Prostaglandin [Esub1] ([PGEsub1]) w...

Prostaglandin [Esub1] ([PGEsub1]) was compared to placebo in a 100-patient (50 [PGEsub1] 50 placebo) randomized, doubleblind, clinical trial to determine whether [PGEsub1] therapy enhances survival of patients with adult respiratory distress syndrome (ARDS) when infused between the walls of a central line at 30 ng/kg/min continuously for seven days. At 30 days postinfusion, 30 [PGEsub1] and 24 placebo patients had died. Total deaths judg to be related to the syndrome were 32 and 28 in the [PGEsub1] and placebo assemblages respectively at six months. We judge that [PGE.sub.1] did not enhance survival in patients with established ARDS. [PGEsub1] augmented the hyperdynamic circulation of these patients from reducing systemic and pulmonary vascular resistance, which followed in a reduction of kindred pressures and increased stroke contortion cardiac output, and heart rate. An improvement in oxygen availability and oxygen consumption was observ with [PGEsub1] therapy. [PGEsub1] was associated with an increased incidence of diarrhea (six patients in the [PGEsub1] dispose vs one in the placebo cluster p<0.05). Other adverse powers included hypotension (ten patients in the [PGEsub1] assign places to vs seven in the placebo group) excitement (six patients in the [PGEsub1] dispose vs three in the placebo group) and non-fatal dysrhythmias (ten in the [PGEsub1] clump vs five in the placebo group)

(Chest 1989; 96:114-19)

The adult respiratory distress syndrome (ARDS) exhibits when the lung is injured by the agency of a variety of processes including as it is diverse insults such as bacterial sepsis, aspiration of gastric contenteds and trauma.[1-3] ARDS is characterized by dint of dyspnea, hypoxemia, diffuse pulmonary infiltrates onward chest roentgenogram, and decreased lung compliance.[1-5] Regardless of the causes, the syndrome is associated with increase of diffuse pulmonary cell injury, interstitial and alveolar edema, and inflammation.[2,3] Patients who survive the initial period of injury can revive normal lung function and go [i]or[/i] come back to productive lives; therefore, therapies that provide protection in the early phases of lung injury are needed

A mortality rate of greater than 50 percent is seen in ARDS patients.[1,2] Sophisticated supportive therapy has not been shown to increase survival rates in the last decade. plane extracorporeal membrane oxygenation used late in the treatment of ARDS did not improve survival. latter attention has focused on the contribution of the acute inflammatory reaction to the pathogenesis of ARDS. With this rationale, controll clinical trials have been convoyed using blockers of the inflammatory reaction to treat ARDS.[6-8] It has been hypothesized that specific pharmacologic therapy for ARDS might counterpart the current supportive therapy and improve survival. A novel single center study of [PGEsub1] showed an improvement in survival compared to placebo.[6] The view of our multicenter study was to determine whether [PGEsub1] would increase the survival rate of patients with ARDS resulting postoperatively or from trauma or sepsis, with no morose concomitant liver, kidney, cardiac, or central nervous hypothesis failure.

Methods

consideration Design

This double-blind, randomized, placebo-controlled clinical trial was waysed in 13 centers in the United States. The central coordinating center was at the Upjohn Company, Kalamazoo, MI. Patients in each treatment center were randomized separately. The meditation was a five-stage, group-sequential trial that allowed enrollment of up to 160 patients, with 32 patients (16 by treatment) in each sequential obstruct Enrollment blocks were filled chronologically through order of randomization date. A 30-day postinfusion survival analysis and safety evaluation was planned at the completion of each sequence (32 patients). To avoid the be deriveds from any one center overpowering those from others, no center could have more than 20 percent of the total patients in a blockade at each of the planned interim analyses. Additional patients registered by that center would be placed into the nearest sequential block. Long-term mortality was assessed in consequence of six months.

Patient Selection

Patients 18 years of age or older of the two sexes, except pregnant women, were eligible for enrollment They were chronicleed if they: 1) had ARDS that occurr postoperatively, or following trauma or sepsis; 2) had a pulmonary artery catheter in place; 3) were mechanically ventilated with a ratio of partial compressing of oxygen in arterial life-blood to fractional inspired oxygen ([PaO.sub.2]:[FIo.sub.2]) les than or equal to 150 with no positive period expiratory pressure (PEEP), or les than or equal to 200 with any PEEP; and 4) had a chest x-ray film showing bilateral lung infiltrates.

Patients were exclud from the investigation for the following reasons:

* history of censorious lung disease (such as chronic obstructive pulmonary disease)

* Glasgow coma scores les than 8 resulting from head trauma

* serum bilirubin measurements greater than 4 mg/dl or a serum creatinine measurement greater than 3 mg/dl