAL SERVICE ROUNDS are held weekly at 11:00 AM on Wednesday. Each patient is discussed by the medical team, Social Workers and Discharge Coordinators. Current patient care plans are discussed and special problems may be identified that will affect discharge. These may include adequacy of the parents, the home and available resources given the medical needs of the infant, availability of necessary follow-up care, transport to home or to a hospital nearer to home, and special medications, supplies or devices that the infant will need. CRITERIA FOR DISCHARGE: For growing preterm infants, discharge can be anticipated when the infant:

•weighs ≥1,800 g •is gaining weight steadily on nipple feedings (breast or bottle) •can maintain body temperature in an open crib •has had no episodes of apnea for at least 5d •has an adequate home environment

Criteria for infants with other medical/surgical conditions vary with the clinical situation. HELPFUL TIPS FOR PLANNING AN INFANT’S DISCHARGE: •Keep “Bumble-Bee” (discharge) form up to date during the infant’s hospitalization. •Check with the parents to determine who will be the primary physician after

discharge. •Stabilize the discharge medications at least 3d before discharge. •For infants on multiple medications, cluster the dose times to minimize the number of

times the parents have to give medications. •For preterm infants on formula feedings, monitor weight gain, on caloric density that

the infant will be receiving at the time of discharge, for at least 3d before discharge. •The discharge physical examination can be done up to 24h before discharge. •Confirm the discharge time and follow-up plans with all consulting teams. •Check with infant’s Social Worker regarding any special family needs or problems. •Notify the Discharge Coordinator at least 3 days before the planned discharge time. •Notify parents at least 3d before the planned discharge. They may have several

questions, be very anxious and need time to adjust to the idea of taking home their infant, who has been so sick.

•For non-English speaking parents, arrange for a translator to be present at the discharge conference.

•If the infant is to be transferred to another hospital, give at least 24h notice to the Attending or Fellow so the Discharge Summary can be completed on time.


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Cross-Covering the Well Baby Nursery and Pedi-Med Service INTRODUCTION: This section of helpful tips was prepared with the help of past residents who suffered through cross-covering infants on the Well-Baby and Pedi-Med Service without the benefit of a readily available manual. ATTENDING PHYSICIANS: The attendings for the Well Baby and Pedi-Med Service are your direct backup and should be called for questions about clinical management, complications, and for all admissions to the Special Care Nursery under the Pedi-Med Service. Remember to identify the on-call attending at evening sign-out rounds.

Attending Pager Attending Pager Jane Anderson 719-1884 Thomas Newman 719-1262 David Becker 719-6089 Marina Tan 719-8995 Jane Lee 719-5355 Alan Uba 719-2126 Carol Miller 719-3837

CRITERIA FOR PLACING INFANTS ON THE VARIOUS SERVICES: 1. Well Baby Nursery (WBN) is intended for term and near-term infants who are sufficiently stable for rooming-in with their mothers. All infants admitted to the WBN must satisfy all of the following criteria:

•Gestation ≥ 36 weeks •Birth weight ≥ 2200 grams •No major congenital anomalies •Temperature is stable without the need of an incubator or warmer •No need for continuous electronic cardio-respiratory monitoring •No need for intravenous lines, nasal/oral gastric tubes, or similar interventions

2. Pedi-Med Service: Infants who require more medical observation or treatment than the well babies. These infants should be placed in the High Observation Nursery or Special Care Nursery and must satisfy all of the following criteria:

•Gestation ≥ 33 weeks •No significant apnea or bradycardia •Birth weight ≥ 2200 grams •No ventilator support •No central vascular catheters •No intravenous alimentation •No baby determined to be unstable

Note: These criteria can be modified only by the attending physician. Infants who do not meet the criteria for either the Well Baby Nursery or the Pedi-Med Service are to be placed on the ICN Service. BREASTFEEDING is to be encouraged. Our goal is to assure that all families who elect to breastfeed their infants will have a successful and satisfying experience. Please note the following:

•Infants are to be put to breast as soon after birth as feasible for both mother and infant, ideally within the first hour after birth.

•Breastfeeding mother-infant pairs are encouraged to room-in together on a 24h basis. •Encourage the infant to nurse at least q2-3h for a minimum of 8 feedings per 24h.

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•No supplementary water or milk is to be given unless ordered by a physician or nurse practitioner for medical indications.

Please refer to the document “Breastfeeding Well Newborns” in the Well Baby Nursery Manual, a black notebook kept in the WBN chart rack. VITAMIN K1 ADMINISTRATION: Every neonate should receive a single parenteral 0.5-1.0 mg dose of vitamin K oxide or phytonadione (AquaMEPHYTON™) within 1h of birth for prevention of vitamin K deficiency bleeding (Hemorrhagic Disease of the Newborn). Occasionally parents will refuse vitamin K or request oral administration. If you encounter this situation:

•Discuss this with parents. Try to use a non-confrontational tone. Be respectful and listen attentively to the parents’ reasoning and concerns. Provide honest answers and be sure to clarify the purpose of our recommendation. It is often helpful to describe vitamin K deficiency bleeding to parents. Orally administered vitamin K has not been shown to be as effective and puts infants at risk for late onset vitamin K deficiency bleeding which is associated with a higher incidence of intracranial hemorrhage.

•If parents persist in their refusal, they must sign the “Refusal to Permit Medical Treatment” form. These forms are kept in the file cabinet behind the unit clerk’s desk in the WBN.

•Circumcision will not be performed on any infant who has not received vitamin K by injection.

EYE PROPHYLAXIS against gonococcal opthalmia neonatorum is mandatory for all neonates. A 1-2cm ribbon of sterile ophthalmic ointment containing 0.5% erythromycin should be administered within 1 hour of birth. Although California state law mandates neonatal eye prophylaxis, parents who refuse may sign a special waiver. This form is entitled “Refusal to Allow Treatment of Eyes of Infant with Prophylactic-Efficient Agent” and is located in the cabinet behind the unit clerk’s desk in the WBN. HYPERBILIRUBINEMIA: Risk factors for non-physiologic hyperbilirubinemia include:

•Blood group or Rh incompatibility, especially if there is a positive Direct Antiglobulin Test (Coomb’s Test)

•Presence of excessive bruising or cephalohematoma •Breastfeeding •Excessive weight loss •Gestational age < 37 weeks •Maternal diabetes •Polycythemia

Consider ordering a total serum bilirubin for jaundiced neonates with risk factors. Start phototherapy as follows: Age(hours) Total Bilirubin(mg/dL) <48 ≥15 49-72 ≥18 >72 ≥20


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Further testing to determine the etiology of hyperbilirubinemia should be individualized, taking into account the maternal/prenatal and family history, physical exam and general clinical setting. HYPOGLYCEMIA: Risk factors for hypoglycemia include:

•SGA/IUGR with birth weight ≤2500 grams •LGA (birth weight ≥4200 grams) •Preterm (<36 weeks gestation) •Post-term (≥42 weeks gestation) •Infant of a diabetic mother or GIP (glucose intolerance of pregnancy) •Polycythemia

An initial blood glucose level is checked on all neonates within 2 hours post delivery by the One-Touch Glucometer™ method. Neonates with any risk factor are monitored with repeated glucose levels at the following ages: ½ hour (insulin dependent mothers only), 1h, 2h, 4h, 6h, 9h, 12h, and 24h post delivery. Treatment of hypoglycemia:

•If blood glucose is ≥40 mg/dL, no intervention or oral supplementation is needed. •If blood glucose is 20-40 mg/dL:

-Recheck value. If still low, send blood sample to Clinical Laboratories STAT for glucose level.

-Nipple feed immediately D5W, a minimum of 5-10 cc/kg. -Recheck blood glucose 20-30 min after nipple feed has been completed. -If low glucose level persists, repeat oral glucose supplementation and consider IV

infusion (see below). -Continue to monitor blood glucose levels per above protocol.

•If blood glucose is <20 mg/dL: -Send blood sample to Clinical Laboratories for STAT glucose measurement. -Immediately nipple feed D5W at 10 cc/kg. -Recheck blood glucose 20 min after oral supplement. If blood glucose is still low

transfer to SCN for intravenous infusion. •Intravenous infusion for persistent hypoglycemia:

-Give initial bolus of D10W IV at 2-4 cc/kg. -Continue IV infusion of D10W at 4-8 mg/kg/min. -Recheck blood glucose 20 min after starting infusion. If glucose is still low,

consider increasing infusion by 2-4 mg/kg/min. -If infusion rate reaches >140 cc/kg/24h, increase glucose concentration to D12.5W. -Central line placement is required if D15W is necessary to maintain normal blood

glucose level. If central line placement becomes necessary, transfer infant to Neonatology team.

•Do not use 25% or 50% glucose as IV treatment. These will raise blood glucose to very high levels and cause rebound hypoglycemia.

SEPSIS, HIV, AND HEPATITIS: Please refer to the sections on infectious diseases in this manual.


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TOXICOLOGY SCREENING: Urine toxicology screen should be ordered under the following circumstances;

•Maternal history of illicit substance use or abuse of prescription medication. •Mother has received ≤3 prenatal visits. •Infant exhibits symptoms of exposure to drugs or alcohol. These include but are not

limited to: high-pitched cry, difficult to console, hypertonicity, excessive stooling, sneezing, temperature instability, hyperphagia or poor feeding.

Maternal consent is not required to obtain a urine toxicology screen on an infant. However, it is our practice to inform the mother that the test has been ordered. MANAGEMENT OF DRUG WITHDRAWAL SYNDROME: Treatment of infants exhibiting signs and symptoms of drug withdrawal should be tailored according to severity. Use of the Neonatal Abstinence Scoring Sheet is a helpful tool for measuring severity, monitoring progression and monitoring effect of treatment. Fifteen items are assigned a numerical score generally by the nursing staff once during each nursing shift.

•For total scores <12, non-drug interventions such as swaddling, placement in a quiet location with diminished lighting, and rhythmical motion such as a swing are often sufficient.

•For total scores ≥12 or greater, environmental measures may need to be augmented with medication such as Tincture of Opium (DTO), Phenobarbital or other sedatives. Infants housed in the WBN who require medications which may depress respiration should be transferred to the Special Care Nursery and placed on a cardio-respiratory monitor. (See section on Perinatal Substance Abuse, P. 172).

POLICE HOLD POLICY: A Police Hold is a process whereby the police place an infant or minor child in temporary protective custody of the Juvenile Court. It removes physical custody from the parents or guardians, and prevents the family from removing the child from the hospital without the express permission of Child Protective Services. While on a police hold, parents retain legal custody and may continue to consent to treatment and procedures. To initiate a police hold, contact the UCSF Police Department. Circumstances which necessitate a police hold include:

•A parent threatens to remove a baby against medical advice, and the discharge is medically unsound and/or life threatening.

•A parent is violent or is threatening violence. •A parent is incapacitated by drugs or alcohol and the baby’s immediate safety is in

question. •A parent is incapacitated by mental illness and the baby’s immediate safety is in

question. Parents must be informed of the hold by the medical staff. A police hold does not necessarily prevent parents from visiting and participating in their infant’s care. However the hospital has the right to set limits on visitation to ensure patient, staff and visitor safety. Nursing will ensure that all visits are supervised. The entire Police Hold Policy can be found in the Well Baby Nursery Manual.


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ADDITIONAL USEFUL TIPS FROM RESIDENTS: “The most important thing to remember is that even though you are the ICN resident, these are not ICN babies. Most well babies require no [invasive] interventions.” “If you write orders in the WBN, tell the nurses because they only run the charts once per shift.” “If you are called to a delivery, please fill out the Newborn Assessment Part I. If for some reason you do not have time, at least fill out the section on peripartum and postpartum interventions.” “Call the ICN charge nurse to advise her of Pedi-Med admissions.”


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Respiratory Distress Syndrome (RDS) INTRODUCTION: RDS, also known as hyaline membrane disease, is the commonest respiratory disorder in preterm infants. The clinical diagnosis is made in preterm infants with respiratory difficulty that includes tachypnea, retractions, grunting respirations, nasal flaring and need for ↑ FIO2. In the last three decades, introduction of antenatal steroids and exogenous surfactant has greatly improved outcomes in RDS; however, it remains a principal clinical problem. EPIDEMIOLOGY: RDS affects 40,000 infants each year in the US and accounts for approximately 20% of neonatal deaths. RDS typically affects infants <35 weeks gestational age (GA) but may affect older infants who have delayed lung maturation. Low GA is the greatest risk factor for RDS, and its incidence varies inversely with birth weight among AGA infants (Table 1). Other factors may also influence the risk of RDS among preterm infants (Table 2). ________________________________________________________________________ Table 1. Incidence of RDS by Birth Weight.

Birth Weight (g) Incidence of RDS 501-750 86% 751-1,000 79% 1,001-1,250 48% 1,251-1,500 27%

________________________________________________________________________ Table 2. Other risk factors for RDS.

Increased Risk Decreased Risk Prematurity Chronic intra-uterine stress Male gender Prolonged rupture of membranes Familial predisposition Maternal hypertension or toxemia Cesarean section without labor IUGR/SGA Perinatal asphyxia Antenatal glucocorticoids Caucasian race Maternal use of narcotics/cocaine Infant of diabetic mother Tocolytic agents Chorioamnionitis Hemolytic disease of the newborn Non-Immune hydrops fetalis

________________________________________________________________________ PATHOPHYSIOLOGY: The primary cause of RDS is inadequate pulmonary surfactant. The structurally immature and surfactant-deficient lung has ↓ compliance and a tendency to atelectasis; other factors in preterm infants that ↑ the risk of atelectasis are decreased alveolar radius and weak chest wall. With atelectasis, well perfused but poorly ventilated areas of lung lead to V/Q mismatch (with intra-pulmonary shunting) and alveolar hypoventilation with resultant hypoxemia and hypercarbia. Severe hypoxemia and systemic hypoperfusion result in decreased O2 delivery, anaerobic metabolism and

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subsequent lactic acidosis. Hypoxemia and acidosis may further impair oxygenation by causing pulmonary vasoconstriction, resulting in right-to-left shunting at the levels of the foramen ovale and ductus arteriosus. Other factors, such as baro/volutrauma and high FIO2, may initiate release of inflammatory cytokines and chemokines causing more endothelial and epithelial cell injury. The injury results in reduced surfactant synthesis and function as well as increased endothelial permeability leading to pulmonary edema. Leakage of proteins into the alveolar space further exacerbates surfactant deficiency by causing surfactant inactivation. Macroscopically, the lungs appear congested, atelectatic and solid. Microscopically, diffuse alveolar atelectasis and pulmonary edema are seen. An eosinophilic membrane composed of a fibrinous matrix of materials from the blood and cellular debris (the hyaline membrane) lines the visible airspaces that usually constitute dilated terminal bronchioles and alveolar ducts. CLINICAL FEATURES: Signs of RDS appear immediately after birth or within 4 h. RDS is characterized by tachypnea (>60 breaths/min), intercostal and subcostal retractions, nasal flaring, grunting, and cyanosis in room air. Tachypnea is due to an attempt to increase minute ventilation to compensate for a decreased tidal volume and increased dead space. Retractions occur as the infant is forced to generate a high intrathoracic pressure to expand the poorly compliant lungs. Grunting results from the partial closure of the glottis during forced expiration in an effort to maintain FRC. After an initial improvement with resuscitation and stabilization, an uncomplicated course is often characterized by a progressive worsening for 48 to 72 h. Recovery usually coincides with a diuresis after an initial period of oliguria. Other clinical features may include hypotension, acidosis and hyperkalemia. The typical chest radiograph shows low lung volumes and a bilateral, reticular granular pattern (ground glass appearance) with superimposed air bronchograms. In more severe cases, there is complete “white out” of the lung fields. Application of positive airway pressure may minimize or even eliminate these radiographic findings. Acute complications include air leaks and intracranial hemorrhage. Long-term, RDS has been associated with an increased incidence of chronic lung disease, ROP, and neurologic impairment. MANAGEMENT: The goals of management of an infant with RDS are to:

•Avoid hypoxemia and acidosis

Surfactant Deficiency

Structurally Immature LungAtelactasis

V/Q Mismatch Hypoventilation

Hypoxemia & Hypercarbia

Respiratory & Metabolic Acidosis

High Fi02 & Baro or Volutrauma

Pulmonary Vasoconstriction Inflammatory Cell Influx

Antioxidant Reduction

Impaired endothelial and epithelial integrity

Proteinaceous exudate

Cytokine Release

Free-radicalreactions

Lung Injury

Chronic Lung Disease / BPDRDS

ACUTE CHRONIC

PREMATURITY


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•Optimize fluid management: avoid fluid overload and resultant body and pulmonary edema while averting hypovolemia and hypotension

•Reduce metabolic demands and maximize nutrition •Minimize lung injury secondary due to volutrauma and oxygen toxicity

The three most important advances in prevention and treatment of RDS have been: (a) antenatal glucocorticoids, (b) continuous positive airway pressure (CPAP) and positive end-expiratory pressure (PEEP), and (c) surfactant replacement therapy. These have dramatically decreased morbidity and mortality from RDS. 1. Antenatal glucocorticoids accelerate fetal lung maturity by increasing formation and release of surfactant and maturing the lung morphologically. Physiologic stress levels of corticosteroids administered to the mother initiate a receptor-mediated induction of specific developmentally regulated proteins in the fetus. Administration of glucocorticoids at least 24 to 48 h (and no more than 7 d) before preterm delivery decreases both incidence and severity of RDS. They are most effective before 34 weeks. However, antenatal steroids should still be considered when therapy is less than 24 h before anticipated delivery because a reduction in neonatal mortality and RDS can still occur in this time frame. Repeated (>3) courses of corticosteroids have been associated with decreased fetal growth and poorer neurological outcomes. Antenatal steroids also reduce the incidence of intraventricular hemorrhage, an effect that is independent of lessened pulmonary morbidity and that may be secondary to stabilization of cerebral blood flow or maturation of cerebral vasculature. The effects of antenatal steroids and surfactant have been demonstrated to be additive in improving lung function. 2. Exogenous surfactant: It has been shown in multiple randomized controlled trials that the use of exogenous surfactant in preterm infants improves oxygenation, decreases air leaks, reduces mortality due to RDS, and decreases overall mortality.

A. Timing of surfactant administration: Two approaches have been used for surfactant delivery: prophylactic and rescue treatment. Prophylactic administration involves giving surfactant soon after birth, as soon as the infant has been stabilized. The theoretical benefit of this approach is that replacement of surfactant before RDS develops will avoid or ameliorate lung injury. Animal studies have shown that the lung epithelium of very premature subjects can be damaged within minutes of onset of ventilation. The damage can result in protein leak which subsequently interferes with surfactant function. Rescue administration involves giving surfactant to infants who have established RDS and require mechanical ventilation and supplemental O2. The advantage of this approach is that patients are not treated unnecessarily. Because surfactant currently can only be given via an endotracheal tube, this would prevent intubation and mechanical ventilation of infants who would do well without surfactant and avoid unnecessary baro/volutrauma, adverse physiological effects of laryngoscopy, and possible inadvertent hyperventilation. Past studies have shown greater reduction in neonatal mortality with prophylactic administration versus rescue, especially in infants greatest at risk for RDS (i.e., <27 weeks GA). However, with the use of nasal CPAP in VLBW infants and higher rates of antenatal steroid administration, there exists controversy on the optimal timing of surfactant administration, balancing the benefits of early surfactant administration


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with the advantages of avoiding mechanical ventilation and volutrauma. The current approach to the timing of surfactant therapy at UCSF is summarized in Table 3.

______________________________________________________________________ Table 3. Guidelines for intubation and timing of surfactant administration in

preterm infants. Gest. Age Antenatal Ventilatory Timing of (Weeks) Steroids* Treatment Surfactant ≤27 No Intubate all Prophylactic infants ≤27 Yes (a) If intubation† & mech. Prophylactic, unless vent. needed at birth in room air by age 20 min (b) Early CPAP, if not stable Rescue intubate† & mech. vent. (c) Early CPAP, if stable Do not give surfactant 27-34 Yes or No Manage as for ≤27 weeks and (+) steroids >34 Use clinical assessment

________________________________________________________________________ *Steroid therapy indicates mother received 2 doses at least 24 h before and not more than

7 d before birth. †For indications for intubation, see Table 4. ________________________________________________________________________

B. Administration and dose of surfactant: For prophylactic administration, the position of the endotracheal (ET) tube should be verified by two people before surfactant is given. Attach the surfactant syringe to the side port of the ET tube, occlude end of ET tube, and administer surfactant as a single aliquot over ≈ 5 sec. For rescue therapy, obtain chest radiograph to confirm tube position. Administer surfactant through a feeding tube inserted to (but not past) the end of the ET tube. Administer in same manner as with prophylactic treatment. Slower administration may interfere with its efficacy. After administration, the infant should be hand ventilated and may transiently require higher ventilatory support. Several studies have shown that two doses, 12 h apart, may be more effective than single dose therapy. More than 2 doses is rarely required and is rarely effective. The dose of surfactant is:

Infasurf™ 3mL/kg Survanta™ 4 mL/kg

C. Criteria for rescue treatment: Rescue treatment with surfactant should be given to

preterm infants who have: •Respiratory distress, necessitating intubation and assisted ventilation, •No radiological evidence of another disease process,


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and require either •FIO2 > 0.3 or a mean airway pressure ≥7 cmH2O

D. Complications: Although surfactant administration is relatively safe, complications include obstruction of the endotracheal tube, transient increases in O2 requirement and ventilatory settings, and pulmonary hemorrhage, an infrequent adverse effect reported in 2-6% of infants given surfactant.

3. Oxygen should be administered to preterm infants in concentrations sufficient to maintain PaO2 between 50-70 mmHg or saturation (by pulse oximetry) between 85-92%. Higher O2 concentrations may exacerbate lung injury and will increase the risk of retinopathy of prematurity. 4. Respiratory Management: Please see the section on Respiratory Support (P. 10) for a more complete discussion of ventilation strategies. The initial decision in respiratory management of an infant with RDS is whether the infant can be adequately managed with nasal CPAP (i.e., no treatment with surfactant) or should receive endotracheal intubation, surfactant therapy and mechanical ventilation. Endotraheal intubation should be performed in infants that require prophylactic surfactant administration or who meet the criteria listed in Table 4. ________________________________________________________________________ Table 4. Indications for intubation of preterm infant during resuscitation. ________________________________________________________________________

•GA ≤27 weeks and no maternal steroids •For other infants, any of the following:

-Apnea -Unable to maintain an adequate airway -Requires FIO2 >0.4 - ↑ work of breathing (grunting, retractions, flaring) -pH <7.25 -PaCO2 >60 mmHg

________________________________________________________________________ The goals of ventilatory management in the intubated infant are to maintain adequate oxygenation and ventilation while minimizing ventilator induced lung injury. To achieve these aims, utilize a strategy of permissive hypercarbia, maintaining PaCO2 between 45-55 mmHg, theoretically reducing volutrauma and preventing deleterious effects of hypocarbia. To reduce further the risk of volutrauma, adjust ventilatory pressures to maintain tidal volume between 4-5 mL/kg. Administration of surfactant improves lung mechanics (↑ lung compliance) and increases oxygenation by reducing atelectasis and increasing FRC. It is extremely important to recognize the time frame of these changes. After surfactant administration, there may be very rapid improvements in pulmonary function that necessitate rapid weaning of ventilator settings. Close attention must be paid to tidal volume, blood gas tensions, transcutaneous CO2 and pulse oximetry values in order to avoid inadvertent hyperventilation, hyperoxia and over-distension of the lung, all of which can result in lung injury. Although it may be necessary to wean FIO2, inspiratory pressure and ventilator rate, one should decrease PEEP with extreme caution. Infants in the early phases of RDS will rarely maintain


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adequate lung inflation if PEEP is <5 cmH2O, even after administration of surfactant. Recently, much effort has been directed towards other, less invasive modalities of respiratory support to prevent lung injury, specifically nasal CPAP. CPAP, as treatment for RDS, was first described in 1971 by George Gregory at UCSF. Modifications in the nasal CPAP delivery system have generated renewed interest in nasal CPAP for the ventilatory management of RDS. Randomized controlled trials have shown a decreased need for mechanical ventilation in VLBW infants treated with nasal CPAP, although the impact on mortality and chronic lung disease have not been defined. Furthermore, recent reports indicate that approximately 70% of infants with birth weight <1,000 g will not be adequately managed with nasal CPAP and will require intubation and mechanical ventilation. Nevertheless, in order to minimize ventilator-induced lung injury, early extubation to nasal CPAP is a reasonable strategy. Criteria for extubation to nasal CPAP in the first week of life are:

•Adequate respiratory drive, and •Mean airway pressure ≤7 cmH2O, and • FIO2 ≤0.35

Nasal CPAP is delivered via a specialized nasal mask or prongs, utilizing a patient-demand flow system. CPAP is administered between 4 and 6 cmH2O. Lower pressures do not maintain lung inflation and higher pressures often cause gastric distension. Limitations to the use of nasal CPAP include hypercarbia, frequent episodes of apnea, gastric distension and breakdown of nasal skin and mucosa from the mask/prongs.

The method and timing of further weaning, from nasal CPAP to supplemental O2 via nasal cannula, varies with gestational age, post-natal age, weight and stability of the individual patient. Some infants require a gradual transition to nasal cannula through “sprinting,” a process in which infants are trialed on nasal cannula for a portion of the day and then returned to nasal CPAP. As the infant demonstrates increased tolerance of these trials, the length of these trials is slowly extended.. The time of these trials often coincides with feeds, in order to minimize handling of VLBW infants (e.g., if feedings are q3 hours, trials of nasal cannula are usually increased in 3 hour intervals). 5. Antibiotic therapy: The clinical and radiographic features of pneumonia may be indistinguishable from RDS at birth. As a result, all infants with RDS should have blood cultures and CBC drawn, and should receive empiric antibiotic therapy (Ampicillin and Gentamicin). Generally, antibiotics may be discontinued if the blood culture has no growth after 48 hours, unless prenatal history or clinical scenario warrants extended treatment. 6. Thermoregulation: Careful temperature control is imperative in all VLBW infants and is especially important in infants with RDS to minimize metabolic demands and oxygen consumption. RDS can limit oxygen uptake leading to hypoxia which limits the ability of an infant to increase their metabolic rate when cold stressed, resulting in a fall in body temperature. An incubator or radiant warmer must be utilized to maintain a neutral thermal environment for the infant. For further discussion, see the sections on VLBW Infants (P. 65) and Health Care Maintenance (P. 48).


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Pulmonary Hypoplasia, including Congenital

Diaphragmatic Hernia INTRODUCTION: As survival for other pulmonary conditions has improved in recent years, pulmonary hypoplasia (P-Hyp, inadequately sized lungs) has become an increasingly important cause of neonatal morbidity and mortality. P-Hyp has been described as the most common anomaly in infants who die in the neonatal period. P-Hyp has several causes, and it can often be suspected on the basis of historical factors or ultrasound findings during the current pregnancy. Appropriate resuscitation of infants with P-Hyp requires special considerations and techniques. ETIOLOGY AND PATHOGENESIS: The lungs are unique in that their growth is dependent primarily on extrinsic factors. The factors which lead to P-Hyp and the clinical conditions associated with these factors are:

•Inadequate intra-thoracic space: Congenital diaphragmatic hernia (CDH); intrathoracic tumors; pleural effusions

•Prolonged oligohydramnios: Renal agenesis; prolonged rupture of fetal membranes

•Decreased or absent fetal breathing movements: CNS lesions; phrenic agenesis With P-Hyp, there is inadequate pulmonary parenchymal tissue and pulmonary blood flow for normal gas exchange. CLINICAL FEATURES of P-Hyp include:

•Immediate respiratory distress with tachypnea, cyanosis, retractions, hypercarbia, acidosis

•With specific conditions, there are typical clinical signs, for example: -CDH: scaphoid abdomen -Oligohydramnios: “Potter’s facies,” arthrogryposis -CNS lesions: other signs of abnormal CNS function

•P-Hyp can also occur as part of certain syndromes (e.g., Pena-Shokier Syndrome)

DIAGNOSIS can be made with certainty only at autopsy by measurement of total lung DNA content. Because of this, the incidence of P-Hyp is probably underestimated. The diagnosis should be suspected in the presence of::

•Historical factors suggestive of P-Hyp (e.g., prolonged oligohydramnios) •Unexpected respiratory distress •Specific clinical findings (e.g., scaphoid abdomen, “Potter’s facies”)

MANAGEMENT: Adequate care begins with a high level of suspicion that P-Hyp is the cause of the infant’s respiratory problems. If there is concern that P-Hyp is present, follow the guidelines below in addition to basic resuscitation techniques (P. 1):

•Intubate infant’s trachea and start assisted ventilation. Unless P-Hyp is very mild, infant will require assisted ventilation.

•Use low ventilatory pressures (PIP <25 cmH20) and high rates (60-90/min) with very short Ti. Infants with P-Hyp have ↑ incidence of pneumothorax.

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•Insert umbilical arterial catheter, especially for measurement of pH and PaCO2. Because these infants often have ↓ peripheral perfusion, capillary samples for pH and blood gas tensions are not adequate.

•Obtain chest radiograph immediately. •Place pre- (right hand) and post-ductal (lower extremity) saturation monitors to help

evaluate for pulmonary hypertension complicating P-Hyp. •Consider early use of inhaled nitric oxide therapy (see P. 89). •Even in cases of apparently severe P-Hyp, continue vigorous resuscitative efforts

for at least several hours. In some cases, there will be rapid resolution of the respiratory distress, as the infant does not actually have P-Hyp, despite historical factors and severe respiratory distress. The reason for the severe respiratory distress mimicking P-Hyp is not evident.

MANAGEMENT OF INFANT WITH KNOWN OR SUSPECTED CDH: In addition

to the above: •Intubate the infant’s trachea immediately. Do not use bag and mask

ventilation. This will cause distension of stomach and small bowel (which are in the chest) and worsen respiratory status.

•If CDH is known prenatally, be prepared to insert umbilical venous catheter to administer morphine and pancuronium (0.1 mg/kg of both) to facilitate assisted ventilation and prevent the infant swallowing air. Because this mixture is not damaging to the vasculature, it can be given as soon as the UVC has been inserted, even if the tip is in the portal circulation.

•Place pre- and post-ductal SpO2 monitors. Use pre-ductal to judge oxygenation. •Insert Replogle tube to suction to decompress stomach and small bowel. •In addition to low pressures for PIP, use low PEEP levels (2-3 cmH20). Infants

with CDH do not tolerate higher PEEP levels for reasons that are not apparent •Do not attempt to correct hypoxemia and hypercarbia rapidly. Infants with

CDH should receive ventilation with low pressures and rapid rates. The aim of assisted ventilation should be to provide adequate oxygenation (SpO2 >75%) and ventilation (PaCO2 ≤60 mmHg). Oxygenation and ventilation almost always improve over the first few hours after birth.

•Notify the Pediatric Surgeons immediately if there is a CDH. Surgical repair of the CDH should be delayed until after stabilization of the respiratory status, which may take several days. The Surgeons should be notified early in case of the need for ECMO and so that they can follow the patient closely with the ICN team.

•Look for other anomalies. Approximately 40% of infants with CDH have congenital heart disease or other significant anomalies.

OUTCOME of infants with P-Hyp is related mainly to lung size and presence of other anomalies. Because of the difficulty of diagnosing P-Hyp clinically, accurate mortality statistics are not available. Prenatal ultrasound can help predict outcome of infants with CDH (Lung:Head Ratio at 22-27 weeks). Severe P-Hyp due to renal causes of olighydramnios generally has a poor prognosis for survival. Survivors of P-Hyp often have chronic lung disease. Infants with CDH also have associated problems with feeding, growth and development.


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Persistent Pulmonary Hypertension of the Newborn (PPHN) DEFINITION: PPHN is persistence after birth of the high pulmonary arterial pressure (PPA), often suprasystemic, that is characteristic of the fetal circulation. PPHN may occur with or without apparent pulmonary disease. PATHOPHYSIOLOGY: In fetal life, pulmonary blood flow (Qp) is low (5-10% of cardiac output [CO]) due to high pulmonary vascular resistance (PVR) and shunts (i.e., foramen ovale, ductus arteriosus) which permit blood to bypass the pulmonary vascular bed. At birth, PVR normally falls dramatically (due to lung inflation and oxygenation), Qp increases to 100% of CO and, by 24 hours after birth, PPA has fallen to about 50% of systemic arterial pressure.

When this normal transition fails, PVR and PPA remain elevated, Qp stays low, right to left shunting occurs at the foramen ovale and ductus arteriosus, and hypoxemia results. Several factors influence PVR; among these, acidosis and alveolar hypoxia are potent pulmonary vasoconstrictors.

PPHN can result from abnormal pulmonary vascular development or with normal development of the pulmonary vasculature, when there is either failure of the normal pulmonary vasodilatation at birth or presence of powerful vasoconstrictive factors. Clinical scenarios associated with PPHN include:

-Abnormal pulmonary vascular development (e.g., increased pulmonary vascular smooth muscle due to chronic fetal hypoxia, maternal diabetes, alveolar capillary dysplasia)

-Pulmonary hypoplasia with associated hypoplasia of pulmonary vasculature (e.g., congenital diaphragmatic hernia, Potter’s syndrome, prolonged oligohydramnios)

-Postnatal elevation in pulmonary vasoconstrictors (e.g., sepsis, pneumonia, aspiration syndromes, perinatal asphyxia)

-Congenital heart disease (e.g., total anomalous pulmonary venous return with obstruction). See section on Congenital Heart Disease, P. 95.

CLINICAL PRESENTATION:

-Term or post-term infant (In preterm infants, the pulmonary vasculature is rarely sufficiently developed to result in PPHN.)

-Onset at birth or within a few hours -History or clinical findings consistent with condition associated with PPHN -Cyanosis, often with pre-ductal (right upper extremity) O2 saturation >post-ductal -Respiratory distress is common -Chest radiograph clear (idiopathic PPHN) or abnormal due to associated condition

EVALUATION and DIFFERENTIAL DIAGNOSIS:

-Begin O2 therapy, assisted ventilation if needed, blood culture and antibiotics immediately as you evaluate the infant.

-Chest radiograph

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-Pre-ductal and post-ductal pulse O2 saturation (SpO2) monitors (to detect R → L shunting at ductus arteriosus). A difference of ≥10% suggests marked pulmonary hypertension.

-Cardiology consultation and echocardiogram to R/O congenital heart disease. -Other abnormalities that can elevate PVR and require treatment include: acidosis,

polycythemia, hypothermia, hypoglycemia, hypomagnesemia. TREATMENT: Early treatment is important. The primary therapy is supplemental oxygen. Consider intubation and mechanical ventilation in infants who have significant respiratory distress or CO2 retention. The aim is reduction of PVR through pulmonary vasodilator therapy, including the following as needed:

-High inspired oxygen concentration. Start with 100% O2. Maintain pre-ductal PaO2 at 90 to 100 mmHg.

-Correct metabolic acidosis (NaHCO3, THAM). Do not administer alkali unless the patient is receiving adequate assisted ventilation. With inadequate alveolar ventilation, NaHCO3 will cause hypercarbia and worsen acidosis. THAM can cause apnea (due to rapid fall in CO2).

-Correct respiratory acidosis with assisted ventilation. Mild hyperventilation (pH 7.40 to 7.45) may be helpful. (Do not hyperventilate to compensate for metabolic acidosis; this will reduce cardiac output.)

-Assisted ventilation. Use lowest effective mean airway pressure, especially in infants without significant parenchymal disease. High frequency ventilation may be effective in those with severe lung disease.

-Inhaled nitric oxide (iNO): dose is 20 ppm (see section on Nitric Oxide, P. 89). -Maintain adequate systemic blood pressure. Keep mean arterial blood pressure in

upper range for infant’s weight (see graphs on P. 36). Use dopamine; begin at dose of 5 mcg/kg per min IV and increase as necessary. Dobutamine is less effective in newborns and may lower blood pressure.

-Adequate sedation, pharmacologic paralysis, as needed. Minimize handling. -ECMO is needed for those in whom less invasive therapy is not effective in

maintaining oxygenation, normal acid-base status or hemodynamic stability. As patient improves with treatment, wean oxygen and ventilatory support slowly. Frequently in infants with PPHN, oxygenation will decrease suddenly and dramatically after small decreases in FIO2 or ventilator pressures, or with airway suctioning, and it may take several hours for oxygenation to recover.


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Inhaled Nitric Oxide (iNO) PHYSIOLOGY: NO is a free radical, produced by the endothelium, that relaxes vascular smooth muscle (via its second messenger, cGMP) producing vasodilation. It is likely that pulmonary NO production is critical for the successful transition from fetal to postnatal circulation. Infants with PPHN have decreased serum levels of NO metabolites (nitrates) and decreased serum cGMP levels. Controlled studies in infants with PPHN have shown that iNO is a safe and effective pulmonary vasodilator, improves oxygenation, has minimal systemic effects and decreases the need for ECMO. iNO is a selective pulmonary vasodilator because hemoglobin binds NO with high affinity, thus eliminating systemic vascular effects. However, this oxidation of hemoglobin results in the production of methemoglobin (metHgb), which is restored to its usual oxygen-carrying state by enzymatic reduction. Methemoglobinemia (metHgb >5%) occurs in approximately 10% of newborns treated with iNO and resolves with decreasing the iNO dose. Infants receiving iNO therapy should have a metHgb level measured daily. DOSE of iNO: Usual dose is 20 ppm. This produces maximal pulmonary vasodilatation in the vast majority of infants with PPHN. WEANING of iNO: As oxygenation improves, decrease FIO2 to ≤0.50. Then, iNO can usually be weaned from 20 to 5 ppm in decrements of 5 ppm every 1 to 2 hours. After that, wean by 1 ppm every 1 to 2 hours. Reduction of iNO from 1 to 0 ppm must be done with care as hypoxemia may result (See below). During the weaning process, monitor the infant closely for decreases in oxygen saturation and increase FIO2 as needed. In infants with severe PPHN or congenital diaphragmatic hernia, an echocardiogram may be useful to evaluate right ventricular function and pressure before discontinuing iNO. REBOUND PULMONARY HYPERTENSION: Sudden discontinuation of iNO will cause rebound pulmonary hypertension that may be severe. This probably results from suppression by iNO of endogenous NO production. Rebound pulmonary hypertension is a risk with cessation of iNO from even low doses (i.e., <5 ppm), after only a few hours of iNO therapy, and regardless of whether the infant initially responded to iNO. Because of the risk of rebound pulmonary hypertension, be certain that the bag system (for manual ventilation) is set up to deliver iNO at the time of the onset of iNO therapy. This will ensure that the infant will continue to receive iNO during suctioning of the airway and in the event of a malfunction of the ventilator.


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Pulmonary Hemorrhage DEFINITION: Pulmonary hemorrhage (P-Hem) is an acute, catastrophic event characterized by discharge of bloody fluid from the upper respiratory tract or the endotracheal tube. The incidence of P-Hem is 1 in 1,000 live births. P-Hem is present in 7 to 10% of neonatal autopsies, but up to 80% of autopsies of very preterm infants. When evident clinically, P-Hem is usually massive, is associated with bleeding in other sites, involves more than one third of the lungs, and has a high mortality rate. ETIOLOGY & PATHOGENESIS: Prematurity is the factor most commonly associated with P-Hem; other associated factors are those that predispose to perinatal asphyxia or bleeding disorders, including toxemia of pregnancy, maternal cocaine use, erythroblastosis fetalis, breech delivery, hypothermia, infection, Respiratory Distress Syndrome, administration of exogenous surfactant (in some studies) and ECMO.

Although the pathogenesis is uncertain, it is probable that P-Hem is hemorrhagic pulmonary edema, as the hematocrit is lower than blood and the concentration of small proteins is higher than in plasma. It is postulated that the infant suffers an asphyxial insult with resultant myocardial failure; this increases pulmonary microvascular pressure resulting in pulmonary edema. Subsequently, there is frank bleeding into the pulmonary interstitial and alveolar spaces. Contributing factors include factors that favor increased filtration of fluid from pulmonary capillaries (e.g., low concentration of plasma proteins, high alveolar surface tension, lung damage, hypervolemia). CLINICAL FEATURES: The onset of P-Hem is characterized by oozing of bloody fluid from the nose and mouth or endotracheal tube with associated rapid worsening of the respiratory status, cyanosis and, in severe cases, shock. Bleeding may be noted from other sites. Radiographic findings range from patchy infiltrates to complete opacification of lung fields. Hematocrit of the P-Hem fluid is usually 15 to 20% less than blood. TREATMENT & OUTCOME: Immediate treatment of P-Hem should include tracheal suction, oxygen and positive pressure ventilation. To assist in decreasing P-Hem, mean airway pressure should be increased, either by a relatively high PEEP (i.e., 6 to 10 cmH2O) or by high frequency ventilation. Correct underlying abnormalities, especially disorders of coagulation. When blood loss is large, prompt blood transfusion may be needed to maintain an adequate circulating blood volume. The outcome is dependent on the cause of P-Hem. Mortality is 30 to 40%.


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Apnea and Bradycardia DEFINITION: Pathologic apnea is a prolonged respiratory pause of ≥20 sec, or one associated with bradycardia or color change. The respiratory pause may be central (i.e., no respiratory effort), obstructive (usually due to upper airway obstruction), or mixed. Short (≤5 sec) episodes of central apnea can be normal at all ages. DIFFERENTIAL DIAGNOSIS:

1. Apnea of prematurity, most common in infants ≤34 weeks gestation. (Note: All following etiologies must be excluded or appropriately treated before a diagnosis of apnea of prematurity can be made).

2. Hypoxemia 3. Infection (sepsis, meningitis, pneumonia) 4. Necrotizing enterocolitis 5. Intracranial hemorrhage 6. Hydrocephalus 7. Seizures 8. Patent ductus arteriosus 9. Hypoglycemia 10. Anemia (Note: Apnea may improve after PRBC transfusion; however, infants who

respond cannot be predicted by their Hct. Infants with a low Hct who respond to transfusion usually have an elevated blood lactate and elevated heart rate.)

11. Polycythemia/hyperviscosity 12. Atelectasis 13. Gastroesophageal reflux. Methylxanthines may exacerbate reflux. If reflux

associated with apnea becomes a persistent problem, the head of the bed should be elevated 20 degrees. Metoclopramide (Reglan™: 0.1 – 0.2 mg/kg/dose, TID or QID), bethanechol, and H2 blocking agents should be used only after reflux has been documented with pH probe analysis.

14. Feeding bradycardia (probably due to vagal stimulation from the NG tube or from gastric distension)

15. Following anesthesia or depressant drugs (This is frequently observed after repair of inguinal hernias in former preterm infants and can be minimized with perioperative caffeine administration. The susceptibility of preterm infants to apnea after anesthesia may persist until 50-60 post conceptional weeks.)

16. Maternal drug withdrawal 17. Elevated environmental temperature 18. Upper Airway obstruction (e.g., due to nasal secretions, choanal atresia or stenosis,

vocal cord paralysis) 19. Tracheal suctioning (due to hypoxemia and/or vagal stimulation) 20. PGE1 infusion 21. Congenital Hypoventilation Syndrome (Methylxanthines are ineffective and these

infants need mechanical ventilation.)

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TREATMENT: If the infant has any of the above conditions, these should be treated appropriately. - Monitoring: Infants at risk for apnea should have continuous monitoring of respiration

and heart rate (because an apnea monitor alone will miss obstructive apnea) until they are at least 34 wks postconceptional age and have been free of apnea and bradycardia for one week.

-Prevent hypoxemic episodes. -Cutaneus stimulation is effective with mild apnea. -Maintain the infant in prone position. -Methylxanthines: When idiopathic apnea of prematurity is severe enough to treat

pharmacologically, the drug of choice is p.o. caffeine (even when the child is n.p.o. – except during necrotizing enterocolitis). A loading dose of caffeine citrate 20 mg/kg p.o. (10 mg/kg caffeine base) should be used, followed in 24 h by a daily maintenance dose of 5.0 mg/kg/d caffeine citrate. Therapeutic levels will usually be achieved within 30–120 minutes of the initial dose. Plasma caffeine levels are usually not measured, because some infants may require higher plasma levels for response and because caffeine toxicity is not generally a problem until plasma levels >50 mg/L. For infants who fail to respond to the above dosages, a second load of 10–20 mg/kg caffeine citrate can be given, followed by a maintenance dose of 7.5 mg/kg/d. If symptoms that could be attributable to methylxanthine toxicity occur (most commonly tachycardia, jitteriness and vomiting), theophylline concentrations as well as caffeine concentrations should be measured. Because of the long half-life of caffeine, therapeutic levels may persist for >7–14 d after discontinuing therapy. Caffeine therapy needs to be discontinued well before discharge.

-Respiratory support: Continuous air flow through nasal cannulae is useful in some infants, and others will respond to nasal CPAP. If apnea is severe, the infant may require mechanical ventilation.

FEEDING AND CONTROL OF BREATHING: Preterm infants have a 50% fall in minute ventilation during nipple feedings, which may progress to hypoxemia, apnea, and bradycardia. Feeding hypoxemia resolves with maturation. It is usually gone by 44 weeks postconceptional age, but occasionally may last longer. Infants are treated by frequent interruptions during a feed, by supplemental oxygen during a feed, or, in extreme cases, by gavage.

HOME APNEA MONITORING: Home monitoring is not indicated for normal infants or for asymptomatic preterm infants. SUPINE POSITION FOR SLEEP: DISCHARGE RECOMMENDATIONS: Supine positioning during sleep reduces the incidence of SIDS in normal infants. Premature infants should be encouraged into the supine position prior to discharge and mothers should be advised of the advantages of the supine position. These recommendations do not apply to preterm infants with apnea in hospital (who are being monitored for apnea), or to those with Pierre Robin sequence, laryngomalacia, or gastroesophageal reflux.


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Chronic Lung Disease (Bronchopulmonary Dysplasia) was first described in 1967 as severe chronic lung disease (CLD) in preterm infants with severe Respiratory Distress Syndrome (RDS) who received treatment with 100% O2, high inspiratory ventilator pressures and no PEEP. With antenatal glucocorticoids, surfactant treatment and improved ventilatory techniques, CLD has almost disappeared in larger preterm infants and now affects very preterm infants with or without antecedent RDS. DEFINITION: CLD is defined as a need for increased oxygen:

• Infants <32 weeks gestation: oxygen requirement at 36 weeks gestational age (GA) or at discharge (whichever comes first)

• Infants ≥32 weeks GA: oxygen requirement at age >28 d or at discharge (whichever comes first)

INCIDENCE of CLD is inversely related to birth weight and GA: Birth weight (g) Incidence of CLD* 501-750 34% *UCSF 1998-2002 751-1,000 20% 1,001-1,250 5% 1,251-1,500 3% PATHOLOGY includes areas of atelectasis and emphysema, hyperplasia of airway epithelium and interstitial edema. Late changes include interstitial fibrosis and hypertrophy of airway smooth muscle and pulmonary arteriolar musculature. ETIOLOGICAL FACTORS include:

• Lung immaturity with (a) ↑ susceptibility to damage from oxygen, barotrauma and volutrauma, (b) surfactant deficiency and (c) immature antioxidant defenses.

• Oxygen toxicity • Barotrauma and volutrauma • Pulmonary edema (excessive fluid administration, patent ductus arteriosus) • Inflammation (multiple associated biochemical changes)

RISK FACTORS include: 1. Maternal: • Chorioamnionitis • Abruptio placenta

• No antenatal steroids • Prenatal indomethacin • Intrauterine growth retardation

2. Neonatal: • Prematurity (<28 weeks GA) • Birth weight <1,000 g • Male gender • Low Apgar scores • Severity of RDS • Air leaks • Patent ductus arteriosus • Infection • Lung disease (CDH, pulmonary hypoplasia) • Genetic factors • Risk: ↑ in Caucasians, ↓ in African-Americans

CLINICAL FEATURES:

• Hypoxia due to V/Q mismatch • ↑ work of breathing

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• Abnormal chest radiograph • ↑ airway resistance is late feature • Pulmonary hypertension • Cor pulmonale (late)

PREVENTIVE MEASURES:

• Minimize barotrauma & volutrauma by using low ventilator inspiratory pressures and tidal volumes. Tolerate mild hypercarbia (PaCO2 ≤55 mm Hg). Higher PEEP (e.g., 6 cm H2O) may help prevent CLD. Early extubation and nasal CPAP may help, but benefit has not been proven.

• Minimize oxygen toxicity: Maintain O2 saturation between 85 and 92% in preterm babies. Higher O2 saturation also ↑ risk of Retinopathy of Prematurity (ROP).

• Careful attention to intake of fluid and Na+. Mild hyponatremia in small preterm infants is common, is tolerated well and is not an indication to ↑ Na+ intake.

TREATMENT of ESTABLISHED CLD:

• Adequate caloric intake (140-160 kcal/kg/d) because of ↑ work of breathing • After 36 weeks GA, maintain O2 saturation >95% to prevent pulmonary

hypertension and cor pulmonale. (Low risk of ROP after 36 weeks GA). Some infants with CLD will require O2 therapy after discharge.

• Restrict intake of fluid and Na+. Hyponatremia with serum sodium ≤125 mEq/L should be treated with fluid restriction, not diuretics and ↑ administration of Na+.

• Diuretics, especially furosemide. Do not use unless there already is restricted intake of fluids and Na+. Side effects are common and include hypercalciuria (leading to osteopenia, & nephrocalcinosis), metabolic alkalosis (due to Cl- loss) and hypokalemia. Alternate day diuretics may be effective with fewer side effects.

• Bronchodilators may be effective. Pulmonary function testing to document bronchoconstriction prevents unnecessary use of these drugs. “Tightness” or “clamping down” diagnosed by auscultation is often due to atelectasis, not bronchoconstriction.

• Steroids are almost never indicated in CLD, rarely have any lasting benefit and significantly ↑ the risk of adverse neurologic outcome. Steroids should be used only in very severe CLD (e.g., infant on high O2 and high ventilator settings who is worsening). Other side effects include systemic hypertension, adrenal suppression, infection, growth suppression and cardiac hypertrophy.

• Infection prevention: Immunization against RSV infection (see section on Immunizations, P. 71).

OUTCOME:

1. Mortality with severe CLD is ~25%. Main causes of death are cor pulmonale, lower respiratory tract infection and sudden death.

2. Long term complications are common and include: • Respiratory: Recurrent infections, central apnea, bronchial hyper-reactivity • Cardiovascular: Pulmonary hypertension, cor pulmonale, bronchopulmonary shunts • Growth delay • GI: Feeding difficulties, GE reflux, aspiration • Associated conditions (but unlikely due to CLD): hearing loss, developmental delay,

cerebral palsy, intraventricular hemorrhage and white matter CNS damage.


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Congenital Heart Disease INTRODUCTION: Congenital heart disease (CHD) affects ~1% of newborn infants and accounts for ~10% of all congenital anomalies. Factors that ↑ risk for CHD include maternal diabetes mellitus, familial presence of genetic syndromes (e.g., Noonan syndrome), history of previous infant with CHD, and genetic factors that are just now starting to be identified. The most common types of CHD are ventricular septal defect, pulmonic stenosis, endocardial cushion defect, atrial septal defect and tetralogy of Fallot. Although some infants with CHD do not have signs or symptoms in the newborn period, others will need immediate intervention because of the severity of their disease. The following discussion of CHD is not exhaustive. It is intended as a guide to the initial management (diagnostic and therapeutic) of infants presenting with clinical findings indicative or suggestive of CHD. SOME GENERAL GUIDELINES:

•Not all newborns with murmurs have CHD. •Not all newborns with CHD have murmurs. •Not all newborns with CHD present in the newborn period. •Not all newborns with clinical findings of CHD need immediate intervention. •It is often difficult to differentiate CHD from pulmonary and other diseases

(especially sepsis) in a newborn infant. •Findings that should alert one to the possibility of serious CHD in a newborn

include: -Cyanosis -Metabolic acidosis (unexplained) -Respiratory distress -Poor peripheral perfusion -↓ pulses -Difference in pulses (arm vs. leg) -Single 2nd heart sound -Abnormally loud 2nd heart sound -Prominent heart murmur -Abnormally prominent pulses -Hyperactive precordium -Shock

•Obtain Cardiology Consult as soon as the diagnosis of CHD is suspected.

EVALUATION OF AN INFANT WITH SUSPECTED CHD: 1. History:

A. Family: hereditary diseases, previous sibling with CHD B. Pregnancy and perinatal: Viral infections, maternal medicines, maternal illness C. Postnatal: Poor feeding, cyanosis, tachypnea, tachycardia, edema

2. Physical examination: A. Auscultation: Do this first, before infant starts crying.

•Heart rate, rhythm •Heart sounds (especially 2nd sound): intensity, split (presence, character) •Murmur: quality (systolic, diastolic, continuous), intensity, timing, location •Other sounds: gallop, click

B. Cardiovascular system (remainder): cyanosis, precordial activity, thrill, pulses, blood pressure (both arms vs. leg), peripheral perfusion (capillary refill time)

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C. Other: respiratory distress (improving or worsening), hepatosplenomegaly, dysmorphic features, urine output

3. Laboratory: A. Chest radiograph: heart size, pulmonary vascularity, pulmonary edema, lung

parenchyma B. Electrocardiogram: rate, rhythm, axes of P and QRS, voltages in precordial leads C. Monitoring: O2 saturation by pulse oximetry, both pre-ductal (right hand) and

post-ductal (foot) D. Arterial pH and blood gas tensions: Evaluate mainly for hypoxemia and

metabolic acidosis. In contrast to older children and adults, CO2 may be elevated in newborn infants with congestive heart failure.

COMMON MODES OF PRESENTATION of CHD include: 1. Respiratory distress:

A. Likely lesions include: •VSD, PDA, ASD: These rarely cause symptoms in first few days of life in term

infants unless more than one lesion is present. •AV canal, aortico-pulmonary window, total anomalous pulmonary venous return

(TAPVR) without obstruction •TAPVR with obstruction: Respiratory signs occur immediately after birth, may

be very severe and worsen progressively. This lesion requires emergency intervention.

•Truncus arteriosus B. Management:

•O2 is rarely helpful and may worsen shunting by decreasing pulmonary vascular resistance.

•Correct anemia (if present), limit sodium and fluid intake, administer diuretics, optimize nutrition.

•Early surgery may be necessary for some. 2. Cyanosis with normal or ↑ pulmonary blood flow:

A. Likely lesions include: •Transposition of great arteries (TGA): the commonest form of CHD causing

cyanosis in the newborn period. (post-ductal saturation > pre-ductal) •Truncus arteriosus (may present with respiratory distress) •Double outlet right ventricle •Ebstein’s anomaly of the tricuspid valve (prominent RV impulse, cardiomegaly)

B. Management: •TGA without VSD: Cyanosis is prominent. In order to ↑ mixing between

pulmonary and systemic circulations and ↑ systemic oxygenation: -Start prostaglandin E1 (PGE1) at 0.05 mcg/kg/min IV to dilate the ductus

arteriosus (see section on PGE1 at end of this chapter). -Balloon atrial septostomy (Rashkind procedure) to allow atrial mixing -Surgical repair is arterial switch procedure. If this is not feasible (e.g.,

abnormal coronary arteries), an atrial baffle procedure can correct the physiological abnormality, but complications are common.

•Congestive heart failure (CHF) is managed with diuretics and/or digoxin.


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3. Cyanosis with ↓ pulmonary blood flow: The most common causes are right-sided obstructive lesions that result in inadequate blood flow to the lungs. Age of presentation varies depending on the lesion. Whereas tricuspid atresia presents rapidly immediately after birth, mild forms of Ebstein’s anomaly may not present until later in life. With some lesions, cyanosis decreases as pulmonary vascular resistance drops.

A. Likely lesions include: •Tetralogy of Fallot (with or without pulmonic atresia). In mild cases, cyanosis

may not be present at birth (acyanotic Fallot, “pink tet”). •Tricuspid atresia, pulmonic atresia with intact ventricular septum, severe

pulmonic stenosis •Ebstein’s anomaly of the tricuspid valve

B. Management: In most cases, infusion of PGE1 increases pulmonary blood flow and stabilizes the infant until surgical intervention is undertaken. Assisted ventilation and increased environmental oxygen are often necessary. For these infants, oxygen saturations in the 75-85% range are adequate.

4. Shock: The differential diagnosis of shock is discussed in the section on Shock (P. 101). The most common types of CHD that cause shock are left-sided obstructive lesions. The mechanism of shock is inadequate systemic blood flow. The onset of signs relates to closure of the ductus arteriosus which may not occur until a few days after birth.

A. Likely lesions include: •TAPVR with obstruction may present with both respiratory distress and shock. •Mitral atresia or severe mitral stenosis (type of hypoplastic left heart complex) •Aortic atresia or severe aortic stenosis (type of hypoplastic left heart complex) •Interrupted aortic arch (often associated with DiGeorge Syndrome) •Coarctation of aorta (usually presents several days after birth)

B. Management: •PGE1 to allow right→left shunting through ductus arteriosus •Assisted ventilation to treat pulmonary edema (as well as apnea from PGE1) •Correct metabolic acidosis (see sections on Resuscitation, P. 1, and Acid Base

Balance, P. 62) •Inotropic agents to improve myocardial function •Be cautious with use of oxygen in setting of a single ventricle. Discuss use of

oxygen with Fellow or Attending. Oxygen will accelerate the closure of the ductus arteriosus and worsen infant’s condition by decreasing systemic output. Therefore, do not increase environmental oxygen until after PGE1 has been started.

•Fluid restriction if there is renal failure •In some cases of hypoplastic left heart, there is excessive pulmonary blood flow

and inadequate systemic output, even with PGE1. In such cases, the following measures may be used in an attempt to decrease pulmonary blood flow and increase systemic output. These infants require mechanical ventilation and it is usually necessary to administer muscle relaxants (i.e., pancuronium bromide) to prevent the infant from hyperventilating:

-Decrease inspired oxygen to ~18% by adding N2 to inspired gas (to ↓ alveolar PO2)


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-Add CO2 to inspired gas (to ↓ arterial pH) -↑ PEEP to try to impede pulmonary blood flow

PROSTAGLANDIN E1 (PGE1) is used to dilate the ductus arteriosus in infants with inadequate mixing between systemic and pulmonary circulations (i.e., inadequate pulmonary blood flow or inadequate systemic output). A. Starting dose of PGE1 is 0.05 mcg/kg/min IV. If no improvement, ↑ dose to 0.1

mcg/kg/min. Discuss with Cardiology before increasing dose further. After the infant’s condition has stabilized, the usual maintenances dose of PGE1 is 0.025 mcg/kg/min.

B. Complications of PGE1: •Apnea is the most common complication and is due to a direct effect of PGE1 on

the CNS. The vast majority of infants who require PGE1 will also need assisted ventilation, either for the severity of their CHD or because of apnea. Therefore, do not start PGE1 unless:

(a) Infant is intubated and receiving assisted ventilation or (b) You are prepared to intubate the infant and start assisted ventilation

immediately after PGE1 has been started. •Hypotension, due to vasodilatation of peripheral circulation and decreased

cardiac output, occurs most commonly at higher doses. Be sure to have arterial access with continuous measurement of arterial blood pressure when PGE1 is started.

•Fever, which makes evaluation for infection difficult. Some cardiologists will administer antibiotics to an infant on PGE1.

•Irritability, abnormal EEG and seizures due to a direct CNS effect and more common at higher doses.

•Diarrhea. Although this may occur, infants who require PGE1 for several days may be tried on enteral feedings, if their condition otherwise permits.

•Longer term effects include hypertrophy of gastric mucosa mimicking congenital pyloric stenosis and periosteitis.


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Patent Ductus Arteriosus (PDA) DEFINITION: The ductus arteriosus is patent in all newborns at the time of delivery. It is closed by 48 h after birth in 100% of infants delivered at ≥40 wks gestation and by 72 h after birth in 90% of infants delivered at ≥30 wks gestation. A ductus open beyond 72 h can be considered to be a persistently patent ductus arteriosus. Twenty-five percent of infants with birth weights 1,000-1,500 g will have a PDA at 72 h, and 70% of these will require treatment for their PDA. Sixty-five percent of infants with birth weights <1,000 g will have a PDA at 72 h, and 85% of these will require treatment for the PDA. CLINICAL FINDINGS: These include:

-Heart murmur: PDA is almost always associated with a systolic murmur that may extend into early diastole and be heard best along the mid to lower left sternal border. In infants on respiratory support, the murmur may be difficult to hear. When listening for a murmur, it may be helpful for another person to disconnect the ventilator very briefly (3 to 5 heart beats) while you listen for the murmur.

-Wide pulse pressure, low diastolic pressure or accentuated pulses to palpation. -Hyperactive precordium -Increased vascular markings on chest radiograph. Increased heart size is a late sign. -Apnea or a worsening in respiratory status -Prolonged capillary filling time when there is decreased systemic output due to a

very large left to right shunt through the PDA. In these cases, metabolic acidosis is an ominous sign.

MEDICAL TREATMENT: General Considerations: Conventional treatment of congestive heart failure (fluid restriction, diuretics, digoxin) is not effective and will delay proper treatment. Unless the PDA is not hemodynamically significant, infants with PDA should be NPO. Indomethacin: 1. Gestation ≥28 weeks at birth: These infants are usually treated only when a hemodynamically significant PDA is present. This practice is aimed to avoid unnecessary treatment. A PDA is considered hemodynamically significant if, in addition to a murmur, two or more of the following signs are present:

-increased pulse volume or widened pulse pressure -hyperactive precordium -increased pulmonary vascular markings on chest radiograph

An untreated hemodynamically significant PDA will prolong the need for oxygen therapy and delay the establishment of feedings. An echocardiogram should be obtained to rule out structural congenital heart disease.

Indomethacin Dosage (IV): Birthweight >1,250 g: Give three doses of 0.2 mg/kg; give the 2nd dose 12 h after the first, and the 3rd dose 24 h after the 2nd. Birth weight 1,000-1,250 g: 1st dose is 0.2 mg/kg; 12 h later, give 0.1 mg/kg for 2nd dose; 24 h after the 2nd dose, give 0.1 mg/kg.

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2. Gestation <28 weeks at birth – (Prophylactic Indomethacin, UCSF approach): Seventy percent of infants <28 weeks gestation will require therapy for a PDA at some point during their hospitalization. Indomethacin is not as effective in this group and surgery is frequently necessary. The earlier infants are treated with indomethacin, the more effective it is in producing permanent closure. At UCSF, all infants <28 weeks gestation are treated prophylactically with indomethacin by 12-15 h after birth. An echocardiogram and serum creatinine are not usually obtained prior to giving the 1st dose. Platelet count >100,000 should be demonstrated prior to the first dose. The 1st dose should be delayed if there is any concern about a bleeding diathesis or coagulopathy. PT and PTT should be measured if there is concern about a coagulopathy. Prophylactic Indomethacin Dosage (IV): Three initial doses: 1st = 0.2 mg/kg, 2nd = 0.1 mg/kg (24 h after the first dose), 3rd = 0.1 mg/kg (24 h after the 2nd dose). Serum creatinine and platelet count should be checked before 2nd and 3rd doses.

Just prior to the 3rd indomethacin dose, obtain an echocardiogram. If there is echocardiographic evidence of patency of the ductus (even if there are no clinical signs), give 4th, 5th, and 6th doses of indomethacin (0.1 mg/kg at 24 h intervals). Repeat the echocardiogram after the 6th dose.

Contraindications to Indomethacin: -Active bleeding:GI and other (Note that presence of an ICH is not a contraindication) -Active or suspected Necrotizing Enterocolitis (NEC) -Creatinine ≥2.0 mg/dL -Urine output <1 mL/kg/h (indomethacin may be restarted when urine output

>1mL/kg/h) -Platelet count <50,000 (consider platelet transfusion prior to indomethacin) -Active (and untreated) infection -Suspected Congenital Heart Disease -Known gastrointestinal or renal anomaly

Management During Indomethacin Treatment: Because indomethacin decreases gastrointestinal blood flow, infants should be kept NPO until at least 48 h after the indomethacin therapy has been completed.

Because indomethacin may cause a transient decrease of urine output (similar to excessive ADH action), IV fluids should be adjusted every 8-24 h, taking into consideration not only fluid intake in mL/kg, but more importantly, the relationship between urine output and fluid intake. An acceptable output to intake ratio in these circumstances is between 0.3 and 0.7, taking the infant’s anticipated weight change into consideration. A decrease in serum Na+ should prompt additional fluid restriction because of retention of free water with indomethacin administration. SURGICAL CLOSURE OF PDA should be considered in the following situations:

-Failure of indomethacin therapy -Hemodynamically significant PDA and presence of contraindication(s) to

indomethacin -Presence of PDA and NEC. In this circumstance, operative closure of the PDA is

almost always necessary before the NEC will resolve and may be required as an emergency procedure.


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Neonatal Shock DEFINITION AND PATHOPHYSIOLOGY: Shock is an acute state in which circulatory function is inadequate to supply sufficient amounts of O2 and other nutrients to tissues to meet metabolic demands. In most cases, cardiac output is low. In early shock, compensatory regional vasoconstriction (skin, skeletal muscle, splanchnic circulation) may temporarily maintain normal blood pressure and adequate blood flow to vital organs. As shock progresses, compensatory mechanisms fail and widespread cellular damage occurs. Insufficient O2 delivery to tissues causes anaerobic metabolism and lactic acidosis. If shock persists, irreversible injury to vital organs occurs; death ensues despite vigorous therapy that may temporarily return cardiovascular measurements to normal. ETIOLOGY: A variety of factors, often in combination, may cause shock:

Hypovolemia (e.g., blood loss, inadequate placental transfusion, feto-maternal transfusion, severe dehydration)

Asphyxia (e.g., antepartum or intrapartum, respiratory failure, impaired oxygen transport due to severe anemia or hemoglobinopathy)

Cardiogenic causes (e.g., cardiomyopathy, dysrhythmia, congenital malformation, hypocalcemia, severe hypoglycemia)

Obstruction of venous return due to tension pneumothorax, excessive ventilator pressures, cardiac tamponade

Sepsis (especially early onset group B beta-hemolytic Streptococcal infection) Drugs (especially when hypovolemic infants, in whom blood pressure has been

maintained by vasoconstriction, are given vasodilators such as PGE1, isoproterenol or magnesium)

Hypocarbia (severe) CLINICAL EVALUATION: There are no clinical or laboratory findings specific to shock. The diagnosis is based on presence of several indicators of inadequate circulatory function. Various clinical and laboratory findings associated with shock include:

Cardiovascular findings: Systemic arterial hypotension (see graphs on P. 36) Narrow pulse pressure Central venous hypotension: with myocardial failure, central venous pressure is ↑ Tachycardia (In early asphyxia, bradycardia is present.)

Respiratory findings: Tachypnea Grunting respirations Retractions Apnea

Other findings: Prolonged capillary filling time Hypothermia Oliguria Metabolic Acidemia

TREATMENT: Specific therapy depends upon the cause of shock. Rapid recognition of shock and identification of underlying cause(s) are essential to prevent irreversible changes. With hypovolemia, intravascular volume must be increased, but cautiously.

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Volume replacement with blood or plasma expander should be in aliquots of 5 mL/kg every few minutes until circulatory function is adequate. Carefully assess the effects of volume replacement on heart rate, blood pressure, respiratory function, acid-base status and perfusion. After an adequate circulating blood volume has been achieved, replacement of other fluid deficits should be done more slowly, over several hours. With asphyxial shock, treatment of respiratory failure with oxygen and assisted ventilation may be the only therapy needed. Do not give blood volume expanders during asphyxia as that will aggravate hypoxic myocardial failure. Alkali should be given only when there is significant metabolic acidemia (base deficit ≥ 10 mEq/L), the infant is receiving adequate assisted ventilation and PaCO2 is in the normal range. NaHCO3, given when ventilation is inadequate, leads to respiratory acidosis and may worsen the patient’s condition. THAM™ may cause apnea because of its effect of rapidly lowering PaCO2. During resuscitation of an infant in shock, certain drugs are useful; these drugs, their indications, and their usual starting doses are listed in the table below. Dopamine is useful for treatment of infants in early shock as it is effective in raising systemic arterial blood pressure and often increases urinary output. Newborns in shock may require a dopamine dose of 30 mcg/kg/min or higher to obtain a pressor response. In contrast to older patients, such high doses of dopamine do not have adverse effects on urinary output in newborn infants. Dobutamine is less effective in newborns and often lowers blood pressure because of its vasodilating effects. Drugs useful in resuscitation of infants in severe shock Drug Dose Route Indication Atropine 0.01 mg/kg IV Sinus bradycardia Calcium chloride 10% 0.25 mL/kg IV Hypocalcemia (25 mg/kg) Calcium gluconate 10% 1.0 mL/kg IV Hypocalcemia (100 mg/kg) Dopamine* 5.0 mcg/kg/min INF Hypotension, low CO Epinephrine (1:10,000) 0.1 mL/kg IV Asystole, bradycardia Glucose 10%* 1-3 mL/kg IV Hypoglycemia over 2-5 min Isoproterenol* 0.1 mcg/kg/min INF Bradycardia with low CO IV, intravenous; INF, continuous IV infusion; CO, cardiac output. *Doses listed for these drugs are usual starting doses. The dose should be increased as

needed until a therapeutic effect is achieved.


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Neonatal Hypertension DEFINITION: Systolic or mean arterial blood pressure (BP) >95th percentile for birth weight, gestational age and post-natal age. (See graphs of normal BP on P. 36.) EPIDEMIOLOGY: -95th percentile for systolic BP = 65 mmHg at 24 weeks and 90 mmHg at 40 weeks post-

conception. -By definition, 5% of all infants have a blood pressure above the 95th percentile, but real

incidence of hypertension in ICN is about 0.8% -In infants with bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH),

umbilical arterial catheters (maintained in “high” position) or patent ductus arteriosus, incidence of hypertension is 9%.

-Incidence varies widely in different ICNs. SIGNS/CONSEQUENCES include lethargy, irritability, apnea, tachypnea, seizures, intracranial hemorrhage, congestive heart failure or cardiogenic shock. DIFFERENTIAL DIAGNOSIS: -Commonest cause of neonatal hypertension is reno-vascular hypertension due to

thrombi from “high” umbilical arterial catheter (UAC). Maintain UAC so that tip is below 3rd lumbar vertebra (L3). (See section on Catheters, P. 25)

-Other renal causes: thromboembolism, renal artery stenosis, coarctation of aorta, renal vein thrombosis, renal anomalies, polycystic or dysplastic kidneys, acute tubular necrosis

-Iatrogenic: glucocorticoids, dopamine (and other pressors), caffeine, pain, fluid/Na+ disturbances

-Neurological: intracranial hypertension, seizures, IVH, subdural hematoma -Endocrine: congenital adrenal hyperplasia, hyperthyroidism, hyperaldosteronism -Pulmonary: hypercarbia, chronic lung disease, pneumothorax (early, followed by

hypotension)

EVALUATION: -Document presence of hypertension with multiple limb BPs and invasive measurement,

if possible. -History: recent and current medications, procedures (UAC) -Physical examination, including state (pain, agitated, seizure, quiet, etc.) -Laboratory: BUN, Creatinine, electrolytes, Ca, UA with micro, chest radiograph, renal

ultrasound with Doppler flow studies, cranial ultrasound -Other laboratory tests (in selected infants with consultation): thyroid function tests,

urinary VMA/HVA, cortisol, aldosterone, echocardiography -Further workup and management with appropriate consultation (e.g., nephrologist,

cardiologist, endocrinologist) TREATMENT varies with cause of hypertension. Treat the etiology, if possible. Correct or treat iatrogenic causes!

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-Unless the hypertension is immediately life-threatening, do not automatically give an anti-hypertensive agent!

-Emergency treatment: hydralazine (0.15-0.6 mg/kg IV). Other emergency therapies include diazoxide, esmolol, labetalol, and sodium nitroprusside, but these are rarely needed in newborn infants.

-Monitor BP closely (preferably by arterial line) during drug therapy as these agents can cause hypotension and shock.

-Maintenance therapy: captopril (0.01-0.5 mg/kg/dose TID). Other potential agents: long acting hydralazine, amlodipine, propanolol and labetalol.


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Neonatal Cardiac Arrhythmias INTRODUCTION: Identification and treatment of arrhythmias in newborns is challenging and differs from older children, and the natural history of arrhythmias presenting in the neonatal period is often dramatically different. METHODS OF DIAGNOSIS AND THERAPY: For management of arrhythmias, consult Cardiology team. 1. Diagnostic methods:

•15 lead electrocardiogram (standard 12 lead plus V3R, V4R, V7) •Heart rate determination (ECG strip, count number of QRS complexes in 6 sec x 10) •Blood pressure (intra-arterial or indirect)

2. Treatment: Electrical (See below for drug therapy) •Artificial pacing :

-Temporary transvenous pacing -Esophageal pacing

•Cardioversion: -Setting: 0.5 - 2.0 Joules/kg -Mode: synchronous for narrow QRS; asynchronous for ventricular fibrillation

IMMEDIATE MANAGEMENT OF ARRHYTHMIAS: *A B C, airway, breathing, circulation

Tachyarrhythmia

narrow-QRS wide-QRS

Bradyarrhythmia

stable unstable stable unstable

synchronized cardioversion

vagal maneuvers adenosine, propranolol or digoxin

Procainamide,lidocaine in VT

synchronized cardioversion no response asynchronous mode

A B C*, O2, atropine & isoproterenol, temporary trans-venous pacing

unstable

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A. Tachy-arrhythmias with narrow QRS:

I. Reentry tachycardias Diagnosis Findings on ECG Treatment

Atrial flutter -"Sawtooth" flutter waves -AV block does not terminate atrial rhythm -Atrial rate up to 500 in newborns -Variable AV conduction common

-Unstable: esophageal pacing or electrical cardioversion -Stable: digoxin, propranolol, or digoxin + procainamide

Accessory pathway mediated tachycardia (WPW)

-P follows QRS, typically on upstroke of T -Superior or rightward P wave axis -AV block always terminates tachycardia -Typically terminates with P wave -After termination, WPW have pre-excitation

Permanent form of junctional reciprocating tachycardia (PJRT)

-Incessant - P wave precedes QRS -Inverted P waves in II, III, AVF -AV block always terminates tachycardia -May terminate with QRS or P wave -No pre-excitation after termination

Atrioventricular node reentry -P usually not visible, superimposed on QRS -AV block usually terminates tachycardia.

-Unstable: esophageal pacing or electrical cardioversion -Stable: vagal maneuvers. adenosine propranolol or digoxin -No response: procainamide or flecainide

Atrial and sinoatrial reentry -P present, precedes next QRS -Terminates with QRS rather than P -AV block does not terminate atrial rhythm -P axis may be superior or inferior

-Unstable: electrical cardioversion -Stable: propranolol, procainamide or amiodarone

Atrial fibrillation -"Irregularly irregular" -No two RR intervals exactly the same -P waves difficult to see, bizarre and chaotic

-Unstable: electrical cardioversion -Stable: digoxin + procainamide

II. Increased automaticity

Sinus tachycardia

-Normal P wave axis -P waves precede QRS -Due to extrinsic factor such as heart failure, fever, anemia, catecholamines, theophylline

-Treat causative extrinsic factor

Atrial ectopic tachycardia

-Incessant -Abnormal P axis which predicts location of focus -P wave precedes QRS -Continues in presence of AV block

-Unstable: IV amiodarone -Stable: propranolol, sotalol or amiodarone, or digoxin + procainamide.

Junctional ectopic tachycardia

-Incessant -Usually with atrio-ventricular dissociation and slower atrial than ventricular rate. -Capture beats with no fusion.

-Unstable: cooling, IV amiodarone -Stable: propranolol, sotalol or amiodarone

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B. Tachy-arrhythmias with wide QRS: Diagnosis Findings on ECG Treatment

Ventricular tachycardia (VT) -Often with AV dissociation -Capture beats with narrower QRS than other beats; fusion beats

-Unstable: electrical cardioversion -Stable: lidocaine, procainamide

Ventricular fibrillation -Complete chaotic rhythm -Rapid and irregular rhythm

(1) asynchronous cardioversion 2j/kg (2) asynchronouss cardioversion 2j/kg (3)asynchronous cardioversion 4j/kg (4)lidocaine + asynch. cardioversion.

SVT with pre-existing bundle branch block

-QRS morphology similar to that in sinus rhythm -QRS morphology is that of right or left bundle branch block

Antidromic SVT in WPW

-QRS morphology similar to pre-excited sinus rhythm, but wider -Never with AV dissociation

-Unstable: esophageal pacing or electrical cardioversion -Stable: vagal maneuvers, adenosine, propranolol or digoxin -No response: procainamide or flecainide

C. Bradyarrhythmias:

Diagnosis Findings on ECG Treatment

Sinus bradycardia -Slow atrial rate with normal P waves -1:1 conduction -Due to underlying causes such as hypoxia, acidosis, increased intracranial pressure, abdominal distension, hypoglycemia, hypothermia, digoxin, propranolol

-Vigorous resuscitation and supportive care -A B C -O2 -Treat underlying causes

Atrioventricular block Complete atrioventricular block

-Atrioventricular dissociation -Regular R-R intervals -Regular P-P intervals -Atrial rate > ventricular rate -P which occur after T have no effect on R-R interval -Infants of maternal lupus

2nd degree atrioventricular block - Mobitz type I (Wenckebach)

-Progressive PR interval prolongation followed by a blocked beat -Usually indicates block in the AV node

- Mobitz type II

- No characteristic PR prolongation as seen in type I. - Usually not reversible with medications. - Type II has worse prognosis than type I.

Sinus exit block - Sinus P waves intermittently disappear due to block of impulses leaving the node.

-Unstable: A B C O2 Atropine, isoproterenol infusion Temporary transvenous pacing -Stable: Treat underlying causes -Permanent pacemaker in AV block with ventricular rate < 55 (newborn)

Premature atrial contractions -Premature P wave superimposed on the previous T wave, deforming it

-Usually does not need treatment.


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Neonatal Anemia BACKGROUND and PATHOPHYSIOLOGY: Normal erythropoiesis is influenced by several factors, especially erythropoietin (EPO), which stimulates maturation of red blood cell (RBC) precursors. Anemia, defined as hematocrit (Hct) or hemoglobin (Hgb) concentration >2 SD below mean for age, may be due to three general causes: blood loss, ↑ RBC destruction or ↓ RBC production. The major physiologic impact of anemia is ↓ oxygen delivery to tissue, resulting in both compensatory responses (see “symptoms”) and acute or chronic consequences including poor growth, decreased activity and limited cardiovascular reserve. Anemia is defined as Hct <45% in a term infant. The table at the end of this section gives some normal hematological values for preterm and term newborn infants. CAUSES OF NEONATAL ANEMIA: 1. Blood loss, the commonest cause of neonatal anemia, including:

A. Obstetrical causes: placental abruption, placenta previa, trauma to placenta or umbilical cord during delivery and rupture of anomalous placental vessels

B. Feto-maternal transfusion: 8% of normal pregnancies have some admixture. C. Feto-placental transfusion due to positioning of infant above level of placenta

after delivery, partial cord occlusion (e.g., with nuchal or prolapsed cord). D. Twin-twin transfusion(see section on Multiple Births, P. 170):

•Occurs only with monochorionic (i.e., monozygotic) twins and when there are placental vessels which allow shunting of blood from one twin to the other.

•Donor will have anemia of variable severity. •Recipient will have polycythemia of variable severity.

E. Internal hemorrhage such as intracranial hemorrhage, subgaleal hemorrhage, cephalohematoma, adrenal hemorrhage, subcapsular hematoma of liver or ruptured viscus

F. Iatrogenic blood loss secondary to sampling of blood for laboratory tests. This is the commonest cause of anemia (and transfusion) in small preterm infants.

2. ↑ RBC destruction: A. Intrinsic causes: Hereditary RBC disorders (rare), including:

•RBC Enzyme defects (e.g., G6PD deficiency) •RBC membrane defects (e.g., hereditary spherocytosis) •Hemoglobinopathies (e.g., α-thalassemia)

B. Extrinsic causes: •Immune hemolysis

-Rh incompatibility -ABO incompitability -Minor blood group incompatibility (e.g., Kell, Duffy) -Hemangiomas (Kasabach Merritt syndrome)

•Acquired hemolysis: -Infection -Vitamin E deficiency (of historical interest, now it is very rare)

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-Drugs

3. ↓ RBC production: A. Anemia of prematurity due to transient deficiency of erythropoietin B. Aplastic or hypoplastic anemia (e.g., Diamond-Blackfan) C. Bone marrow suppression (e.g., with Rubella or Parvovirus B19 infection) D. Nutritional anemia (e.g., iron deficiency), usually after neonatal period

CLINICAL FINDINGS vary with the severity of anemia and other associated conditions. There may be no signs with mild anemia. With more severe anemia, findings include:

•Pallor •Tachycardia •Tachypnea •Apnea •↑ O2 requirements •Lethargy •Poor feeding •Hepatosplenomegaly (hemolytic disease) •Jaundice •Wide pulse pressure •Hypotension •Metabolic acidosis with severe anemia •↓ tolerance of labor with fetal anemia

DIAGNOSTIC EVALUATION of anemia: 1. History:

•Family: Anemia, ethnicity, jaundice •Maternal and perinatal: Blood type and Rh; anemia; complications of labor or

delivery •Neonatal: Age of onset; presence of other physical findings

2. Laboratory Evaluation may include the following, depending history and physical findings:

•CBC with platelets, smear and reticulocyte count •Blood group and type, Direct Antiglobulin test (Coombs Test) •Bilirubin (total and direct) •Kleihauer-Betke Test (on maternal blood to look for fetal red cells as evidence of

feto-maternal hemorrhage) •Ultrasonogram for internal bleeding (head, abdomen) •Rarely, hemoglobin electrophoresis and RBC enzymes •Bone marrow aspiration is almost never necessary to diagnose anemia in a newborn

MANAGEMENT will depend on cause and severity of anemia. 1. Prenatal: Diagnosis of significant fetal anemia is unusual except in hemolytic disease of the newborn (see P. 121) and Parvovirus B-19 infection. Fetal transfusion may be needed for severe anemia. 2. Postnatal:

A. Anemia of prematurity: The main methods of management are: •Limit blood drawing for laboratory tests •Treatment with recombinant human erythropoietin (r-Hu-EPO) (see Guidelines

for Use of Erythropoietin, P. 111)

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•Transfusion with packed red blood cells (PRBCs) for severe anemia (see guidelines on P. 40-41)

B. Other causes of anemia: Treat underlying cause when feasible. Transfusion guidelines for treatment of anemia in newborns are given in the section, Administration of Blood Products (P. 40). C. Severe anemia: With severe, symptomatic anemia, the infant’s cardiovascular system may not be able to tolerate the ↑ blood volume from simple transfusion of PRBCs. In such cases, perform a partial exchange transfusion with PRBCs. See sections on Exchange Transfusion (P. 42) and Polycythemia (P. 112) for the technique. To calculate the volume of PRBCs to exchange, use the following formula:

Volume of PRBCs = (Desired Hct – Patient’s Hct) x weight (kg) x 90 cc/kg for exchange (cc) (PRBC Hct – Patient’s Hct)

Table. Average hematological values for term and preterm infants. Gestation (weeks) Hct (%) Hgb (g/dL) Retic (%) 37-40 53 16.8 3-7 32 47 15.0 3-10 28 45 14.5 5-10 26-30 41 13.4 __


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Guidelines for Use of Erythropoietin INTRODUCTION: These guidelines approximate the criteria from the large controlled trials of recombinant human erythropoietin (r-Hu-EPO) in preterm infants. For other situations in which r-Hu-EPO may be useful (e.g., severe BPD, late anemia after intra-uterine transfusion), consult with the Neonatology Fellow, Attending Physician, Dr. Roderic Phibbs or Dr. Kevin Shannon (Division of Pediatric Hematology/Oncology). CRITERIA: 1. Any infant with birth weight ≤1,250 g and gestation <31 weeks who has all of the

following: (a) Total caloric intake ≥ 50 kcal/kg/d, of which at least half is enteral (b) Hematocrit (Hct) <40% or 40-50% but falling 2% per day (c) Mean airway pressure <11 cmH2O and FIO2 <0.40 (d) Postnatal age >6d and gestational age <33 weeks

2. Any infant with birth weight 1,251-1,500 g and phlebotomy losses >5 mL/kg/week

who meet criteria (a) through (d) above. EXCLUSIONS: Major anomalies, dysmorphic syndromes, hemolytic anemia, active

major infection. DOSE AND DURATION: 750 u/kg/week subcutaneously divided into three doses QOD (e.g., 250 u/kg on Mon, Wed, Fri). Discontinue r-Hu-EPO when infant reaches 34 weeks gestational age. (Multiple patients can be treated using the same vial of r-Hu-EPO.) IRON: Start oral iron at 2 mg/kg/d as soon as tolerated and increase to 4 mg/kg/d when feeds reach 100 mL/kg. If not on iron after 2 weeks of r-Hu-EPO treatment, consult with Dr. Shannon or Dr. Phibbs. Consider:

1. Intravenous iron (1 mg/kg/d in intravenous alimentation fluid) or 2. Discontinue r-Hu-EPO.

When at full feeds, start UCSF preterm vitamins (see section on Vitamins, P. 55). MONITORING OF R-Hu-EPO THERAPY:

•Measure Hct and reticulocyte count weekly. •Reticulocyte count should reach 200,000 after 1-2 weeks of treatment with r-Hu-EPO. •If Hct reaches 45% without transfusion, discontinue r-Hu-EPO, and consult with Dr.

Shannon or Phibbs before restarting.

POST THERAPY: Hct and reticulocyte count will decline. Endogenous EPO will be released only when the infant becomes anemic (usually at Hct in the mid 20s). Only then will reticulocytes rise again. If reticulocyte count has not started to rise at the time of the infant’s discharge, alert the primary MD to the need to follow the Hct and reticulocyte count.


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Polycythemia/Hyperviscosity INTRODUCTION: Polycythemia, defined as a venous hematocrit (Hct) >65%, occurs in about 4% of term infants, and is more common with SGA (IUGR), LGA, infants of diabetic mothers, trisomy 21, twin-twin transfusion, Beckwith-Wiedemann syndrome and otherwise normal infants who receive an excessive placental transfusion. PATHOPHYSIOLOGY: 1. Hct is the main determinant of blood viscosity, which is also affected by plasma proteins, especially fibrinogen. As Hct increases, viscosity increases, elevating vascular resistance and decreasing blood flow at any given perfusion pressure. As Hct rises above 60%, viscosity tends to increase exponentially. The effects of increased Hct on viscosity are greater in the pulmonary circulation; in experimental animals, pulmonary vascular resistance exceeds systemic vascular resistance when Hct >70%. 2. Clinically useful methods of measuring viscosity are currently not available. Therefore, Hct is used as a proxy for viscosity. Because viscosity is affected by other factors (e.g., flow rate in small vessels, plasma protein concentrations, acidosis, red blood cell deformability), viscosity does not correlate directly with Hct. 3. Increased viscosity results in slowing of blood flow and sludging of red blood cells. As blood flow is further reduced, occlusion of small vessels may result in ischemia and consumption of platelets. Because glucose is transported mainly in plasma and relative plasma volume is decreased, the decreased blood flow can result in hypoglycemia. CLINICAL FINDINGS depend on organ system affected, as indicated below:

Organ system Signs & Symptoms Skin Plethora, prolonged capillary filling time CNS - Mild Lethargy, irritability, tremors, abnormal cry CNS – Severe Apnea, seizures, hypotonia Pulmonary Respiratory distress, cyanosis, persistent pulmonary hypertension Renal Hematuria, oliguria/ anuria, renal vein thrombosis Hematologic Thrombocytopenia, or other signs consistent with DIC Gastro-intestinal Abdominal distension, blood in stools, necrotizing enterocolitis Metabolic Persistent hypoglycemia

HEMATOCRIT SCREENING: •Asymptomatic infants with no risk factors: Hct measurement is not necessary. •Measure Hct in:

-Any infant at risk for polycythemia (see Introduction above) -Any infant with symptoms that may be due to polycythemia

HEMATOCRIT SOURCE: Hct varies with source of blood. Capillary Hct (heel stick) is 5-15% >venous. Arterial Hct averages 6% <venous. Decisions regarding treatment of polycythemia should be made on the basis of venous Hct.

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TREATMENT OF POLYCYTHEMIA is to reduce Hct by partial exchange transfusion (Partial ExTx) with a plasma substitute. Do not perform phlebotomy, which decreases blood volume, reduces blood pressure, and actually increases viscosity as blood flow rate decreases. Perform Partial ExTx for the following situations:

• Hct >65% in a symptomatic infant • Hct >70% in an asymptomatic infant • Consider partial exchange transfusion in symptomatic infants with Hct 60-65%

PARTIAL EXCHANGE TRANSFUSION (Partial ExTx): 1. Volume to be exchanged is calculated by the following equation:

Volume (mL) = Initial Hct – Desired Hct x Weight (kg) x 90 mL/kg Initial Hct

-Desired Hct should be 50 to 55%. -Hypervolemia is common in polycythemia; use 90 mL/kg as estimated blood volume. -Volume to be exchanged in a term infant is almost always in the range of 40-60

mL/kg. If calculated volume is outside this range, re-check the calculations. 2. Use 0.9% NaCl (isotonic saline) for Partial ExTx. It effectively maintains lowered

Hct. Fresh Frozen Plasma and 5% albumin contain proteins that may add to viscosity. 3. As soon as the decision has been made to lower the Hct, obtain informed consent

from parents. Risks of polycythemia/hyperviscosity include cerebrovascular accidents, renal vein thrombosis, hypoglycemia, necrotizing enterocolitis and jaundice. Those outweigh the potential risks of Partial ExTx (thrombosis, infection, vascular perforation, limb ischemia, hemorrhage), which are rare with Partial ExTx.

3. Technique of Partial ExTx: Perform Partial ExTx as soon as decision has been made to lower Hct. Use aliquots of 5 mL/kg; withdraw blood first, then infuse an equal amount of saline. Routes of Partial ExTx are, in decreasing order of preference:

-Umbilical arterial catheter (UAC): Insert UAC in proper position (tip in descending aorta, below 3rd lumbar vertebra). Obtain radiograph (chest and abdomen) to ensure proper position. If patient has cardio-respiratory distress, consider using UAC for further monitoring; otherwise, remove UAC after completion of Partial ExTx.

-Umbilical venous catheter (UVC): This can be done in one of two ways: (a) Insert UVC only as far as needed to withdraw blood. Then, while

simultaneously infusing an equal volume of saline through a peripheral vein, withdraw calculated volume of blood from UVC. UVC may need frequent flushing with 1-2 mL of heparinized 0.9% NaCl.

(b) Insert UVC so tip is in right atrium (See section on Intravascular Catheters, P. 25). Use push-pull technique. Remove UVC at end of procedure.

-Peripheral arterial cannula: Use this for blood withdrawal and peripheral IV for simultaneous infusion of saline. This method is theoretically the safest. However, due to technical difficulties, it often prolongs the procedure unnecessarily.

4. For all umbilical catheters (arterial and venous), measure blood pressure, pH and blood gas tensions. At completion of procedure (any route), measure Hct and platelet count.

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5. Monitor vital signs throughout procedure and observe for catheter related problems. If these occur, discontinue procedure and remove catheter.

6. After Partial ExTx, keep infant NPO for at least 4h. Give IV glucose water to

prevent hypoglycemia. If thrombocytopenia is present, keep infant NPO until platelet count is in normal range. Repeat Hct measurement 4h after procedure.


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Neonatal Coagulation Disorders BACKGROUND AND PATHOPHYSIOLOGY: Neonatal bleeding results from disorders of platelets, coagulation proteins, and disorders of vascular integrity. While healthy newborns have low levels of some coagulation proteins, this is normally balanced by the paralleled decrease in fibrinolytic activity. CAUSES OF NEONATAL BLEEDING: 1. Platelet Disorders

A. Thrombocytopenia (platelet count <150 x 109/L) occurs in 1-4% of term newborns, 40-72% of sick preterms and 25% of ICN admissions; of these, 75% present before age 72h. Causes include: •Decreased platelet production occurs in congenital infections (e.g., CMV, Rubella,

HIV), certain syndromes (e.g., Thrombocytopenia Absent Radius, Fanconi), sepsis and Hemolytic Disease of Newborn.

•Increased platelet consumption, occurs in: -Maternal auto-immune disease (e.g., ITP, SLE) -Asphyxia/Shock -Neonatal Alloimmune Thrombocytopenia -Maternal thiazide intake -IUGR with toxemia of pregnancy -Necrotizing enterocolitis -Thrombosis (due to catheters, hemangiomas) -Sepsis -Hemolytic disease of the newborn -Exchange transfusion -Heparin-induced thrombocytopenia -Polycythemia/Hyperviscosity

B. Impaired platelet function is rare in the newborn except for: •Decreased platelet adhesivenesss associated with indomethacin therapy •Von Willebrand’s Disease

2. Coagulation Protein Disorders A. Congenital factor deficiencies:

•X-linked recessive: Hemophilia A (Factor VIII) and Hemophilia B (Factor IX) •Autosomal recessive (rare): Factors V, VII, X, XI, XII, XIII, afibrinogenemia

B. Acquired deficiencies: Most common is Vitamin K deficiency. 3. Combined Platelet and Coagulation Factor Disorders:

A. Disseminated Intravascular Coagulation (DIC) occurs secondary to inappropriate systemic activation of normal clotting mechanisms after endothelial injury. Infants have low platelet counts and fibrinogen levels, prolonged PT and PTT, and elevated Fibrin Degradation Products.

B. Hepatic Dysfunction due to several causes (e.g., shock, infection, inherited conditions); most have prolonged PT and decreased factor and fibrinogen levels.

4. Disorders of Vascular Integrity such as hemangiomas or vascular malformations, that may rupture and directly bleed, or sequester platelets and secondarily cause bleeding. SIGNS AND SYMPTOMS vary with the cause of bleeding, magnitude of blood loss and the underlying disease. Signs of abnormal bleeding tendency include petechiae, excessive bruising, prolonged bleeding from puncture sites, umbilical oozing, gastrointestinal bleeding, hematuria, pulmonary hemorrhage, subgaleal hemorrhage and

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intracranial hemorrhage. When blood loss is large, the infant may present with signs of hypovolemia (pallor, weak pulses, tachycardia, hypotension, metabolic acidosis). DIAGNOSTIC EVALUATION OF ABNORMAL BLEEDING: 1. History:

•Family history of bleeding disorders or neonatal deaths (but may be negative even with inherited disorders)

•Maternal history of bleeding disorders, medication intake, previous neonatal deaths, auto-immune disease

•Perinatal: Toxemia of pregnancy, IUGR, infections, antepartum bleeding •Neonatal: History of asphyxia, birth trauma, administration of Vitamin K, gender

(X-linked disorders) 2. Neonatal physical examination:

•Signs of bleeding •Signs of infection (hepatosplenomegaly) •Signs of hypovolemia •Hemangiomas, vascular malformations •Other malformations •Other illness (e.g., NEC, hemolytic disease)

3. Laboratory investigation: A. Initial screen

•CBC, differential, smear •Platelet count •Prothrombin time (PT) •Partial Thromboplastin Time (PTT) •Fibrinogen

Draw blood from non-heparinized source (or ask Laboratory to add Heptasorb). B. If Neonatal Allo-Immune Thrombocytopenia (NAIT) is suspected, send

mother’s and infant’s blood for platelet count and typing. With NAIT, maternal platelet count is normal and, in most cases, the mother will be HPA-1 negative (Only 2% of population is HPA-1 negative.). Infants with NAIT are at risk for serious intracranial hemorrhage. For severe thrombocytopenia, platelet transfusion is indicated. Washed maternal platelets (to remove antibody) are the treatment of choice. If not practical, HPA-1 negative platelets are the second choice, but are difficult to obtain. Random-donor platelets should be used if other choices are not available. IVIG therapy will often increase the platelet count.

C. Subsequent evaluation: If abnormal bleeding is not secondary to an underlying illness and appears to be a primary coagulopathy, obtain Hematology consult immediately. They will direct subsequent evaluation and treatment.

MANAGEMENT: For secondary bleeding disorders, treat underlying disease. Replacement of clotting factors is often necessary: 1. Severe, life threatening bleeding:

•Maintain adequate circulating blood volume. (See: Neonatal Shock, P. 101) •Send blood for clotting studies (See 3A above). •If clotting defect is not known, consider giving all of the following:

-Vitamin K 1 mg IV slowly over 1 min (Rapid infusion of Vitamin K can cause cardiac dysrhythmias).

-Fresh Frozen Plasma 10 mL/kg over 5-10 min. -Platelets 1 unit -Cryopreciptate 1 unit

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•Send repeat clotting studies in 4-6h •Obtain Hematology Consult if bleeding is not controlled quickly.

2. Bleeding with known abnormal clotting screening tests (See 3A above). A. Prolonged prothrombin time (PT), normal PTT, platelets and fibrinogen:

Give Vitamin K 1 mg IV slowly over 1 min (Rapid infusion of Vitamin K can cause cardiac dysrhythmias). Repeat PT in 4h. If not improved, consider Hematology Consult to R/O specific factor deficiency.

B. Prolonged PT and PTT: Give Fresh Frozen Plasma 10 mL/kg and Vitamin K 1 mg. Send repeat clotting studies in 2h.

C. Low fibrinogen: Give cryoprecipitate 1 unit. D. Thrombocytopenia: Serious bleeding usually does not occur unless there is

severe thrombocytopenia (i.e., <20 x 109/L ). With “sick” infants (i.e., other severe disease; receiving assisted ventilation), bleeding may occur at higher levels. Therefore, for these infants, use platelet transfusions to maintain platelets >50 x 109/L. Platelets should be type and Rh specific, irradiated, and CMV negative (If infant is possibly immunocompromised). (For treatment of NAIT, see 3B above.)

3. For any bleeding problem that is not controlled adequately and quickly, obtain Hematology Consult.

4. For significant bleeding from any cause, consider cranial ultrasound, especially in preterm infants.

Table. Products for Treatment of Coagulopathies. Factor Usual Product Content Dose Indications Fresh frozen All factors 10-20 mL/kg Disseminated intravascular coagulation plasma (DIC); liver disease; protein C deficiency Exchange All factors, Double volume Severe DIC; liver disease transfusion* platelets Factor VIII Factor VIII 25-50 U/kg Factor VIII deficiency (Hemophilia A) concentrate Factor IX Factor IX 50-100 U/kg Factor IX deficiency concentrate Vitamin K 1-2 mg Vitamin K deficiency Platelet Platelets 1-2 units/5 kg‡ Severe thrombocytopenia concentrate Intravenous IgG 1-2 g/kg Severe sepsis; thrombocytopenia due to gamma globulin transplacental antibodies *If fresh whole blood is used. ‡Response to platelets can vary markedly, depending on underlying condition.


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Neonatal Jaundice PHYSIOLOGIC JAUNDICE (non-pathologic unconjugated hyperbilirubinemia): 1. Term Infants:

•50-60 % of all newborns are jaundiced in the first week of life. •Total serum bilirubin peaks at age 3–5 d (later in Asian infants). •Mean peak total serum bilirubin is 6 mg/dL (higher in Asian infants).

2. Preterm Infants: •Incidence of visible jaundice is much higher than in term infants. •Peak is later (5-7d). •Because of ↑ risk of bilibubin encephalopathy (see below), “physiologic” jaundice is

more difficult to define and jaundice should be followed closely. DEFINITION of NON-PHYSIOLOGIC JAUNDICE:

•Jaundice in the first 24 hours •Bilirubin rising faster than 5 mg/dL in 24 hours •Clinical jaundice >1 week •Direct bilirubin >2 mg/dL •In healthy term infants total serum bilirubin concentration >15 mg/dL •Lower levels in preterm infants, “sick” infants, and hemolytic disease (See section on Hemolytic Disease of the Newborn, P. 121)

BILIRUBIN METABOLISM: As red blood cells are lysed, they release hemoglobin. Heme molecules (from hemoglobin) are converted to bilirubin. Bilirubin (unconjugated or indirect) is bound to serum albumin and transferred to the liver where it is conjugated to glucuronate by glucuronyl transferase. Conjugated (direct) bilirubin is excreted into bile. A fraction of bilirubin from the stool is reabsorbed into the blood via the portal circulation (enterohepatic circulation). BILIRUBIN ENCEPHALOPATHY: The mildest form of bilirubin encephalopathy is sensorineural hearing loss due to damage to the cochlear nuclei. Severe encephalopathy causes kernicterus. Factors predisposing to neurotoxicity of unconjugated hyperbilirubinemia include:

•When bilirubin concentration exceeds the binding capacity of serum albumin •Displacement of bilirubin from albumin by acidosis or certain drugs (e.g.,

sulfonamides, ceftriaxone) •Sepsis •Preterm infants due to↑ risk due lower serum albumin concentrations and ↑ risk for

acidosis and sepsis.

CAUSES of UNCONJUGATED (INDIRECT) HYPERBILIRUBINEMIA: 1. Increased lysis of RBCs (i.e., increased hemoglobin release)

•Isoimmunization (blood group incompatibility: Rh, ABO and minor blood groups) •RBC enzyme defects (e.g., G6PD deficiency, pyruvate kinase deficiency) •RBC structural abnormalities (hereditary spherocytosis, elliptocytosis) •Infection (sepsis, urinary tract infections) •Sequestered blood (e.g., cephalohematoma, bruising, intracranial hemorrhage)

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•Polycythemia •Shortened life span of fetal RBCs (80 vs. 120 d)

2. Decreased hepatic uptake and conjugation of bilirubin •Immature glucuronyl transferase activity in all newborns: term infants have 1% of

adult activity, preterm infants have 0.1%. •Gilbert Syndrome •Crigler Najjar Syndrome (Non-hemolytic Unconjugated Hyperbilirubinemia):

inherited conjugation defect (very rare) •Pyloric stenosis (mechanism is unknown) •Hypothyroidism •Infants of Diabetic Mothers (polycythemia is also common) •Breastmilk Jaundice (pregnanediol inhibits glucuronyl transferase activity)

3. Increased enterohepatic reabsorption •Breast feeding jaundice (due to dehydration from inadequate milk supply) •Bowel obstruction •No enteric feedings

EVALUATION of JAUNDICE (UNCONJUGATED) 1. Initial evaluation:

•Total and direct bilirubin •Blood type and Rh (infant & mother) •Hematocrit •Direct Antiglobulin (Coombs) Test on infant

2. Later evaluation (as indicated): •RBC smear, reticulocyte count (if evidence or suspicion of hemolytic disease) •Blood culture, urinalysis, urine culture •Thyroid function tests, G6PD assay, Hgb electrophoresis

MANAGEMENT of UNCONJUGATED HYPERBILIRUBINEMIA: 1. Healthy Term Newborn

Treatment Age (h) Bilirubin (mg/dL) Phototherapy Exchange Transfusion ≤ 24 Visible Jaundice Consult attending physician

≥ 15 X 25-48 ≥ 20 X X ≥ 18 X 49-72 ≥ 25* X X ≥ 20 X > 72 ≥ 25* X X

Recent data suggest that even healthy term infants may suffer mild neurologic damage with bilirubin concentrations >20 mg/dL. 2. Sick Term Newborns: Start above therapies at lower total serum bilirubin levels.

Consult attending physician for specific values.

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3. Preterm Infants: Because of ↑ risk of bilibubin encephalopathy, therapy should be started at lower bilirubin concentrations. In general, bilirubin shoud not be allowed to exceed the infant’s weight in kg x 10 (e.g., for 1.0 kg infant, keep bilirubin <10 mg/dL).

CONJUGATED (DIRECT) HYPERBILIRUBINEMIA (CHOLESTASIS): Clinically, jaundice is green compared to jaundice due to unconjugated hyperbilirubinemia (yellow). 1. Hepatocellular diseases:

A. Hepatitis: •Neonatal idiopathic hepatitis •Viral (Hepatitis B, C, TORCH infections) •Bacterial (E. coli, urinary tract infections)

B. Total parenteral nutrition C. Hepatic ischemia (post-ischemic damage) D. Erythroblastosis fetalis (late, “Inspissated Bile Syndrome”) E. Metabolic disorders (partial list):

•Alpha-1 antitrypsin deficiency •Galactosemia, tyrosinemia, fructosemia •Glycogen storage disorders •Cerebrohepatorenal disease (Zellweger) •Cystic fibrosis •Hypopituitarism

2. Biliary tree abnormalities: A. Extrahepatic biliary atresia: In first 2 weeks,, unconjugated bilirubin

predominates; elevated conjugated bilirubin is late. B. Paucity of bile ducts (Alagille’s vs. non-syndromic) C. Choledochal cyst D. Bile plug syndrome

EVALUATION and MANAGENMENT of CHOLESTASIS: 1. Initial evaluation:

•Total and direct bilirubin •AST, ALT, GGT, urine reducing substances •Hepatic ultrasound

2. Later evaluation (as indicated): •Hepatitis B and C serology •α1-antitrypsin deficiency studies •Very long chain fatty acids •Brain sonogram •HIDA scan •Cholangiogram

3. Management: •Conjugated bilirubin is not toxic. •Management is treatment of cause. •Phototherapy will cause “bronzing” with conjugated hyperbilirubinemia.


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Hemolytic Disease of the Newborn INTRODUCTION and DEFINITION: Hemolytic Disease of the Newborn (HDN), also known as erythroblastosis fetalis, isoimmunization, or blood group incompatibility, occurs when fetal red blood cells (RBCs), which possess an antigen that the mother lacks, cross the placenta into the maternal circulation, where they stimulate antibody production. The antibodies return to the fetal circulation and result in RBC destruction.

DIFFERENTIAL DIAGNOSIS of hemolytic anemia in a newborn infant: -Isoimmunization -RBC enzyme disorders (e.g., G6PD, pyruvate kinase deficiency) -Hemoglobin synthesis disorders (e.g., alpha-thalassemias) -RBC membrane abnormalities (e.g., hereditary spherocytosis, elliptocytosis) -Hemangiomas (Kasabach Merritt syndrome) -Acquired conditions, such as sepsis, infections with TORCH or Parvovirus B19 (anemia

due to RBC aplasia) and hemolysis secondary to drugs.

ISOIMMUNIZATION A. Rh disease (Rh = Rhesus factor)

(1) Genetics: Rh positive (+) denotes presence of D antigen. The number of antigenic sites on RBCs varies with genotype. Prevalence of genotype varies with the population. Rh negative (d/d) individuals comprise 15% of Caucasians, 5.5% of African Americans, and <1% of Asians. A sensitized Rh negative mother produces anti-Rh IgG antibodies that cross the placenta. Risk factors for antibody production include 2nd (or later) pregnancies*, maternal toxemia, paternal zygosity (D/D rather than D/d), feto-maternal compatibility in ABO system and antigen load.

(2) Clinical presentation of HDN varies from mild jaundice and anemia to hydrops fetalis (with ascites, pleural and pericardial effusions). Because the placenta clears bilirubin, the chief risk to the fetus is anemia. Extramedullary hematopoiesis (due to anemia) results in hepatosplenomegaly. Risks during labor and delivery include asphyxia and splenic rupture. Postnatal problems include:

Asphyxia Pulmonary hypertension Pallor (due to anemia) Edema (hydrops, due to low serum albumin) Respiratory distress Coagulopathies (↓ platelets & clotting factors) Jaundice Kernicterus (from hyperbilirubinemia) Hypoglycemia (due to hyperinsulinemnia from islet cell hyperplasia)

(3) Laboratory Findings vary with severity of HDN and include: Anemia Hyperbilirubinemia† Reticulocytosis (6 to 40%) ↑ nucleated RBC count (>10/100 WBCs) Thrombocytopenia Leucopenia + Direct Antiglobulin Test‡ Hypoalbuminemia Rh negative blood type‡ Smear: polychromasia, anisocytosis, no spherocytes

*HDN can occur in 1st pregnancy, but this is uncommon. †Cord blood bilirubin >4 mg/dL indicates severe isoimmunization.

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‡With severe HDN, high quantities of antibody may block Rh antigen site resulting in an Rh+ infant typing as Rh- and having a negative Direct Antiglobulin test.

(4) Intra-uterine Transfusion (IUT): When iso-immunization is severe, IUTs are given to the fetus to prevent hydrops fetalis and fetal death. After multiple IUTs, most of the baby’s blood will be Rh negative donor blood. Therefore, the Direct Antiglobulin test will be negative, but the Indirect Antiglobulin Test will be positive. After IUTs, the cord bilirubin is not an accurate indicator of rate of hemolysis or of the likelihood of the need for post-natal exchange transfusion.

B. Minor Blood Group Incompatibility is uncommon, occurs in ~0.8% of pregnant women and usually with E, c, Kell, Kidd or Duffy. Clinical presentation is similar to Rh disease. Anti-Kell disease may be severe due to hemolysis or erythroid suppression. Lewis antigen stimulates only IgM production, so maternal antibody screen may be positive, but fetus is not affected.

C. ABO Incompatibility (1) Genetics: With maternal blood types A and B, isoimmunization does not occur

because the naturally occurring antibodies (anti-A and -B) are IgM, not IgG. In type O mothers, the antibodies are predominantly IgG, cross the placenta and can cause hemolysis in the fetus. The association of a type A or B fetus with a type O mother occurs in ~15% of pregnancies. However, HDN occurs in only 3%, is severe in only 1%, and <1:1,000 require exchange transfusion. The disease is more common and more severe in African-American infants. Unlike Rh, ABO disease can occur in first pregnancies, because anti-A and anti-B antibodies are found early in life from exposure to A- or B-like antigens present in many foods and bacteria.

(2) Clinical presentation: generally less severe than with Rh disease. (3) Laboratory findings that differ from Rh disease:

Smear: microspherocytosis MCV <95, microcytic for a newborn (normal for adult) Direct Coombs test is often weakly +.

MANAGEMENT: A. Preparation prior to delivery should include:

-Blood: type O Rh negative packed RBCs, cross-matched against the mother. For severe HDN, have blood in the Resuscitation Room to correct severe anemia immediately after birth by partial exchange transfusion (ExTx). Anticipate need for later ExTx for hyperbilirubinemia and have additional blood for these.

-Surfactant, if infant is preterm. -Catheters (e.g., angiocaths) for immediate drainage of hydropic fluid.

B. Resuscitation: At birth, the major problems are cardiopulmonary and relate to effects of severe anemia, hydrops and prematurity. Because of the multiple problems with severe HDN, effective resuscitation requires several individuals. -Obtain cord blood for bilirubin (total & direct), albumin, blood type & Rh, Direct

Coombs test, CBC, platelets, reticulocyte count and nucleated RBCs.


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-If the infant is hydropic, intubate immediately and begin assisted ventilation with oxygen. If ventilation is difficult, drain pleural and ascitic fluid; during paracentesis, take care to avoid puncturing the enlarged liver and spleen.

-Insert umbilical arterial (UAC) and venous catheters (UVC) (See section on Umbilical Catheters, P. 25) and immediately measure blood pressures, arterial pH and blood gas tensions, hematocrit (Hct) and blood sugar.

-Correct metabolic acidosis with alkali, but only if giving assisted ventilation (see section on Acid Base Balance, P. 62).

-Correct anemia, which is essential for effective resuscitation. •If arterial blood pressure is low, give simple transfusion of packed RBCs

(e.g., for Hct of 30%, push 10 mL/kg over 5 min; for Hct of 20%, push 10 mL/kg over 5 min, then repeat).

•Do not infuse packed RBCs or blood through UAC because of risk of damage to spinal cord from emboli.

•With normal blood pressure, elevated central venous pressure, metabolic acidosis or hydrops, correct anemia by partial ExTx (exchange 20 mL/kg, then repeat hematocrit).

-Measure blood sugar frequently and correct hypoglycemia. -Follow platelet counts; consider platelet transfusion for counts <50,000.

(C) Hyperbilirubinemia results from continued hemolysis and inability of the neonatal liver to handle a large bilirubin load. Kernicterus (bilirubin encephalopathy) results from high levels of indirect bilirubin (>20 mg/dL in a term infant with HDN). Kernicterus occurs at lower levels of bilirubin in the presence of acidosis, hypoalbuminemia, prematurity and certain drugs (e.g., sulfonamides). -Measure bilirubin in cord blood and at least q4h for the first 12 to 24h. Plot

bilirubin concentrations over time. A graph for plotting bilirubin over time is available at the unit clerk’s desk.

-Begin phototherapy shortly after birth. Although phototherapy may not eliminate the need for ExTx, it may delay ExTx and decrease the number required.

-Use ExTx for hyperbilirubinemia not controlled by phototherapy (see P. 42). •Indications depend upon absolute serum concentration of bilirubin, the rate of

rise of bilirubin, gestational age, albumin concentration and acid-base status. In general, perform ExTx for cord bilirubin >5 mg/dL, for a rate of rise of bilirubin >0.7 mg/h, and to prevent bilirubin >20 mg/dL in a term infant, and lower levels in preterm infants (e.g., maintain serum bilirubin <10X the birthweight in kg).

•Blood should be reconstituted (to Hct ~40-50%) from fresh, O negative packed RBCs cross-matched against the mother and type-specific fresh frozen plasma.

•Technique: About 30 min before ExTx, give albumin 1 g/kg to increase the bilirubin bound to albumin in the circulation and make the ExTx more effective. Exchange 2X the blood volume (estimate blood volume at 85 mL/kg). Preferred technique is isovolumic ExTx, withdrawing blood from UAC and infusing through UVC (with tip in IVC or low right atrium). Do not infuse blood through UVC if tip is in portal circulation. Alternatively, ExTx can be done through a single catheter (UAC or UVC) using aliquots <5% of the


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infant’s blood volume (e.g., 5 mL/kg). The blood should be warmed and the bag agitated every few minutes (to prevent settling of the RBCs).

•Complications of ExTx:

-Hypocalcemia due to Ca++ binding by citrate. Give Ca-gluconate 100 mg after every 100 mL of blood exchanged.

-Hypoglycemia, particularly after the ExTx, due to dextrose load from anti-coagulant of donor blood and hyperinsulinism in HDN.

-Thrombocytopenia and granulocytopenia due to washout with the ExTx. -Hyperkalemia, especially with older units of blood. -Hypothermia, associated with inadequate warming of blood.

OUTCOME: (A) Late anemia: Antibodies persist for weeks, cause continued hemolysis and can cause

anemia as late as age 6 months (especially in infants who had received IUTs). After discharge, follow Hct weekly. Erythropoietin treatment will help prevent severe anemia and further transfusions (see P. 111).

(B) Neurological prognosis is good. Commonest problem is sensorineural hearing loss.


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Acute Bacterial Infections INTRODUCTION: Infants of any gestational age (GA) are at high risk for acute bacterial infections for several reasons, both innate and extrinsic. While a thorough discussion of risk factors is beyond the scope of this section, it is important to note that risk factors for infection are inversely related to GA. As a consequence, preterm infants acquire bacterial infections more readily than term infants, and morbidity and mortality are greater for those born earlier in gestation.

Bacterial pathogens that cause neonatal infections are varied, and the identity of each may be suggested by timing of infection, presentation of signs and symptoms, and response to empirically prescribed antibiotics. For all organisms, successful management requires thorough, thoughtful assessment of risk factors, complete and careful clinical and laboratory studies, and prompt initiation of antibiotics and supportive treatment. Below are discussions of the two temporal categories of acute neonatal bacterial infection: early and late onset sepsis. This distinction permits a clearer elaboration of risk factors, modes of transmission, causative organisms, manners of presentation and outcomes. Nevertheless, this section is only a guide to aid in management, rather than an absolute list of facts or an exhaustive program of clinical and laboratory evaluation. In addition, it is important to remember that the most important intervention for preventing infection in the ICN is careful and frequent handwashing. EARLY ONSET SEPSIS: Incidence: Acute bacterial infection during the first 3 d after birth occurs in 1 to 10 per 1,000 live births. Although the majority occur in term infants, the likelihood of infection is greater among preterm infants. Culture proven early onset sepsis will develop in about 2% of all infants with birthweight <1,500 grams, although 10 times that number are treated as if they are infected. Risk Factors interconnected with vertical transmission of causative organisms include:

-Premature and/or prolonged rupture of chorio-amniotic membranes -Maternal colonization with Group B beta-hemolytic Streptococcus (GBS) -Intrapartum maternal fever -Prematurity -Chorio-amnionitis

Causative Organisms: Since the advent of intrapartum antibiotic prophylaxis to prevent neonatal GBS infection, Gram-negative organisms have become the most common pathogens, accounting for nearly 2/3 of all infections. Among these, Escherichia coli is the most common. Among Gram-positive causative organisms, GBS is most common, is associated with rapid onset of respiratory disease and shock and is often fatal. Presentation: Signs are nonspecific and may include any of the following::

-Lethargy -Hypotonia -Irritability with hyperreflexia -Seizures -Apnea -Cyanosis -Respiratory distress -Metabolic acidosis -Hypoglycemia -Hyperglycemia -Shock

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Evaluation & Management: Early, rapid and thorough evaluation is essential for successful treatment. An asymptomatic term or near-term newborn with even one risk factor for sepsis requires careful physical examination and a screening complete blood count (CBC) with differential and platelet count. In the presence of multiple risk factors, also obtain a blood culture, and consider starting antibiotic therapy. For a preterm infant with any risk factors, and for any symptomatic newborn, obtain CBC and blood culture and start antibiotics. Laboratory studies should include:

-CBC with differential and platelet count. -Blood culture (aerobic culture system is sufficient for early onset sepsis). -Lumbar puncture is essential for a symptomatic infant or asymptomatic infant

with a positive blood culture While it is optimal to obtain cerebrospinal fluid (CSF) prior to starting antibiotics, do not delay antibiotic therapy if multiple attempts at lumbar puncture are required. Evaluation of CSF should include culture, cell count and differential, protein and glucose (with a blood glucose obtained at the same time).

-Serial serum C-reactive protein (CRP) levels are useful to rule-out early onset sepsis in infants with GA ≤28 wks. If CRP is <1.0 mg/dL at 12 and 36 hours after birth or onset of symptoms, the likelihood of proven or probable sepsis is only 0.3%. However, with neutropenia, CRP is not reliable to rule-out sepsis.

-Chest radiograph for evidence of pneumonia. -Tracheal aspirate for culture, if there are signs of respiratory disease.

Treatment: As soon as cultures have been obtained, begin antibiotic therapy. Ampicillin and gentamicin IV are the currently recommended drugs for neonatal sepsis in this ICN. For doses, see Table at end of this section. Outcome: Early onset sepsis is associated with an increased likelihood of respiratory distress syndrome, chronic lung disease, severe intraventricular hemorrhage, and periventricular leukomalacia. Despite diagnostic and therapeutic advances, early onset sepsis is associated with a high mortality and substantial morbidity; preterm newborns are more severely affected. Among very preterm infants, mortality is about 35%.

LATE ONSET SEPSIS (After age 3 days): Incidence among healthy term infants is much less than early onset sepsis. However, preterm infants and term infants with various medical or surgical conditions are at greater risk for late onset sepsis. More than 20% of infants with birthweight <1,500 grams will have at least one episode of late onset sepsis. Risk Factors for late onset bacterial infection are closely related to horizontal transmission of causative organisms and include endotracheal intubation, indwelling urinary and vascular catheters, especially venous catheters, lack of enteric feeding, and exposure to broad-spectrum antibiotics, which may alter normal flora and permit overgrowth and dissemination of fungal species and resistant bacteria. Causative Organisms: In contrast to early onset infections, Gram-positive organisms predominate and account for approximately 2/3 of cases. Coagulase-negative Staphylococcus species (common skin flora) are the most common isolates, especially among very preterm infants. However, Gram-negative bacteria (e.g., E. Coli, Klebsiella pneumoniae, Pseudomonas aeruginosa) also cause a significant proportion of late onset

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disease. Fungal infections (with Candida species) occur frequently in small preterm infants (see section on Candidiasis, P. 128). Presentation in most cases of late onset sepsis is gradual, rather than fulminant. The first indications may be subtle signs such as feeding intolerance, need for increased environmental oxygen, or persistent tachycardia. However, some infants become gravely ill very quickly (especially with Pseudomonas infections), and the presentation may include any signs mentioned above in Early Onset Sepsis. Evaluation & Management: As with early onset sepsis, it is imperative to perform an early and thorough diagnostic evaluation that should include blood culture, CBC with differential and platelet count. Because CNS infection is more likely with late onset sepsis, lumbar puncture with complete evaluation of CSF is essential (See above under Early Onset Sepsis). Unlike early onset disease, urine infection is frequent. Urine should be collected for urinalysis and culture. To prevent contamination of the specimen, urine should be obtained by suprapubic needle aspiration. Urine by bag collection should never be sent for culture. Also in contrast to early onset sepsis, serial CRP levels may be useful to ruleout late onset sepsis in infants of any gestational age. If the CRP is <1.0 mg/dL at 12 and 36 hours after the onset of symptoms, the likelihood of proven or probable sepsis is 2.4%.

As soon as cultures have been obtained, antibiotic therapy should be instituted without delay. While the spectrum of causative organisms differs from early onset sepsis, ampicillin and gentamicin are appropriate initial antibiotic therapy. Outcome: As with early onset infection, late onset disease is associated with significant morbidity and mortality and preterm infants are more severely affected with a mortality of up to 20%. Late onset sepsis is associated with an increased likelihood of patent ductus arteriosus, bronchopulmonary dysplasia, necrotizing enterocolitis and death. Table. Antibiotic doses for newborn infants suspected of sepsis. Age: 0 to 4 wk <1 wk ≥1 wk BW: <1200 g 1200-2000 g >2000 g ≤2000 g >2000 g Ampicillin* 25-50 q12h 25-50 q12h 25-50 q8h 25-50 q8h 25-50 q6h Gentamicin* 2.5 q18-24h 2.5 q12h 2.5 q12h 2.5 q8-12h 2.5 q8h Age, age after birth; BW, birthweight. *Doses are in mg/kg of current body weight and should be given IV over 15 to 30 min.


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Candidiasis in the Newborn DEFINITIONS: Candidiasis refers to infection with fungi of the genus Candida. Candidemia is presence of Candida fungi in the blood. Catheter-related candidemia refers to candidemia that resolves rapidly after catheter removal and initiation of therapy. Disseminated, or invasive, candidiasis refers to persistent infection after removal of a catheter and/or isolation of Candida from other normally sterile body sites. EPIDEMIOLOGY: Invasive candidiasis in neonates is a serious and common cause of late onset sepsis and has a high mortality (25 to 35%). The incidence of such fungal infections has increased 11 fold over the past 15 years. Candida species are the 3rd most frequent organism (after coagulase negative Staph. and Staph. aureus) isolated in late-onset sepsis in very low birth weight (VLBW) infants (i.e., <1,500 g). Preterm infants are predisposed to Candida infections because of immaturity of their immune system and invasive interventions. Transmission of Candida may be vertical (from maternal vaginal infection) or nosocomial. Colonization of health workers is as high as 30%. Initial site of colonization is usually the gastrointestinal tract. Risk factors for candidiasis include: a) low birth weight (<1,500 g); b) use of broad spectrum and/or multiple antibiotics; c) central venous catheters; d) parenteral alimentation and intravenous fat emulsion; e) colonization with Candida and/or previous episode of mucocutaneous candidiasis; f) prolonged urinary catheterization. Although initial reports indicated most cases were due to due Candida albicans, more recent studies show emergence on non-albicans species including C. parapsilosis (cause of majority of cases in some centers), C. glabrata, C. krusei, C. lusitaniae and C. tropicalis. CLINICAL MANIFESTATIONS: The classic clinical picture of systemic candidiasis in neonates is indistinguishable from bacterial sepsis. Common presenting symptoms are worsening respiratory function, apnea, thrombocytopenia and localized signs of candidal infection at one or more of the following sites:

-Skin and mucous membranes (thrush, diaper rash or other areas) -Central nervous system: Meningitis is present in up to 64% of fatal cases, and

survivors have a high incidence of severe sequelae including hydrocephalus, psychomotor and mental retardation, and aqueductal stenosis

-Eyes: Fundoscopic examination is essential for early diagnosis of invasive disease, as the incidence of Candida endophthalmitis is as high as 50%.

-Heart: Candida endocarditis is the 2nd most common form of endocarditis in VLBW infants. Clinical findings may include cardiac murmurs, petechiae, skin abscesses, arthritis, hepatomegaly and splenomegaly. Right-sided intracardiac fungal masses can manifest with heart failure or even with pulmonary fungal embolism.

-Kidneys: Candida is the most frequent cause of urinary tract infection in intensive care nurseries. Up to 50% of these babies have candidemia and are predisposed to renal candidiasis, with development of renal fungus balls or abscesses and unilateral or bilateral renal obstruction. Renal insufficiency may be the first clinical manifestation of invasive candidiasis.

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-Bones and Joints: Warmth and swelling of the extremities in combination with radiographic evidence of osteolysis or arthritis.

Congenital Candidiasis: A rare entity in which intrauterine infection is evident at birth. Two forms have been described: 1) Congenital cutaneous candidiasis in which an extensive skin rash presents within 12

hours of birth. A macular erythema that may evolve from a pustular, papular or vesicular phase finally results in extensive desquamation.

2) Congenital systemic candidiasis: An invasive infection with a high mortality rate, especially in VLBW infants. At least 50% do not have a cutaneous rash. Presenting signs are pneumonia (most common), meningitis, candiduria and/or candidemia.

DIAGNOSIS: Consider Candida in the differential diagnosis of neonatal sepsis, particularly late-onset. When blood culture is positive for Candida, a thorough evaluation to rule out disseminated infection should include cultures of urine and CSF, ophthalmological examination, echocardiogram, renal ultrasound and, if clinical signs of arthritis or osteomyelitis are present, radiographic skeletal survey and consider diagnostic aspiration of affected area. TREATMENT: Remove central venous catheter, unless blood stream infection clears rapidly with antifungal therapy. Amphotericin B, the gold standard for neonatal antifungal therapy, exerts its mechanism of action and toxicity through binding to ergosterol in the cell membrane of fungal and host cells, resulting in formation of membrane pores, cell depolarization followed by cell death. Side effects include nephrotoxicity, hypokalemia, hypomagnesemia, anemia, thrombocytopenia and infusion reactions (temperature and hemodynamic instability. Liposomal Amphotericin B allows targeted antifungal therapy with less toxicity. The drug is cleared through the reticuloendothelial system allowing higher liver and spleen concentrations and reduced renal concentrations. Flucytosine (5-FC) interferes with DNA synthesis. Because of toxicity and development of resistant strains, it is of limited use in neonatal infections. However, if the infant can tolerate oral medications, flucytosine is very useful for CNS infections and may act synergistically with amphotericin B. Fluconazole, a fungistatic drug, is the most effective of the azoles. Hepatotoxicity, the main side effect, is transient and resolves with cessation of therapy. It has decreased activity against C. glabrata and C. krusei. Consultation with the Infectious Disease Service should be obtained for all neonatal fungal infections except those limited to skin and mucous membranes.


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Other Congenital and Perinatal Infections

I. CONGENITAL INFECTIONS BACKGROUND and PATHOPHYSIOLOGY: Commonly called TORCH infections (Toxoplasma, Other agents, Rubella, Cytomegalovirus [CMV] and Herpes simplex virus [HSV]). Transmission may be transplacental, hematogenous, or via birth canal. Timing of infection influences fetal effects. Maternal primary (usually) infection in 1st trimester is more likely to result in fetal loss or organ malformation compared with infection later in pregnancy, which may be asymptomatic. SIGNS AND SYMPTOMS common to most congenital infections are hepatosplenomegaly, jaundice, fetal growth retardation and microcephaly. Signs and symptoms more common with specific infections include:

Toxoplasma: Hydrocephalus with diffuse intracranial calcifications Chorioretinitis (may be isolated and may present late)

Syphilis: Osteochondritis (metaphyseal plates) and periostitis, symmetric

osteomyelitic lesions (humerus and tibia), saber shins Hemolytic anemia Maculopapular rash on face, palms & soles (treponeme +) and bullous

lesions on palms and soles Mucocutaneous lesions and “snuffles” (rhinitis)

CMV: Microcephaly with periventricular calcifications Thrombocytopenia and purpura Hepatitis Pneumonitis (interstitial) Hearing loss (late and progressive) Rubella: Cataracts, glaucoma, chorioretinitis “Blueberry muffin” rash, purpura “Celery-stalking” lucency of long bones Peripheral pulmonary artery stenosis, PDA HSV: Hepatitis, chorioretinitis, pneumonitis, fever Lymphocytic Choriomeningitis Virus (LCMV): Hydrocephalus, chorioretinitis Parvovirus B19: Hydrops fetalis and anemia Varicella: Skin scarring, limb atrophy DIAGNOSTIC WORK-UP: (A) Maternal: History of:

(1) Maternal serologies and when obtained (2) Exposure to undercooked or raw meat, soil, animals (3) History of sexually transmitted diseases (STDs) for mother and partners

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(4) Risk factors for HIV exposure (5) Illnesses during pregnancy (fever, rashes) (6) Exposures during pregnancy to ill children (day care, teacher)

(B) Neonatal:

(1) CBC, smear, platelets, reticulocyte count, total and direct bilirubin, liver enzymes (2) Directed studies (depending on clinical suspicion):

-CSF: cell count and protein (See below under 3. HSV) -Ophthamology exam -Radiographs of long bones

(3) Specific diagnostic studies (Based on clinical suspicion; if in doubt, consult ID) -Toxoplasma IgG and IgM -VDRL: CSF & blood -Rubella IgM; Rubella cultures: eye, urine, nasopharynx (NP) -CMV: urine culture (<2 weeks of age; if older, may be postnatal transmission) -HSV: DFA; Cx: skin lesion, eye, NP, rectal; CSF PCR (per ID Consult) -Parvovirus: PCR (blood) -LCMV: Serology: IgM (infant), IgG (infant and mother)

SPECIFIC TREATMENT is indicated for specific infections (e.g., Syphilis, HSV, Toxoplasma). Consult ID service or AAP Red Book for current recommendations.

II. PERINATAL INFECTIONS ENTEROVIRUS and HSV: These infections present in the first 28 d after birth, although presentation before age 3 d is unusual. Enterovirus: Systemic infection which may be very severe with myocarditis, meningoencephalitis, DIC and hepatitis. There is often a history of maternal illness a few days before birth. Diagnosis is by viral cultures of NP, rectum, CSF, blood (per ID only). Treatment is supportive only. HSV: Encephalitis, fever, seizures, vesicular rash and keratoconjunctivitis. Maternal history of HSV may not be present. For diagnosis, see above. Treatment is with acyclovir and should be guided by ID Service. Neurologic sequelae are common. GENERAL MANAGEMENT ISSUES: -Universal body substance precautions to prevent vertical and nosocomial spread. -Consider temporary isolation with untreated infections, although this should be

unnecessary with the universal precautions. -Consider screening of family members for HIV, syphilis, Hepatitis B infection (HBV). -Consult ID Service to help direct work up, ensure proper tests are done in a timely

manner, appropriate treatment is started and appropriate follow up is arranged.

III. OTHER CONGENITAL INFECTIONS/EXPOSURES Human Immunodeficiency Virus (HIV): Management of infant of serology + mother, whether or not she has received treatment:

-Laboratory work at birth: HIV-DNA PCR, CBC w/diff & platelets

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HIV (cont’d): -Consult with Immunology Service (476-9373) -Begin AZT therapy according to current protocol. >36 wks GA: 2mg/kg Q6h PO; <36 wk GA: Discuss with Immunology -Age 1-2 wks: Immunology visit to adjust AZT dose as needed and repeat DNA PCR. -Age 4-8 wks: Immunology visit to stop AZT after 2 negative DNA PCRs. Begin

PCP prophylaxis with Septra (75 mg/m2 BID 3 consecutive d/wk). Repeat DNA PCR. If rapid weight gain occurs before 6 wks, recalculate dose.

-If persistently negative DNA PCR, repeat test at age 4 months of age. -Confirm HIV status with ELISA at age 12 months. -Note: Infant’s HIV status or exposure is confidential under California law.

Disclosure to biological father or others must be endorsed by the mother. Breastfeeding is contraindicated with maternal HIV infection. Circumcision is not contraindicated.

Hepatitis B Virus (HBV) -Immunoprophylaxis:

-Infants of mothers who are known to be hepatitis B surface antigen (HbsAg) negative should be immunized per the usual schedule of infant immunizations.

-Infants of mothers who are HBsAg positive: Give HepB Vaccine & hepatitis B immune globulin (HBIG) before age 12 h. Complete the HepB Vaccine series in 1st 6 months*

-Infants of mothers with unknown HBsAg status: A. Term infants:

-HepB Vaccine before age 12 h. -If mother is found to be HBsAg positive, give HBIG before age 7 d** -Complete HepB Vaccine series in 1st 6 months.

B. Preterm infants (BW < 2 kg): -HepB Vaccine & HBIG before age 12 h -If mother is found to be HBsAg positive: Complete 3 additional doses of

HepB Vaccine series per usual preterm schedule

*For preterm babies (BW< 2 kg), administer 3 additional vaccine doses per the usual preterm immunization schedule.

**HBIG only effective if given within 7 d of birth. HepB Vaccine series is highly effective alone.

Note: Breastfeeding by HBsAg positive mother is not known to increase risk of transmission and, therefore, is not contraindicated Hepatitis C Virus (HCV)

-No known immunoprophylaxis. -Breastfeeding with HCV positive mother is not known to increase risk of transmission

and is not contraindicated. However, because HCV RNA and HCV antibody have been detected in milk of mothers infected with HCV, transmission by breastfeeding is theoretically possible. Therefore, the decision to breastfeed should be based on informed discussion between a mother and her health care professional.


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Necrotizing Enterocolitis (NEC) INTRODUCTION: NEC, the most common acquired acute gastro-intestinal illness in the neonatal period, affects about 5% of infants with birthweight ≤1,500 g and typically is characterized by abdominal distension, bloody stools and pneumatosis intestinalis. The actual spectrum of illness ranges from mild cases of feeding intolerance and abdominal distension to severe cases characterized by intestinal necrosis, perforation, and septic shock. Fulminant cases may progress from minimal symptoms to peritonitis and death within 12h. Although NEC usually presents in preterm infants with risk factors and who have been fed, it also occurs in term infants and infants who have never received enteral feedings. NEC most commonly involves terminal ileum and colon, although in severe cases the entire small and large bowel may be affected. ETIOLOGY is not definitely known and is probably multifactorial. Suggested etiologies include immaturity of intestinal mucosa, intestinal ischemia/reperfusion injury, infection, and immature immune response. There is probably a common, final pathway involving endogenous production of inflammatory mediators (e.g., PAF, TNF, cytokines) that precipitate intestinal injury. RISK FACTORS include:

-Prematurity (>95% of cases) -Aggressive advance (volume and strength) of enteral feedings in preterm infants -Hyperosmolar formulas -Bacterial colonization or overgrowth (predominantly with E. coli, Klebsiella,

Enterobacter, C. dificile): may be inciting event or a permissive factor. -Polycythemia -Patent ductus arteriosus (PDA, decreased systemic output due to left→right shunt) -Indomethacin (decreased intestinal perfusion through inhibition of cyclo-oxygenase) -Steroids, when given in conjunction with indomethacin -Umbilical arterial catheter (UAC) with tip at or above inferior mesenteric artery -Umbilical venous catheter (UVC) with tip in portal system (especially with exchange

transfusion) -Cocaine exposure in utero -Respiratory Distress Syndrome

PRESENTATION:

A. Clinical Findings include any of the following: -Abdominal distension -Abdominal tenderness or redness -Feeding residuals, often bilious -Absent bowel sounds -Gross or occult blood in stool -Bluish discoloration of abdominal wall -Non-specific signs (temperature instability, glucose instability, lethargy,

apnea/bradycardia, hypotension)

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B. Radiographic Findings (in order of severity): -Non-specific bowel dilatation -Thickening of bowel wall -Fixed, dilated loop (unchanged on >1 radiograph) -Pneumatosis intestinalis (small gas bubbles in bowel wall, almost always associated

with dilated bowel loops) -Portal venous gas -Free intraperitoneal gas (indicative of intestinal perforation)

C. Laboratory Findings include: -Thrombocytopenia -Metabolic acidosis (poor prognostic sign) -Abnormally ↑ or ↓ WBC -Left shift of WBC (toward immature precursors) -Neutropenia -Evidence of DIC

STAGING of NEC by Bell’s Criteria (DIAGNOSIS): Stage 1. Suspected NEC: gastric residuals, abdominal distension, occult or gross blood

in stool, x-ray normal to mild distension, temperature instability, apnea, bradycardia Stage 2. Definite NEC: mild to moderate systemic illness, absent bowel sounds,

abdominal tenderness, pneumatosis intestinalis or portal venous gas, metabolic acidosis, ↓ platelets

Stage 3. Advanced NEC: severely ill, marked distension, signs of peritonitis, hypotension, metabolic & respiratory acidosis, DIC, pneumoperitoneum if bowel perforation present

MANAGEMENT: With any feeding intolerance, maintain high level of suspicion for

NEC, especially with preterm infants. A. Suspected NEC:

-Make patient NPO -Start maintenance IV fluids -Obtain baseline KUB -Perform serial abdominal examinations -Test all stools for occult blood -Consider gastric decompression -CBC, platelets & blood culture -Consider starting antibiotics -Culture urine & CSF if systemic signs -Consider stool culture -R/O surgical cause of distension -Observe closely for worsening -If improvement occurs, consider cautious feeding in 3d

B. Definite/Advanced NEC: -Obtain consult with Pediatric Surgery. -NPO for at least 7-10d -IV fluids: Because of “third spacing,” patient may require fluid resuscitation to

improve bowel perfusion (e.g., D5-Lactated Ringer’s at 150 mL/kg per 24 h). -Follow urine output closely; renal failure is common due to hypoperfusion. -Gastric decompression (Replogle tube to low, continuous suction) -Abdominal radiographs (AP & cross table lateral q6-8h) to look for perforation -Endotracheal intubation and assisted ventilation as needed -Circulatory support: Monitor arterial blood pressure and maintain in normal range

with volume expanders and dopamine (Dobutamine is less effective in infants and may actually cause hypotension).

-Blood culture and start antibiotics: ampicillin & gentamicin for 7-10d (Anaerobic

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coverage is usually not necessary unless infant is several weeks old). -Follow CBC, platelets, PT, PTT, fibrinogen; replace clotting factors products prn. -Frequent measurements of arterial pH and blood gas tensions -Correct metabolic acidosis. -Frequent measurements of electrolytes; watch for hyperkalemia.

C. Surgical Considerations: - Operative intervention is indicated for bowel perforation, evidence of necrotic

bowel (fixed loop, metabolic acidosis, DIC, shock), or progressively worsening clinical condition despite intensive medical management

-A peritoneal drain may be inserted in extremely ill infants to delay or avoid laparotomy.

-If NEC develops in a baby with PDA, begin medical management and consider urgent operative closure of PDA. Do not give indomethacin to an infant with suspected or definite NEC.

OUTCOME:

-Mortality rate is 20-30% depending on severity of illness and amount of bowel removed.

-Complications include: •Intestinal stricture with bowel obstruction •Short bowel syndrome •Cholestasis, if prolonged dependence on TPN

PREVENTIVE MEASURES:

-Intestinal priming (gut stimulation feedings): dilute, low volume feedings to stimulate GI mucosal development

-Advance feedings slowly in small preterm infants (see section on Feeding of Preterm Infants, P. 50).

-Do not advance feedings if there are gastric residuals, especially if bile stained -Fresh human milk appears to be protective against NEC. -Do not feed infants with PDA, UAC, or UVC. -Do not give enteral feedings during and for 48-72h after indomethacin. -Minimize antibiotic use, as they alter intestinal flora and select for resistant species. -Epidemiologic controls: cohorting of multiple cases (possible infectious cause) -Antenatal glucocorticoids for lung maturation also accelerate intestinal maturation. -Suggested possible future approaches: enteral IgG/IgA, formula acidification,

anaerobic bacterial supplementation (bifidobacteria)


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Neonatal Parenteral Nutrition INTRODUCTION: Many sick newborn infants cannot obtain adequate nutrition via the GI tract and, thus, require parenteral nutritional (PN) support. In some, GI function is adequate to allow some feedings. For these infants (e.g., very premature infants), the parenteral route is used to supply some nutritional intake. In others, the GI tract may not function for days to weeks (e.g., necrotizing enterocolitis, bowel anomalies), so the infant receives all nutrition parenterally (Total Parenteral Nutrition, TPN). GENERAL GUIDELINES: •Sick newborns usually have increased caloric requirements. •Minimal caloric requirements to prevent catabolism are at least 40 kcal/kg/d. •For growth, minimal requirements are 80 kcal/kg/d and protein intake of >2 gm/kg/d.

For adequate growth, aim for 100 kcal/kg/d and protein intake of 3 g/kg/d for term infants and 3.5 g/kg/d for preterm infants..

•Nutritional support should be initiated within 3 d of birth and should include protein. • Start PN when at least 30 cc/kg/d can be used for this route. •Although growth can be obtained with PN, enteral feedings should be initiated as soon

as feasible, because of risks associated with PN. INFUSION ROUTES: 1. Peripheral route is used for partial or supplemental PN. This route is usually used for short-term nutritional support. Peripheral PN solutions cannot exceed 12.5% dextrose (D12.5) or 3.5% amino acids due to the risk of thrombophlebitis and should not contain calcium because of the serious complications resulting from extravasation of calcium. 2. Central PN is delivered by a venous catheter with the tip in a central location (see the section on Peripherally Inserted Central Catheters, P. 31). This route is used for patients who require long-term nutritional support, usually TPN. COMPONENTS OF PARENTERAL NUTRITION include: 1. Protein is administered as a solution of amino acids, either Travasol™, a standard adult amino acid preparation, or Trophamine™/Premasol™, a preparation designed for pediatric patients. All infants in the ICN should receive Trophamine™/Premasol™.

• Start amino acids at 1 g/kg/d. Advance by 0.5 gm/kg/d in preterm infants and by 0.5-1 gm/kg/d in term infants.

•Recommended maximum is 3 g/kg/d in term infants and 3.5 g/kg/d in preterm infants.

•When using solutions with <1% amino acid concentration, use only one mineral (calcium, phosphorus or magnesium) because of their limited solubility.

•Include protein in your calorie count. Protein yields 4 kcal/g. •Potential complications/risks include:

-Acidosis -Elevated BUN -Hyperammonemia -Cholestasis with prolonged administration

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2. Carbohydrate is administered as dextrose monohydrate. •Begin usually with 4-6 mg/kg/min using D10-D12.5. Alternatively, calculate the

glucose infusion rate that the infant is already receiving and advance from there. •Very preterm infants may not tolerate that much dextrose and may even need insulin

as an infusion to achieve adequate caloric intake without hyperglycemia. •Advance by 1-3 mg/kg/min daily to a maximum of 12 mg/kg/min (up to 15

mg/kg/min in selected cases). •Dextrose yields 3.4 kcal/g. •Consult reverse side of TPN order sheet for maximal allowable dextrose/amino acid

concentrations. •Potential complications/risks include:

-Hyperglycemia or hypoglycemia -Glycosuria and potential osmotic diuresis -Cholestasis and/or hepatic steatosis with high caloric intake usually from long-

term high concentration infusion. 3. Fat: Intravenous lipid emulsions are essential components of TPN. They provide essential fatty acids and are a concentrated energy source critical for growth and development of infants not receiving enteral feedings. There are potential safety concerns regarding administration of lipid emulsions to very low birth weight infants and infants with hyperbilirubinemia, pulmonary hypertension and serious pulmonary disease. To maximize benefits of lipids and minimize their adverse effects, use the following guidelines: (a) provide sufficient lipids to prevent essential fatty acid deficiency; (b) monitor for evidence of lipid intolerance; (c) adjust lipid dose based on clinical status.

•A lipid intake of 0.25-0.5 g/kg/d is required to prevent essential fatty acid deficiency. •Include lipid emulsion in calculations of total fluid intake. •Lipids yield 10 kcal/g. •IV lipid preparations are available as a 20% soybean emulsion that yields 2 kcal/mL. •See Table below for starting and advancing lipids. •Deliver IV lipids over 24 hours. •Do not allow lipids to exceed 60% of total caloric intake. •Potential complications/risks include:

-Hyperlipidemia -Potential risk of kernicterus at low levels of unconjugated bilirubin because of

displacement of bilirubin from albumin binding sites by free fatty acids. As a general rule, do not advance lipids beyond 0.5 g/kg/d until bilirubin is below threshold for phototherapy (see section on Jaundice, P. 118).

-Potential increased risk or exacerbation of chronic lung disease -Potential exacerbation of Persistent Pulmonary Hypertension (PPHN) -Lipid overload syndrome with coagulopathy and liver failure

Table. Guidelines for initiating and increasing intravenous lipid emulsions according to clinical status.


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Administration of Lipids Initiate Advance by Goal is Gestation Weight/Diagnosis (0.5 g/kg/d) 0.5 g/kg/d 3 g/kg/d by Preterm <1,500 g, stable DOL 3 DOL 7 DOL 11

≥1,500 g, stable DOL 3 DOL 4 DOL 9

Very unstable DOL 3 When status improves (e.g., severe RDS,

↑ bilirubin)

Term No pulm. disease DOL 3 DOL 4 DOL 9

Severe pulm. disease, Consider When status improves PPHN, meconium at DOL 7 aspiration syndrome

(DOL, day of life; pulm., pulmonary; PPHN, persistent pulmonary hypertension of newborn) 4. Electrolyte requirements are stated on the parenteral nutrition order form and must be adjusted according to serum values and clinical condition. In utero accretion rates are:

•Calcium 3.3 mmol (130mg) /kg/d •Phosphorus 2.39 mmol (74mg) /kg/d •Magnesium 0.13 mmol (3.2mg) /kg/d

To maximize phosphorus and avoid precipitation, it may be necessary to give calcium by peripheral IV bolus infusion. Consult the TPN order form for tables of solubility ratios for calcium/phosphorus. Goals for serum levels differ from those of older infants and children. Goals for newborns are:

-ionized calcium: 1.2-1.4 mmol/L -phosphorus: 6-8 mg/dL -magnesium: 2-2.5 mg/dL

Start phosphorus at I mmol/kg/d. Do not start magnesium until its serum level has decreased to <2.5 mg/dL. Note: Initial PN solutions may be started without added electrolytes. Add electrolytes gradually as the patient becomes more stable. 5. Acetate is metabolized to HCO3

- and is added to adjust acid-base status. It can be ordered as maximize, minimize, or balance with chloride depending upon infant’s pH. 6. Other Additives include:

•Trace elements are recommended as 0.2 mL/kg/d of trace element solution containing zinc, manganese, copper, and chromium. See parenteral nutrition order form.

-Preterm infants need additional zinc (300 mcg/kg/d) and selenium (2 mcg/kg/d). -Term infants on TPN >4 weeks also need selenium (2 mcg/kg/d). -In infants with cholestasis (i.e,. direct bilirubin >2.5 mg/dL), discontinue the

trace element solution and give: Zinc 100 mcg/kg/d for term infants “ 400 mcg/d TOTAL for preterm infants


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Chromium 0.17 mcg/kg/d Selenium 2.0 mcg/kg/d

-Discontinue selenium with patients on renal dialysis. •Vitamins: Pediatric multivitamins are recommended as 2.0 mL/kg/d up to a

maximum of 5 mL/kg/d. Components are listed on the PN order form. •Heparin (1 unit/mL) is added to all central venous lines and to all peripheral

infusions running at <2 mL/hr in order to maintain catheter patency. METABOLIC MONITORING of infants receiving parenteral nutrition should include: Test Initial When stable Electrolytes Daily 2-3x/week BUN/creatinine Daily 2-3x/week Chemstrip/glucose q6hr-daily Daily, more frequently

when changing CHO Magnesium weekly Calcium Daily 2-3x/week Phosphorus, bilirubin (T/D), Weekly AST or ALT, alkaline phosphatase, albumin Triglycerides when lipid infusion reaches 1.5 g/kg/d and at 3 g/kg/d, then weekly CBC/Diff and platelets Weekly The Pediatric TPN panel includes all above laboratory tests except CBC and glucose and requires 0.4 cc in each of 2 microtainer tubes (i.e., 0.8 cc total). MONITORING GROWTH of infants receiving PN is essential, including weekly measurements of head circumference. Measurements (weight, length and head circumference) should be plotted on standard post-natal growth charts. DISCONTINUING PARENTERAL NUTRITION: PN may be stopped when the infant is tolerating ≥100 cc/kg of enteral feedings or is receiving ≤25 cc/kg/d of PN. The rate of dextrose administration should be tapered to prevent rebound hypoglycemia. Chemstrips should be done q6h. Newborns need a slower tapering than older children and require continued monitoring of glucose after the solution has been stopped. Lipids may be stopped without tapering. If the PN catheter clots or infiltrates, start another IV with dextrose concentration ≤12.5% depending on the current glucose concentration. For additional information regarding PN:

-Please see the following web site: http://yew.ucsf.edu/DIAS/parenteral_nutr_guide_Neo_ped.htm

or -Request consult from Nutrition Services: 353-1461 or 353-1814, Ext. 1; on

weekends, page the Nutritionist on call at 719-4822.


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Neonatal Seizures DEFINITION: A seizure is a paroxysmal behavior caused by hypersynchronous discharge of a group of neurons. Neonatal seizures are the most common overt manifestation of neurological dysfunction in the newborn. BACKGROUND & PATHOGENESIS: Seizures are usually related to significant illness, occasionally requiring specific therapy. Seizures may interfere with cardiorespiratory function and with nutrition and may have detrimental long-term effects on cerebral development. Potential mechanisms of brain injury with repeated neonatal seizures include:

-Hypoventilation/apnea causing hypoxia (leading to cardiovascular collapse, diminished cerebral blood flow [CBF] and increased risk of hypoxic ischemic injury), or hypercarbia (leading to a rise in CBF and increased risk of intracranial hemorrhage (ICH).

-Elevated blood pressure increases CBF and risk of ICH. -Increased glycolysis leading to hypoglycemia which exacerbates seizure induced brain injury. -Excitatory amino acids (increased release) resulting in excitotoxic brain injury.

Most of these can be prevented with good intensive care and control of the seizures. DIAGNOSIS: Seizure type Occurs in Clinical signs Subtle Preterm and Term Eye deviation (Term) Blinking, fixed stare (Preterm) Repetitive mouth & tongue movements Apnea Pedaling, tonic posturing of limbs Tonic Primarily Preterm May be focal or generalized

Tonic extension or flexion of limbs (often signals severe ICH in preterm infants)

Clonic Primarily term May be focal or multifocal

Clonic limb movements (synchronous or asynchronous, localized or often with no anatomic order to progression)

Consciousness may be preserved Often signals focal cerebral injury.

Myoclonic Rare Focal, Multifocal, or Generalized Lightning-like jerks of extremities (upper>lower)

Differentiation of Seizures from Nonconvulsive Movements: -Jitteriness is distinguished clinically from clonic seizures by (1) no associated ocular

movements or autonomic phenomena, (2) stimulus sensitivity, (3) tremor that is suppressed by flexing the limb.

- Distinguish benign neonatal sleep myoclonus (occurs in healthy newborns) from myoclonic seizures.

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-Simultaneous monitoring with electroencephalography (EEG) and video display in newborns with subtle seizures and generalized tonic seizures has not shown consistent electrographical discharges. Some of these movements may be brainstem release phenomena rather than “epileptic seizures”.

MAJOR CAUSES OF NEONATAL SEIZURES: Several causes often coexist! Cause Usual Age at Onset Preterm Term Hypoxic-ischemic encephalopathy <3 days +++ +++ Metabolic

Hypoglycemia <2 days + + Hypocalcemia

Early-onset 2–3 days + + Late-onset >7 days +

Hypomagnesemia (often with Hypocalcemia) Hyper/Hyponatremia Drug Withdrawal <3 days + + Local Anesthetic Toxicity Pyridoxine (Vitamin B6) Dependency Disorders of Small Molecules

(Amino Acid, Organic Acid &Urea Cycle Disorders) Disorders of Subcellular Organelles

(Mitochondrial & Peroxisomal Disorders) Intracranial infection <3 days ++ ++

Bacterial meningitis (E. coli, Group B Strep, Listeria) Viral Encephalitis (Herpes Simplex, Enterovirus)

Intrauterine Infection (CMV, Toxoplasm., HIV, Rubella, Syphilis) >3 days ++ ++ Cerebral Vascular

Intraventricular hemorrhage <3 days ++ Primary subarachnoid bleed <1 day ++ Subdural/epidural hematoma Focal Ischemic Necrosis (Stroke) Variable ++ Sinus Thrombosis Variable +

Developmental defects Variable ++ ++ Neurocutaneous Disorders (Tuberous Sclerosis Complex, Incontinentia Pigmenti)

Epilepsy Syndromes Epileptic Encephalopathies (Early Myoclonic Encephalopathy, Early Infantile Epileptic Encephalopathy) Benign Familial Neonatal Convulsions

(Relative Frequency: +++ = most common; ++ = less common; + = least common. If no +, then uncommon.) ELECTROENCEPHALOGRAPHY (EEG) is essential in diagnosis and management of neonatal seizures. As there may not be ictal activity on EEG even during a seizure (electro-clinical dissociation), serial EEGs or continuous EEG monitoring (when available) are of benefit. The EEG is analyzed for ictal activity (focal or multifocal spikes or sharp waves and focal monorhythmic discharges) and for background activity. Background abnormalities are predictive of (1) risk of electrographic seizures and (2) prognosis.

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NEUROIMAGING: Imaging the brain is essential in determining the etiology of neonatal seizures. In the acute setting, after control of the seizures (see below), MRI scanning is very effective for determining the presence and extent of hypoxic-ischemic injury and of parenchymal brain injury. If MRI scanning is not possible acutely, CT scan is effective for determining the presence of hemorrhage and calcification (e.g., congenital infection, cortical dysplasia). A more detailed look at the brain with MRI can often be done after the acute period. Unfortunately, ultrasound is not an adequate study for the diagnosis of neonatal seizures as it is not effective at detecting subdural or epidural bleeds or identifying parenchymal injury. MANAGEMENT: Neonatal seizures require urgent treatment to prevent brain injury. Give anticonvulsant medication only after adequate ventilation and perfusion have been established and the blood glucose concentration has been measured. Seizures with hypoglycemia or hypoxia are detrimental to the brain!

1. Ensure adequate ventilation and perfusion.

2. Correct metabolic disturbances. Hypoglycemia: (10% glucose in water) 2 mL/kg IV (0.2 g/kg) as bolus. Follow with

continuous infusion at up to 8 mg/kg/min IV (see section on Hypoglycemia, P. 153). Hypocalcemia: (calcium gluconate 10%) 100mg/kg IV over 1 to 3 minutes (Note: Monitor cardiac rhythm for bradycardia) Follow with maintenance of 500 mg/kg/24 hrs IV or PO Hypomagnesemia: (magnesium sulfate) 25-250 mg/kg/dose IV/IM

3. Begin anticonvulsant therapy. Phenobarbital: 20 mg/kg IV. If necessary, additional 10-20 mg/kg IV in 10 mg/kg aliquots

(Note: monitor blood pressure and respiration) Maintenance: 4–6 mg/kg/24 hrs IV/PO If 40 mg/kg of Phenobarbital is not effective, proceed to Lorazepam and obtain consult with the Neurology Service for advice regarding seizure treatment. (While the literature supports the use of Phenytoin as a second line agent, our experience is that Lorazepam is more effective in the acute setting.) Before giving second dose or second medication ask yourself: (1) Do I have the correct diagnosis? (2) Are ventilation and perfusion optimal? (3) Have I recognized and corrected any metabolic disturbance?

Lorazepam: 0.05 mg/kg to 0.10 mg/kg IV in 0.05 mg/kg increments over several minutes. (Note: Monitor closely for respiratory depression.) The half-life in asphyxiated newborns is ~40 hours; duration of action 6-24 hours!

Phenytoin: 20 mg/kg IV (diluted in 0.9% NaCl) (Maximal rate: 1 mg/kg/min. Monitor cardiac rate and rhythm). Maintenance 5–10 mg/kg/24h IV (Phenytoin is VERY poorly absorbed PO in the newborn).

Fourth line anticonvulsants include Paraldehyde. If you must proceed to this stage, then Neurology should have been consulted for guidance with dosage and other management issues.

Pyridoxine deficiency is a rare cause of neonatal seizures and should be considered in any newborn with intractable seizures. The diagnosis is made by pyridoxine IV with concurrent EEG.

OUTCOME AND DURATION OF TREATMENT: The outcome following neonatal seizures depends primarily on the underlying cause. The presence of both clinical and electrographic seizures in the newborn often indicates some degree of brain injury and may alter the prognosis of the underlying disorder (e.g., hypoxic-ischemic injury).

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The duration of treatment following neonatal seizures is also determined by the underlying cause (i.e., related to risk of recurrence), the physical examination and the EEG. The following guidelines aim to continue Phenobarbital for the briefest time possible:

-When seizures have stopped and if the neurological examination is normal, consider stopping Phenobarbital.

-If the neurological examination remains abnormal, then consider stopping medication if the EEG is normal.

-Make this evaluation prior to discharge and then frequently after discharge, if the child has been discharged on Phenobarbital.

-Stop Phenytoin when IV therapy is stopped as this drug is very difficult to maintain PO.


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Intraventricular Hemorrhage (IVH) INTRODUCTION: IVH, the most common type of neonatal intracranial hemorrhage, occurs mainly in preterm infants ≤32 weeks of gestation. The incidence ranges from 13-65% in different centers, decreases with advancing gestational age and is influenced by certain perinatal risk factors (see below). PATHOGENESIS is related to: (1) Intra-vascular factors:

-Impaired cerebral autoregulation -Fluctuating cerebral blood flow (related to fluctuating arterial blood pressure)* -↑ cerebral blood flow (e.g., due to hypercarbia, excess volume expansion)* -↑ cerebral venous pressure (e.g., with pneumothorax, asphyxial heart failure)* -Hypotension and reperfusion* -Coagulation abnormalities

(2) Vascular factors: -Germinal matrix, a highly vascular structure with poor capillary support, is present

<35 weeks and is a critical factor in pathogenesis of IVH. -Germinal matrix capillaries are very vulnerable to hypoxic-ischemic injury. -Arterial development: acute transition from large vessels to a capillary network

without gradual arborization -Venous drainage: "hairpin loop" configuration in germinal matrix is conducive to

outflow obstruction and is important in pathogenesis of periventricular hemorrhagic infarction.

(3) Extra-vascular factors: Preterm infants have -Increased fibrinolytic activity -Poor vascular support in cerebral tissue -↑ risk of hypoxia, hypercarbia and acidosis due to immature respiratory system*

(*Factors that can often be prevented or alleviated with meticulous intensive care!) CLINICAL PRESENTATION: 90% occur in the first 3 days after birth. -Catastrophic: Acute IVH with bulging fontanel, split sutures, change in level of

consciousness, pupillary and cranial nerve abnormalities, decerebrate posturing, and often with rapid decrease in blood pressure and/or hematocrit.

-Saltatory: Gradual deterioration in neurological status, may be subtle abnormalities in level of consciousness, movement, tone, respiration and eye position/movement.

-Asymptomatic: 25-50% of IVH. Discovered on Ultrasound (U/S, see below). Fall in hematocrit or failure of hematocrit to rise with transfusion should cause concern.

GRADING OF IVH (per J. Volpe): -Grade I: Bleeding confined to periventricular area (germinal matrix) -Grade II: Intraventricular bleeding (10-50% of ventricular area on sagittal view) -Grade III: Intraventricular bleeding (>50% of ventricular area or distends ventricle)

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-Intra-parenchymal echodensity (IPE) represents periventricular hemorrhagic infarction and is often referred to as Grade IV IVH.

OUTCOME and PROGNOSIS: Progressive Ventricular Neurological Severity of IVH Mortality (%) Dilatation (%) Sequelae (%) Grade I 5 5 5 Grade II 10 20 15 Grade III 20 55 35 IPE 50 80 90 (In general, outcomes with IVH Grade I or II are similar to infants without IVH.) MECHANISMS of BRAIN INJURY from IVH include: -Preceding hypoxic ischemic injury that predisposes to IVH -Increased intracranial pressure with massive IVH which decreases cerebral perfusion -Destruction of germinal matrix -Injury to periventricular white matter due to infarction or to damage from blood

products (K+, other vasoactive factors) -Post-hemorrhagic hydrocephalus due to impaired absorption of CSF by blood

PREVENTION of IVH is primary goal of management and important factors are: Prenatal: ▪Prevention of prematurity ▪Improved perinatal management, including:

-Maternal transport of women in preterm labor to regional center prior to delivery -Antenatal glucocorticoids: accelerate lung maturation and decrease IVH incidence -Optimal obstetrical management

Postnatal: ▪Skilled resuscitation to avoid hypoxia and hypercarbia ▪Circulatory support to avoid hypotension and fluctuating arterial blood pressure ▪Correction of coagulation abnormalities

MANAGEMENT: Other than early diagnosis and careful supportive care (including correction of coagulopathies, circulatory and respiratory support), there is no therapy for IVH. Consider consultation with Neurology for all IVH cases except Grade I and mild Grade II. For progressive ventricular dilatation (post-hemorrhagic hydrocephalus), the essential point is early recognition. Head circumference does not increase until after there has been considerable ventricular dilatation. Therefore, do serial head U/S examinations in infants with IVH ≥grade II. Some cases of ventricular dilatation will respond to serial lumbar punctures and/or acetazolamide (carbonic anhydrase inhibitor) or other diuretics (to decrease CSF production). Persistent, progressive ventricular dilatation requires a ventricular reservoir or ventriculo-peritoneal shunt by a neurosurgeon.

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SCHEDULE for CRANIAL ULTRASOUNDS (U/S) for preterm iinfants: Age Indication for U/S 1 day Perinatal asphyxia, in utero drug exposure 3 days Unstable clinical course 7 days All preterm infants ≤32 weeks gestation Then: -If any IVH, U/S in one week (for early detection of hydrocephalus). Subsequent

examinations depend on clinical course. -If no IVH, repeat U/S at age 4 to 6 weeks, for detection of cystic PVL. PERIVENTRICULAR WHITE MATTER LESIONS Differential diagnosis:

1) Periventricular hemorrhagic infarction: usually asymmetric and grossly hemorrhagic. Presents in first few days of life.

2) Periventricular leukomalacia (PVL): usually bilateral and small. Presents several days to weeks after birth.

Both have association with abnormal neurological outcome.


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Pain Management and Sedation

INTRODUCTION and DEFINITION: Pain is defined as “an unpleasant sensory or emotional experience associated with actual or potential tissue damage or perceived in terms of such damage.” From 24 weeks post-conceptional age, all neurotransmitters and receptors associated with pain modulation are present and responsive; thus, the fetus and newborn can feel pain. Premature infants and term infants <6 months old may have immature inhibitory pathways and thus experience greater discomfort because they are unable to “gate” painful sensations. Physiologic maturity at different gestational ages affects pharmacokinetics of analgesic drugs. Although it may not be feasible to eliminate all pain, the goal should be to reduce it to the lowest level possible. PHYSIOLOGICAL EFFECTS OF PAIN: Pain can cause immediate adverse physiologic effects including:

-Tachycardia -Blood pressure changes (↑ or ↓) - ↑ O2 consumption -Hypoxemia - ↓ cerebrovascular autoregulation -↑ intracranial pressure -Temperature changes -Pallor, flushing -Reduced tidal volume -Abnormal respirations -Prolonged catabolism -State changes -Release of catecholamines, cortisol, endorphins -Pupillary dilatation

For any potentially painful interventions, pain management or analgesia should be considered as either:

-Moderate analgesia (“conscious sedation”): drug-induced depression during which patients cannot be easily aroused but respond to light tactile stimuli. Spontaneous breathing, airway patency and cardiovascular function are usually maintained.

-Deep sedation: drug-induced depression during which patients cannot be easily aroused but respond to repeated or painful stimuli. Patients may require assistance for breathing and airway patency, but cardiovascular function is usually maintained.

PAIN ASSESSMENT is typically done using scoring tools such as the Neonatal Infant Pain Scale (NIPS) (Table 1), which uses behavioral cues and two physiological variables. Infants are scored on a 1-10 point scale, in coordination with clinical nursing judgment. A low pain scale score does not necessarily indicate pain medication is not warranted. Daily examinations by housestaff should also assess the level of pain and discomfort and the adequacy of pain control.

GUIDELINES FOR PAIN MANAGEMENT: A. To prevent or minimize pain:

-Reduce number of needle punctures by drawing blood tests at one time if feasible. -Use indwelling venous or arterial catheters when appropriate. -Avoid invasive monitoring when possible. -Select most competent staff to perform invasive procedures. -Use minimal amount of tape and remove tape gently. -Ensure proper premedication before invasive procedures.


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-Use appropriate equipment (smallest gauge needle, automatic heel lancet, etc.)

Table 1. Neonatal Infant Pain Scale (NIPS) Variable Finding PointsFacial expression Relaxed (Restful face, neutral expression) 0 Grimace (Tight facial muscles, furrowed brow, chin, jaw) 1 Cry No cry (Quiet, not crying) 0 Whimper (Mild moaning, intermittent) 1 Vigorous crying (Loud scream, shrill, continuous). If

infant is intubated, score silent cry based on facial movement.

2

Breathing pattern Relaxed (Usual pattern for this infant) 0 Change in breathing (Irregular, faster than usual,

gagging, breath holding) 1

Arms Relaxed (No muscular rigidity, occasional random movements of arms)

0

Flexed/extended (Tense, straight arms, rigid and/or rapid extension, flexion)

1

Legs Relaxed (No muscular rigidity, occasional random leg movements)

0

Flexed/Extended (Tense, straight legs, rigid and/or rapid extension, flexion)

1

State of Arousal Sleeping/Awake (Quiet, peaceful, sleeping or alert and settled)

0

Fussy (Alert, restless and thrashing) 1 Heart Rate Within 10% of baseline 0 11-20% of baseline 1 >20% of baseline 2 O2 Saturation No additional O2 needed to maintain O2 saturation 0 Additional O2 required to maintain O2 saturation 1

B. Treatment guidelines: Assess each infant on an individual basis. Using the NIPS, the nurse and the medical team determine a pain score and the appropriate intervention for pain management, as suggested by the guidelines shown in Table 2. MONITORING: Respiratory depression and/or arrest may occur with narcotic agents as well as with barbiturates, midazolam, diazepam and lorazepam, particularly when these agents are given in combination. Careful and appropriate monitoring of infants receiving these agents is essential, especially when the patients are not receiving mechanical ventilation.


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Table 2. Guidelines for Pain Management Pain Score Guidelines for Intervention 0-3 Mild Non Pharmacologic (primary method)

-Pacifiers, sucrose, hand-to-mouth, non-nutritive sucking -Whiskey nipple* -Swaddling, nesting, holding -Position changes, correct positioning for procedures -Decrease environmental stimuli (light, noise, abrupt movements) -Decreased handling with rest periods between procedures -Comfort measures noted to be effective with individual neonate -Soothing vocalizations, recorded intrauterine sounds Pharmacologic -Acetaminophen (Tylenol™)

4-6 Moderate

Non Pharmacologic -See above Pharmacologic: (primary method) -Narcotic bolus

7-10 Severe

Pharmacologic: (primary method) -Narcotic intermittent bolus -Consider narcotic drip

*Whiskey nipple: 1/5 dilution of bourbon in D5W; ~3 cc/kg dripped into a cotton filled nipple (as pacifier) PHARMACOLOGIC MANAGEMENT OF PAIN Analgesics are the mainstay of pharmacologic treatment of pain. Sedative, hypnotic and anxiolytic drugs do not provide analgesia. Muscle relaxants (paralytic agents) do not provide analgesia and pain is difficult to assess in patients receiving neuromuscular blockade Pharmacological agents commonly used in the ICN to reduce or prevent pain include:

-Mild analgesia: Acetaminophen (Tylenol™) also has antipyretic properties. Usual dose is 15 mg/kg PO or PR q6-8h (not to exceed 75 mg/kg/d).

-Local Anesthesia: Lidocaine (Xylocaine™). Use 0.5-1% solution without epinephrine. To avoid toxicity, total dose must be <0.5 mL cc/kg of 1% solution.

-Narcotic analgesia: •Morphine can be used for analgesia, sedation and opiate withdrawal. Usual dose

is 0.1 (0.05-0.2) mg/kg q2-4 h prn IV, IM, or SC. •Fentanyl is used for analgesia, sedation and anesthesia.

-Dose for analgesia or sedation: 1-2 mcg/kg q4-6 prn IV (slowly) or SC, or as continuous IV infusion: 2 mcg/kg/h.

-Dose for anesthesia: 10-50 mcg/kg IV over 2 to 10 min. (Titrate to effect). •Meperidine is not recommended for use in newborns. •Methadone can be used for treatment of post-operative pain but has no advantages

over morphine or fentanyl.


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-Adjunctive Drugs (e.g., diazepam, midazolam, lorazepam, chloral hydrate) are useful for sedation when pain is adequately managed.

SPECIFIC SITUATIONS for which analgesia or sedation is recommended and suggested agent: -Circumcision: EMLA (eutectic mixture of local anesthetics: lidocaine-prilocaine)

topically 1h prior to procedure, or dorsal penile block (1% lidocaine) immediately before procedure.

-Lumbar puncture (analgesia when feasible): EMLA prior to procedure, or morphine (0.05 – 0.1 mg/kg IV) at least 5 min prior to procedure.

-Nasal CPAP: Lidocaine jelly to nostrils q6h -Non-emergent endotracheal intubation: Morphine (0.05 – 0.1 mg/kg IV) at least 5

min prior to intubation. -Mechanical ventilation:Typical sedation involves one of the following:

•Morphine 0.05 - 0.1 mg/kg IV q 4-6h, or continuous infusion of 0.01-0.025 mg/kg/h. Titrate dose to lowest that achieves analgesic/sedative effect.

•Fentanyl 1-3 mcg/kg IV q1-2 h, or continuous infusion of 1-5 mcg/kg/hr. Titrate dose to lowest that achieves analgesic/sedative effect.

•Phenobarbital is useful for long-term ventilation at 2.5 mg/kg IV or PO q12-24 h. -Chest tube thoracostomy: Morphine 0.05-0.1 mg/kg IV. Attempt to give at least 5 min

prior to chest tube insertion. Unless it is a dire emergency, use local infiltration with 1% lidocaine.

-Venipuncture or minor procedures (IV catheter placement) may be painful, especially if difficult to accomplish. Therefore, consider giving morphine 0.05 - 0.1 mg/kg IV at least 5 min prior to procedure.

-CT or MRI scanning: Sedation is often unnecessary, especially if infant has been fed just before scan, is well-bundled, and efforts are made to minimize sound of scanning. Otherwise, use pentobarbital (Nembutal™) 1.5-3.0 mg/kg IV immediately before placing in scanner.

-Post-operative pain: •Major surgery (e.g., thoracotomy, abdominal laparotomy): Morphine 0.1-0.2

mg/kg q3-4h IV prn for at least 24h after the operation. Discuss subsequent pain medication with Neonatology Fellow and with Surgeons.

•Minor Surgery (e.g., hernia repair, pyloromyotomy): Acetominophen is usually adequate. Discuss with Fellow and with Surgeons.

-Withdrawal of life support: The major aim is to relieve suffering as much as possible. Discuss this with Neonatology Fellow and/or Attending. In many cases it is appropriate to give relatively large doses of narcotics to alleviate suffering. In these circumstances, morphine almost never causes apnea.

WEANING OF OPIATE ANALGESICS (morphine, fentanyl) should be done if the agents have been given routinely for more than 3 d. Method of weaning depends upon length of opiate therapy: 1. Short term therapy (<1 week): Initially reduce dose by 20%. Then reduce dose by

10% (of original dose) q6-8h. Discontinue drug as tolerated. 2. Long term therapy (>1 week): Reduce dose by 20% over first 24h. Then reduce dose

by 10% (of original dose) q12h as tolerated. Drug can usually be discontinued when it is at about 20% of original dose, although subsequent small doses may be needed.


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Infants of Diabetic Mothers (IDMs) BACKGROUND AND PATHOPHYSIOLOGY: With insulin-dependent diabetes mellitus, maternal hyperglycemia, hypoglycemia and ketosis can occur during fetal organogenesis, and there is increased incidence of fetal anomalies. Careful attention to pre-conception control of diabetes decreases the risk of anomalies. With gestational diabetes, because glucose intolerance does not occur during organogenesis, the risk of anomalies is not increased. Glucose transport across the placenta is not limited. Fetal hyperglycemia stimulates beta-cell hypertrophy, increases insulin production and fetal oxygen consumption. Insulin has mitogenic and anabolic effects on many tissues (e.g., adipocytes, skeletal and cardiac muscle, hepatic and connective tissue), but not brain. Therefore, delivery of IDMs may be complicated by large shoulders and abdomen that can cause dystocia. CLINICAL PROBLEMS IN IDMs: Congenital anomalies: Incidence 6-9%, and these account for 50% of mortality. No single anomaly is pathognomonic, but several are much more frequent including:

•Cardiovascular (e.g.,VSD, transposition of great vessels) •Skeletal: Especially, the caudal regression syndrome •CNS: Meningomyelocele, anencephaly, holoprosencephaly •Other: Renal, gastrointestinal

Unexplained fetal demise. Polyhydramnios is associated with poor control. Macrosomia (birthweight ≥4,000 grams) Most macrosomic infants are born to non-diabetic mothers. Risk of macrosomia is reduced by good glycemic control during 20-30 weeks of gestation. Shoulder dystocia is more likely in IDM than non-IDM macrosomic infants of similar weight. Macrosomia increases risk of traumatic delivery (e.g., brachial plexus palsy, fracture of clavicle) and asphyxia. Intrauterine growth retardation occurs usually with severe diabetes (chronic hypertension, vascular disease) and is associated with congenital malformations. Hypoglycemia is common and occurs in LGA and SGA. Screen all IDMs for hypoglycemia (see section on Hypoglycemia, P. 153). First nadir in glucose is 30-90 min post delivery and may take several days to resolve. Glucose requirements may be very high (10-15 mg/kg/min). Rebound hypoglycemia occurs in response to large, rapid boluses of glucose. IDMs are less symptomatic (than non-IDMs), even with significant hypoglycemia. Hyperbilirubinemia (see section on Jaundice, P. 118) Hypocalcemia occurs in 17%, usually 2-3 d after birth, and often with hypomagnesemia. Respiratory Distress Syndrome: Risk is increased 6-fold. Septal hypertrophy of heart occurs in infants of gestational and insulin dependent diabetics. Left ventricular compliance and cardiac output are decreased. Obtain Cardiology consult. Consider treatment with propranolol (to slow heart rate and allow increased ventricular filling). Hypertrophy gradually resolves by age 6-12 months.

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Small left colon (Hypoplastic left colon syndrome) presents as lower bowel obstruction and may be confused with Hirschsprung’s Disease. Cause is thought to be delayed innervation of distal bowel. Diagnosis is made by barium enema and history of maternal diabetes. Condition should clear within several days. Polycythemia is associated with poor glycemic control or maternal vascular disease. (see section on Polycythemia, P. 112) Persistent pulmonary hypertension (see P. 91 for management) Low cardiac output: IDMs who have had perinatal asphyxia with metabolic acidosis, hypoglycemia and/or hypocalcemia may have cardiomagaly with ↓ contractility. This responds to combined correction of all metabolic abnormalities. Poor feeding is common. An IDM may take several days to establish nipple feedings. MANAGEMENT of IDMs: •Screen all IDMs for hypoglycemia, hypocalcemia and polycythemia, and treat appropriately. •Careful examination and observation looking for conditions described above.


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Neonatal Hypoglycemia BACKGROUND and PATHOPHYSIOLOGY: Glucose is the major energy source for fetus and neonate. The newborn brain depends upon glucose almost exclusively. Up to 90% of total glucose used is consumed by the brain. Alternate fuels (e.g., ketones, lactate) are produced in very low quantities. The usual rate of glucose utilization is 4-8 mg/kg/min. Glucose regulatory mechanisms are sluggish at birth. Thus, the infant is susceptible to hypoglycemia when glucose demands are increased or when exogenous or endogenous glucose supply is limited. Severe or prolonged hypoglycemia may result in long term neurologic damage. DEFINITION: Hypoglycemia in the first few days after birth is defined as blood glucose <40 mg/dL. In preterm infants, repeated blood glucose levels below 50 mg/dL may be associated with neurodevelopmental delay. ETIOLOGY: conditions associated with an increased risk for neonatal hypoglycemia include: 1. Decreased substrate availability:

•Intra-uterine growth retardation •Glycogen storage disease •Inborn errors (e.g., fructose intolerance) • Prematurity •Prolonged fasting without IV glucose

2. Hyperinsulinemia: •Infant of diabetic mother •Islet cell hyperplasia •Erythroblastosis fetalis •Exchange transfusion •Beckwith-Wiedemann Syndrome •Maternal ß-mimetic tocolytic agents •”High” umbilical arterial catheter •Abrupt cessation of IV glucose

3. Other endocrine abnormalities: •Pan-hypopituitarism •Hypothyroidism •Adrenal insufficiency

4. Increased glucose utilization: •Cold stress •Increased work of breathing •Sepsis •Perinatal asphyxia

5. Miscellaneous conditions: •Polycythemia •Congenital heart disease •CNS abnormalities

SIGNS AND SYMPTOMS of hypoglycemia are nonspecific and include: jitteriness, irritability, lethargy, seizures, apnea, grunting and sweating (uncommon). Hypoglycemic infants may not always be symptomatic. Therefore, routine glucose monitoring for at-risk infants is mandatory. Lack of symptoms does not guarantee absence of long term sequelae. DIAGNOSTIC WORKUP: Specimens for measurement of glucose should be obtained from heelstick, venipuncture, or from an indwelling catheter that does not have glucose infusing in it.

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SCREENING OF AT RISK INFANTS: Infants at risk for hypoglycemia should be screened by measuring blood sugar by Glucometer at ages 1, 2, 4, 6, 9 and 12h. Less frequent measurements are appropriate if blood glucose is stable. However continued surveillance and more frequent measurements may be needed until blood glucose is stable >40 mg/dL or >50 mg/dL in very preterm infants. MANAGEMENT OF HYPOGLYCEMIA: •Glucometer reading >40 mg/dL and infant is feeding normally: follow usual nursery protocol. •Glucometer reading 20-40 mg/dL, infant is term and is able to feed:

-Draw blood for stat blood glucose. -Feed 5 mL/kg of D5W. -Repeat blood glucose or Glucometer 20 min after feeding.

•Glucometer reading: (a) <20 mg/dL or (b) <40 mg/dL and NPO or preterm or (c) <40 mg/dL after feeding or (d) <40 mg/dL and symptomatic

-Draw blood for stat glucose measurement. -Give IV bolus of 2-3 mL/kg of D10W. -Begin continuous infusion of D10W at 4-6 mg/kg/min. -If infant of diabetic mother, begin D10W at 8-10 mg/kg/min (100-125 cc/kg/d). -Repeat blood glucose in 20 min and pursue treatment until blood sugar >40 mg/dL.

•For persistent hypoglycemia despite above measures: -Increase rate of glucose infusion stepwise in 2 mg/kg/min* increments up to 12-15

mg/kg/min glucose. Use increased volume with caution in infants where volume overload is a concern. Maximal concentration of glucose in peripheral IV is D12.5.

-If infant requires IV dextrose concentrations >12.5%, insert central venous catheter. •Do not use D25W or D50W IV or large IV volume boluses as this creates rebound hypoglycemia in infants who are hyperinsulinemic. In addition, administration of D25W or D50W can cause dangerous increase in plasma osmolarity. •If hypoglycemia is not controlled with above measures: Obtain Endocrine Consult to guide further diagnostic evaluation and management. While awaiting consult, send blood (while blood sugar is low) for glucose, plasma cortisol, growth hormone and insulin concentrations. Further management may include glucocorticoids, diazoxide, somatostatin or pancreatectomy. •Weaning IV dextrose infusion: When blood glucose has been stable for 12-24 h, begin decreasing IV infusion by 1-2 mL/hr q3-4 hours if blood glucose remains ≥60 mg/dL. * To calculate rate of glucose administration, use either of the following formulas: % glucose x mL/kg/d = glucose infusion rate (mg/kg/min) 144 or

% glucose x mL/h = glucose infusion rate (mg/kg/min) 6 x body weight (kg)


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Inborn Errors of Metabolism INTRODUCTION and PATHOPHYSIOLOGY: Inborn Errors of Metabolism (IEM) comprise a group of disorders in which a single gene defect causes a clinically significant block in a metabolic pathway resulting either in accumulation of substrate behind the block or deficiency of the product. All IEMs are all genetically transmitted typically in an autosomal recessive or X-linked recessive fashion. The major categories are: Organic acidemias (e.g., methylmalonic or propionic acidemia, multiple carboxylase deficiency) are caused by abnormal metabolism of proteins, fats or carbohydrates and are characterized by marked metabolic acidosis with ketosis, often with elevated lactate and mild to moderate hyperammonemia. Common signs include vomiting, signs of encephalopathy, neutropenia and thrombocytopenia. Fatty acid oxidation defects (e.g., short, medium, and long- chain acyl-CoA dehydrogenase deficiencies) also known as Beta-oxidation defects, are a distinct type of organic acid disorder, characterized by hypoketotic hypoglycemia, hyperammonemia, and cardiomyopathy, and may present clinically with Reye’s syndrome. Medium-chain acyl-CoA dehydrogenase deficiency (MCAD) is among the most common of all IEMs and may account for 5% of SIDS cases. Primary Lactic Acidoses (e.g., pyruvate dehydrogenase, pyruvate carboxylase and cytochrome oxidase deficiencies) present with severe lactic acidosis. Aminoacidopathies (e.g., phenylketonuria, hereditary tyrosinemia, nonketotic hyperglycinemia, maple syrup urine disease [MSUD] and homocystinuria) may have similar presentation to the organic acidemias, but are a very heterogeneous group of disorders. Hereditary tyrosinemia can present in the neonate with a bleeding diathesis due to liver disease, or later in infancy with a renal Fanconi syndrome. The severe form of nonketotic hyperglycinemia presents as unremitting seizures with hypotonia and hiccoughs. MSUD classically presents at the end of the first week of life with feeding difficulties, lethargy, coma, seizures and the characteristic odor. Urea cycle defects (e.g., citrullinemia, ornithine transcarbamylase deficiency, and arginosuccinic aciduria) result from the inability to detoxify nitrogen and are characterized by severe hyperammonemia and respiratory alkalosis, with a typical onset after 24 hours of age. Disorders of carbohydrate metabolism (e.g., galactosemia, hereditary fructose intolerance, fructose 1,6-diphosphatase deficiency and the glycogen storage diseases) are a heterogeneous group caused by inability to metabolize specific sugars, aberrant glycogen synthesis, or disorders of gluconeogenesis. They may manifest with hypoglycemia, hepatosplenomegaly, lactic acidosis or ketosis. Lysosomal storage disorders (e.g., mucopolysaccharidosis, Tay-Sachs, Niemann-Pick disease, Gaucher’s disease) are caused by accumulation of glycoproteins, glycolipids, or glycosaminoglycans within lysosomes in various tissues. They usually present later in

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infancy, not with a specific laboratory abnormality, but with organomegaly, facial coarseness and neurodegeneration and show a progressively degenerative course. Peroxisomal disorders (e.g., Zellweger syndrome and neonatal adrenoleukodystrophy) result from failure of the peroxisomal enzymes. They may present with features similar to the lysosomal storage disorders. Common features of Zellweger syndrome include large fontanel, organomegaly, Down-like facies, seizures and chondrodysplasia punctata. Others include disordered steroidogenesis (congenital adrenal hyperplasia or Smith-Lemli-Opitz), disorders of metal metabolism (Menkes syndrome, neonatal hemochromatosis). Transient hyperammonemia of the newborn is more prevalent in slightly premature infants receiving mechanical ventilation; onset is usually within the first 24 hours of life. The ammonia level may be markedly elevated and dialysis may be necessary. The cause is unknown and, if the newborn survives, there is no further evidence of impaired ammonia metabolism. CLINICAL FINDINGS suggestive of an IEM include: -History of consanguinity, mental retardation, or SIDS; symptom onset with institution

of feedings or formula change; history of growth disturbances, lethargy, recurrent emesis, poor feeding, rashes, seizures, hiccoughs, apnea, tachypnea.

-Physical findings: tachypnea, apnea, lethargy, hypertonicity, hypotonicity, hepatosplenomegaly, ambiguous genitalia, jaundice, dysmorphic or coarse facial features, rashes or patchy hypopigmentation, ocular findings (cataracts, lens dislocation or pigmentary retinopathy), intracranial hemorrhage, unusual odors.

-Laboratory findings: metabolic acidosis with increased anion gap, primary respiratory alkalosis, hyperammonemia, hypoglycemia, ketosis or ketonuria, low BUN, hyperbilirubinemia, lactic acidosis, high lactate/pyruvate ratio, non-glucose-reducing substances in urine, elevated liver function tests including PT and PTT, neutropenia and thrombocytopenia.

INITIAL APPROACH: -Rule out non-metabolic causes of symptoms such as infection or asphyxia. -Obtain consult from Genetic/Metabolic Service -Laboratory assessment prior to therapy:

• Blood: glucose, newborn screen, CBC with differential, platelets, pH and PaCO2, electrolytes for anion gap, liver function tests, total and direct bilirubin, PT, PTT, uric acid, ammonia. Other studies may be indicated as described in algorithm below. Blood ammonia, lactate and pyruvate should be collected without a tourniquet, kept on ice and analyzed immediately.

• Urine: color, odor, pH, glucose, ketones, reducing substances (positive for galactosemia, fructose intolerance, tyrosinemia and others), ferric chloride reaction (positive for MSUD, PKU and others) and DNPH reaction (screens for alpha-keto acids). Amino and organic acids as described in algorithm below.

• CSF: glycine (for nonketotic hyperglycinemia), lactate, pyruvate if appropriate. -Figures 1 and 2 are adapted from Burton BK: Inborn errors of metabolism in infancy: A

guide to diagnosis. Pediatrics 102:E69, 1998. These flow charts are guides to the differential diagnosis of hyperammonemia (Figure 1) and metabolic acidosis (Figure 2 ) in newborns. Another helpful algorithm is in Rudolph’s Pediatrics, 20th ed., P. 292. Not all inborn errors of metabolism will present with acidosis, hyperammonemia,


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or hypoglycemia. Neurological signs (e.g., seizures, obtundation) may be the predominant feature in several IEMs (e.g., nonketotic hyperglycinemia, molybdenum cofactor deficiency, peroxisomal disorders).

Figure 1. Flow chart for differential diagnosis of hyperammonemia. (ASA,

arginosuccinic acid; CPS, carbamyl phosphate synthetase; OTC, ornithine transcarbamylase; PC, pyruvate carboxylase). Chart is adapted from Burton BK: Pediatrics 102: E69, 1998.

FURTHER MANAGEMENT: Although treatment differs for each specific disorder, each should be managed by considering the potential disease category and by following the following steps, along with consultation with a metabolic specialist. -Hydration/nutrition/acid-base management: Rehydrate infant. Stop all oral intake to

eliminate protein, galactose and fructose. Provide calories with IV glucose at 8-10 mg/kg/min (even if insulin is required to keep the blood glucose level normal). Give IV lipids only after ruling out a primary or secondary fatty acid oxidation defect. Withhold all protein for 48 to 72 hours, while the patient is acutely ill, and until an aminoacidopathy, organic aciduria or urea cycle defect has been excluded. Special special enteral formulas and parenteral amino acid solutions are available for many disorders. Treat significant acidosis (pH<7.22) with a continuous infusion of NaHCO3.

Symptoms after age 24h

Acidosis

ORGANIC ACIDEMIAS

No acidosis

UREA CYCLE DEFECTS

PLASMA AMINO ACIDS

Absent Citrulline

Urine Orotic Acid

Low

CPS deficiency

Elevated

OTC deficiency

Citrulline moderatelyelevated, ASA present

Arginosuccinicaciduria

Citrulline markedlyElevated, no ASA

Citrullinemia

NEONATAL HYPERAMMONEMIA

Symptoms in 1st 24h

Preterm

Transient Hyperammonemia

of Newborn

Full Term

INBORN ERROR OF METABOLISM

(i.e., organic acidemiaor PC deficiency)


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-Elimination of toxic metabolites: Treatment of hyperammonemia is urgent. The severity of neurological impairment in infants with urea cycle defects depends upon the duration of the hyperammonemic coma. For severe hyperammonemia, hemodialysis is indicated. Dialysis may also be indicated for intractable anion gap metabolic acidosis.

Figure 2. Flowchart for evaluation of metabolic acidosis in the young infant.

(Fructose-1,6-DP, fructose-1,6-diphosphatase; GSD, glycogen storage disease; L:P ratio, lactate to pyruvate ratio)

Chart is adapted from Burton BK: Pediatrics 102: E69, 1998. ________________________________________________________________________ -Treatment of coexisting/precipitating factors (e.g., infection, thrombocytopenia). -Cofactor replacement: Certain enzyme deficiencies are vitamin-responsive, including:

• The vitamin-responsive form of propionic acidemia, beta-methylcrotonyl deficiency, holocarboxylase synthetase deficiency, and biotinidase deficiency: biotin (5 mg daily, oral or parenteral).

• Vitamin-responsive methylmalonic acidemia: Vitamin B12 (1 mg daily, IM). • Vitamin-responsive maple syrup urine disease: thiamine (50 mg daily, oral).

No hypoglycemia

PYRUVATE DEHYDROGENASE

DEFICIENCY; PYRUVATE CARBOXYLASE DEFICIENCY

Normal or low pyruvate;elevated L:P ratio

RESPIRATORY CHAIN DEFECTS; PYRUVATE

CARBOXYLASE DEFICIENCY

Normal organic acids

METHYLMALONIC ACIDEMIA;PROPIONICACIDEMIA; MULTIPLE

CARBOXYLASE DEFICIENCY; OTHERS

Dicarboxylic aciduria

FA TTY ACID

OXIDATION DEFECTS

Abnormalorganic acids

Abnormal organic acids

ORGANIC ACIDEMIA

METABOLIC ACIDOSIS WITH INCREASED ANION GAP

Normal lactate Elevated lactate

GSD TYPE 1; FRUCTOSE 1,6-DP DEFICIENCY;

PEP CARBOXYKINASE DEFICIENCY

Elevated pyruvate;normal L:P ratio

Hypoglycemia


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It is important to make a specific diagnosis, even in a dying child, to help parents understand what happened and to provide information that might affect future reproductive planning. -If an autopsy is not permitted, request consent for pre-mortem or immediately post-

mortem specimens. -Blood should be centrifuged and the plasma should be frozen. -Urine and spinal fluid should be refrigerated. -A sterile skin biopsy (used for fibroblast culture) can be performed within 1-2 hours

after death. Alcohol should be used to clean the skin; do not use betadine, as it will inhibit cell growth. Place skin sample in sterile saline at room temperature and send to the cytogenetics lab for culture and processing.

-Other tissue samples (e.g., liver, skeletal muscle, cardiac muscle, brain, kidney) may be useful depending on the disorder.

-If there are dysmorphic features, consider a full skeletal radiological series. OUTCOME: At present, for most IEMs, prognosis for survival or normal neurological outcome is guarded, despite appropriate and aggressive therapy. It is likely that the outcomes will improve with (a) presymptomatic diagnosis (i.e., by prenatal detection or expanded neonatal screening), (b) identification of genes and other factors which impact on phenotype, response to treatment, and outcome, and (c) alternative novel approaches to therapy.


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Common Neonatal Surgical Conditions INTRODUCTION: Approximately 15% of all infants admitted to the UCSF ICN have a primary surgical diagnosis (in addition to those with congenital heart disease). For many of the other patients, surgical problems develop during their hospitalization. Appropriate care of these infants requires close cooperation and communication between the ICN medical team and the Pediatric Surgeons. This section deals with some common neonatal surgical conditions. Others are covered in the sections on Necrotizing Enterocolitis (P. 133) and Pulmonary Hypoplasia and Diaphragmatic Hernia (P. 85). GENERAL GUIDELINES:

•Patients in the ICN with surgical problems are managed jointly by the medical and surgical teams. Each patient should be discussed at least once daily with the Pediatric Surgical team.

•Notify Pediatric Surgery as soon as you are aware of a pending admission or birth of a patient with a surgical problem.

•When patient returns from the Operating Room, obtain sign-out from the Surgical Resident and discuss orders for postoperative care. Also, obtain sign-out from the Anesthesia Resident regarding (a) anesthesia, other drugs, and fluids that the patient received and (b) events during the operative procedure.

•Notify Pediatric Surgery immediately if there are any major changes in the condition of a surgical patient.

•Do not begin feedings on a surgical patient without first discussing it with the Pediatric Surgeons.

•Whenever possible, accompany your patient to the Operating Room. It is an excellent opportunity for learning and for discussing post-operative management with the surgical team.

1. ESOPHAGEAL ATRESIA WITH OR WITHOUT TRACHEO-ESOPHAGEAL

FISTULA (TEF): A. Diagnosis and preoperative management:

•Esophageal atresia may often be suspected prior to the first feeding by a history of polyhydramnios or observation of copious oral secretions than require very frequent suctioning.

•Attempt to pass feeding tube with radiopaque line into the stomach. If the tube does not pass, leave in place and obtain chest x-ray and KUB.

•Do not obtain contrast study. This may result in aspiration. •If the tube curls up in blind esophageal pouch and there is no air in bowel, assume

a diagnosis of esophageal atresia. •If the tube curls up in blind esophageal pouch and there is air in the distal bowel,

assume a diagnosis of esophageal atresia with distal TEF. •Call Pediatric Surgery. •Keep infant in a position with the head up to prevent aspiration.

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•Place Replogle tube on continuous suction to drain the blind pouch. •Avoid bag and mask ventilation and nasal CPAP to prevent over-distension of the

stomach. If the baby needs respiratory assistance, intubate the infant. •If the baby has severe lung disease and a distal TE fistula, ventilation of the lungs

may be extremely difficult because of the low resistance through the fistula into the stomach and bowel. Notify surgery immediately as the baby may need immediate closure of the fistula or an emergency gastrostomy with placement of a distal esophageal balloon to facilitate adequate ventilation.

•Examine infant carefully for other anomalies associated with VATER or CHARGE, including vertebral abnormalities, radial anomalies, choanal atresia, imperforate anus, renal abnormalities, congenital heart disease, coloboma or evidence of Down syndrome.

B. Post operative management: •Regular maintenance IV fluids with extra boluses of normal saline as needed for

oliguria, hypotension, or poor perfusion. If infant requires >15 mL/kg of extra fluid, consider starting dopamine at 5 mcg/kg/min to ↑ blood pressure and perfusion to kidneys.

•If a chest tube is in place draining the area of the anastomosis, do not connect the pleuravac to suction without consulting with the Attending Surgeon. The chest tube is usually in place for 7-10d until x-ray studies show no leak at the anastomosis.

•If the anastomosis is under tension, the surgeons will often want to keep the baby on muscle relaxants postoperatively for a few days to a week, to prevent disruption of the anastomosis.

•Do not extubate until the baby is extremely stable on very low ventilatory settings, because positive pressure mask ventilation must be avoided to prevent transmission of pressure to the esophagus, which may rupture the anastomotic suture line.

•If the baby needs to be reintubated, the most experienced person should do this. Faulty (i.e., esophageal) intubation could result in injury to the anastomosis.

•Leave the orogastric or nasogastric tube in place until x-ray studies show no leak at the anastomotic site, and Pediatric Surgery agrees to removal of the tube. If the tube accidentally comes out, do not reinsert tube without consulting with the Attending Pediatric Surgeon, as you may damage the anastomosis.

•X-ray contrast study should be done at approximately 10 days postoperatively to assess for leakage at the anastomotic site prior to starting oral feedings. Gastrostomy tube feedings and NG tube feedings may be started earlier.

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2. INTESTINAL OBSTRUCTION

A. Diagnosis and preoperative management: •Intestinal obstruction should be suspected with maternal history of

polyhydramnios, large amount (>20 mL) of gastric fluid at birth, bilious or non-bilious emesis, or progressive abdominal distension.

•Common causes include duodenal, jejunal, ileal, or colonic atresia, malrotation with mid gut volvulus, meconium ileus with associated cystic fibrosis, meconium plug, Hirschsprung’s disease, imperforate anus, and hypoplastic left colon.

•Infants with bowel atresia may pass meconium. •The higher the obstruction, the more prominent is the vomiting. The lower the

obstruction, the more prominent is the distension. •Make infant NPO, start IV, and monitor electrolytes, urine output and weight. •Place Replogle tube to continuous suction and measure output. •Obtain KUB looking for

-“double bubble” sign of duodenal atresia. If present, no further GI workup is needed and patient should go to surgery when stable.

-multiple dilated loops of bowel indicating a more distal obstruction -intraperitoneal calcifications suggestive of perforation with meconium ileus -air throughout bowel to the rectum suspicious for Hirschsprung’s disease -bubbly-appearing stool filling the bowel suggestive of meconium ileus and

cystic fibrosis •Upper GI contrast study (with dilute Hypaque™or Gastrograffin™) may be

required to assess for malrotation and possible volvulus. •Contrast enema using Gastrografin™ or dilute Hypaque™ may be done to identify

an area of obstruction or to relieve meconium plug or meconium ileus. •Suspect acute volvulus secondary to malrotation if the baby has signs of shock,

metabolic acidosis or peritonitis. If there are signs suggesting volvulus, emergency operation is indicated since gut viability may be threatened.

•Suspect Hirschsprung’s disease with repeated episodes of abdominal distension or very delayed passage of meconium. Diagnosis can be made with suction rectal biopsy. If no ganglion cells are seen, a surgical biopsy will confirm the diagnosis.

•Infants with Hirschsprung’s disease are at risk for development of fatal toxic megacolon until the bowel has been decompressed by corrective surgery or colostomy. Surgeons may choose to decompress initially with rectal irrigation. This is different from simple enemas.

•Imperforate anus may be the sole abnormality or may be part of the VATER association. Look carefully for evidence of recto-vaginal, recto-urethral or perineal fistula. Ultrasound may help determine if the defect is low (and easily repaired) or high (requiring colostomy drainage). These patients will need eventual workup for tethered spinal cord and urinary tract anomalies.

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B. Post operative management: •IV fluid replacement at maintenance levels with parenteral nutrition (see P. 136)

starting within 2d of operation. Intermittent fluid boluses may be required in the first 48h to maintain adequate urine output and to treat hypotension and hypoperfusion. Consider early use of low-dose dopamine (3-5 mcg/kg/min).

•If there has been extensive bowel manipulation, the baby may require baseline fluid administration 1.5 times normal (i.e., 150 mL/kg/d) because of capillary leak. Use Lactated Ringer’s Solution with 5% or 10% dextrose for at least the first 24h after operation.

•Maintain Replogle tube to continuous suction and measure output. If drainage is more than 10 mL/kg per 12h shift, replace volume loss with an equal volume of 0.45% NaCl.

•Replogle tube may be removed when drainage is minimal and non-bilious. •After the baby has passed stool, start feedings with small volumes and advance

slowly over the next 48h to ensure that baby is not developing abdominal distension secondary to postoperative ileus or to stricture at the anastomotic site.

3. OMPHALOCELE AND GASTROSCHISIS:

A. Diagnosis and preoperative management: •Often diagnosed prior to delivery by ultrasound. •Resuscitation team should be present at delivery. •Because fluid losses from the exposed bowel can be massive, the lower half of the

infant’s body should be placed in a sterile bowel bag (turkey bag) with some sterile 0.9% NaCl at the bottom to keep the environment moist. Close the bag above the defect

•With gastroschisis or large omphalocele, make sure that the blood supply to the bowel is not kinked by the weight of the bowel. The baby may be placed on his side (right side down or with towels underneath the bowel bag) to help support the externalized intestine and insure adequate blood flow.

•Place baby under radiant warmer to prevent hypothermia from high heat loss from the exposed bowel.

•Insert a Replogle tube to continuous suction to prevent bowel distension. •Notify Pediatric Surgery. •Start IV maintenance fluids and prophylactic antibiotics. IV fluid requirement

may be as high as 300mL/kg/day, especially for gastroschisis. •Omphalocele is a herniation of bowel, and occasionally other organs including

stomach and liver, into the umbilical cord and they are usually covered by a peritoneal sac, which may rupture prior to or during birth.

•Omphalocele has a high association (>50%) with other anomalies, especially congenital heart disease, chromosomal abnormalities, Pentalogy of Cantrell and Beckwith-Wiedemann syndrome. Therefore chest x-ray, renal ultrasound, and echocardiogram should be obtained prior to operation.

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•Gastroschisis is a herniation of abdominal contents through a small right sided abdominal wall defect lateral to the umbilical cord. The exposed bowel is never covered by a peritoneal sac. Only approximately 10% of infants with gastroschisis have associated abnormalities, usually intestinal atresias.

B. Surgical management:

•If there is adequate space within the abdominal cavity, a primary closure of the abdominal wall may be done, often with a gastrostomy tube for decompression. Usually this is possible for omphaloceles, which tend to be small, and occasionally for small gastroschises.

•Often a 2-stage procedure is required with the initial placement of a sterile Goretex™ silo to cover the bowel. Each day, the silo is tightened by the Surgeons so that the bowel is gradually pushed back into the abdominal cavity. The final closure is performed in the operating room with removal of the silo and, occasionally, placement of a mesh graft to help close the anterior abdominal wall.

•Risks of silo include infection and bowel necrosis. To decrease infection rate, the silo should be closed within 4-7d.

•The surgeons will insert a central Broviac catheter for parenteral nutrition. This is often not necessary with primary repair of small omphaloceles.

C. Post operative management: •Check chest X-ray immediately post-operatively to evaluate lung fields and

position of catheter. •If primary closure has been difficult or if a silo is used, the baby will require

assisted ventilation and will usually be kept on muscle relaxants for at least the first few days after operation

•Ensure adequate ventilation and oxygenation by increasing inspiratory and end expiratory pressures to maintain adequate lung volume and tidal volume as abdominal girth increases secondary to capillary leak syndrome.

•Replacement of the bowel inside the abdomen and tightening of the silo will lead to increased intra-abdominal pressure that will decrease diaphragmatic excursion and make ventilation more difficult.

•The increased intra-abdominal pressure may also lead to decreased urine output. •Provide adequate pain relief, usually by continuous infusion of morphine. •Maintain good hydration and avoid hypotension postoperatively to ensure adequate

bowel perfusion. For the first 24h postoperatively, use D10% Lactated Ringer’s solution at 1.5 times maintenance (i.e., 150 mL/kg/d). Frequent extra boluses of normal saline may be required to maintain adequate urine output. Consider early use of dopamine.

•Continue preoperative antibiotic therapy. •After 48 hours postoperatively, consider starting central parenteral nutrition (see P.

136 for guidelines). •Maintain Replogle tube to continuous suction, record volume of fluid drainage,

and replace with 0.9% NaCl if the amount exceeds 10 mL/kg per 12h shift.

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•If infant is receiving muscle relaxants, insert indwelling urinary catheter for accurate measurement of urine output.

•When infant is ready to start enteral feedings, use an elemental formula such as Pregestimil™, start with small volumes and advance slowly (see section on Feeding of Preterm Infants, P. 50). Infants with gastroschisis are at very high risk for necrotizing enterocolitis (see P. 133).

•Because infants with gastroschisis are also at increased risk for intestinal atresia, observe infant closely for abdominal distension as feedings are advanced.

•Infants who require secondary closure of their abdominal wall defect will usually not be on full enteral feedings until at least 3 weeks postoperatively.


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Meningomyelocele INTRODUCTION: Failure of closure of the neural tube during the third week of gestation leads to the constellation of defects observed in patients with meningomyelocele (MMC). The open neural tube is continuous with the surface of the skin. For this reason, infants with MMC are at risk for bacterial meningitis due to the spinal defect. Leak of cerebrospinal fluid (CSF) leak is commonly observed. The major indication for early operative repair (within 48h of delivery) is prevention of infection. Although protection of the exposed neural tissue from trauma and drying is essential, the neurological deficit caused by MMC is fixed and rarely improves following repair. Deterioration, however, can occur.

DIAGNOSIS AND PRE-OPERATIVE MANAGEMENT: •Currently, MMC is usually diagnosed prenatally by ultrasound during the second

trimester. Positive screening for maternal serum alpha-fetoprotein may also prompt a fetal ultrasound. A select group of patients are being evaluated for inclusion in a randomized trial between conventional post-natal MMC repair and fetal surgery. Document if the mother is a participant in the clinical trial and, if she is, whether the fetus had prenatal repair and whether the procedure was associated with any complications. Contact the Nurses at the Fetal Treatment Center (476-0445) of the expected delivery; they will inform you whether the mother is in the clinical trial.

•Notify Neurosurgery of the expected delivery. •Pediatric team should be present for delivery, which will almost always be by cesarean

section. •Use sterile non-latex gloves. •After birth, position infant on side or on abdomen. Resuscitate as needed. Although

all MMC patients have a Chiari II malformation (hindbrain herniation) visualized on MR imaging, only a minority will be symptomatic at birth. This may consist of stridor and upper airway obstruction.

•If infant did not undergo prenatal repair of MMC: -Carefully examine MMC to estimate the anatomic level of lesion and whether sac

is intact. A small amount of CSF usually ‘weeps’ from the translucent edges of the neural placode. If the sac ruptures, it usually decompresses and drops to the level of the back.

-Using sterile technique, cover lesion with sterile Telfa™ dressing soaked in bacitracin (50,000 units/ 1,000 mL of 0.9% NaCl) and apply transparent dressing (Do not use Silvadene™, Betadine™, or other anti-infective agents).

-Once the dressing is in place and if repair is planned within 24-48h, do not change dressing unless it is soiled. If closure is delayed greater than 48h, change the dressing bid and keep it moist with bacitracin solution.

-Avoid contamination of site and dressing from stool and urine. •If infant did have prenatal repair of MMC:

-Examine operative site for evidence of breakdown, leakage of CSF, or inflammation.

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-If operative site is well healed, no special wound care is needed. -If there is leakage of CSF, breakdown of site, or evidence of inflammation, cover

lesion with sterile Telfa™ dressing soaked in bacitracin (50,000 units/ 1,000 mL of 0.9% NaCl) and apply transparent dressing.

-Consult with Neurosurgery and Pediatric Surgery regarding possible need for further surgery and/or special treatment.

•Perform a careful neurological examination to determine the levels of the sensory and

motor defects. Note the presence of any orthopedic deformities such as clubfeet. •Measure the head circumference and look carefully for clinical findings of

hydrocephalus. Obtain a baseline head ultrasound. The decision to place a ventricuo-peritoneal shunt is individualized for each patient. In general, symptomatic hydrocephalus, progressive increase in head size, or leakage of CSF from the repaired defect site are indications for shunt placement. Usually a shunt is placed several days after the initial repair, although infrequently this may need to be done at the same time as the repair.

•Keep infant flat and either prone or on side. •Monitor infant closely for signs of meningitis. •Check with Neurosurgery regarding further investigation (e.g., cranial and abdominal

ultrasound, radiograph of spine), timing of surgical repair and whether feedings can be started.

POST-OPERATIVE MANAGEMENT: •After surgical repair, a dry Telfa™ dressing should be applied to the incision daily or

PRN if soiled. Gently clean the incision with sterile normal saline and apply a layer of bacitracin ointment. Place Duoderm™ around the incision and use paper tape to prevent skin breakdown. DO NOT use Tegaderm™ or Opsite™ post-operatively. Observe carefully for signs of wound infection or CSF leak.

•Discuss orders with Neurosurgery regarding positioning of infant, antibiotics, feeding, and timing of post-operative cranial ultrasounds.

•Obtain abdominal and hip ultrasound and request Urology and Orthopedic consults for evaluation of urinary function and associated orthopedic abnormalities.

Prior to discharge, arrange with Neurosurgical Nurse Specialist for patient to be enrolled in Spina Bifida Clinic.


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Fetal Therapy DEFINITION: A therapeutic intervention for the purpose of correcting or treating a fetal anomaly or condition. In almost every case, the fetus is at risk of intrauterine death from the abnormality. INTRODUCTION: UCSF has utilized or pioneered several types of fetal therapy. These interventions are limited to a few specific conditions, where therapy has either proven beneficial or is under investigation. Largely as a result of the Fetal Treatment Program, the perinatal patient population at UCSF (maternal and neonatal) is unique with regard to the number of fetuses and newborns with unusual or rare conditions. These patients are discussed at the weekly multidisciplinary Fetal Treatment Meeting (Tuesday, 1:00 PM). PATIENT SELECTION: For all interventions, mothers are counseled extensively by appropriate specialists (e.g., Pediatric Surgeons, Perinatologists, Neonatologists, Anesthesiologists, Ultrasonographers, Neurosurgeons, Social Workers) with regard to the nature of the condition, possible risks and benefits, alternative treatments, and potential outcomes. The most common conditions for which fetal interventions are considered are:

Erythroblastosis Fetalis: In very severe cases, fetal intrauterine transfusion is performed to treat the hemolytic anemia. For further information, see the section on Hemolytic Disease of the Newborn (P. 121). Congenital Diaphragmatic Hernia (CDH): The major causes of morbidity and mortality with CDH are pulmonary hypoplasia and persistent pulmonary hypertension. In experimental animals, fetal tracheal occlusion stimulates lung growth by lung distension with fetal lung fluid. Although fetal tracheal occlusion is no longer used for most cases of CDH, it is occasionally considered for the most severe cases of CDH for whom survival is <10%. Fetuses with tracheal occlusion must be delivered by EXIT procedure (partial delivery of the fetus, removal of the tracheal occlusion, administration of surfactant and institution of assisted ventilation while the infant is still on placental support). Urinary Tract Obstruction: Complete obstruction of the fetal urinary tract results in severe renal damage as well as pulmonary hypoplasia from severe oligohydramnios. Despite early enthusiasm for fetal decompression of the urinary tract, fetal intervention has seldom been beneficial and is now rarely performed. Fetal Tumors Causing Hydrops Fetalis: When the relatively rare fetal tumors, congenital cystic adenomatoid malformation of the lung (CCAM) and sacrococcygeal tumor (SCT), are associated with hydrops fetalis, fetal mortality approaches 100%. These tumors cause hydrops by either venous obstruction due to

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mediastinal shift (CCAM) or high output heart failure (SCT). Operative removal of these tumors has resulted in survival of ~50% of the affected fetuses. Twin-Twin Transfusion Syndrome (TTTS): Monochorionic twins have a high frequency of placental vascular shunts that may lead to one twin (donor) over-perfusing the other (recipient). Complications include oligohydramnios and growth retardation (donor), polyhydramnios and hydrops fetalis (recipient), and fetal death. Currently, UCSF is participating in an NIH sponsored multi-center controlled trial of fetal intervention (amnio-reduction, obliteration of shunt vessels). Meningomyelocele (MMC): Currently, UCSF is participating (with Children’s Hospital of Philadelphia and Vanderbilt University) in an NIH-sponsored multi-center controlled trial of fetal repair of MMC. This trial is notable because fetal repair of MMC is the first fetal intervention for a condition that is not life-threatening to the fetus. The primary outcome variable is the need for ventriculo-peritoneal shunt as treatment for hydrocephalus, which occurs in approximately 80% of infants after post-natal repair of MMC. Other Conditions: It is likely that other conditions will become subjects of attempted fetal correction or treatment. Currently, consideration is being given to fetal intervention for certain cases of hypoplastic left heart syndrome.

NEONATAL CARE: A still unsolved complication of most fetal interventions is premature birth. The degree of prematurity varies with the condition, the type of fetal intervention, and the gestation at which it was performed. In some cases (e.g., TTTS), no specific neonatal care is needed other than care of the premature infant. In other cases (e.g., CDH), the infant will require intensive and complex resuscitation necessitating a large neonatal team.


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Hydrops Fetalis INTRODUCTION: Hydrops fetalis is an excess accumulation of fluid in the fetus. Depending on the severity and cause of hydrops, there may be edema of fetus and placenta, ascites, pleural effusions and/or pericardial effusions. In previous years, most cases of hydrops were caused by severe erythroblastosis fetalis secondary to Rh iso-immunization (see Hemolytic Disease of the Newborn, P. 121). With the marked decrease in this condition (due to prophylaxis with immune globulin), most cases of hydrops fetalis are now caused by other conditions and are known as non-immune hydrops. The rest of this section deals only with non-immune hydrops fetalis. ETIOLOGY: Non-immune hydrops fetalis can be caused by a wide variety of factors. A list of the more common causes is shown in Table 1. In approximately 1/4 of all cases, the cause is not determined. MANAGEMENT: 1. Antenatal management should be directed towards making a diagnosis, with the aim of identifying those in whom either prenatal or immediate post-natal intervention may be effective. Diagnostic techniques include fetal ultrasonography, fetal echocardiography, examination of maternal blood for fetal erythrocytes (Kleihauer-Betke test), amniocentesis and sampling of fetal blood. In some cases, fetal intervention is effective (e.g., fetal transfusion for anemia due to Parvovirus B19 infection, treatment of fetal tachycardia). In others, delivery corrects the underlying problem (e.g., chorioangioma of placenta). Very few hydropic infants survive if delivered before 30 weeks of gestation. 2. Postnatal treatment includes

A. Vigorous resuscitation with interventions (e.g., thoracentesis, paracentesis) to remove excess fluid (see Resuscitation of hydropic infants, P. 6).

B. Treatment of asphyxia, which is common in these infants. C. Diagnosis of cause of hydrops, both for management of the patient and counseling

of the parents regarding risk of recurrence in future pregnancies. This may require extensive diagnostic interventions, including careful post-mortem examination, skin sample for karyotyping and full body radiographs in those who do not survive.

D. Treatment of underlying cause

OUTCOME: Approximately 50% of fetuses with non-immune hydrops fetalis die in utero, and about half of the liveborn infants survive. As can be seen from the table, survival and long term outcome are dependent upon the underlying condition.

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Table 1. Conditions associated with non-immune hydrops fetalis. (Adapted from Phibbs RH: Non-immune hydrops fetalis. In Rudolph’s Pediatrics, 20th Edition, AM Rudolph, JIE Hoffman, and CD Rudolph, Eds., Appleton & Lange, Stamford, CT, 1996, p. 256) ________________________________________________________________________ Hemolytic anemia

-α-thalssemia -RBC enzyme deficiencies

Other anemias -Feto-maternal hemorrhage -Twin-twin transfusion (donor)

Cardiac -Fetal arrhythmias -Premature closure of foramen ovale -Hypoplastic left heart -Hypoplastic right heart -Ebstein’s anomaly of tricuspid valve -Cardiomyopathy -Cardiac tumors -Premature closure of ductus

arteriosus -Other structural anomalies

Chromosomal abnormalities -Trisomy 21, 18 -Turner syndrome

Infections -Viral (Parvovirus B19, Herpes,

CMV) -Toxoplasmosis -Syphilis -Chagas Disease

Vascular malformations -Chorioangioma (placenta, umbilical

vessels) -Liver hemangioma -Cerebral A-V malformation -Sacrococcygeal teratoma -Klippel-Trenaunay syndrome

Vascular accidents -Intracranial hemorrhage -Thrombosis of renal veins, IVC -Twin-twin transfusion (recipient)

Lymphatic malformations

-Pulmonary lymphangiectasis -Cystic hygroma -Multiple pterygium syndrome -Noonan syndrome

Chest masses -Cystic adenomatoid malformation -Diaphragmatic hernia -Pulmonary sequestration -Intrathoracic mass

Skeletal conditions -Asphyxiating thoracic dystrophy -Osteogenesis imperfecta -Chondrodysplasia

Genetic metabolic disease -Gaucher Disease -Mucopolysaccharidosis -Nieman-Pick Disease -Neonatal hemochromatosis

Fetal Hypomobility -Arthrogryposis -Neu-Laxova syndrome -Pena-Shokier syndrome -Myotonic dystrophy

CNS anomalies -Absent corpus callosum -Encephalocele -Holoprosencephaly

Other -Bowel obstruction with perforation

(meconium peritonitis, volvulus) -Infant of diabetic mother -Prune belly syndrome -Congenital nephrosis -Maternal indomethacin therapy


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Multiple Births INTRODUCTION: Multiple gestations are high-risk pregnancies. The rate of monozygotic (MZ) twins is relatively constant at 3-5/1000 deliveries, whereas the dizygotic (DZ) twinning rate varies from 4-50/1000 deliveries and is influenced by race, heredity, maternal age, parity and nutrition. The incidence of multiple births is increasing, partly due to older maternal age and use of assisted reproductive technology. ZYGOSITY and PLACENTATION: MZ twins result when a single ovum is fertilized and subsequently divides into two embryos. The placenta-membrane relationship, determined by timing of the division (Table 1), may be dichorionic-diamnionic (di-di), monochorionic-diamnionic (mono-di), or monochorionic-monoamnionic (mono-mono). Conjoined twins are very rare and occur when the embryo incompletely divides after the 13th day of fertilization. DZ twins develop from two fertilized ova and the placenta is always di-di. Higher-order fetuses may be either MZ or multizygotic. The perinatal mortality rate is closely related to type of placentation (Table) with mono-mono twins at highest risk. Zygosity can be determined for most twins by placentation, gender and blood type. Immunologic studies or DNA analyses can prove zygosity. Table. Zygosity and placentation. Timing of Percent Vascular Perinatal Zygosity division Placentation of twins shunts mortality MZ first 3d di-di 10% very rare low 4th-8th d mono-di 22% very common higher 9th-13th d mono-mono 1% very common highest DZ 2 fertilized ova di-di 66% very rare lowest Note: Di-di placenta can develop with either DZ or MZ. MANAGEMENT: Early diagnosis and close follow-up are critical in multiple pregnancies. Early signs include increased uterus size for dates, multiple fetal heartbeats and elevated maternal serum alpha-fetoprotein levels. Ultrosonography can confirm the diagnosis, determine the type of placentation and identify anomalies and complications. COMPLICATIONS: Multiple pregnancies have increased incidences of preterm delivery, intrauterine growth restriction (after 29 weeks in twins, 27 weeks in triplets), congenital anomalies (MZ>DZ), polyhydramnios, oligohyramnios, cord accidents, fetal demise, malpresentation and birth asphyxia. A unique risk in multiple pregnancies, the twin-twin transfusion syndrome (TTTS) results from vascular anastomoses between circulations of MZ twins, or very rarely in fused dichorionic placentas. The clinical presentation varies with types of anastomoses (A-A, A-V and V-V) and degree and time course of transfusion. Ongoing transfusions from early gestation via A-V shunts leads to the classic TTTS. The donor exhibits anemia, growth retardation and oligohydramnios. The recipient develops hypervolemia, polycythemia, increased growth, polyhydramnios and cardiac hypertrophy. Hydrops fetalis may develop in either twin. Recent transfusion

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leads to anemia in the donor and polycythemia in recipient. Acute and massive shift of blood may occur via A-A or V-V anastomoses when perfusion pressures become unbalanced at birth or after demise of one fetus. Demise of one twin places the survivor at risk for exsanguination, acute hypotension and embolization (which may lead to CNS lesions), limb amputation, intestinal atresia and gastroschisis. TTTS complicates 5-15% of all monochorionic twins and has 80-100% mortality without treatment and a 15-50% risk of handicap in survivors. Significant growth discordance (>25% disparity in weights) increases perinatal mortality. In severe cases, the SGA fetus is compacted into a small, oligohydramniotic sac, and is referred to as a “stuck twin,” in whom pulmonary hypoplasia is common. Cord entanglement and knotting are frequent in mono-mono twins, which accounts for their high mortality rate (50-60%). Diagnosis of TTTS is suggested when monochorionic twins show a hemoglobin difference of >5 gm/dL. Vascular communications can be demonstrated during pregnancy by ultrasonography or by examination of placenta at birth. Currently, UCSF is participating in a multi-center trial of obstetrical intervention for TTTS (see section on Fetal Therapy, P. 166). PEDIATRIC MANAGEMENT of MULTIPLE BIRTHS: -Obtain information needed for preparing for resuscitation including number of fetuses,

gestational age, estimated fetal weights, type of placentation, presence of anomalies and complications (e.g., TTTS, hydrops, stuck twin).

-A pediatric team with personnel assigned to each infant should attend the delivery and be prepared to resuscitate infants with asphyxia (the 2nd born twin is at greater risk for asphyxia) and other identified complications and anomalies.

-Examine infants for signs of prematurity, growth retardation and anomalies. Rapidly measure chem strip and hematocrit and begin appropriate therapy.

-If TTTS is suspected, have whole blood or PRBCs cross-matched against the mother available in resuscitation room. Measure arterial and central venous pressures and arterial pH and blood gas tensions immediately after initial resuscitation to assess the circulatory status. If polycythemia is present, reduce hematocrit (see Polycythemia, P. 112). Management of the anemic donor is less straightforward. Recent acute blood loss requires the same management as other hypovolemic infants (see Neonatal Shock, P. 101). The donor with prolonged, severe anemia may not tolerate blood volume expansion. In this case, perform partial exchange transfusion with PRBCs to raise hematocrit (see section on Neonatal Anemia, P. 108).

OUTCOME: Perinatal mortality and morbidity for twins are five times higher than for singletons. Prematurity, low birth weight and TTTS are the major contributors. Higher-order multiples deliver earlier and, therefore, are at even greater risks. Twins, especially MZ, have higher incidences of cerebral palsy and mental retardation.


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Perinatal Substance Abuse BACKGROUND: Approximately 11% of infants are exposed to alcohol and/or illicit drugs before delivery. Major maternal substances of abuse that affect newborns are opiates, cocaine, amphetamines, alcohol and tobacco. These substances can have serious adverse neonatal and long term effects. SCREENING AND INTERVENTION: A history of drug and alcohol use should be obtained at initial contact with every pregnant patient and when taking a newborn history. With a positive history, intervention should begin immediately with counseling on risk reduction and referrals for social services and for treatment programs. Drug screening of the mother cannot be done without her consent and screening of the infant should never occur without the mother being informed of the testing and reasons for the testing. The screening protocol shown below is based on high-risk behavior associated with perinatal drug abuse. Screening should always ensure the right of privacy of the mother and still allow physicians to optimize medical care to both mother and infant. The primary focus should be to ensure that interventions are designed to foster the health of both patients. • Every infant born to a substance abuser should be evaluated for HIV infection. URINE TOXICOLOGY SCREENING is recommended for the following infants:

-Maternal history of drug abuse (past or current), participation in methadone program -Maternal evidence of drug use (track marks, altered mental status) -History of a partner using drugs -History of previous children removed from the home -Maternal homelessness, prostitution or history of psychiatric illness -Maternal history of incarceration -No prenatal care, inadequate prenatal care, late onset of prenatal care -Neonatal signs consistent with drug effects

EFFECTS OF MATERNAL DRUGS: A. Opiates: Perinatal complications associated with opiate use include:

-Spontaneous abortions -Placental abruption -Chorioamnionitis -Fetal distress -Preterm labor and delivery (~25-40%) -Cesarean section -Perinatal infections (e.g., syphilis, HIV) -Intrauterine growth retardation -Perinatal asphyxia -Drug withdrawal syndrome

1. Clinical signs associated with neonatal withdrawal from opiates include:

Central Nervous System Dysfunction -Jitteriness, tremulousness -Hypertonicity, hyperactive reflexes -Sleep disturbance -Seizures -Irritability -Excessive crying Autonomic Dysfunction -Sweating -Mottling -Temperature instability (hyperthermia) -Hypertension

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Respiratory -Apnea -Tachypnea -Yawning Gastrointestinal -Ineffective feeding -Excessive sucking -Diarrhea -Hyperphagia Note: During withdrawal from maternal methadone, symptoms may be later in onset

(several days) and may last weeks.

2. Medical Management of opiate withdrawal: The goal is to maintain infant comfort and enable the infant to feed, sleep, and gain weight appropriately. Withdrawal scoring systems are used to assess severity of withdrawal and to help guide treatment. Management combines behavioral and soothing methods with pharmacologic interventions when necessary. • Behavioral & soothing: swaddling, rocking and reduced environmental stimulation • The mainstay of pharmacologic treatment for opiate withdrawal is treatment with

opiates, either alone or in combination with other medications. Medications used are dilute tincture of opium (DTO), phenobarbital, and benzodiazepines. Dosage is titrated according to severity of withdrawal using a scoring system. -DTO: Usual starting dose is 0.1 mL/kg PO q3-4h. Increase dose by 0.05 to 0.1

mL increments until symptoms are controlled. Usual dose for withdrawal at birth ranges from 0.2 to 0.5 mL q3-4h. Higher doses may be necessary to control significant physiologic signs including diarrhea, pyrexia, hypertension and hypertonicity.

-Phenobarbital does not adequately treat diarrhea and seizures and should not be used as the sole treatment for withdrawal.

-Diazepam can be a useful adjuvant drug but should not be used as the sole medication. Usual dose is 0.1 mg/kg PO q6h prn to decrease irritability and increase infant comfort.

3. Weaning of treatment medication: Once DTO has been titrated to a level that

controls the symptoms of drug withdrawal, a judicious weaning of medication should begin. A common method is to decrease the dose of DTO by 10% (every day or every 2 days), with continued surveillance of the infant for tolerance of this decrease. The goal of weaning the medication is to allow the infant to acclimate to the lower dose while assuring that the infant is consolable and is able to sleep, eat, and gain weight appropriately. Objective measurements using a drug withdrawal scoring system should be used to evaluate the rate and success of weaning of the medication.

B. Cocaine increases maternal arterial blood pressure, decreases uterine blood flow, and transiently increases fetal systemic blood pressure. Perinatal complications associated with cocaine use include:

-Spontaneous abortion and stillbirths -Placental abruption -Preterm labor and delivery -Intrauterine growth retardation -Fetal hypoxemia and distress -Fetal vascular accidents

Cocaine-exposed infants manifest neurobehavioral abnormalities initially described as drug withdrawal, but are more likely due to acute intoxication, including:


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-Hypertonicity, irritability, tremors -Tachycardia -Abnormal cry, sleep and feeding patterns - Tachypnea, apnea

Medical management usually involves only behavioral and soothing methods. Signs are present at birth or at a few days of life, and decrease as cocaine and its metabolite, benzoylecgonine, are cleared. C. Alcohol: Incidence of fetal alcohol syndrome (FAS) in the United States ranges from 2-5/1,000 live births and is highest among women who report “heavy” drinking. Accurate incidence and prevalence rates of FAS are difficult to obtain because the diagnosis is often missed in the neonatal period; most cases are diagnosed after the age of 6 years. Diagnosis of FAS is by history and physical examination. There are no laboratory tests to identify or quantify alcohol exposure. FAS has three main features:

-Growth retardation (prenatal and postnatal) -Facial features:

•Short palpebral fissures •Midface hypoplasia •Flat, broad nasal bridge •Broad philtrum •Thin vermillion border • Low set, dysplastic ears •Ptosis •Strabismus

-CNS abnormailities: •Microcephaly • Neurosensory hearing loss •Dysgenesis of corpus callosum •Hypoplasia of basal ganglia and cerebellum •Hypotonia •Feeding difficulties

Long term problems include: attention-deficit hyperactivity disorder, speech and behavioral problems and learning disabilities. D. Amphetamines, like cocaine, cause sympathomimetic effects in the mother and fetus. Signs in the newborn are similar to those for cocaine exposed infants. In some cases, there may be increased metabolic rate with very large insensible water loss. Perinatal complications associated with use of amphetamines include:

-Preterm labor and delivery -Intrauterine growth retardation -Intracranial hemorrhage -Strokes

E. Cigarettes and Nicotine are the drugs most often used during pregnancy. Nineteen percent of pregnant women between ages 15 to 44 years smoke. Perinatal complications occur in a dose-dependent fashion. Cigarette smoking represents the most influential, identifiable and common factor adversely affecting perinatal outcomes. Maternal smoking increases risk for:

-Spontaneous abortion and stillbirth -Placental abruption -Fetal growth retardation -Prematurity -Sudden Infant Death Syndrome (SIDS) -Asthma and otitis media during infancy

Nicotine concentrates in fetal blood, amniotic fluid and breast milk. Nicotine in fetal blood and amniotic fluid may exceed maternal concentrations. The mechanism of adverse effect on pregnancy is unknown but possibilities include decreased uterine blood flow, increased fetal carbon monoxide, fetal hypoxemia, disturbed protein metabolism and effects from other toxic substances in cigarette smoke.


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BREAST-FEEDING AND DRUG EXPOSURE A. Cocaine, methadone, amphetamines, alcohol, cigarettes, and PCP (phencyclidine hydrochloride) all cross into breast milk. Because of drug toxicity and associated infections, breast-feeding should be discouraged for women who abuse these drugs. B. Alcohol intake is not a contraindication to breast-feeding, but excessive maternal alcohol intake during nursing may be deleterious for the infant and should be avoided. C. Smoking in the postnatal period is associated with measurable levels of nicotine and cotinine in breast milk. The risk for SIDS is increased in infants exposed either to ante-natal or post-natal maternal smoking. Smoking should be discouraged throughout the perinatal period. D. Methadone Treatment Program: While not recommended by the American Academy of Pediatrics Committee on Drugs (1994), some methadone programs allow breastfeeding. Methadone is excreted in small quantities in breast milk regardless of the daily dose. Breastfeeding may be allowed if there is close supervision with regard to degree of maternal participation in the methadone program, evidence of abstinence from illicit drug use, and negative maternal HIV status.


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Renal Disorders in the Newborn EPIDEMIOLOGY: Renal disorders are a heterogeneous group of congenital and acquired conditions. Anomalies are detected in ~1% of fetuses by prenatal ultrasound, in <1% of newborns by physical examination and in 7-9% of individuals at autopsy. Factors that increase the risk of renal anomalies are maternal diabetes and maternal drug use, including alcohol. Early diagnosis of abnormalities of renal structure or function may help prevent complications including hypertension, obstructive or reflux uropathy, infections and renal failure. PRENATAL DIAGNOSIS OF RENAL DISEASE is usually by fetal ultrasonograms that detect signs of obstructive uropathy. Fetal hydrops may occur with congenital nephrotic syndrome. Oligohydramnios occurs with severe urinary tract obstruction or renal agenesis, which is associated with pulmonary hypoplasia (Potter’s syndrome). CLINICAL MANIFESTATIONS of renal disease vary with the type and severity of abnormality. Certain findings are indicative or suggestive of renal disease:

•Potter’s syndrome (renal agenesis and pulmonary hypoplasia) is a fatal condition that has typical physical abnormalities: flat nose, low set ears, receding chin, arthrogryposis and, often, a bell-shaped chest. With prolonged oligohydramnios due to other causes (e.g., obstructive uropathy, prolonged rupture of fetal membranes), the infant may show similar physical features and the severity of pulmonary hypoplasia varies from absent to severe, depending on duration and severity of oligohydramnios.

•Dysmorphic features suggestive of renal disease include abnormal ears, single umbilical artery, hypospadius, anorectal abnormalities, polythelia (supernumerary nipples), vertebral anomalies and esophageal atresia (with or without tracheo-esophageal fistula).

•Lateral abdominal mass: polycytic or multicystic kidneys, hydronephrosis, tumor (Wilm’s)

•Ascites (urinary) due to rupture of obstructed urinary tract •Suprapubic mass may be an enlarged bladder secondary to urethral obstruction •Abdominal wall defects: exstrophy of bladder, cloacal exstrophy, “prune belly”

(absence of abdominal wall muscle due to fetal urinary ascites) •Failure to palpate kidney: unilateral renal agenesis, renal malposition, horseshoe

kidney •Hypertension is frequently due to renal disease. The commonest cause of neonatal

hypertension is renovascular disease secondary to clots or emboli from a “high” umbilical arterial catheter.

•Anuria or oliguria: However, only 90% of normal infants urinate in the first 24 hours after birth; therefore, 10% of normal infants do not urinate on the first day.

The presence of any of the above signs should alert one to the possibility of renal dysfunction and raise the possibility of further diagnostic work-up including, in addition to careful measurement of intake and urine output, serum creatinine, BUN and electrolytes, abdominal ultrasound.

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ACUTE RENAL FAILURE (ARF) , defined as a serum creatinine >1.5 mg/dL, occurs in 6-23% of ICN patients and is described as either oliguric ARF (urine output <1 mL/kg/hr) or non-oliguric ARF (urine output is maintained despite decreased glomerular and tubular function). There are three categories of ARF:

•Functional (Prerenal): due to ↓ renal perfusion, not the kidney itself •Intrinsic (Renal): usually renal tubular dysfunction.caused by an acute insult •Obstructive (Postrenal): due to anatomic urinary tract obstruction

1. Findings in ARF: A. Clinical signs associated with ARF include:

•Oliguria or anuria •Hematuria, proteinuria •Fluid overload •Hypertension •Cardiac dysrhythmias (with ↑ K+)

B. Laboratory findings in ARF include: •Creatinine > 1.5 mg/dL (An elevated creatinine on the first post-natal day is more

likely due to elevated maternal creatinine or increased production of creatinine from tissue breakdown.)

•Abnormal electrolytes (especially, ↑ K+) •↑ BUN

C. Initial Evaluation of ARF: •Careful perinatal & neonatal history •Physical examination for signs suggestive of renal disease (see above) •Abdominal ultrasound •Laboratory tests:

-Serum: electrolytes, BUN, creatinine, CBC, pH and blood gas tensions -Urine: pH, urinalysis, culture, gram stain Na+, K+, Cl-, osmolality

D. Diagnostic Indices in ARF (useful in determining type of ARF):

Findings in Test Pre-Renal ARF Renal ARF Urine osmolality (mmol/L) >400 <400 Urine Na+ (mEq/L) 31 ± 19 63 ± 35 Urine/Plasma Creatinine 29 ± 16 10 ± 4 Fractional excretion of sodium <2.5 >2.5

(FENa, %) [Urine Na+] [Serum Creatinine] x 100 [Serum Na+] [Urine Creatinine]

2. Causes of ARF:

A. Functional Renal Failure, the commonest type, is characterized by inadequate renal perfusion, and is often called prerenal azotemia. Causes are any conditions that lead to inadequate renal perfusion (e.g., dehydration, hypovolemia, shock, myocardial failure, patent ductus arteriosus). Treatment is correction of the underlying cause and supportive care.

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B. Intrinsic Renal Failure: The most common cause is acute tubular necrosis (ATN) resulting in renal tubular dysfunction. ATN may be precipitated by shock, prolonged prerenal state, or nephrotoxic drugs. Oliguria or anuria is prominent. With recovery, there may by polyuria with dehydration and electrolyte disorders. Treatment includes:

•Strict I & O (urinary catheter) •At onset, consider fluid challenge (10-20 mL/kg) to R/O functional ARF •If no response to fluid challenge, restrict intake to insensible water loss and

urine output. •Consider one dose of furosemide •Consider low dose dopamine (2-4 mcg/kg/min) to ↑ renal blood flow •Restrict intake of K+ and PO4 •D/C any nephrotoxic drugs •Obtain Nephrology Consult •Dialysis as needed

C. Obstructive Renal Failure is due to bilateral urinary tract obstruction (in males usually posterior urethral valves). Obstruction in fetal life can result in cystic dysplasia of the kidney. Treatment consists of diagnosis and relief of the obstruction and careful supportive care. With relief of obstruction, there may be polyuria with electrolyte disorders. Infection is common and patients receive urinary antibiotic prophylaxis.

OTHER NEONATAL RENAL DISORDERS: 1. Renal tubular acidosis (RTA), caused by defects in reabsorption of HCO3- and secretion of H+ ions, generally presents metabolic acidosis and inappropriately high urine pH (>6.0). This occurs frequently in preterm infants and is transient. RTA can also be associated with a wide variety of other conditions.

2. Syndrome of Inappropriate Secretion of Antidiuretic Hormone (SIADH) is a very infrequent disorder of fluid and electrolyte balance due to excessive release of antidiuretic hormone leading to water retention and hyponatremia. Findings include oliguria, low serum osmolality, hyponatremia, concentrated urine and elevated urine sodium. Treatment is strict restriction of fluid intake.

3. Renal Cystic Disease: There are two types:

A. Autosomal recessive polycystic kidney disease presents with abdominal masses, hypertension, renal insufficiency, hepatic and biliary fibrosis and there may be pulmonary failure from lung hypoplasia.

B. Autosomal dominant polycytic kidney disease usually has its onset in the 3rd to 5th decade of life. In some newborns, it can present with bilateral flank masses, hypertension, renal insufficiency and cystic involvement of other organs.

4. Congenital nephrotic syndrome may be secondary to congenital infections, but most commonly is Finnish-type congenital nephrotic syndrome, an autosomal recessive disease. These infants present with proteinuria that may be severe enough to cause fetal hydrops.


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Neonatal Clinical Physiology Laboratory The Neonatal Clinical Physiology Laboratory (NCPL) is a “point-of-care” facility located in the Intensive Care Nursery. The staff of the NCPL provides the following services on a 24h, 7d basis to the patients in the Intensive Care Nursery: Blood Tests:

•pH and blood gas tension measurements -for patients in ICN* -at intensive resuscitations (“set-ups”) in the Neonatal Resuscitation Room in

the Obstetrical Delivery Suite -on umbilical arterial and venous blood from doubly-clamped segment of

umbilical cord for all infants born at UCSF •Electrolytes (Na+, K+, Cl-, and ionized Ca++)* •Hematocrit (Hct, spun) •Hemoximetry (oxyhemoglobin saturation, total Hgb, Met-Hgb and CO-Hgb) •Activated clotting time (ACT, for ECMO patients only)

*Results for these tests are reported to the infant’s bedside Nurse within 15 min after the sample is obtained.

Other Tests: •Neonatal pulmonary function testing (pulmonary mechanics only). Ask the

Neonatology Fellow to request this test. •Neonatal hearing screening: This is done prior to discharge on all ICN and Well

Baby Nursery infants. Results are reported in the infant’s chart. Other services: The staff of the NCPL also is responsible for:

•Pulse oximetry monitoring •Transcutaneous CO2 monitoring •Maintaining the ICN Database and the Obstetrical Database

For any questions about the NCPL, contact Mr. Gene Qin, Supervisor of the NCPL, or Ms. Mureen Schlueter, Manager of the NCPL. NCPL phone: 353-1755

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