Table 3.

Summary of Clinical Studies of Vasodilators in Acute Lung Injury (ALI)/Acute Respiratory Distress Syndrome (ARDS)

Intervention	Author & Year	Study Design	Study Population & Number of Patients	Results
Continuous IV PGE 1, dose titrated to 30 ng/kg/min for 48–72 h or placebo	Shoemaker et al 1986 [207]	Prospective, randomized, blinded, placebo- controlled trial, phase I/II	Severely ill adult surgical patients with ARDS, N = 9	Decrease in PA pressures, PVR, and SVR and increase in oxygenation, oxygen delivery, and cardiac output
Continuous IV PGE 1, maximum dose 30 ng/kg/min for 7 d or placebo	Holcroft et al 1986 [91]	Prospective, randomized, double-blind, placebo controlled trial, phase II	Adult surgical patients with ARDS, N = 41	Trend toward survival benefit; 30-d mortality in PGE 1 group vs placebo 29% vs 65%, respectively (P = .08)
Continuous IV PGE 1, maximum dose 30 ng/kg/min for 7 d or placebo	Bone et al 1989 [93] Slotman et al 1992 [92]	Prospective, randomized, double-blind, placebo- controlled, multiple-center trial, phase II	Adult patients with ARDS attributable to trauma, surgery, or sepsis, N = 100; N = 147	No survival benefit; 30-d mortality in PGE 1 group vs placebo was 30/50 vs 24/50, respectively; RR 1.15 (95% CI 0.89–1.55)
Continuous IV PGE 1, dose titrated to 30 ng/kg/min for 7 d or placebo	Rossignon et al 1990 [94]	Prospective, randomized, double-blind study, phase II	Adult patients with ARDS, N = 23	No significant effect on the function activity of polymorphonuclear leukocytes
Liposomal IV PGE 1, dose titrated to 3.6 μg/kg every 6 h for 7 d or placebo	Abraham et al 1996 [96]	Prospective, randomized, double-blind, placebo- controlled, multiple-center trial, phase II	Adult patients with ARDS, N = 25	Statistically significant improvement in oxygenation (day 3), lung compliance, and ventilator dependency (day 8) in PGE 1 group. Mortality difference in PGE 1 group vs placebo (6% vs 25%, P = .23) not significant
Liposomal IV PGE 1, dose titrated to 3.6 μg/kg every 6 h for 7 d or placebo	Abraham et al 1999 [97]	Prospective, randomized, double-blind, placebo- controlled, multiple-center trial, phase III	Adult patients with ARDS per AECC criteria, N = 350	No difference in mortality or duration of mechanical ventilation. Mortality rate in PGE 1 group vs placebo 32% vs 29% (P = .55) and median number of days to off mechanical ventilation 16.9 vs 19.6 (P = .94)
Liposomal IV PGE 1, dose titrated to 1.8 μg/kg every 6 h for 7 d or placebo	Vincent et al 2001 [98]	Prospective, randomized, double-blind, placebo- controlled, multiple-center trial, phase III	Adult patients with ARDS per AECC criteria, N = 102	No difference in mortality or duration of mechanical ventilation; 28-d mortality rate in PGE1 group 30% vs 28% for placebo (P = .78). Ventilator-free days 16 d in PGE1 group vs. 16.6 with placebo (P = .94)

IV – intravenously; PGE 1 – prostaglandin E1; PA – pulmonary artery; PVR – pulmonary vascular resistance; SVR - systemic vascular resistance; RR – relative risk; CI – confidence interval; AECC – American European Consensus Conference.

Adverse events reported: hypotension, nonfatal arrythmias, diarrhea, and flushing.