HYALINE MEMBRANE DISEASE (RESPIRATORY DISTRESS SYNDROME)

I. Definition. Hyaline membrane disease (HMD) is another name for RDS. This clinical diagnosis is

warranted in a preterm newborn with respiratory difficulty, including tachypnea (>60 breaths/min),

chest retractions, and cyanosis in room air that persists or progresses over the first 48-96 h of life,
and

a characteristic chest x-ray appearance (uniform reticulogranular pattern and peripheral air

bronchograms). The clinical course of the disease varies with the size of the infant, severity of

disease, use of surfactant replacement therapy, presence of infection, degree of shunting of blood

through the patent ductus arteriosus (PDA), and whether or not assisted ventilation was initiated.

Clinical presentation

A. History. The infant is often preterm, either by dates or by gestational examination, or has a

history of asphyxia in the perinatal period. Infants have some respiratory difficulty at birth, which

becomes progressively more severe. The classic worsening of the atelectasis seen on chest x-ray film

and increasing oxygen requirement for these infants have been greatly modified by the availability
of

exogenous surfactant therapy and our increased ability to provide effective mechanical ventilatory

support.

B. Physical examination. The infant with HMD exhibits tachypnea, grunting, nasal flaring, and

retractions of the chest wall. The infant may have cyanosis in room air. Grunting occurs when the

infant partially closes the vocal cords to prolong expiration and develop or maintain some FRC. This

mechanism actually improves alveolar ventilation. The retractions occur and increase as the infant is

forced to develop high transpulmonary pressure to reinflate atelectatic air spaces.

Management

A. Prevention.

1. Antenatal corticosteroids. The 1994 National Institutes of Health Consensus Development

Conference on the effect of corticosteroids for fetal maturation on perinatal outcomes concluded
that

antenatal corticosteroids reduce the risk of death, HMD, and IVH. Use of antenatal betamethasone
to

enhance fetal pulmonary maturity is now established and generally considered to be standard of
care.
The recommended glucocorticoid regimen consists of the administration to the mother of two 12-
mg

doses of betamethasone given intramuscularly 24 h apart. Dexamethasone is no longer

recommended

because of increased risk for cystic periventricular leukomalacia among very premature infants

exposed to the drug prenatally (Baud et al, 1999).

2. Several preventive measures may improve the survival of infants at risk for HMD and
includeantenatal ultrasonography for more accurate assessment of gestational age and fetal well-
being,

continuous fetal monitoring to document fetal well-being during labor or to signal the need for

intervention when fetal distress is discovered, tocolytic agents that prevent and treat preterm labor,

and assessment of fetal lung maturity before delivery (lecithin-sphingomyelin [L-S] ratio and

phosphatidylglycerol; see Chapter 1) to prevent iatrogenic prematurity.

B. Surfactant replacement (see also Chapter 6) is now considered a standard of care in the

treatment of intubated infants with HMD. Since the late 1980s, more than 30 randomized clinical

trials involving >6000 infants have been conducted. The systematic review of these trials (Soll &

Andruscavage, 1999) demonstrates that surfactant, whether used prophylactically in the delivery

room to prevent HMD or in the treatment of the established disease, leads to a significant decrease
in

the risk of pneumothorax and the risk of death. These benefits were observed in both the trials of

natural surfactant extracts and synthetic surfactants. Surfactant replacement, although proved to be

immediately effective in reducing the severity of HMD, has not clearly been shown to decrease the

long-term oxygen requirements or the development of chronic lung changes. Currently, long-term

follow-up studies have not shown significant differences between surfactant-treated patients and

nontreated control groups with regard to PDA, IVH, ROP, NEC, and BPD. Evidence exists that the

length of stay on mechanical ventilation and total ventilator days have been reduced with the use of

surfactant at all gestational age levels, even with the increase of extremely low birth weight infants.
A

dramatic fall in deaths from HMD began in 1991. This probably reflected the introduction across the

nation of surfactant replacement therapy. In long-term follow-up studies, no adverse effects

attributable to surfactant therapy have been identified.

C. Respiratory support

1. Endotracheal intubation and mechanical ventilation are the mainstays of therapy for
infants with HMD in whom apnea or hypoxemia with respiratory acidosis develops. Mechanical

ventilation usually begins with rates of 30-60 breaths/min and inspiratory-expiratory ratios of 1:2. An

initial PIP of 18-30 cm H2O is used, depending on the size of the infant and the severity of the

disease. A PEEP of 4-5 cm H2O results in improved oxygenation, presumably because it assists in the

maintenance of an effective FRC. The lowest possible pressures and inspired oxygen concentrations

are maintained in an attempt to minimize damage to parenchymal tissue. Ventilators with the
capacity

to synchronize respiratory effort may generate less inadvertent airway pressure and lessen

barotrauma. The early use of HFOV has become an increasingly popular and frequently used

ventilator mode for low birth weight infants (Gerstmann et al, 1996; Plavka et al, 1999).

2. CPAP and nasal synchronized intermittent mandatory ventilation (SIMV). Nasal CPAP

(NCPAP) or nasopharyngeal CPAP (NPCPAP) may be used early to delay or prevent the need for

endotracheal intubation. To minimize lung injury associated with intubation and mechanical

ventilation, there has been a recent interest in using CPAP as an initial treatment strategy to treat

HMD even in very low and extremely low birth weight infants. In some centers, this practice has

been used successfully and resulted in decreased incidence of BPD (Aly, 2001; De Klerk & De

Klerk, 2001; Van Marter et al, 2000). In addition, early treatment with surfactant, administered

during a short period of intubation followed by extubation and application of NCPAP is increasingly

being used in Europe. This approach has been used in premature infants <30 weeks' gestation and

significantly reduces the subsequent need for mechanical ventilation (Kamper, 1999; Verder et al,