The New England Journal of Medicine, 1996, Vol.334(22), pp.1417-1422
Background Patients with acute respiratory distress syndrome (ARDS) have a deficiency of surfactant. Surfactant replacement improves physiologic function in such patients, and preliminary data suggest that it may improve survival. Methods We conducted a prospective, multicenter, double-blind, randomized, placebo-controlled trial involving 725 patients with sepsis-induced ARDS. Patients were stratified according to the risk of death at base line (indicated by their score on the Acute Physiologic and Chronic Health Evaluation [APACHE III] index) and randomly assigned to receive either continuously administered synthetic surfactant (13.5 mg of dipalmitoylphosphatidylcholine per milliliter; 364 patients) or placebo (0.45 percent saline; 361 patients) in aerosolized form for up to five days. Results The demographic and physiologic characteristics of the two treatment groups were similar at base line. The mean (±SD) age was 50±17 years in the surfactant group and 53±18 years in the placebo group, and the mean APACHE III scores at randomization were 70.4±25 and 70.5±25, respectively. Hemodynamic measures, measures of oxygenation, duration of mechanical ventilation, and length of stay in the intensive care unit did not differ significantly in the two groups. Survival at 30 days was 60 percent for both groups. Survival was similar in the groups when analyzed according to APACHE III score, cause of death, time of onset and severity of ARDS, presence or absence of documented sepsis, underlying disease, whether or not there was a do-not-resuscitate order, and medical center. Increased secretions were significantly more frequent in the surfactant group; the rates of other complications were similar in the two groups. Conclusions The continuous administration of aerosolized synthetic surfactant to patients with sepsis-induced ARDS had no significant effect on 30-day survival, length of stay in the intensive care unit, duration of mechanical ventilation, or physiologic function. When Ashbaugh et al.1 described the acute respiratory distress syndrome (ARDS) in 1967, they suggested that the clinical and pathological findings in patients with this condition were in part due to abnormalities in the alveolar wall. Petty et al.2,3 later reported both qualitative and quantitative abnormalities in lung surfactant in patients with ARDS. Hallman et al.4 confirmed that surfactant not only is decreased in quantity but also is functionally abnormal in patients with ARDS. These studies offer evidence that ARDS is a condition of surfactant deficiency.5 Recent data suggest that mechanical ventilation may induce lung damage. Dreyfuss et al. . . .
Administration, Inhalation–Adverse Effects ; Aerosols–Therapeutic Use ; Double-Blind Method–Adverse Effects ; Drug Combinations–Therapeutic Use ; Fatty Alcohols–Adverse Effects ; Female–Therapeutic Use ; Humans–Drug Therapy ; Male–Etiology ; Middle Aged–Mortality ; Phosphorylcholine–Complications ; Polyethylene Glycols–Complications ; Prospective Studies–Complications ; Pulmonary Surfactants–Complications ; Respiratory Distress Syndrome, Adult–Complications ; Sepsis–Complications ; Survival Rate–Complications ; Treatment Failure–Complications ; Abridged ; Aerosols ; Drug Combinations ; Fatty Alcohols ; Pulmonary Surfactants ; Phosphorylcholine ; Polyethylene Glycols ; Dipalmitoylphosphatidylcholine, Hexadecanol, Tyloxapol Drug Combination;