Evaluation of prostaglandin E1 for prevention of respiratory failure in high risk trauma patients: a prospective clinical trial and correlation with plasma suppressive factors for neutrophil activation.
A group of 48 critically injured patients were entered into a prospective, double-blind, placebo-controlled trial to evaluate the efficacy of early infusion of PGE1 for reducing the incidence of severe respiratory failure and mortality. Secondary assessments examined the effects of the PGE1 infusion on plasma mediated suppression of PMN superoxide production and loss of PMN granule enzyme content. The incidence of severe respiratory failure was lower in the PGE1 group--13% versus 32%, but this did not reach significance. The overall morality was equivalent between the two groups--26% (PGE1) versus 28% (placebo). The suppressive activity of the patient plasma was assayed by measurement of normal PMN superoxide production relative to normal control plasma (ratio P:C). The baseline ratio P:C was 62 +/- 5% in the PGE1 group versus 60 +/- 5% in the placebo group. The day 1 plasma samples showed significant reversal of plasma suppressive activity in the PGE1 group--ratio P:C 88 +/- 5% versus 67 +/- 5% in the placebo group (P less than 0.02). In patients who received the full 7 days of infusion, the plasma suppressive activity remained significantly diminished in the PGE1 group--ratio P:C 77 +/- 4% versus 61 +/- 5% (P less than 0.04). The baseline lysozyme content of patient PMN's relative to that of normal control PMNs (ratio P:C) was 119 +/- 14% in the PGE1 group. A significant loss of lysozyme content was observed in the PGE1 group on day 1 of the infusion--ratio P:C 79 +/- 8% (P less than 0.03), and was associated with a reduction in the plasma suppressive activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Vassar
M J
MJ
Department of Surgery, UC Davis Medical Center, Sacramento 95817.
Fletcher
M P
MP
Perry
C A
CA
Holcroft
J W
JW
D000328:Adult; D000527:Alprostadil / Q000494:pharmacology / Q000627:therapeutic use*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003422:Critical Care; D003594:Cytoplasmic Granules / Q000201:enzymology; D004311:Double-Blind Method; D006801:Humans; D015994:Incidence; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D011446:Prospective Studies; D011654:Pulmonary Edema / Q000188:drug therapy / Q000209:etiology / Q000401:mortality / Q000503:physiopathology / Q000517:prevention & control*; D012306:Risk; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014947:Wounds and Injuries / Q000150:complications* / Q000401:mortality
D013481:Superoxides; D000527:Alprostadil