Researchers everywhere the country...

Researchers everywhere the country are diligently searching for fresh therapeutic agents that could be effective in treating patients with the adult respiratory distress syndrome (ARDS). The prognosis for patients with this syndrome remains dismal, with survival rates generally reported to be approximately 35 to 40 percent[12] Fifty percent of all patients with this syndrome die by dint of day 13 after onset.[1] Effective mix with drugs therapy to change the course of ARDS has been evaluated and includes corticosteroids, heparin, nonsteroidal anti-inflammatory medicines and vasopressors. To date, none of these various agents has produc any real differences in the issue of ARDS patients. Although many of these treatments have produc measurable changes in pulmonary vascular or parenchymal physiology, the mortality rate for physic treated-patients has remained the same as that for placebotreated patients.

This issue of Chest (see page 114) contains the summary report by the agency of Bone et al evaluating the use of parenterally infused prostaglandin [Esub1] ([PGEsub1]) as a therapeutic agent in patients with ARDS. [PGEsub1] is a monenoic prostaglandin that acts as a forcible vasodilator of pulmonary veins. This vasodilator capacity is minimized in the pulmonary vascular bed in subordination to resting conditions but becomes frequently more active in vessels with increased tone induced by dint of hyperoxia. [PGE.sub.1] is also effective in preventing platelet aggregation in vivo, and the agent has been shown to stiffen the pulmonary hypertensive effects of infused adenosine diphosphate.[3,4] Systemic arterial urgency falls following [PGE.sub.1] infusion, and this issue is thought to be a be derived of both decreased peripheral vascular resistance and decreased systemic venous return

Dr Bone's contemplation group was formed in replication to a single center report by way of Holcroft et al,[5] which raise an improvement in survival of ARDS patients treated with [PGEsub1] compared with a placebo-treated clump The Holcroft group's 41 patients were obtained from a surgical ICU and they reported that 71 percent of the 21 [PGE.sub.1]-treated patients survived 30 days postinfusion, with solely 35 percent of the 20 placebo-treated patients surviving for 30 days. Of note, seven of the patients who were alive at 30 days did ultimately die on 70 days (four of the regulate subjects died between days 30 and 37)

The at hand study in Chest by Bone et al was a larger (50 [PGEsub1] 50 placebo) randomized, doubleblind clinical trial that included patients in the pair medical and surgical ICUs. These authors set up that [PGE.sub.1] did not enhance ARDS patient survival, with 60 percent of the [PGE.sub.1]-treated patients and 48 percent of the placebo-treated patients dying in the first 30 days following infusion. Similar changes in hemodynamic parameters were reported from both Holcroft's and Bone's clumps in [PGE.sub.1]-treated patients with decreases in systemic and pulmonary vascular resistances, nevertheless these changes did not translate into differences, in mortality in the patients with ARDS.

with what intent did these two studies exhibit such different results despite using the same therapeutic agent given in an identical fashion? The answer may lie in differences in patient populations entering into the trials. The Holcroft cogitation was heavily weighted with trauma patients who have a higher ARDS survival than medical ARDS patients with sepsis or the septic syndrome The prevalence of congestive heart failure (CHF) in the Holcroft ARDS patients was also not documented as clearly as the Bone multicenter research which used pulmonary artery wedge urgencys to eliminate patients with CHF from entering into the trial. Finally, the severity of ARDS as estimated by way of the [PaO.sub.2]:[FIo.sub.2] ratio was different in these sum of two units studies, with the Bone consideration requiring this ratio to be 150 or les without peer before entry, and the Holcroft subject of attention including 22 patients with ratios > 150 forward entry.

The bottom line concerning the use of [PGEsub1] in ARDS revealed that in the larger, more tightly controll multicenter reflection [PGE.sub.1] was not more effective in changing the mortality of ARDS than placebo. Since one as well as the other the Holcroft and Bone studies reported a number of side purports in patients receiving [PGE.sub.1], pulmonary physicians should not commonly be using this agent to treat patients with ARDS because we have not identified any substantial differences in mortality from [PGEsub1] infusion, although we have defined several significant risks. The bad moderns emerging from this latest trial is that [PGEsub1] is not the magic bullet to change mortality in patients with ARDS. Research into of recent origin pharmacologic agents must be continued with the trust that an effective therapy will rise into view in the future.

Stephen G Jenkinson, MD FCCP San Antonio

Professor and Chief, Division of Pulmonary Diseases/Critical Care Medicine, University of Texas Health Science Center

REFERENCES

[1] Flower, AA, Hamman RF Zerbe journey Benson KN, Hyers TM. Adult respiratory distress syndrome Am Rev Respir Dis 1985; 132:472-78