Respiratory problems in neonate

DR/Mohamed abdelaziz ali ali

31-12-2013

Embryology and post-natal development of the respiratory system

• Embryonic phase (3-5 weeks' gestation) - the lung bud begins as an endodermal outgrowth of foregut. This branches into the surrounding mesoderm to form the main bronchi

• Pseudoglandular phase (6-1 6 weeks) - airways branch further to terminal bronchioles (preacinar airways). Cartilage, lymphatics and cilia form. Main pulmonary artery forms from sixth left branchial arch

• Canalicular phase (1 7-24 weeks) - airways lengthen, epithelium becomes cuboidal, pulmonary circulation develops The acinar structures (gas-exchanging units) begin to develop and surfactant production begins by 24 weeks' gestation a type 1 and 2 pneumocytes become distinguishable. Lungs fill with amniotic fluid, which facilitates further lung growth

• Terminal sac phase (24-40 weeks) - further development of the acinar structures (respiratory bronchioles, alveolar ducts and terminal sacs (alveoli)) occurs and increasing amounts of surfactant are produced. Type 1 pneumocytes eventually cover approximately95% of the alveolar surface and facilitate gas exchange. The surfactant-producing type 2

cells cover only about 5%. 'Development of the pulmonary circulation continues and results in a thicker intra-arteriolar smooth muscle layer by term, which may respond to intrauterine hypoxia by vasoconstriction. This regresses rapidly after birth

• Post-natal lung development - the number and size of alveoli increases rapidly during the first 2 years (approximately 150 million at term to 400 million by 4 years). The conducting airways also increase in size

• Diaphragm development - arises as a sheet of mesodermal tissue, the septum transversum. It begins close to the third, fourth and fifth cervical segments and therefore its nerve supply, the phrenic nerve, is derived from this area. The primitive septum transversum migrates caudally to form the pleural space and the two posterolateral canals in which the lung buds develop fuse. Failure to do this results in a Bochdalek hernia. Failure of the retrosternal part of the septum transversum to form causes a Morgagni-type diaphragmatic hernia. The diaphragm is completed as primitive musclecells migrate from the body wall. If this fails eventration of the diaphragm results

1-Surfactant deficiency• Endogenous surfactant is produced by type 2 pneumocytes, which line 5- 10% of

the alveolar surface. Surfactant-containing osmiophilic granular inclusion bodies cause these to appear different from the thinner and more numerous type 1 pneumocytes, which are responsible for gas exchange.

• Composition of endogenous surfactant 1-Phospholipids - 85%

2-Neutral lipids - 1O%

3-Apolipoproteins - 5 %

• Estimated incidence of surfactant deficiency by gestational age (without maternalsteroids)

Gestation (completed weeks) Incidence of surfactant deficiency (%)

26 90%

28 80%

30 70%

32 55%

34 25%

36 12%

38 3%

40 >1-2%

Surfactant deficiency is decreased in:

• Female sex• PROM• Maternal opiate use• IUGR• Antenatal glucocorticoids• Prophylactic surfactant

Surfactant deficiency is increase in:

• prematurity• male sex• sepsis• maternal diabetes• second twin• elective caesaren section• strong family history

Amniotic fluid (or gastric aspirate) lecithin : sphingomyelin (L : S) ratios .

<1.5 = immature - 70% risk of surfactant deficiency 1.5-1.9 = borderline - 40% risk of surfactant deficiency 2.0-2.5 = mature - very small risk unless mother is diabetic >2.5 = safe

Management of surfactant deficiency:

1-maternal antenatal corticosterids (betamethasone or dexamethasone before preterm birth reduse the effects of surfactant and have been shown to:• reduce neonatal mortality by about 31%• decrease inttraventricular hge by about 46%• reduce risk of necrotisig enterocolitis (NEC)• decrease need of respiratory support for respiratory distress syndrome(RDS)• reduce risk in infection in the frist 24 hs

the current royal college of obestetrician and gynnecologist (RCOG) suggest given corticosteroids to women with likely preterm birth betweeb week 24 and 34 of gestation, and also consider in those from 23 week as well as before before any elective caesarean section up to 38 week.

1-no evidence that routine high-frequency oscillation is of any long-termbenefit in pre-term infants with surfactant deficiency, although this mode of ventilation maybe used as a 'rescue' in severe cases. 2-Routine paralysis is not used in most neonatal units,although this sedation with opiates and various modes of trigger ventilation may help to reduce the incidence of pneumothoraces.

3-Exogenous surfactant considerably reducesortality and incidence of pneumothoraces and chronic lung disease. Early treatment withsurfactant and use of animal rather than synthetic surfactants enhance these outcomes.

The production of pulmonary surfactant

Sufactant deficiency use

2-Chronic lung disease (bronchopulmonary dysplasia)

Definition:• respiratory support with supplementary oxygen +I- mechanical ventilation for>28

days with typical chest X-ray changes.• In very-low-birth-weight (VLBW)infants an alternative definition has been suggested

- requiring oxygen +I- mechanical ventilation >36 weeks' corrected gestational age and typical chest X-ray changes.

Risk factors for chronic lung disease:• Prematurity• Prolonged mechanical ventilation with high pressures and high functional inspired

oxygen (Fi02)• Baro- (volume) trauma• Pulmonary air leak (pneumothoraces or pulmonary interstitial emphysema)• Gastro-oesophageal reflux• Patent ductus arteriosus (PDA)• Pulmonary infection (particularly Ureaplasma urealyticum)

Radiological stages:

Stage 1 1 st few days indistinguishable from surfactant deficiencyStage 2 2nd week generalized opacity of lung fields

Stage 3 2-4 weeks streaky infiltratesStage 4 >4 weeks hyperinflation, cysts, areas of collapse or

consolidation,cardiomegally

Management of chronic lung disease:

• Ventilatory support as required

•Supplementary oxygen to maintain oxygen saturations 94-96% or p(02) >7 kPa (to reduce risk of pulmonary hypertension and cor pulmonale)

•Good nutrition is of paramount importance; increased alveolar growth accompanies general growth - particularly in the first 1-2 years

•Treatment of underlying exacerbating factors - infection, gastro-oesophageal reflux, fits, cardiac problems, etc.

•Dexamethasone - the only proven benefit is to facilitate weaning off mechanical ventilation but concern has been raised over short- and long-term side-effects, particularly adverse neurodevelopmental outcome

•Inhaled steroids - only proven benefit is to reduce the need for systemic steroids Bronchodilators

•Diuretics – only likely to be of benefit in the presence of PDA, cor pulmonale or excessive weight gain

•Respiratory syncytial virus (RSV) prophylaxis with monoclonal antibodies (Palivizumab) has been shown to reduce hospitalization in high risk cases, but use is controversial because of the high cost of the drug and the need for monthly intramuscular injectionsthroughout the RSV season

bronchopulmonary dysplasia

3-Meconium aspiration syndrome (MAS)

Risk factors• Term or post-term (incidence much higher in births after 42 weeks)• Small for gestational age• Perinatal asphyxia • Rare in pre-term but said to occur with congenital listeriosis (more likely to be pus

than meconium). The passage of meconium in fetal distress may. -be the result of increased secretion of motilin. Meconium may be inhaled antenatally or- post-natally. Antenatal inhalation is more likely in fetal distress because of abnormal fetal breathing (equivalent to gasping) that occurs with hypoxia and acidosis.

Major effects of MAS on lung function• Airway blockage

lncreased airways resistance with ball-valve mechanism and gas trapping

High risk of pneumothorax• Chemical pneumonitis• lncreased risk of infection

Even though meconium is sterile

Escherichia coli is the most common infective agent• Surfactant deficiency

Lipid content of meconium displaces surfactant from alveolar surface

Persistent pulmonary hypertension of the newborn

MAS changes on chest X-rays include initial patchy infiltration and hyperinflation.

Pneumothoraces are common at this stage. A more homogeneous opacification of the lung

management

• Uncontrolled trials of vigorous airway suction immediately after delivery suggest that it is possible to reduce the incidence of MAS.

• Intubation for lower airway suction is only neededif meconium can be seen below the vocal cords.

• Thoracic compression and routine bronchial lavage have no proven benefit.

• Thoracic compression and routine bronchial lavage have no proven benefit. Intermittent positive-pressure ventilation with a relatively long expiratory time to prevent further gas trapping may be required in moderate to severe MAS.

• Surfactant replacement therapy in infants with MAS has proven benefit, but large doses may be required.

• Extracorporeal membrane oxygenation (ECMO) may be used in the most severe cases.

Meconium aspiration syndrome

4-Pneumonia

Pneumonia can be congenital, intrapartum or nosocomial. CongenitalOnset is usually within 6 hours of birth.• Bacterial

Streptococci (group B streptococcus)

Coliforms (E. coli, Klebsiella, Serratia, Shigella, Pseudomonas etc.)

Pneumococci

Listeria• Viral

CMV

Rubella virus

Herpes simplex virus

Coxsackievirus• Other

Toxoplasmosis

Chlamydia

Ureaplasma urealyticum

Candida

IntraparturnOnset is usually within 48 hours.• Bacterial Group B streptococci Coliforms (as above) Haemophilus StaphylococciPneumococci Listeria•Viral Herpes simplex virus Varicella zoster virus

NosocomialOnset is after 48 hours.•Bacterial Staphylococci Streptococci Pseudornonas Klebsiella•Viral RSV Adenovirus Influenza viruses Parainfluenza viruses Common cold viruses

5-Pulmonary air leak

Pneumothorax:• Occurs in up to 1% of otherwise healthy term infants (it is usually asymptomatic).

• Overdistension of alveoli is more likely to occur in immature lungs because of a decreased number of pores of Kohn, which redistribute pressure between alveoli. Air ruptures through overdistended alveolar walls and moves towards the hilum where it enters the pleural or mediastinal space.

• More common in surfactant deficiency, MAS, pneumonia and pulmonary hypoplasia.

• Risk is reduced by lower ventilator pressures to avoid overdistension, faster rate ventilation with shorter inspiratory times, paralysis of infants fighting the ventilator and sutfactant replacement therapy.

Pulmonary interstitial emphysema:• May occur in up to 25% of VLBW infants, usually confined to those with the worst surfactant deficiency

• May be more common in chorioamnionitis

• Alveolar rupture results in small cysts in the pulmonary interstitium

• Ventilation is difficult and mortality and incidence of chronic lung disease are high

Pneumomediastinum•May complicate surfactant deficiency or other forms of neonatal lung disease, when it may coexist with pneumothorax or may be iatrogenic following tracheal rupture secondary to intubation

•No symptoms may occur in isolated pneumomediastinum, but respiratory andcardiovascular compromise are more likely to occur if pneumothorax is also present

6-Congenital lung problemsPulmonary hypoplasia Primary pulmonary hypoplasia is rare but may present with persistent

tachypnoea which resolves with lung growth several months after birth

Secondary pulmonary hypoplasia may be the result of:

• Reduced amniotic fluid volume - Potter syndrome (renal agenesis) or other severe congenital renal abnormalities resulting in markedly decreased urine volume (infantile (autosomal recessive) polycystic kidney disease, severe bilateral renal dysplasia, posterior urethral valves)

• Pre-term rupture of membranes - only occurs if membranes ruptured before 26 weeks; 23% of pregnancies with rupture of membranes before 20 weeks are unaffected; outcome with rupture of membranes before 24 weeks is usually poor,

• Amniocentesis - mild to moderate respiratory symptoms are more likely to occur in the neonatal period and incidence of respiratory symptoms in the first year of life is increased

• Lung compression - pulmonary hypoplasia is common in small-chest syndromes including asphyxiating thoracic dystrophy and thanatophoric dwarfiim, diaphragmatic hernia, congenital cystic adenomatoid malformation and pleural effusions Reduced fetal movements - pulmonary hypoplasia occurs in congenital myotonic dystrophy, spinal muscular atrophy and other congenital myopathies.

• Outcome with pulmonary hypoplasia depends on the severity and the underlying cause.

Pulmonary hypoplasia

Congenital diaphragmatic hernia• Commonest congenital abnormality of the respiratory system - incidence is 1 in 2,500-3,500 births

• Twice as common in males

• Other congenital malformations are common: 30% have karyotype abnormalities and 17% have other lethal abnormalities; 39% have abnormalities in other systems - malrotation occurs in 20%; those with other congenital abnormalities have double the mortality rate

• 90% are Bochdalek or posterolateral hernias

• 85-90% are left-sided

• Bilateral pulmonary hypoplasia occurs - ipsilateral >contralateral

• Usually diagnosed on routine antenatal ultrasound. May present with polyhydramnios. Those that have a normal routine antenatal ultrasound scan are likely to have a betteroutcome because the hernia usually occurs later, allowing for reasonable lung growth. In utero repair and tracheal plugging have been attempted but with variable outcomes

• Respiratory distress (usually severe), heart sounds on the right side of the chest, bowel sounds on the left side, a scaphoid abdomen and vomiting may be found at birth. Less severe cases may not present initially but develop increasing respiratory distress over the first 24 hours as the gut becomes more air-filled. Differential diagnosis is congenital cystic adenomatoid malformation (or even pneumothorax)

During resuscitation

• Bag and mask positive-pressure ventilation should be avoided

• Wide-bore nasogastric tube should be placed as soon as possible to deflate gut and to confirm diagnosis, and therefore distinguish between differential diagnoses of congenital cystic adenomatoid malformation or pneumothorax on subsequent chest X-ray

• Consider paralysing baby to avoid air swallowing and to reduce the risk of pneumothorax

Surgical management

• There is some evidence to suggest that stabilizing the baby before surgery improvesoutcome• Malrotation is corrected if present; the diaphragmatic defect is usually closed with asynthetic patch

Post-operative care’

• High-frequency oscillation, nitric oxide or ECMO may be of benefit, but evidence for routine use of these is lacking• Mortality overall is approximately 50-6O%• Survivors may have problems associated with underlying puimonary hypoplasia

Diaphragmatic hernia

Congenital cystic adenomatoid malformation (CCAM)

• Rare, abnormal proliferation of bronchial epithelium, containing cystic and adenomatoid portions• Lower lobes affected more frequently• May disappear or become smaller spontaneously before or after birth• Differential diagnosis is congenital diaphragmatic hernia• Prognosis worse with associated hydrops, pre-term birth and with type 3 lesions• Recurrent infection and malignant change have been described

There are three types

Type 1 CCAM • Single or small number of large cysts• Commonest type (50% cases)• May cause symptoms by compression or may be asymptomatic initially• Good prognosis after surgery

Type 2 CCAM• Multiple small cysts• Usually cause symptoms by compression of surrounding normal lung• Prognosis variable

Type 3 CCAM• Airless mass of very small cysts giving the appearance of a solid mass• Worst prognosis

Congenital cystic adenomatoid malformation (CCAM)

Congenital lobar emphysema

• Affected lobe is overinflated

• Left upper lobe is most commonly affected (also right middle and upper lobes); rare in lower lobes

• More common in males

• Associated with congenital heart disease in 1 : 6 cases (usually as a result of compression of airways by aberrant vessels)

• Unaffected lobes in affected lung are compressed

• Mediastinal shift and compression of the contralateral lung may also occur

• Presents with signs of respiratory distress, wheezing, chest asymmetry and hyperresonance

• Chest X-ray shows hyperlucent affected lobe +Ic-om pression of other lobes

• Reduced ventilation and perfusion of the affected lobe is seen on a ventilationlperfusion scan in more severe cases

• Surgical correction of underlying vascular abnormalities or resection of the affected lobe

• may be required but symptoms and signs may resolve following bronchoscopy

Chylothorax

• Effusion of lymph into the pleural space as a result of either: Underlying congenital abnormality of the pulmonary lymphatics Iatrogenic following cardiothoracic surgery

• Diagnosis by antenatal ultrasound scan allows antenatal drainage by insertion of intercostal drains, which may reduce the risk of pulmonary hypoplasia and facilitate resuscitation after birth

• Ventilatory support may be required post-natally, along with intermittent intercostal drainage

• Volume of chyle can be reduced by using a medium-chain triglyceride milk formula or avoiding enteral feeds for up to several weeks as the underlying abnormality resolves with time; protein and lymphocyte depletion may complicate this

• Surgical treatment is needed for the small number of cases that do not resolve spontaneously

7-Chest wall abnormalitiesAsphyxiating thoracic dystrophy•Autosomal recessive•Variable severity•Short ribs with bell-shaped chest•May have polydactyly and other skeletal abnormalities also•Long-term prognosis good in infants who survive >1 year

Ellis van Crefeld syndrome•Autosomal recessive•Short ribs, polydactyly, congenital heart disease, cleft lip and palate•Pulmonary hypoplasia is usually not severe and symptoms improve later

Short-rib polydactyly syndromes

• Four variants - all autosomal recessive• Death from severe respiratory insufficiency occurs in the neonatal period

Thanatophoric dysplasia

• Usually sporadic• Very short limbs - femur X-ray described as 'telephone handle' shape• Very small, pear-shaped chest• Death from lung/chest hypoplasia occurs in the neonatal period

Camptomelic dysplasia

• Autosomal recessive• Very bowed, shortened long bones• Death from respiratory insufficiency usually occurs in childhood

8-Upper airway obstruction

• Neonates are obligate nasal breathers.

Choanal atresia:• Incidence is 1 : 8,000• More common in females• Occurs as a result of a failure of breakdown of bucconasal membrane• May be unilateral or bilateral, bony or membranous• 60% associated with other congenital abnormalities including the CHARGE

association: C = colobomata, H = heart defects, A = atresia of choanae, R = retarded growth and development, G = genital hypoplasia in males, E = ear deformities.

• Presents at birth with respiratory distress and difficulty passing a nasal catheter. Oral airway insertion relieves respiratory difficulties. Diagnosis confirmed by contrast study or CT scan

• Surgical correction by perforating or drilling the atresia requires post-operative nasal stents .

Laryngomalacia• Commonest cause of stridor in the first year of life• lnspiratory stridor increases with supine position, activity, crying and upper

respiratory tract infections,• Usually resolves during the second year of life• Upper airway endoscopy is merited if persistent accessory muscle use occurs,

with recurrent apnoea or faltering growth.

Pierre Robin sequence

• Consists of protruding tongue, small mouth and jaw, and cleft palate

• Incidence 1 : 2,000

• Problems include obstructive apnoea, difficulty with intubation and aspiration

• To maintain airway patency and prevent obstructive apnoea, prone position should beused initially; If this fails an oral airway should be inserted; intubation may be needed in severe case which may eventually require tracheostomy

• Glossopexy and other surgical procedures have been attempted with some degree of success.

• Gradual resolution of airway problems occurs as partial mandibular catch-up growth occurs during the first few years of life.

Subglottic stenosis: May be congenital but usually acquired risk factors for acquired subglottic stenosis:• prematurity.• Recurrent re intubation.• prolonged intubation.• traumatic intubation.• large or small endotracheal tube.• black babies(keloid scar).• oral in opposite to nasal tube(theoretical but unproven)• gastro-osephegeal reflux.• infections.

Systemic steroids may facilitate extubation in mild to moderately severe subglottic stenosis. Laser or cryotherapy to granulomatous tissue seen on upper airway endoscopy may also be of benefit in these cases, Severely affected babies require surgery - anterior cricoid split or tracheostomy.

Tracheomalacia:

• Causes expiratory stridor• Usually caused from extrinsic compression - most commonly as a result of vascular rings• Also associated with tracheo-oesophageal fistula • Surgical treatment of underlying pathology usually leads to resolution, but tracheostomy and positive-pressure ventilation may be required.

Principles of mechanical ventilation in neonates

• Aims are: To ensure adequate oxygenation

To adequately remove carbon dioxide to prevent respiratory acidosis

To minimize the risk of lung injury

• Pressure-limited, time-cycled ventilation is used most commonly via either an oral or a nasal endotracheal tube. Patient-trigger modes may improve

synchronicity with the baby's own respiratory efforts thus improving oxygenation, reducing the risk of air leak and facilitating weaning from the

ventilator

• Volume cycle ventilation is being used more recently because of advances in ventilator technology, and may reduce the time taken to wean off the ventilator

• High-frequency oscillation may be used initially for any cause of neonatal respiratory failure, but is usually used as 'rescue' in severe cases where

conventional ventilation has failed

• Nasal continuous positive airway pressure is often used in pre-term babies once extubated. This maintains functional residual capacity aid reduces the

work of breathing

Extracorporeal membrane oxygenation (ECMO)

• A membrane 'lung' is used to rest the lungs and allow them to recover in severe respiratory failure. ECMO may be:

• Venoarterial (VA) - blood removed from right atrium (usually via right internal jugular vein) and returned via a common carotid artery

• Venovenous (VV) - a double-lumen, right atrial cannula is used• ECMO should be considered in severe neonatal respiratory failure if:

Lung disease is reversible

Infant is > 35 weeks' gestation

Weight > 2 kg

Cranial ultrasound scan shows no intraventricular haemorrhage > grade1

No clotting abnormality

Oxygenation index > 40

• Oxygenation index (0I) is used to quantify the degree of respiratory failure It is measured as:

• 0I= (mean airway pressure X Fi02 X 100) + p(02)• where mean airway pressure is in cmHzO, Fi02 (fractional inspired oxygen) is

a fraction and PO2 is in mmHg.• 01 > 25 indicates severe respiratory failure• 01 > 40 indicates very severe respiratory failure with a predicted mortality of

>8O0%

ECMO

Thank you