Respiratory Distress Syndrome

Introduction
Definition:
Acute lung disease of the newborn caused by surfactant deficiency.
-The most frequent cause of respiratory distress in premature infants, during the first days
after birth.
- 60-80%of <28wk GA ; 15-30% of 32-36wk GA ; 5% of 37wk-term
- Incidence and severity is inversely proportional to gestational age

Contributing factors
Neonates younger than 33-38 weeks.
Weight less than 2500g
Maternal diabetes
Cesarean delivery without preceding labor
Fetal asphyxia
Second of twins
Factors decrease the risk of RDS
Use of antenatal steroids
Pregnancy-induced or chronic maternal
Hypertension
Prolonged rupture of membranes
Pathogenesis
Lung surfactant deficiency is the primary cause , Pulmonary surfactant synthesis, in type
II pneumocytes begins at 24-28 weeks of gestation, and gradually increases until full
gestation

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Pathology
Gross : Lung firm, red, liverlike
Microscopic : Diffuse atelectasis, pink membrane lining alveoli & alveolar ducts.
Pulmonary arterioles with thick muscular coat,
small lumen. Distended lymphatics
Electron microscopic : Damage / loss of alveolar epithelial cells, swelling of capillary
endothelial cells

clinical features
Risk factors:
Prematurity, maternal diabetes, perinatal asphyxia, C-section
Genetic factor, 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
Physical Examination
Signs of respiratory distress:
Cyanosis
Tachypnea, Grunting , Retraction (Subcostal, substernal, intercostal )
Nasal flaring
-Chest X rays
-ABG

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Bilateral Reticular granular appearance or Ground glass appearance Air bronchogram
Poor lung expansion
Prenatal Diagnosis
History of premature delivery
Concentration of lecithin in amniotic fluids
Ratio of lecithin/sphingomyelin
Lecithin indicate lung maturity
Sphingomyelin remains constant during pregnancy
L/S ratio 2:1 indicate lung maturity
Differential Diagnosis
Pneumonia
Transient tachypnea of the newborn (TTN)
Aspiration syndromes
Congenital anomalies of the lungs (eg, diaphragmatic hernia, lobar emphysema,
bronchogenic cyst

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MANAGEMENT
(i) Prevent hypoxemia and acidosis
(ii) Optimize fluid management
(iii) Reduce metabolic demands
(iv) Prevent worsening atelectasis and pulmonary edema;
(v) Minimize oxidant lung injury
(vi) Minimize lung injury caused by mechanical ventilation
CPAP
Nasal prong CPAP
Indication: Significant respiratory distress, Using CPAP soon after delivery reduces the
number of babies requires ventilation In delivery room for babies at risk of RDS
Babies on low flow oxygen with respiratory Distress
CPAP is initiated at 5-6 cmH2O and increased to a maximum of 7-8 cmH2O
Problems:
High CPAP may decrease venous return
Abdominal distension, Mechanical ventilation
Mechanical ventilation
Mechanical ventilation is indicated in the presence of respiratory acidosis with a PaCO2
>65 mmHg, a PaO2 <50 mmHg or
oxygen saturation <90% with an FiO2 above 0.5 or with the presence of severe frequent
apnea
Surfactant administration
Surfactant prophylaxis
early selective surfactant administration for babies showing signs of RDS .
If the baby needed intubation for stabilization, surfactant should be given .
Supportive therapy
-Temperature regulation: prevent hypothermia.
- Fluids, metabolism, and nutrition: closely monitor and maintain blood glucose,
electrolytes, acid balance, calcium, phosphorous,
-renal function, and hydration.
- Once the infant is stable, intravenous nutrition with amino acids and lipid. After the
respiratory status is stable, initiate small volume gastric feeds (preferably breast milk) via
a tube to initially stimulate gut development
- Circulation and anemia: monitor heart rate, peripheral perfusion, and blood pressure.
Blood or volume expanders may be required

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 - Antibiotics: start antibiotics in all infants who present with respiratory distress at birth
after obtaining blood cultures.
- Discontinue antibiotics after three to five days if blood cultures are negative
Support of parents and family: keep the parents well informed. Encourage parents to
frequently visit and stay with their baby
Complications
Acute complications
Air leak : Pneumothorax,
ET complications : Blocked
Infection
Intracranial hemorrhage
Long-term complications
Bronchopulmonary dysplasia (BPD)
Retinopathy of prematurity (ROP)
Neurologic impairment
Prognosis
Very low birth weight <501 grams survival rate is 10% and 100% risk of BPD and very
high risk of ROP
Birth weight between 1001-1500 grams survival rate is ~ 96% and few develop BPD and
ROP as well.

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 Neonatal Jaundice
Learning Objectives:

 Define hyperbilirubinemia.
 Differentiate between physiological and pathological jaundice.
 State causes of hyperbilirubinemia.
 Discuss the pathophysiology of hyperbilirubinemia.
 Describe the most dangerous complication of hyperbilirubinemia.
 List the three elements of therapeutic management.
 Design plan of care for baby has hyperbilirubinemia.

Neonatal Jaundice (Hyperbilirubinemia):

 Definition: Hyperbilirubinemia refers to an excessive level of accumulated

bilirubin in the blood and is characterized by jaundice, a yellowish
discoloration of the skin, sclerae, mucous membranes and nails.
 Unconjugated bilirubin = Indirect bilirubin.
 Conjugated bilirubin = Direct bilirubin.

Neonatal Jaundice:

 Visible form of bilirubinemia

o Newborn skin >7 mg / dl
 Occurs in 80% of term and most of preterm neonates
 However, significant jaundice occurs in 3 % of term babies (serum bilirubin
level >15 mg/dl)
BILIRUBIN PHYSIOLOGY:

 Increased production in neonate due to larger red cell volume, which produces
bilirubin as cells are broken down and shorter RBC life span, so broken down
faster.
 Heme is catabolized within the reticuloendothelial system by heme oxygenase to
form biliverdin.
 Biliverdin is metabolized to bilirubin in the presence of biliverdin reductase

BILIRUBIN PHYSIOLOGY:

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  Ligandins responsible for transport from plasma membrane to endoplasmic
reticulum.
 Bilirubin conjugated in presence of UDPGT (uridine diphosphate glucuronyl
transferase) to mono and diglucoronides, which are then excreted into bile
canaliculi.

Enterohepatic Circulation:

 Conjugated bilirubin is unstable and easily hydrolyzed to unconjugated bilirubin.

 This process occurs non-enzymatically in the duodenum and jejunum and also
occurs in the presence of beta-glucuronidase, an enteric mucosal enzyme, which is
found in high concentration in newborn infants and in human milk.

Conjugation:

 After birth, the levels of UDPGT rise rapidly but do not reach adult levels until 4-6
weeks of age.
 Ligandins, which are necessary for intracellular transport of bilirubin, are also low
at birth and reach adult levels by 3-5 days.

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Physiological jaundice:

Characteristics

 Appears after 24 hours

 Maximum intensity by 4th-5th day in term & 7th day in preterm
 Serum level less than 12 mg / dl
 Clinically not detectable after 14 days
 Disappears without any treatment
Note: Baby should, however, be watched for worsening jaundice.

The clinical courses divided into two phases:

 Phase I: the first 5 days of life in term infants , rapid increase in TSB levels for 3
or 4 days after which the level begins to decline.
 Phase II: stable, but elevated TSB levels lasting about 2 weeks.
After phase II, TSB levels become comparable with adult levels.

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Course of physiological jaundice:

Why does physiological jaundice develop?

 Increased bilirubin load.

 Defective uptake from plasma; bilirubin binding protein (ligandin).
 Defective conjugation; reduced UDPG-T activity.
 Decreased excretion.
 Increased entero-hepatic circulation.

Pathological jaundice:

 Appears within 24 hours of age

 Increase of bilirubin > 5 mg / dl / day
 Serum bilirubin > 15 mg / dl
 Jaundice persisting after 14 days
 Stool clay / white colored and urine staining clothes yellow
 Direct bilirubin> 2 mg / dl

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Classifications:
 Direct-reacting hyperbilirubinemia
o Hepatitis
o Cholestasis
o Inborn errors of metabolism
o Sepsis

 Indirect-reacting hyperbilirubinemia
– Hemolysis
o Reticulocytosis
o Evidences of red blood cell destruction
o A positive Coomb’s test
o Blood group incompatibility
o Positive results of specific examination

 Direct and indirect- reactin hyperbilirubinemia

o Hepatitis
o Sepsis
o Liver damage complicated by Hemolysis

Causes of jaundice:
Appearing within 24 hours of age:
 Hemolytic disease of NB : Rh, ABO
 Infections: TORCH, malaria, bacterial
 G6PD deficiency

Appearing between 24-72 hours of life:

 Physiological
 Sepsis
 Polycythemia
 Intraventricular hemorrhage
 Increased entero-hepatic circulation
After 72 hours of age:
 Sepsis
 Cephalhaematoma
 Neonatal hepatitis
 Extra-hepatic biliary atresia
 Breast milk jaundice
 Metabolic disorders (G6PD).

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Acute bilirubin encephalopathy:

It is the clinical manifestation of bilirubin toxicity seen in the neonatal period. It can be
divided into three phases:

 Early phase: hypotonia, lethargy, high-pitched cry, and poor suckling

 Intermediate phase: hypertonia (with opisthotonus), irritability, seizures.
 Advanced phase: pronounced opisthotonus, apnea, seizures, coma and death

KERNICTERUS:

 Chronic bilirubin encephalopathy (Kernicterus)

 It is marked by athetosis, deafness, limitation of upward gaze, and intellectual
deficits.

BREASTMILK/BREASTFEEDING JAUNDICE:

 Breastfeeding jaundice occurs early

 It is due to the lack of breast milk
 It is often associated with poor passage of meconium.
 Treatment should be aimed at supporting breastfeeding while supplementing as
needed to avoid extreme weight loss, dehydration, and worsening jaundice.

BREASTMILK/BREASTFEEDING JAUNDICE:cont.

 Occurs in 2-4% of term neonates.

 Breast milk jaundice is a different, more benign entity, which tends to occur late in
the first week or afterwards.
 The mechanism is not entirely clear but it is a result of an unidentified factor in
breast milk that interferes with bilirubin metabolism, with also an increased
enterohepatic circulation because of the presence of glucuronidase enzyme in some
breast milk.
 Usually weight gain is good, and the baby is otherwise well.

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BREASTMILK/BREASTFEEDING JAUNDICE:cont.

 By day 4, the bilirubin level continues to rise instead of decreasing.

 The bilirubin level may reach 20-30 mg/dl by 14 days of age. If breastfeeding is
continued, the levels will stay elevated and then fall slowly at 2 weeks of age,
returning to normal by 4-12 weeks.
 Stopping breast milk leads to a rapid fall in serum bilirubin within 48 hrs
(definitive diagnostic test, it is not routinely recommended.
Diagnostic evaluation:

History:

 Day of onset, Maternal blood group and Rh

 Family history of jaundice, anemia, splenectomy, liver disease
 Previous sibling with jaundice or anemia
 Maternal disease (diabetes mellitus )
 Maternal drug intake e.g., sulfonamides, aspirin
 Perinatal history: traumatic delivery, sphyxia
 Postnatal history: vomiting, Infrequent stooling, delayed breastfeeding
 The infant is breastfed or formula-fed

Examination:

 Observe in good daylight. Jaundice progresses in cephalocaudal direction (highest

bilirubin levels are associated with jaundice below knees and in the hands) .
 Prematurity, (SGA)
 Extravasated blood
 Hepatosplenomegaly: hemolytic anemia- infection
 Signs of neonatal sepsis
Color of jaundice:

► Signs of bilirubin encephalopathy (kernicterus)

Clinical assessment of jaundice:

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Diagnostic evaluation:

Laboratory investigations

 Serum bilirubin total and direct

 Blood group and Rh of the infant and the mother
 Coomb‟s test
 Complete blood count (Hb, Hct, WBC total, and differential, red cell morphology)
 Reticulocytic count

Therapeutic Management:

Purposes:

 reduce level of serum bilirubin and prevent bilirubin toxicity

 Prevention of hyperbilirubinemia: early feeds, adequate hydration
 Stop those drugs that interfere with bilirubin metabolism.
 Correct hypoxia, infection and acidosis.
 Reduction of bilirubin levels:
 Phototherapy- Exchange transfusion- Drugs

THERAPIES-PHOTOTHERAPY:

 Phototherapy should be initiated according to the guidelines

 A blue light with a wave length of 425-475 nm is the most efficient.
Photochemical reactions:

 Photo-isomerization .
 Structural isomerization: UCB is converted to lumirubin - urine without
conjugation.
 Photo-oxidation- urine.
PHOTOTHERAPY:

Technique:

 The infant should be undressed except for a diaper and eye patches. Eye patches
 The lamp should be 5-8 cm over the incubator and 45 cm above the infant.
 Phototherapy is given continuously and the infant should be turned every 2 hrs .
 The infant‟s temperature
 Infants should be weighed daily (increase fluid therapy by 20%).

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Babies under phototherapy:

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Exchange transfusion:

 This procedure removes bilirubin and hemolytic antibodies and corrects anemia.
 Indications for exchange transfusion according to the guidelines
 Factors; The overall state (sick or well), birth weight, gestational age and age of
the infants
 A double blood volume exchange is done (2 × 80-85 ml × body weight in kg).

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 Pharmacologic agents:
1. Intravenous Immunoglobulin (IVIG)
 IVIG (500-1,000 mg/kg IV over 2-4 hrs) can reduce the need for exchange
transfusion in infants with isoimmune hemolytic disease.
 IVIG inhibit hemolysis by occupying the Fc receptors of reticuloendothelial cells.
 IVIG dose may be repeated in 12 hrs if necessary.
2. Phenobarbital
 Phenobarbital increases the conjugation and excretion of bilirubin.
 Phenobarbital is not used to treat indirect neonatal hyperbilirubinemia, except in
Crigler-Najjar syndrome type II.
 It causes lethargy and poor feeding and needs 3-4 days to take effect.

Prognosis:
 Early recognition and treatment of hyperbilirubinemia prevents severe brain
damage.

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