Effects of ibuprofen on the physiology and survival of hypothermic sepsis

Objectives: The objective was to compare the clinical and physiologic chara cteristics of febrile septic patients with hypothermic septic patients; and to examine plasma levels of cytokines tumor necrosis factor alpha (TNF-alp ha) and interleukin 6 (IL 6) and the lipid mediators thromboxane B-2 (TxB(2 )) and prostacyclin in hypothermic septic patients in comparison with febri le patients. Most importantly, we wanted to report the effect of ibuprofen treatment on vital signs, organ failure, and mortality in hypothermic sepsi s, Setting: The study was performed in the intensive care units (ICUs) of seve n clinical centers in the United States and Canada. Patients: Four hundred fifty-five patients admitted to the ICU who met defi ned criteria for severe sepsis and were suspected of having a serious infec tion. Intervention: Ibuprofen at a dose of 10 mg/kg (maximum 800 mg) was administ ered intravenously over 30 to 60 mins every 6 hrs for eight doses vs, place bo (glycine buffer vehicle). Measurements and Main Results: Forty four (10%) septic patients met criteri a for hypothermia and 409 were febrile, The mortality rate was significantl y higher in hypothermic patients, 70% vs. 35% for febrile patients, At stud y entry, urinary metabolites of TxB(2) prostacyclin, and serum levels of TN F-alpha and IL 6 were significantly elevated in hypothermic patients compar ed with febrile patients. In hypothermic patients treated with ibuprofen, t here was a trend toward an increased number of days free of major organ sys tem failures and a significant reduction in the 30 day mortality rate from 90% (18/20 placebo treated patients) to 54% (13/24 ibuprofen treated patien ts). Conclusions: Hypothermic sepsis has an incidence of similar to 10% and an u ntreated mortality twice that of severe sepsis presenting with fever. When compared with febrile patients, the hypothermic group has an amplified resp onse with respect to cytokines TNF-a and IL 6 and lipid mediators TxB(2) an d prostacyclin. Treatment with ibuprofen may decrease mortality in this sel ect group of septic patients.