Management of Respiratory Distress in

Preterm Infants

Albert Owusu-Ansah, MD, FAAP

Medical Director of NICU

BryanLGH Medical Center

Management of Respiratory Distress in

Preterm Infants

Albert Owusu-Ansah, MD, FAAP

Medical Director of NICU

BryanLGH Medical Center

Objectives

• Identify and interpret signs of respiratory

distress in the newborn

• Differentiate between respiratory and

cardiac causes of cyanosis

• Identify the indications for assisted

ventilation in the neonate

• Discuss recent trends in CPAP use in

infants

Disclosures

• None

Respiratory Distress

• Cause of significant morbidity and mortality

• Indicates abnormal pulmonary function

• Incidence depends on • gestational age, mode of delivery, sex,

maternal diabetes, asphyxia, etc

• Early recognition and appropriate management essential

Respiratory Distress

• Tachypnea- RR>60/min

• Retractions

• Subcostal

• intercostal

• Grunting

• Nasal flaring

• Cyanosis

Retractions

Retractions

Respiratory Distress

Causes

• Pulmonary– Most common cause

• Cardiac- Congenital heart disease

• CNS- Asphyxia, IC bleed

• Other Causes-Hypoglycemia, acidosis, hypervolemia, hyperviscosity (polycythemia), anemia, hypothermia, metabolic acidosis

Respiratory Distress - Ruling out Cardiac Disease

• Differentiating cardiac and respiratory causes of cyanosis is a common clinical problem.

• A hyperoxia test may assist in differentiating between the two.

• Pulse oximetry may help to decide whether a formal hyperoxic test is useful.

• A neonate who exhibits cyanosis without marked respiratory distress and has an O2 saturation of less than 85% in both room air and 100% oxygen likely has an intracardiac shunt.

• If the O2 saturation increases to more than 85% on 100% oxygen, a full hyperoxia test should be performed

Hyperoxia Test

• The test consists of obtaining a baseline right radial (preductal) arterial blood gas measurement with the child breathing room air and repeating the measurement while the infant is receiving 100% O2. A PaO2 measurement greater than 300 mm Hg on 100% oxygen is normal, more than 150 mm Hg suggests pulmonary disease, and 50 to 150 mm Hg suggests cardiac disease (or severe pulmonary hypertension).

• Echocardiography is the definitive investigation.

Respiratory Distress- Pulmonary

Obstructive problems

• Anything obstructing airway from nose to air sacs

• Mucus in nasal cavity

• Misplaced photherapy mask

• Congenital abnormalities of the airway

• Choanal atresia, Pierre Robin Syndrome

• Conditions restricting lung expansion within chest

cavity

• Pneumothorax, diaphragmatic hernia

Respiratory Distress –Pulmonary causes

• Respiratory Distress Syndrome (RDS)

• Pneumonia (Sepsis)

• Meconium Aspiration Syndrome (MAS)

• Transient Tachypnea ofNnewborn (TTN)

• Persistent Pulmonary Hypertension of the Newborn

(PPHN)

Respiratory Distress-Other Causes

• Tracheo-esophageal fistula

• Diaphragmatic hernia

• Congenital Cystic Lung Diseases

• Congenital Cystic Adenomatoid Malformation

• Lobar emphysema

• Pulmonary sequestration

• Bronchogenic cysts

• Lung hypoplasia

History • Good History important

• Gestation

• Antenatal Steroids

• PROM

• Onset of respiratory distress

• Apgar score

• MSAF?

• Feeding problems and relation to respiratory distress

Assessment of respiratory distress

Score * 0 1 2

1. Resp. rate <60 60-80 >80

2. Central None None with Needs

cyanosis 40% FiO2 >40% FiO2

3. Retractions None Mild Severe

4. Grunting None Minimal Obvious

5. Air entry Good Decreased Very poor

* Score > 6 indicates severe distress

Silverman-Anderson Index

Feature Score 0 Score 1 Score 2

Chest Mov’t Equal Respiratory lag See-saw

respiration

Intercostal

retractions

None Minimal Marked

Xiphoid retractions None Minimal Marked

Nasal Flaring None Minimal Marked

Expiratory Grunt None Audible with

stethoscope

Audible without

stethoscope

• Respiratory Distress

Syndrome

• RDS

Respiratory Distress Syndrome RDS

• RDS aka HMD is the major cause of respiratory distress in preterm infants.

• Onset is early and it is progressive.

• RDS is a result of surfactant deficiency, which leads to increase in surface tension in the air-liquid interface of the terminal respiratory units.

Respiratory Distress Syndrome • Surfactant deficiency leads to atelectasis, increases

ventilation perfusion mismatch, and leads to lung injury,

which is mediated by a marked pulmonary inflammatory

response

• In 1950s RDS developed in 14% of infants weighing 1 to 2.5

kg, and 56% of them died.

Clinical features • Risk factors:

• Prematurity

• maternal diabetes, maternal bleeding, perinatal asphyxia,

C-section without labor

• White race, male sex

• Features :

• Early onset, from birth to four hours

• Uncomplicated clinical course with progressive worsening

until day 2-3 and onset of recovery by 72 hours

Gestational age and RDS

Clinical features (contd)

• Physical Examination

• Brief but thorough

• Signs of respiratory distress :

• Cyanosis

• Tachypnea ( >60/min, shallow, rapid )

• Grunting ( delayed expiration maintains FRC )

• Retraction ( Subcostal, substernal, intercostal )

• Flaring ( 50% airway resist in nose& pharynx)

• Temperature, Blood pressure, Skin perfusion

Organisation of the airway

Pharynx

Right primary bronchus

Nose

Nasal cavity

Oral cavity

Larynx

Trachea

Lungs

Terminal Airway

Terminal bronchiole

Alveolar duct

Respiratory bronchioles

Smooth muscle

Alveoli

Perfusion of the alveoli

Capillaries

Terminal bronchiole

Branch of pulmonary artery

Alveolus

Branch of pulmonary vein

Respiratory bronchiole

Alveolar Design

Aqueous layer

Aqueous macrophage

Lamella body (stores surfactant)

Type ll pneumocyte-lining cell (produces surfactant)

Type l Lining cell

Capillary

CO2 O2

Lung Development

• Knowledge of lung development central to

understanding pathophysiology of RDS

Lung development

Embryonic (4-7 weeks)

Pseudoglandular (5-17 weeks)

Canalicular (16-26 weeks)

Alveolar period (36 weeks) – post natal years

Saccular period (24-38 weeks)

Phases of Lung development

Phases of Lung Development

Canicular period

Diameter of airway increases

Primitive alveolus is formed

Type I and Type II cells differentiate

Surfactant production begins

Pulmonary Surfactant

• A complex mixture composed mostly of lipids, 90%

(primarily phospholipids), and about 10% proteins

• Lipid - ~70% is phosphatidylcholine species

• Protein – Four surfactant-specific proteins identified:

SP-A, SP-B, SP-C, SP-D

• SP-A, SP-D: Host defence

• SP-B, SP-C: Facilitates surface absorption and

spreading of lipids

1 2 3 4 5

6

7

DPPC - dipalmitoylphosphatidylcholine

50%* • Reduces alveolar surface tension

PG - phosphatidylglycerol 7%* • Promotes the spreading of surfactant throughout the lungs

Apoproteins or surfactant specific proteins 2%*

1. Serum proteins 8%* 2. Other lipids 5%* 3. Other phospholipids 3%* 4. Phosphatidylinositol 2%* 5. Sphingomyelin 2%* 6. Phosphatidylethanolamine 4%* 7. Unsaturated Phosphatidylcholine 17%* * By molecular weight

Composition

Surfactant: Synthesis and

secretion

• Synthesized within the alveolar type II cells

and stored as lamellar bodies

• Lamellar bodies secreted into alveoli to

contribute to formation of surface film

which reduces surface tension

• Secreted surfactant moves back into type

II cells where it is recycled back into the

cell.

Surfactant Metabolism

TYPE II CELL

Loss from lungs

Choline fatty acids

Lysosomes MVB

Degradation

Endoplasmic reticulum

Golgi Synthesis and secretion

Lamellar bodies

Recycling

Precursors

Reuptake

Catabolic

Anabolic

Alveolar transformations

ALVEOLUS Other losses - Macrophages - Airways - Other lung cells

Surfactant cycle

Pathophysiology of RDS

• Surfactant deficiency leads to:

• Increased surface tension which leads to

instability of the lung at end-expiration, low lung

volume, decreased compliance

• Hypoxemia due to ventilation-perfusion mismatch

due to atelectasis and intrapulmonary and

extrapulmonary shunts

• Lung inflammation and respiratory epithelial injury

leading to pulmonary edema and increased airway

resistance

where:

P = pressure ST = surface tension r = radius of the

bubble

P = 2ST/r

Laplace’s law

P = 2x1 = 0.2

10

P = 2x1 = 0.4

5

10

5

Connected bubbles

Alveoli as bubbles

Pulmonary Function and Gas

Exchange

• Surfactant deficiency leads to:

• Low compliance and low lung volume

(FRC), and increased lung resistance

• Exogenous surfactant prevents or corrects

these pulmonary functional abnormalities

Surfactant Therapy

• Prior to the introduction of exogenous surfactant RDS was

associated with significant morbidity and mortality

• In a large multicenter blinded controlled trial 789 infants (b

wt 600g -1750g) who developed RDS within 6 hours were

randomly assigned to either placebo or surfactant.

Surfactant was associated with significantly lower mortality

rate (18 vs 27 percent) and a lower risk of developing

pulmonary interstitial emphysema (19 vs 39 percent) and

other pulmonary leak complications including

pneumothorax (12 vs 26 percent).

Properties of surfactant

Rapid adsorption

Efficient spreading

Lower surface tension

Stimulus for release

Gas entering lungs

Alveolar stretch (inspiration)

Adrenergic innervation

Prostaglandins

Hypoxemia

• Hypoxemia in RDS due to:

• Mismatch of ventilation and perfusion

with intrapulmonary shunting

• Extrapulmonary shunting across the

foramen ovale and patent ductus

arteriosus

Diagnosis

• Clinical picture

• Preterm, progressive respiratoy distress

soon after birth, increase oxygen

requirement

• Chest X-ray

• Low lung volume and

reticulogranular groung glass

appearance, air bronchograms

Other lab findings

• Blood gas shows hypoxemia

• Hyponatremia may develop from fluid

retention

Management

• Specific RDS management

• Adequate oxygenation, ventilation, and

possible administration of exogenous

surfactant

• General supportive measures

• Optimize the neonates metabolic and

cardiorespiratory status

Specific RDS Management

• Administration of antenatal corticosteroids

• Administration of exogenous surfactant

• Provision of assisted ventilation

Antenatal Corticosteroid Therapy

• Given to pregnant women at risk of preterm labor to

prevent or decrease the severity of neonatal RDS

Surfactant Therapy

• Selection of surfactant preparation

• Indications for surfactant therapy

• Timing of administration

• Technical aspects of administration

Selection of Surfactant

• Types of Surfactant

• Natural

• Synthetic

• Lucinactant: first peptide containing surfactant to

be approved by FDA (March 2012)

Indications and Timing for

Surfactant

• Rescue

• Surfactant given when the diagnosis of RDS is established (based on oxygen requirement (paO2< 80 with FiO2 >0.4), clinical examination, chest radiograph).

• Prophylactic (Early therapy)

• Infants <30 weeks

• Continued therapy • Surfactant administered a total 3 or 4 doses based on

continued oxygen needs and the specific surfactant preparation

Surfactant Administration Techniques

• Endotracheal intubation and instillation

surfactant

• Complicated by transient airway

obstruction

Surfactant deficiency - ―vicious cycle‖

Respiratory acidosis

Severe hypoxia

Further inhibition of surfactant by serum proteins

Epithelial damage occurs through suction effect of gasping

Depleted surfactant

Decreased FRC Increased dead space Alveolar collapse

Reduced compliance

Increased work of breathing

Assisted Ventilation Techniques • Continuous Positive Airway Pressure (CPAP)

• Nasal Intermittent Positive Pressure Ventilation (NIPPV)

• Mechanical Ventilation

• Intubation and mechanical ventilation should still be performed in

infants in respiratory failure, verified by one of the following:

respiratory acidosis (pH <7.2), hypoxemia, severe apnea.

Continuous Positive Airway Pressure (CPAP)

• Several studies have shown benefits

• SUPPORT trial in US

• 1316 ELBW 24 to 26 6/7 weeks, randomized to

CPAP or intubation with survanta. No difference

b/n groups re death or BPD

• COIN trial, Australia

• 610 infants 25 to 28 weeks, CPAP or intubation

with ventilation at 5 minutes of age . No difference

b/n groups re death and need for O2 at 36 weeks

GA

CPAP

• VON trial 648 infants GA 26 to 296/7

weeks, no difference in the primary

outcome of combined death or BPD in

CPAP v intubation and prophylactic

surfactant. Both groups did better than

third group with intubation, prophylactic

surfactant and a period of mechanical

ventilation.

CPAP

• These data demonstrate an initial CPAP-

based approach in which surfactant is not

administered is a reasonable option for

preterm infants without respiratory failure.

• Success of this approach may be

enhanced by early onset of caffeine

therapy to increase respiratory drive

Indications for CPAP

• Hypoxemia is the most universally accepted indication for using cPAP (to maintain paO2 > 50-60mmHg)

• To decrease use of mechanical ventilation

• cPAP has a variable effect on CO2

• Optimum cPAP is that at which SaO2 and PaO2 are optimized without adverse effect on cardiac output

CPAP

• CPAP increases lung vol by

• Increasing alveolar size

• Preventing atelectasis

• Recruiting collapsed alveoli

• Increase lung vol increase oxygenation by improving V-Q mismatch

• Makes breathing slower and more regular while grunting generally ceases

The CPAP delivery system consists of three components:

the circuit for continuous flow of inspired gases, the interface connecting the CPAP circuit to the

infant’s airway, and a method of creating positive pressure in the CPAP circuit.

CPAP Delivery Systems

CPAP Delivery System

Bubble CPAP system

Techniques- Interface

• Nasal prongs

• ET tube

• Face mask

• Nasal mask

Problems with cPAP

• Local

• mucosal necrosis

• Overdistension leading to decreased

venous return, decreased cardiac output

and decreased oxygen transport

Care of babies on CPAP

• Interface care

• Humidification

• Suctioning

• Gastric decompression

• Monitoring

Initiating CPAP

• Start with PEEP of 5 cm H2O pressure, flow

5-10 lpm, FiO2 0.40-0.60

• Increase pressure in steps of 1-2 cm H2O till

8 depending on resp effort and PO2.

Weaning of CPAP

• Wean by decreasing FiO2 in

steps of 0.05 till 0.40, then

wean CPAP in steps of 1-2 cm

H2O till 4-5, then discontinue.

CPAP….Advantages

• Less Invasive than mechanical ventilation

• Less barotrauma

• Early Lung recruitment in RDS

• Helpful in management of Obstructive and

Mixed apnea

CPAP

• Problems:

• High CPAP may decrease venous return

• High CPAP may decrease minute ventilation

• Abdominal distension, open mouth, crying

Disadvantages

• CPAP does not improve ventilation, High pressures may worsen it

• Technically difficult to maintain in large active infants

• Inadequate in severe changes in Pulm Resistance and compliance

• Swallowed air causes elevation of the diaphragm

How is CPAP given…

• CPAP mode on a conventional ventilator

• Manually- anesthesia bag, T- Piece

resuscitator

• CPAP machines

• Bubble CPAP

Nasal Intermittent Positive Pressure

Ventilation

• Augments CPAP by delivering ventilator

breaths via nasal prongs (or nasal mask)

• Metaanalysis from 3 clinical trials suggest

infants treated with NIPPV less likely than

infants treated with CPAP to require

mechanical ventilation at 72 hours

History of Assisted Ventilation

Elisha was come into the house, Behold

the child was dead… he went up and lay

upon the child and put his mouth upon his

mouth …. Stretched himself upon the

child and the flesh of the child waxed

warm

Mechanical Ventilation

• Several modalities:

• Pressure control

• Volume control

• High Frequency Ventilation

• Regardless of choice of ventilator, goal is to use

settings that minimize volutrauma, barotrauma and

oxygen toxicity, thereby reducing the risk of BPD

Complications of Mechanical

Ventilation

• Endotracheal tube complications

• Pulmonary air leak

• Bronchopulmonary Dysplasia

Target oxygen saturation and pCO2 levels

• Oxygen saturation—A range of oxygen

saturation so that bothe hypoxia and the

excess use of oxygen can be avoided.

• paCO2 levels– In preterm infants target 45

to 60mmHg to keep pH above 7.25

Supportive Care

• Thermoregulation

• Fluid management

• Cardiovascular management

• Nutrition

Algorithm for Evaluation of Resp Distress

Prevention of Respiratory Distress

Syndrome

• Since RDS is due to lung immaturity, the

best prevention is to prevent premature

birth. Potential therapies include:

• Cervical cerclage, use of tocolytic

agents, prevention and treatment of

infections

Prevention of RDS

• If premature birth can’t be prevented

• Antenatal corticosteroids to accelerate

fetal lung maturation and surfactant

production

• Use of exogenous surfactant

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