Excerpt from Hyaline Membrane Disease

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Background

Respiratory distress syndrome (RDS), also known as hyaline membrane disease (HMD), is an acute lung disease of the newborn caused by surfactant deficiency. It is seen primarily in neonates younger than 36-38 weeks' gestational age and weighing less than 2500 g. In comparison, HMD tends to occur in neonates younger than 32 weeks' gestational age and weighing less than 1200 g.

The incidence and severity of RDS is inversely related to gestational age. RDS is the most common cause of respiratory failure during the first days after birth. In addition to prematurity, other factors contributing to the development of RDS are maternal diabetes, cesarean delivery without preceding labor, fetal asphyxia, and being the second born of twins.

In recent years, the outcome of patients with RDS has improved with the increased use of antenatal steroids to improve pulmonary maturity, early postnatal surfactant therapy to replace surfactant deficiency, and gentle techniques of ventilation to reduce barotrauma to the immature lungs.

Pathophysiology

RDS is the result of anatomic pulmonary immaturity and a deficiency of surfactant. Pulmonary surfactant synthesis, in type II pneumocytes, begins at 24-28 weeks of gestation, and gradually increases until full gestation. Pulmonary surfactant decreases surface tension in the alveolus during expiration, allowing the alveolus to remain partly expanded, thereby maintaining a functional residual capacity.

In premature infants, an absence of surfactant results in poor pulmonary compliance, atelectasis, decreased gas exchange, and severe hypoxia and acidosis. Premature infants must expend a great deal of effort to expand their lungs with each breath, and respiratory failure ensues.

The lack of surfactant and the resultant poor compliance of the lungs causes debris consisting of damaged or desquamated cells, exudative necrosis, and leaked protein, which lines the alveolar sacs. On hematoxylin-eosin staining, this lining stains like hyaline cartilage.

HMD was originally named for these hyaline membranes, but their presence is not specific for the disease. These hyaline membranes can be seen with other conditions, such as meconium aspiration, bronchopulmonary dysplasia (BPD), and neonatal pneumonia. In addition, hyaline membranes are frequently absent in infants with RDS who die at less than 4 hours of age. (Approximately 4 hours of breathing are usually required for pathologically identifiable hyaline membranes to form.) The disparity between the clinical and pathologic findings has led to use of the term respiratory distress syndrome, or RDS, instead of hyaline membrane disease, or HMD.

Hyaline membranes may form in response to pulmonary hemorrhage; pulmonary edema; and various irritants to the terminal airways, alveolar sacs, and alveoli.

Intrauterine stress may cause an outpouring of endogenous steroids, which cause the type 2 alveolar-lining cells to mature and produce surfactant. This steroid output also causes the thymus to shrink, as thymic atrophy can be induced by corticosteroids or corticotropin. Therefore, a premature neonate with no thymus is less likely than other neonates to have RDS.

Frequency

United States

RDS occurs in approximately 40,000 infants each year (1-2% of newborn infants or in 14% of infants weighing less than 2500 g).

The incidence of RDS increases from 5% at 35-36 weeks to 65% at 29-30 weeks of gestation. The incidence of RDS is altered by antenatal maternal glucocorticoid use, as follows:

• For infants born earlier than 30 weeks of gestation, rates are 60% without glucocorticoid therapy versus 35% with antenatal glucocorticoid therapy.
• For infants born between 30 and 34 weeks of gestation, rates are 25% without glucocorticoid therapy versus 10% with antenatal glucocorticoid therapy.
• For infants born after 34 weeks of gestation, the overall incidence is about 5%.

International

RDS is reported worldwide in premature infants of all races.

Mortality/Morbidity

RDS is a leading cause of mortality in infants and accounts for 20% of all neonatal deaths.

• Mortality rates have dramatically decreased in infants with RDS with the use of continuous positive-pressure ventilation with end-expiratory positive pressure and surfactant replacement therapy.
• Mortality rates associated with HMD are less than 10% for neonates older than 28 weeks' gestation.
• The major long-term sequela is the development of chronic lung disease, which is defined as the need for oxygen or ventilation after 1 month of age. This complication occurs in 20% of survivors of RDS. As many as 10% of infants who develop chronic lung disease die in the first 2 years of life because of respiratory failure, pulmonary infection, or sudden death.

Race

White infants are more commonly affected than black infants

Sex

RDS is twice as common in boys as in girls at every gestational age.

Age

RDS predominantly occurs in infants younger than 32 weeks' gestational age and in those weighing less than 1200 g.

• RDS frequently occurs in infants born to mothers with diabetes, in infants born by means of cesarean delivery without maternal labor, in the second born of twins, and in infants with family history of RDS.
• Secondary surfactant deficiency may occur in infants with intrapartum asphyxia, pulmonary infections, pulmonary hemorrhage, meconium aspiration pneumonia, and oxygen toxicity to the lungs.
• The use of antenatal steroids or conditions that induce prepartum stress and thus increase production of maternal steroids and accelerate surfactant production can prevent RDS. Examples of these conditions are pregnancy-induced or chronic maternal hypertension, prolonged rupture of membranes, and maternal narcotic addiction.

Clinical Details

Infants with RDS have all of the clinical signs of respiratory distress. The clinical presentation of expiratory grunting (due to partial closure of glottis), tachypnea, subcostal and intercostals retractions, nasal flaring, and cyanosis usually manifests in the first few hours and almost always before 8 hours of age. If symptoms do not develop until after 8 hours of normal breathing, RDS is excluded. On auscultation, air movement is diminished despite vigorous respiratory effort.

Cyanosis and hypoxia frequently become severe. Tachypnea, with respiratory rate greater than 60 breaths per minute, develops early. Functional residual capacity and pulmonary compliance are greatly reduced. Cyanosis, apnea, and circulatory collapse are grave clinical prognostic indicators. A mixed respiratory and metabolic acidosis usually develops. Arterial blood gas studies show hypoxemia, hypercapnia, and respiratory acidosis. Hypoglycemia, hyperkalemia, and hypocalcemia are also common.

Increased pulmonary vascular resistance develops because of a noncompliant lung, hypoxia, and acidosis. This effect increases the right-to-left shunt through a patent ductus arteriosus (PDA). Perfusion of atelectatic air spaces and uneven distribution of inspired air result in a ventilation-perfusion mismatch that initiates a chain of physiologic events that accounts for most of the findings in RDS. Death often directly results from pulmonary disease. However, it may also result from complications related to hypoxemia (eg, intracranial hemorrhage, disseminated intravascular coagulation [DIC], pulmonary hemorrhage, congestive heart failure [CHF] due to left-to-right shunting through PDA), or air blockage complications of assisted ventilation (eg, pulmonary interstitial emphysema [PIE], pneumothorax, pneumomediastinum, gas embolism).

The symptoms of RDS usually peak by the third day, and they may resolve quickly when diuresis starts and when infants begin to need less oxygen and mechanical ventilation. Clinical improvement is accompanied by a rapid fall in pulmonary vascular resistance and a rise in systemic arterial pressure, which sometimes leads to the development of a large left-to-right shunt through a PDA. Therefore, the patient's recovery may be interrupted by the development of CHF and pulmonary edema.

In RDS, symptoms appear shortly after birth and always within first 8 hours of life. Respiratory symptoms starting after 8 hours of age are unlikely to be the result of RDS. Findings include dyspnea, inspiratory retractions, tachypnea, nasal flaring, expiratory grunting, and progressive cyanosis. Subxiphoid retraction reflects decrease lung volume. In fetal aspiration syndrome, TTN, and neonatal pneumonia, clinical symptoms appear in 12-24 hours, within 6 hours, and in less than 6 hours, respectively. In addition, lung volumes are usually increased in these conditions. The absence of cyanosis excludes congenital pulmonary lymphangiectasis as a diagnosis.

In infants not receiving assisted ventilation, clinical improvement is associated with the slow clearing of the lungs and a patchy return of normal alveolar aeration. No residual changes are observed, and postrecovery pulmonary function is normal. In contrast, in infants of RDS who receive assisted ventilation, residual pulmonary changes are common and referred to as BPD.

Preferred Examination

RDS is usually diagnosed with a combination of clinical signs and/or symptoms, chest radiographic findings, and arterial blood gas results.

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