04/08/23 1

Post -resuscitation management of an asphyxiated neonate

DR MOHD MAGHAYREH

PRTH

04/08/23 2

Hypoxic-Ischemic Encephalopathy

Definition : The World Health Organization has defined

birth asphyxia as “failure to initiate and sustain breathing at birth” and based on Apgar score as an Apgar score of <7 at one minute of life.

04/08/23 3

INCIDENCE

1 -1.5% of live births It is inversely related to gestational age

and birth weight It occur in (o.5%(of live born infants with

gestational age >36wk It account for 20% of perinatal deaths

04/08/23 4

Risk factors

1. Ante partum events (20%)1. Maternal:

1. cardiac problem,2. hemorrhage, 3. diabetes 4. pre eclamptic toxemia,

2. fetal: IUGR, congenital anomalies2. Intrapartum events (35%)

1. birth trauma, 2. abruption,3. uterine rupture,4. uteroplacental insufficiency

3. Ante partum and Intrapartum (35%)4. Postpartum events (10%)

1. apnea, 2. bradycardia,3. septic shock,4. pulmonary disease, 5. some CHD (LVOT obstr), PDA (premie

04/08/23 5

Mechanisms of asphyxia during labor, delivery, and the immediate postpartum period

1. Interruption of the umbilical circulation (cord compression).

2. Inadequate perfusion of the maternal side of the placenta (maternal hypotension, hypertension, abnormal uterine contractions).

3. Impaired maternal oxygenation (cardiopulmonary disease, anemia).

4. Altered placental gas exchange (placental abruption, previa, insufficiency).

5. Failure of the neonate to accomplish lung inflation and successful transition from fetal to neonatal cardiopulmonary circulation

04/08/23 6

The essential criteria for diagnosing perinatal asphyxia as outlined by ACOG & AAP are

1. Prolonged metabolic or mixed acidemia (pH < 7.00) on an umbilical cord arterial blood sample

2. Persistence of an Apgar score of 0-3 for > 5 minutes

3. Clinical neurological manifestations e.g. seizure, hypotonia, coma or hypoxic-ischaemic encephalopathy in the immediate neonatal period

4. Evidence of multiorgan system dysfunction in the immediate neonatal periods

04/08/23 7

Perinatal asphyxia PATHOPHYSIOLOGY

1. Insult to the fetus / newborn

Lack of oxygen - hypoxia &/or Lack of perfusion – ischemia

2. Effect of ischemia & hypoxia Both contribute to tissue injury.

04/08/23 8

CARDIOVASCULAR RESPONSES TO ASPHYXIA

ASPHYXIA (PaO2, PaCO2, pH)

Redistribution of Cardiac Output

Cerebral, Coronary, AdrenalRenal, Intestinal

Blood Flow Blood Flow

Ongoing Asphyxia

Cerebral Blood Flow

04/08/23 9

CEREBRAL CORTICAL LESIONS

PATHOPHYSIOLOGY

Asphyxia (continues )

Shunting within the brain

Anterior Circulation

Suffers

Posterior Circulation Maintained

04/08/23 10

PATHOLOGY Target organs of perinatal asphyxia

Kidneys 50%

Brain 28 %

Heart 25%

Lung 23%

Liver, Bowel, Bone marrow < 5%

04/08/23 11ROS Release

ISCHEMIA AND REPERFUSION INJURY

Ischemia ATP depletion

Calcium influx

Phospholipase activation

Arachidonic acid release

Prostaglandins Proteases, lipases

VasodilationMicrovascular permeabilityReperfusion

04/08/23 12

At cellular level

Cerebral O2

Substrate supply

Synaptic inactivation (Reversible)

Energy failure

Memb. pump failure

04/08/23 13

Major circulatory changes during asphyxia (summary)

1. Loss of cerebrovascular autoregulation under conditions of Hypercapnia, Hypoxemia, Acidosis

2.Cerebral blood flow (CBF) becomes "pressure passive," leaving the infant at risk for

1. cerebral ischemia with systemic hypotension 2. cerebral hemorrhage with systemic hypertension

04/08/23 14

CONTINUE

3. Increase in CBF secondary to Redistribution of cardiac output. Initial systemic hypertension. Loss of cerebrovascular auto regulation, Focal accumulation of vasodilator factors (H+, K+,

adenosine, and prostaglandins).

4. With prolonged asphyxia, there is a Decrease in cardiac output. Hypotension. Fall in CBF..

04/08/23 15

Neuropathologic findings

A. Cortical changes. Cortical edema, with flattening of cerebral convolutions cortical necrosis cortical atrophy microcephaly.

B. Selective neuronal necrosis is the most common type of injury observed in neonatal HIE.

C. Other findings seen in term infants include : 1-status marmoratus of the basal ganglia and thalamus 2-parasagittal cerebral injury

04/08/23 16

Neuropathologic findings continue

D-Periventricular leukomalacia (PVL)1. It is hypoxic-ischemic necrosis of peri ventricular white matter resulting

from cerebral hypo perfusion and the vulnerability of the oligodendrocyte within th white matter to free radicals, excitotoxin neurotransmitters, and cytokines

1. It is the most significant problem contributing to long-term neurologic deficit in the premature infant, although it does occur in sick full-term infants as well.

3 The incidence of PVL increases with the length of survival and the severity of postnatal cardiorespiratory disturbances

3 - involving the pyramidal tracts usually results in spastic diplegic or quadriplegic CP. Visuoperception deficits may result from involvement of the optic radiation

04/08/23 17

Neuropathologic findings continue

E. Porencephaly, hydrocephalus, hydranencephaly, and multicystic encephalomalacia may follow focal and multifocal ischemic cortical necrosis, PVL, or intraparenchymal hemorrhage.

F. Brainstem damage is seen in the most severe cases of hypoxic-ischemic brain injury and results in permanent respiratory impairment

04/08/23 18

Clinical consequences of perinatal asphyxia

Brain ( Hypoxic Ischemic Encephalopathy, HIE )

1. Altered sensorium

2. Irritability,

3. lethargy,

4. deeply comatose

5. Tone disturbances :hypotonia of proximal girdle muscles (lack of head control & weakness of shoulder muscle in term infants )

04/08/23 19

Clinical consequences of perinatal asphyxia (cont.) Brain ( Hypoxic Ischemic

Encephalopathy,HIE ) Autonomic disturbances eg. hypotension,

increase salivation, abnormal pupillary reflex Altered neonatal reflexes -Moro’s, sucking ,

swallowing Seizures

04/08/23 20

Fetal and neonatal assessment

Fetal Heart rate monitoring1. fetal bradycardia2. repetitive late decelerations of the fetal heart rate,3. low fetal scalp or cord pH

Passage of Meconium Failure to establish spontaneous

respiration low Apgar Scores

1. Hypoxic - Ischemic Encephalopathy 2. Multi organ Involvement

04/08/23 21

Principles of management

Prevent further organ damage Maintain oxygenation, ventilation & perfusion Correct & maintain normal metabolic & acid

base milieu Prompt management of complications

04/08/23 22

Grade 1 (mild)Grade2 (moderate)Grade 3 (severe)

Level of consciousnessIrritable/hyperalertLethargyComa

Muscle toneNormal or hypertoniaHypotoniaFlaccid

Tendon reflexesIncreasedIncreasedDepressed or absent

SeizuresAbsentFrequentFrequent

Complex reflexesNormalweakAbsent

PrognosisGoodVariableHigh mortality and neurologicl disability

Sarnat staging of hypoxic-ischemic encephalopathy.

04/08/23 23

According to Sarnat classification of severity

stage 1 100 % normal

stage 2 80 % normal

stage 3 50 % death 50 % major sequalae

04/08/23 24

Initial management

Admit in nursery,if -Apgar score <3 at 1 minute -Babies requiring intubation chest

compressions or medications Nurse in thermo-neutral temperature to maintain skin

temperature at 36.5oC Secure IV line , fluids 2/3 rd of maintenance Fluid bolus if CRT > 3 secs or blood pressure low Inj vit k Stomach wash

04/08/23 25

Clinical monitoring

HR, RR, colour, CRT, O2 saturation, BP & temperature Assessment of neurologic status

Tone, seizures, consciousness, pupillary size & reaction, sucking, swallowing

Abdominal circumference Urine output

04/08/23 26

Biochemical monitoring

Blood gases & pH Bedside blood sugar by Dextrostix Hematocrit S. electrolytes ( Na, K) S. calcium BUN, creatinine

04/08/23 27

Other investigations

Sepsis screen & blood culture to exclude in- utero or acquired infection during resuscitation

X-ray chest to look for pneumothorax, malformations, cardiac enlargement

04/08/23 28

Computed tomography (CT) scan

First week after an insult :

1. Cortical neuronal injury

2. Edema The value of CT several weeks after severe

asphyxial insults:

1. The assessment of diffuse cortical neuronal injury

2. identification of focal and multiple ischemic brain injury.

04/08/23 29

Ultrasonography is the method of choice for routine screening of the premature brain.

1-intraventricular hemorrhage

2- necrosis of basal ganglia and thalamus.

3- It is superior to CT in identifying both the acute and subacute-chronic manifestations of periventricular white matter injury.

04/08/23 30

Ultrasonography limitations in the first weeks of life include its inability to

1. Reliably identify mild injury

2. Lesions that are peripherally located

3. Distinguish between hemorrhagic and ischemic lesions in the cerebral parenchyma.

04/08/23 31

Magnetic resonance imaging (MRI) is

the technique of choice for evaluation of hypoxic ischemic cerebral injury in term and premature newborns

The advantages of MRI include the following:

1. It does not expose the neonate to radiation.2. better anatomic imaging detail and resolution.3. It clearly demonstrates the myelinization delay that

almost invariably accompanies asphyxial brain injury.

4. MRI may provide insight into the timing and duration of the asphyxial injury..

04/08/23 32

4. MRI is probably the best method available to diagnose hypoxic brain injuries in mildly to moderately affected patients and to detect discrete lesions of the cerebellum and brainstem.

5. It may provide clues to other disorders (eg, metabolic or neurodegenerative disorders) that may also present as obtundation or coma in the newborn period.

Magnetic resonance imaging (MRI)CONTINUE

04/08/23 33

6. Ischemic lesions can be identified as early as 24 h after the insult.

7. MRI can help differentiate between partial asphyxia and anoxia

8. MRI demonstrates the structural sequelae of asphyxial injury on follow-up and has prognostic value.

Repeat MRI at 3 months of age will usually show the full extent of brain injury.

Magnetic resonance imaging (MRI)CONTINUE

04/08/23 34

Evoked electrical potentials

(auditory, visual, or somatosensory) performed within the first hours of life may

help to select infants for treatment with neuroprotective agents.

They also have prognostic value in defining areas of CNS damage

Persistence of deficits beyond the neonatal period correlates with persistence of other signs of brain injury.

04/08/23 35

Potentially useful techniques

1. Magnetic resonance spectroscopy (MRS) provides a measure of "energy reserve." Using phosphorus-/(31P) MRS

It has been shown that asphyxiated newborns tend to have lower phosphocreatine/inorganic phosphate ratios (impaired brain oxidative phosphorylation)

lower ATP/total phosphorus ratios than normal patients.

2. Proton MRS allows noninvasive observations to be made of the derangement of cerebral metabolites (N-acetylaspartate (NAA) and lactic acid) when oxidative phosphorylation is impaired. The normalization of phosphorous metabolite ratios with time may reflect loss of severely affected

neurons. Neuronal loss, gliosis, and delay in myelination would be reflected by a relative loss of NAA.

3. Near-infrared spectroscopy on the first day after injury may demonstrate increased cerebral venous oxygen saturation and decreased cerebral oxygen extraction, despite increased cerebral oxygen delivery, suggestive of a postasphyxial decrease in oxygen utilization

.

04/08/23 36

EEG

1. Evolution of EEG changes may provide information on the severity of the asphyxial injury,

2. The type of EEG abnormality may be indicative of a specific pathologic variety.

3. Identification of EEG abnormalities within the first hours after delivery may be helpful in selecting infants for treatment with neuroprotective agents

04/08/23 37

Aims of specific management

Maintain temperature, perfusion, oxygenation, ventilation & normal metabolic state Temperature 36.5 C – 37.5 C Perfusion:

BP Mean 40-60 mm Hg ( Term) CRT maintain < 3 sec

Oxygen PaO2 60-80mmHg saturation 90-93 %

CO2 35-45 mm of Hg Glucose 70-110 mg/dl Calcium 9-11 mg/dl

04/08/23 38

Specific management

Maintain perfusion Normal blood pressure CRT < 3 secs Normal urine output ( >1ml/kg/hr) Absence of metabolic acidosis

04/08/23 39

Specific management

Maintain perfusion Maintain mean arterial pressure and CRT by

giving slow bolus of crystalloid 10 ml/kg over 20 minutes. Repeat one more time , if still does not improve

Use vasopressors Dopamine and /or Dobutamine to increase BP

Sodium bicarbonate 1-2 ml/kg diluted in 5 % dextrose can be used for babies with documented acidosis after establishing respiration

04/08/23 40

SUBSEQUENT MANAGEMENT

Oxygenation & ventilation Adequate perfusion Normal glucose & calcium Normal hematocrit Treat seizure

Oxygenation & ventilation Adequate perfusion Normal glucose & calcium Normal hematocrit Treat seizure

04/08/23 41

TREATMENT OF SEIZURESTREATMENT OF SEIZURES

Correction of hypoglycemia, hypocalcemia & electrolyte

Prophylactic Phenobarbitone ?

Therapeutic Phenobarbitone 20 mg / kg (loading), 5 mg / kg / d (maintenance)

Lorazepam – 0.05 – 0.1 mg / kg

Diazepam to be avoided

Correction of hypoglycemia, hypocalcemia & electrolyte

Prophylactic Phenobarbitone ?

Therapeutic Phenobarbitone 20 mg / kg (loading), 5 mg / kg / d (maintenance)

Lorazepam – 0.05 – 0.1 mg / kg

Diazepam to be avoided

04/08/23 42

Phenobarbital is the drug of choice.

1. continued until the EEG is normal and there are no clinical seizures for ³2 months.

2. The benefit of prophylactic therapy remains controversial.

3.

04/08/23 43

Potential new therapies should aim at preventing delayed neuronal death

once an asphyxial insult has occurred. It is estimated that there is a 6- to 12-h window of

opportunity after acute asphyxia whereby administration of a neuroprotective agent could reduce or prevent brain damage.

1. Magnesium has an inhibitory effect on excitation of the N-methyl-D- aspartate type of

glutamate receptors competitively blocks Ca2+ entry through voltage-dependent Ca2+

channels during hypoxia SIDE EFFECT

Apnea may occur, and Higher doses carry a significant risk of hypotension. Use of magnesium sulfate (MgSO4) remains controversial.

04/08/23 44

Prevention of free radical formation (CONTINUE)

1. . Xanthine oxidase inhibitor. In a pilot study (Van Bel et al,

1998), allopurinol 1. reduced free radical formation and2. enhanced electrical brain activity in severely asphyxiated

newborns.3. addition, allopurinol reduced nonprotein iron ( prooxidant)

2. Resuscitation with room air. In the Resair 2 trial (Saugstad 2001), room air-resuscitated

1. infants recovered more quickly as assessed by time to first cry, 5-min Apgar score, and sustained pattern of respiration.

2. Neonates resuscitated with 100% oxygen manifest biochemical changes indicative of prolonged oxidative stress at 4 weeks of age (Vento et al, 2001

04/08/23 45

Potential new therapies should aim at preventing delayed neuronal death (CONTINUE)

3. Excitatory amino acid antagonists. 4. Calcium channel blockers. 5. Inhibition of nitric oxide production. Increased

plasma nitric oxide levels has been shown as a marker for severity of brain injury and poor neurologic outcome (Shi et al, 2000).

6. Selective head cooling. Hypothermia is thought to protect the brain from injury by preventing the decline in high-energy phosphates. Phosphocreatine and adenosine triphosphate are maintained

04/08/23 46

Predictors of poor neuro-developmental outcome Failure to establish resp. by 5 minutes Apgar score of 3 or less at 5 minutes Onset of seizures with in 12 hours Abnormal EEG & failure to normalise by 7

days of life Refractory seizures Stage III HIE Inability to establish oral feeds by 1 wk Abnormal neuro-imaging

04/08/23 47

Preventing asphyxia

Perinatal assessment Regular antenatal check ups High risk approach Anticipation of complications during labour Timely intervention ( eg. LSCS)

Perinatal management Timely referral Management of maternal complications

04/08/23 48

04/08/23 49

There is always more to come!

Thank you