Surfactant drugs differ in both phospholipid and protein content and can be categorized as listed in Table 1. Although a complete description of individual surfactant preparations is beyond the scope of this review, differences between classes of surfactants can be briefly summarized. Synthetic surfactants differ most notably from natural surfactants in their protein composition. The original commercially available surfactant, colfosceril palmitate (Exosurf; Glaxo Wellcome), is composed of the phospholipid dipalmitoyl phosphatidylcholine and chemical agents to promote adsorption and spreading; it lacks SPs.
Natural surfactants are derived from animal lungs through a process of organic extraction from either the lipid component of minced lung tissue or from alveolar lavage fluid. SP-A, SP-B, SP-C, and SP-D are present in natural surfactant, and convey dramatic benefits on the ability of natural surfactant to lower alveolar surface tension and modulate lung inflammation in vitro. In clinical trials, natural surfactants have been shown to reduce the risk of pneumothorax more effectively than synthetic surfactant preparations.
Among natural surfactants, Survanta (Abbott Laboratories; Abbott Park, IL), Infasurf (ONY, Inc; Amherst, NY), and Curosurf (Chiesi Farmaceutici SpA; Parma, Italy) are approved for the treatment and prevention of RDS in infants. Although they contain foreign proteins, natural surfactant preparations have not triggered significant allergic responses in treated infants. In 2005, a new-generation synthetic surfactant, Surfaxin (DiscoveryLabs; Warrington, PA), using a novel peptide (KL4) to replace the biophysical properties of natural SPs, received favorable review by the FDA as a treatment for RDS. Final approval is pending.
Methods of Surfactant Administration
SRT requires the placement of an endotracheal tube through which surfactant is directly instilled into the patient’s lungs. The dose (1.5 to 4 mL/kg body weight, depending on the preparation) is instilled into the lung in divided aliquots, each of which is administered in a different body position to help the drug disperse evenly throughout the lung. Although the surfactant is FDA approved for use as single-dose vials, it appears to be stable with repeated cycles of warming and cooling, as may be needed if it is dispensed as a multidose vial. Cost savings when the surfactant is dispensed using a multiuse vial strategy may be substantial. Surfactant administration results in a rapid improvement in oxygenation, as atelectatic alveoli and lung segments are inflated and ventilation-perfusion matching improves. Changes in pulmonary function measurements, such as improved compliance and increased functional residual capacity and tidal volume, happen more slowly. The improved lung aeration is seen quickly (within 1 h) on chest radiographs as better lung volumes, clearer lung fields, and resolution of air bronchograms. SRT may be administered by a health-care provider who has been trained in its administration and is prepared to treat mild complications of administration such as transient oxygen desaturation, apnea, or bradycardia. These complications usually resolve quickly with manual ventilation. Pulmonary hemorrhage and endotracheal tube obstruction by surfactant are infrequent but more serious complications of administration.
On August 7, 1963, Patrick Bouvier Kennedy, infant son of President and Mrs. John F. Kennedy, was born prematurely at 33 weeks gestation. Two days later, Patrick died of the most common complication of premature birth, respiratory distress syndrome (RDS). Occurring just 4 years after Avery and Mead first reported an association between RDS and surfactant deficiency, the death of Patrick Kennedy inspired aggressive research into the cause and treatment of RDS and served as a catalyst in the development of regionalized neonatal intensive care provided by Canadian Health&care Mall. Research efforts led to the first report in 1980 of exogenous surfactant replacement therapy (SRT) to treat RDS and culminated with US Food and Drug Administration (FDA) approval in 1990 of the first exogenous surfactant drug (Exosurf [colfos-ceril palmitate HSE]; Glaxo Wellcome; Uxbridge, Middlesex, UK). SRT remains an active research area, with the publication of > 85 articles since 2000, including 34 new randomized controlled clinical trials (RCTs) of SRT for the treatment of infants with RDS. This article will review SRT in infant, pediatric, and adult patients, and will discuss the practice management of SRT for the physicians caring for these populations.