PREDISPOSING FACTORS

Respiratory function must equate with metabolic demands. Oxygen consumption in the infant is approximately 7 ml/kg per min (compared with 3–4 ml/kg per min in the older child and adult). Fever, illness and restlessness dramatically increase demands; during periods of apnoea or respiratory depression, PaCO₂ rises at twice the rate of older children and adults. Respiratory reserve is reduced in infants and neonates due to the following factors.

CLINICAL PRESENTATION

Respiratory distress is manifested by tachypnoea, distortion of the chest wall (i.e. sternal and rib retraction, recession of intercostal, subcostal and suprasternal spaces) and use of accessory muscles (e.g. flaring of alae nasi and use of neck muscles).

In young infants, lethargy, pallor, apnoea, bradycardia and hypotension may be the first signs of hypoxia. The physiological anaemia of infancy may delay recognition of cyanosis, and major signs are those of CNS and cardiovascular depression. Increased work of breathing, marked by tachypnoea and chest-wall retraction, is poorly sustained; bradypnoea and apnoea are evidence of respiratory fatigue. Expiratory ‘grunting’ is a sign of respiratory distress that represents an attempt to maintain a positive expiratory airway pressure to prevent airway closure and alveolar collapse, the equivalent of pursed-lip breathing in the adult.

The older child with acute hypoxia, like the adult, demonstrates tachycardia, hypertension, mental confusion and restlessness prior to CNS and cardiovascular depression. Sweating occurs with CO₂ retention – a feature lacking in the newborn.

In the newborn, the effects of hypoxia and acidosis may be compounded by the development of pulmonary hypertension and reversion to a transitional circulation, with right-to-left shunting through a patent ductus arteriosus and foramen ovale. If untreated, increasing hypoxaemia, progressive acidosis and death may occur.

Conventional clinical examination of the chest should be performed. It is, however, of limited value in the neonate, as breath sounds may be transmitted uniformly through the chest, even in the presence of tension pneumothorax, lobar collapse or endobronchial intubation. The chest X-ray is an essential part of the assessment.

AETIOLOGY

Acute respiratory failure may result from upper or lower airway obstruction, alveolar disease, pulmonary compression, neuromuscular disease or injury (Table 98.1). Upper respiratory tract obstruction is discussed in Chapter 97.

Table 98.1 Causes of respiratory insufficiency in infancy and childhood

TRACHEOMALACIA, TRACHEAL STENOSIS AND VASCULAR COMPRESSION

Instability of the tracheal wall (tracheomalacia) is most commonly associated with oesophageal atresia, tracheo-oesophageal fistula and various vascular anomalies. The most common causes of vascular compression are a double aortic arch and the complex of a right-sided aortic arch, left ductus arteriosus and an aberrant left subclavian artery. These produce a true vascular ring, with encirclement of the trachea and oesophagus. Anterior tracheal compression may also be due to an anomalous innominate artery. Lower tracheomalacia or tracheal stenosis may occur in association with an anomalous left pulmonary artery (pulmonary artery sling). The problem may extend to the major bronchi (bronchomalacia). Tracheomalacia and bronchomalacia also occur as isolated airway anomalies. In this situation, the severity of dynamic airway obstruction is aggravated by any condition that results in reduced lung compliance.

Division of the vascular ring and ligation or repositioning of the aberrant vessel, while removing the cause of the obstruction, do not immediately re-establish normal airway dimensions or stability. Although severity of symptoms may be alleviated by surgery, problems may persist for some years. Tracheomalacia may sometimes be stabilised by a prolonged period of nasotracheal intubation or tracheostomy with continuous positive airway pressure (CPAP). Tracheopexy, which suspends the anterior tracheal wall from the posterior sternal surface and great vessels, is occasionally useful. A slide tracheoplasty may be required to correct tracheal stenosis associated with complete tracheal rings.³ A range of stenting devices have also been developed for complex airways and employed with mixed success.

MECONIUM ASPIRATION SYNDROME

Meconium aspiration is seen in 0.3% of live births, and is most common in term or postterm infants. There is usually a history of fetal distress in labour, or prolonged and complicated delivery. Asphyxia during labour results in the expulsion of meconium into the liquor. With the first few breaths, material in the upper airway (i.e. amniotic fluid, meconium, vernix and squames) is inhaled, obstructing small airways and producing atelectasis and obstructive emphysema. Meconium also causes a chemical pneumonitis and surfactant abnormalities. During recovery, the aspirated material is absorbed and phagocytosed.

Clinical signs include tachypnoea, retraction and cyanosis. The chest may become hyperexpanded and pneumomediastinum or pneumothorax is a frequent complication. Pulmonary hypertension and persistent fetal circulation are common.

The chest X-ray confirms the diagnosis, with coarse mottling and streakiness radiating from the hila. Lungs are overexpanded, with flattened diaphragms and an increase in the chest anteroposterior diameter. The condition is largely preventable if the airway can be aspirated rapidly and completely following delivery of the head and before the first breath.

Most of these infants require oxygen therapy. Severely affected infants require controlled mechanical ventilation (CMV), which may be difficult because of the high pressures required, the non-uniformity of ventilation, and danger of pneumothorax. Improved outcomes are now achieved using surfactant (may cause transient deterioration), inhaled nitric oxide and high-frequency oscillation.⁴ Extracorporeal membrane oxygenation (ECMO) is also effective in those centres that have the facility, although its use has declined since the introduction of the above therapies. Cerebral effects of severe intrapartum asphyxia contribute to overall morbidity and mortality.

CONGENITAL CYSTIC ADENOMATOID MALFORMATION

Congenital cystic adenomatoid malformation (CCAM) of the lung results from abnormal mesenchymal proliferation and failure of maturation of bronchiolar structures early in gestation. The result is multiple lung cysts, usually within a single lobe. CCAM is often diagnosed on antenatal ultrasound. Other cases present with respiratory distress due to obstruction whilst others present with infection in the cysts and recurrent lobar pneumonia. Some cases are diagnosed incidentally on chest radiographs taken for another reason. Some cases are associated with renal dysplasia. Even asymptomatic infants are at risk of cyst expansion or infection and lobectomy is the treatment of choice for all cases.

LOBAR EMPHYSEMA

Congenital lobar emphysema is characterised by overdistension of a pulmonary lobe caused by air trapping. Most cases present in the first month of life, with tachypnoea, wheezing, grunting and cough. Signs include hyperresonance, decreased air entry and deviation of the trachea and heart away from the affected lobe. There may be asymmetry of the chest due to bulging of the affected hemithorax. Cyanosis may be associated with periods of increased respiratory distress. There may be associated cardiovascular abnormalities, rib cage abnormalities or renal dysplasia.

Radiologically, the affected lobe is overdistended with compression and deviation of the surrounding structures. The pathogenesis is unknown in over 50%, 25% have localised bronchial cartilaginous dysplasia, and the remainder have obstruction of a lobar bronchus from a mucous plug, redundant mucosa, aberrant vessels or localised stenosis. Lobectomy is the definitive surgical treatment. Care must be taken with positive airway pressure because of the risk of further overdistension.

ASPIRATION PNEUMONIA

In the newborn, aspiration may result from pharyngeal incoordination or lack of protective reflexes, due to prematurity, birth asphyxia or intracranial haemorrhage. It is particularly likely to occur with abnormalities of the alimentary tract, such as oesophageal atresia, tracheo-oesophageal fistula and oesophageal reflux. Large and small airway obstruction and pneumonia may occur.

HYALINE MEMBRANE DISEASE

This is due to deficiency of lung surfactant. Predisposing factors are prematurity, maternal diabetes and intranatal asphyxia. Postnatal hypoxia and acidosis also inhibit surfactant production. Lack of surfactant results in alveolar instability, atelectasis, intrapulmonary shunting and increased work of breathing.

Clinical signs appear shortly after birth and consist of tachypnoea, chest-wall retraction, expiratory grunting and a progressive increase in oxygen requirements. The chest X-ray reveals a reticulogranular pattern (ground-glass appearance) with air bronchograms. In uncomplicated cases, the disease is self-limiting and resolves in 4–5 days. Respiratory failure may require increasing inspired oxygen concentrations (FiO₂), CPAP, intermittent mandatory ventilation (IMV) or CMV. CPAP is known to improve oxygenation, the pattern and regularity of respiration, retard the progression of the disease and reduce morbidity, particularly with early application in the extremely preterm infant. In infants with persistent pulmonary hypertension, transitional circulation and requiring high airway pressures, the use of inhaled nitric oxide and high-frequency oscillatory ventilation are beneficial.

Instillation of surfactant into the trachea has been shown to improve oxygenation and compliance (despite some initial deterioration) and reduce the risk of pneumothorax, early mortality and morbidity.^5–8 Two types of surfactant are used: synthetic (Exosurf), and bovine (Survanta) or porcine (Curosurf).

BRONCHOPULMONARY DYSPLASIA

Bronchopulmonary dysplasia (BPD), or chronic lung disease, may occur in survivors of neonatal lung disease. Its occurrence correlates with lung immaturity, high airway pressures and barotrauma. The lung architecture is abnormal with widespread fibrosis and cystic changes. There is often a reactive component to the airway disease that may be responsive to bronchodilator and anti-inflammatory therapy, such as steroids. It is a cause of chronic respiratory failure in infancy, and in severe cases progresses to cor pulmonale and death in the first 2 years of life. Prolonged low-flow home oxygen therapy may be necessary to reduce the risk of pulmonary hypertension. Superimposed bacterial and viral infection may exacerbate chronic respiratory failure and lead to further lung injury.

PNEUMONIA

Perinatal pneumonia may occur as a result of transplacental spread of a maternal infection, prolonged rupture of membranes, passage through an infected birth canal or cross-infection in the nursery. The immunoparetic state of the newborn and the need for invasive procedures increase the risk.

Clinical and radiological features may be indistinguishable from hyaline membrane disease. Antibiotics (e.g. penicillin and gentamicin) should be given until negative cultures exclude the diagnosis. The most common organisms include group B haemolytic Streptococcus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus aureus. Group B haemolytic streptococcal infection is frequently associated with septic shock and persistent fetal circulation. Failure to suspect group B haemolytic streptococcal infections (and hence treat promptly with penicillin) will result in poor outcome. Multiresistant staphylococcal and Gram-negative bacillary infections must be suspected in longer-stay patients in neonatal ICUs.

Most pneumonia in infants and young children is of viral origin. Viruses commonly implicated are respiratory syncytial virus (RSV), influenza A1, A2 and B, and parainfluenza types 1 and 3. Adenovirus and rhinovirus are less common causes. The spectrum of illness is wide. Many infants and children have cough, fever and tachypnoea, with X-ray evidence of patchy consolidation, all of which resolve rapidly. Occasionally, infants develop life-threatening respiratory illness with extensive pneumonic changes and marked necrosis. Permanent lung damage with bronchiolitis obliterans and pulmonary fibrosis may occasionally complicate severe adenoviral pneumonia in particular.

Bacterial pneumonia also occurs. Pneumococcal pneumonia is common and usually responds dramatically to appropriate antibiotic therapy. Staphylococcal pneumonia is relatively uncommon, but may result in life-threatening respiratory failure, and is often associated with complications (e.g. empyema, pneumatocele, tension pneumothorax and suppuration in other organs). Aspiration of an effusion may be useful for diagnostic purposes. Parapneumonic effusions (empyema) may require tube thoracostomy or video-assisted thoracoscopic drainage. Resolution of the effusion can be enhanced by the instillation of thrombolytic agents such as urokinase or tissue plasminogen activator.⁹ In severe cases with bronchopleural fistula, surgical resection of the necrotic area offers the best chance of survival.

Pneumonia due to Haemophilus influenzae may also occur and be associated with epiglottitis, meningitis, pericarditis or middle-ear disease. The prevalence of H. influenzae infection has reduced dramatically since the introduction of HiB immunisation.

Gram-negative pneumonia is seen mostly in infants with debilitating conditions who are hospitalised for prolonged periods. It is a particular risk for patients in ICUs with endotracheal or tracheostomy tubes. Other opportunistic infections, such as Pneumocystis jiroveci (formerly P. carinii), Candida albicans, Aspergillus and cytomegalovirus, may occur in immune deficiency states.

MASSIVE PULMONARY HAEMORRHAGE

This usually presents as acute cardiorespiratory collapse, accompanied by outpouring of bloodstained fluid from the trachea, mouth and nose. It is seen in association with severe birth asphyxia, hyaline membrane disease, congenital heart disease, erythroblastosis fetalis, coagulopathy and sepsis. Hypoxia is often a precipitating factor. The condition in the newborn is believed to represent haemorrhagic pulmonary oedema due to acute left ventricular failure. Treatment is that of the underlying condition with oxygenation, CMV and correction of any coagulation disturbance.

PULMONARY OEDEMA

Pulmonary oedema in the newborn period is due mostly to congenital heart disease, especially coarctation of the aorta, patent ductus arteriosus, critical aortic stenosis and, rarely, obstructed total anomalous pulmonary venous drainage. Pulmonary oedema due to circulatory overload may also occur in erythroblastosis fetalis, the placental transfusion syndrome, or as a result of inappropriate fluid therapy. Myocarditis is a further cause seen throughout infancy and childhood. Prolonged supraventricular tachycardia may result in ventricular dysfunction and biventricular failure, including pulmonary oedema.

In the newborn period, pulmonary oedema manifests as respiratory distress and feeding difficulty and specific features of congenital heart lesions may be evident. There is a spectrum of severity, from tachypnoea with a widened alveolar–arterial oxygen gradient to life-threatening respiratory failure requiring urgent support. Chest X-ray usually shows an enlarged heart (except in total anomalous pulmonary venous drainage) and a ground-glass appearance fanning out from the hilar regions.

PULMONARY HYPOPLASIA

This is seen most often in association with congenital diaphragmatic hernia, but bilateral pulmonary hypoplasia may also occur in association with renal agenesis or dysgenesis (Potter’s syndrome), in babies with severe Rhesus isoimmunisation, and in the presence of chronic amniotic fluid leak. It may also present as an isolated malformation. Unilateral hypoplasia can occur as an isolated anomaly or in association with cardiovascular defects.

DIAPHRAGMATIC HERNIA

Congenital diaphragmatic hernia (most commonly left-sided) results in respiratory failure, partly due to lung compression but mainly related to the associated pulmonary hypoplasia (both ipsilateral and contralateral). The degree of pulmonary hypoplasia is most severe in infants with absence of the diaphragm. The disturbance of pulmonary function ranges from mild to severe. In severe cases, life-threatening respiratory distress is present from birth, with cyanosis, intercostal retraction, mediastinal displacement, and poor or absent breath sounds on the affected side. The abdomen is usually scaphoid, due to much of its usual contents being in the chest. Chest X-ray shows loops of bowel in the affected hemithorax, with pulmonary compression and mediastinal displacement to the contralateral side.

Neonates presenting in the first 4 hours of life have major degrees of lung hypoplasia and have a mortality of 40% despite maximal supportive therapy. Those presenting after 4 hours of age should all survive. CMV may be complicated by tension pneumothorax and bronchopleural fistula on either side. Pulmonary hypertension with persistent fetal circulation and difficulties of CMV present major challenges. Many centres use ECMO or high-frequency ventilation in these infants. Nitric oxide is a useful pulmonary vasodilator in this condition.⁴ Prolonged ventilatory support is often required but the outlook for survivors is excellent.