Prostaglandin E1 and Survival in Patients with the Adult Respiratory Distress Syndrome

Abstract

A 7-day infusion of prostaglandin E1 (PGE1), an immunomodulator, was evaluated in a prospective, randomized, placebo-controlled, double-blinded trial in surgical patients with the adult respiratory distress syndrome (ARDS). The drug seemed to improve pulmonary function--only two PGE1 patients died with severe pulmonary failure compared with nine placebo patients (p = 0.01). Survival at 30 days after the end of the infusion--the predetermined end point of the study--was significantly better in the patients given PGE1 (p = 0.03), with 15 of 21 PGE1 patients (71%) alive at this time compared with seven of 20 placebo patients (35%). Improvement in overall survival in the PGE1 patients did not reach statistical significance (p = 0.08). Overall survival in patients initially free of severe organ failure, however, was significantly better in the PGE1 patients (p = 0.03). Of the six PGE1 patients free of severe organ failure at time of entry, all survived to leave the hospital; of the 10 placebo patients initially free of severe organ failure, four survived. The drug had no serious side effects and did not potentiate susceptibility to infection. PGE1 is a promising agent for the treatment of ARDS.

Pharmacology of Acute Lung Injury

“…It has provements in gas exchange and survival, a been shown to inhibit chemotaxis and the activation randomized, double-blinded, multicenter trial of of neutrophils in animal models of sepsis and ALI/ patients with ARDS showed no survival advantage. 85,86 ARDS, the release of tumor necrosis factor by macroAs a result of that study, PGE 1 fell out of favor until phages in response to endotoxin, and platelet aga recent randomized, double-blinded trial that used gregation in response to inflammatory stimuli. 76 liposomal encapsulated PGE 1 in 177 patients with Several animal models of lung injury have dem-ARDS.…”

Prostaglandin E1 and arterial occlusive disease: pharmacological considerations

“…The combined anti-inflammatory and anti-aggregatory activity suggested that PGE, might also be useful for the treatment of ARDS, which is often seen in association with major trauma, surgery of sepsis. Although the pathogenesis of ARDS remains unknown, the syndrome seems to be related to pulmonary damage by inflammation and coagulation [33,78]. In a prospective, randomized, placebo-controlled, double-blind pilot trial, the survival 30 days after the end of infusion was significantly better in patients given PGEl (71 %) than in the placebo group (35%) [78], indicating a potential therapeutic efficacy of PGEl in this syndrome.…”

Gas Exchange in the Respiratory Distress Syndromes

“…A number of investigators have studied the effects of systemic vasodilators (e.g., sodium nitroprusside, diltiazem, ketanserin, prostaglandin E 1 , and nitroglycerin) in patients with ARDS/ALI (86)(87)(88)(89)(90)(91)(92). While all these medications caused pulmonary vasodilation, all also increased intrapulmonary shunting indicating that at least some of the pulmonary hypertension in ARDS is the result of increased vascular tone, presumably in response to alveolar and/or mixed venous hypoxia.…”