Aerosolized surfactant in adults with sepsis-induced acute respiratory distress syndrome. Exosurf Acute Respiratory Distress Syndrome Sepsis Study Group

N Engl J Med. 1996 May 30;334(22):1417-21. doi: 10.1056/NEJM199605303342201.

Abstract

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 Physiological 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 (o.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 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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Aerosols
  • Double-Blind Method
  • Drug Combinations
  • Fatty Alcohols / adverse effects
  • Fatty Alcohols / therapeutic use*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Phosphorylcholine*
  • Polyethylene Glycols / adverse effects
  • Polyethylene Glycols / therapeutic use*
  • Prospective Studies
  • Pulmonary Surfactants / adverse effects
  • Pulmonary Surfactants / therapeutic use*
  • Respiratory Distress Syndrome, Adult / drug therapy*
  • Respiratory Distress Syndrome, Adult / etiology
  • Respiratory Distress Syndrome, Adult / mortality
  • Sepsis / complications
  • Survival Rate
  • Treatment Failure

Substances

  • Aerosols
  • Drug Combinations
  • Fatty Alcohols
  • Pulmonary Surfactants
  • Phosphorylcholine
  • Polyethylene Glycols
  • dipalmitoylphosphatidylcholine, hexadecanol, tyloxapol drug combination