The effects of ibuprofen on the physiology and survival of patients with sepsis. The Ibuprofen in Sepsis Study Group.
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.
Bernard
G R
GR
Division of Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Wheeler
A P
AP
Russell
J A
JA
Schein
R
R
Summer
W R
WR
Steinberg
K P
KP
Fulkerson
W J
WJ
Wright
P E
PE
Christman
B W
BW
Dupont
W D
WD
Higgins
S B
SB
Swindell
B B
BB
D000140:Acidosis, Lactic / Q000188:drug therapy; D004311:Double-Blind Method; D011464:Epoprostenol / Q000652:urine; D005260:Female; D005334:Fever / Q000188:drug therapy; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption / Q000187:drug effects; D012128:Respiratory Distress Syndrome / Q000517:prevention & control; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D012769:Shock / Q000517:prevention & control; D015996:Survival Rate; D013931:Thromboxanes / Q000652:urine
D013931:Thromboxanes; D011464:Epoprostenol; D007052:Ibuprofen