Safety and potential efficacy of an aerosolized surfactant in human sepsis-induced adult respiratory distress syndrome.
OBJECTIVE
To evaluate the safety and potential efficacy of aerosolized surfactant in intubated patients with adult respiratory distress syndrome (ARDS).


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


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


METHODS
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.


METHODS
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.
Weg
J G
JG
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0026.
Balk
R A
RA
Tharratt
R S
RS
Jenkinson
S G
SG
Shah
J B
JB
Zaccardelli
D
D
Horton
J
J
Pattishall
E N
EN
D018806:APACHE; D000328:Adult; D000336:Aerosols; D000368:Aged; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005233:Fatty Alcohols / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006439:Hemodynamics; D006801:Humans; D007440:Intubation; D008297:Male; D008875:Middle Aged; D010767:Phosphorylcholine; D010865:Pilot Projects; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*; D011446:Prospective Studies; D011663:Pulmonary Surfactants / Q000008:administration & dosage / Q000627:therapeutic use*; D012121:Respiration, Artificial; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D012129:Respiratory Function Tests; D018805:Sepsis / Q000503:physiopathology; D016019:Survival Analysis
D000336:Aerosols; D004338:Drug Combinations; D005233:Fatty Alcohols; D011663:Pulmonary Surfactants; D010767:Phosphorylcholine; D011092:Polyethylene Glycols; C047049:dipalmitoylphosphatidylcholine, hexadecanol, tyloxapol drug combination