Safety and potential efficacy of an aerosolized surfactant in human sepsis-induced adult respiratory distress syndrome

JAMA. 1994 Nov 9;272(18):1433-8.


Objective: To evaluate the safety and potential efficacy of aerosolized surfactant in intubated patients with adult respiratory distress syndrome (ARDS).

Design: A prospective, double-blind, placebo-controlled, randomized, parallel, multicenter pilot clinical trial.

Patients: A total of 51 patients with sepsis-induced ARDS were entered into the study within 18 hours of developing sepsis or sepsis syndrome.

Intervention: Patients were randomized into four treatment groups in a 2:1:2:1 ratio, as follows: 12 hours of surfactant per day, 12 hours of 0.6% saline per day, 24 hours of surfactant per day, and 24 hours of 0.6% saline per day. Surfactant or saline was aerosolized continuously for up to 5 days using an in-line nebulizer that aerosolized only during inspiration.

Main outcome measures: Ventilatory data, arterial blood gases, and hemodynamic parameters were measured at baseline, every 4 or 8 hours during the 5 days of treatment, 24 hours after treatment, and 30 days after treatment, at which time mortality was also assessed. Safety was evaluated throughout the 30 days of the study.

Results: Surfactant was administered safely in ventilated patients when given continuously throughout the 5 days using the nebulizer system. Although there were no differences in any physiological parameters between the treatment groups, there was a dose-dependent trend in reduction of mortality from 47% in the combined placebo group to 41% and 35% in the groups treated with 12 hours and 24 hours of surfactant per day, respectively.

Conclusions: Aerosolized surfactant was well tolerated when administered on a continuous basis for up to 5 days; however, at the doses given, it did not result in significant improvements in patients with sepsis-induced ARDS.

Publication types

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

MeSH terms

  • Adult
  • Aerosols
  • Aged
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Combinations
  • Fatty Alcohols / administration & dosage
  • Fatty Alcohols / therapeutic use*
  • Female
  • Hemodynamics
  • Humans
  • Intubation
  • Male
  • Middle Aged
  • Phosphorylcholine*
  • Pilot Projects
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / therapeutic use*
  • Prospective Studies
  • Pulmonary Surfactants / administration & dosage
  • Pulmonary Surfactants / therapeutic use*
  • Respiration, Artificial
  • Respiratory Distress Syndrome / drug therapy*
  • Respiratory Distress Syndrome / etiology
  • Respiratory Distress Syndrome / physiopathology
  • Respiratory Distress Syndrome / therapy
  • Respiratory Function Tests
  • Sepsis / physiopathology
  • Survival Analysis


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