The effects of ibuprofen on the physiology and survival of patients with sepsis

被引:571
作者
Bernard, GR
Wheeler, AP
Russell, JA
Schein, R
Summer, WR
Steinberg, KP
Fulkerson, WJ
Wright, PE
Christman, BW
Dupont, WD
Higgins, SB
Swindell, BB
机构
[1] VANDERBILT UNIV, MED CTR, DIV PULM & CRIT CARE MED, NASHVILLE, TN 37232 USA
[2] VANDERBILT UNIV, MED CTR, DIV BIOSTAT, NASHVILLE, TN 37232 USA
[3] VANDERBILT UNIV, MED CTR, DIV BIOMED ENGN & COMP, NASHVILLE, TN 37232 USA
[4] UNIV BRITISH COLUMBIA, VANCOUVER, BC V5Z 1M9, CANADA
[5] ST PAULS HOSP, DEPT MED, PROGRAM CRIT CARE MED, VANCOUVER, BC V6Z 1Y6, CANADA
[6] UNIV MIAMI, SCH MED, MIAMI, FL USA
[7] DEPT VET AFFAIRS MED CTR, MIAMI, FL USA
[8] LOUISIANA STATE UNIV, MED CTR, DEPT PULM & CRIT CARE MED, NEW ORLEANS, LA USA
[9] UNIV WASHINGTON, HARBORVIEW MED CTR, DIV PULM & CRIT CARE MED, SEATTLE, WA 98104 USA
[10] DUKE UNIV, MED CTR, DIV PULM & CRIT CARE MED, DURHAM, NC USA
[11] METHODIST HOSP, DIV PULM MED, INDIANAPOLIS, IN USA
关键词
D O I
10.1056/NEJM199703273361303
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background In patients with sepsis the production of arachidonic acid metabolites by cyclooxygenase increases, but the pathophysiologic role of these prostaglandins is unclear. In animal models, inhibition of cyclooxygenase by treatment with ibuprofen before the onset of sepsis reduces physiologic abnormalities and improves survival. In pilot studies of patients with sepsis, treatment with ibuprofen led to improvements in gas exchange and airway mechanics. Methods From October 1989 to March 1995, we conducted a randomized, double-blind, placebo-controlled trial of intravenous ibuprofen (10 mg per kilogram of body weight [maximal dose, 800 mg], given every six hours for eight doses) in 455 patients who had sepsis, defined as fever, tachycardia, tachypnea, and acute failure of at least one organ system. Results In the ibuprofen group, but not the placebo group, there were significant declines in urinary levels of prostacyclin and thromboxane, temperature, heart rate, oxygen consumption, and lactic acidosis. With ibuprofen therapy there was no increased incidence of renal dysfunction, gastrointestinal bleeding, or other adverse events. However, treatment with ibuprofen did not reduce the incidence or duration of shock or the acute respiratory distress syndrome and did not significantly improve the rate of survival at 30 days (mortality, 37 percent with ibuprofen vs. 40 percent with placebo). Conclusions In patients with sepsis, treatment with ibuprofen reduces levels of prostacyclin and thromboxane and decreases fever, tachycardia, oxygen consumption, and lactic acidosis, but it does not prevent the development of shock or the acute respiratory distress syndrome and does not improve survival. (N EnglJ Med 1997;336:912-8.) (C) 1997, Massachusetts Medical Society.
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页码:912 / 918
页数:7
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