Effects of ibuprofen on the physiology and survival of hypothermic sepsis

Murray M. Arons, Arthur P. Wheeler, Gordon R. Bernard, Brian W. Christman, James A. Russell, Roland Schein, Warren R. Summer, Kenneth P. Steinberg, William Fulkerson, Patrick Wright, William D. Dupont, Bridgett B. Swindell, Alana Drummond, Maria Pena, Bennett DeBoisblanc, Brenda Everett, Chris Glenn, Denise Tebbe, Laurence C. Carmichael, Mary J. StroudStanley B. Higgins, Keyuan Jiang, Walton D. Plummer, Frank E. Carroll, Leonard D. Hudson, Doreen Anardi, Mary Jo Abernathy, Lee Mallatratt, Pat Weston, Patrick E. Wright, Kelly Colvin

Research output: Contribution to journalArticle

181 Citations (Scopus)

Abstract

Objectives: The objective was to compare the clinical and physiologic characteristics of febrile septic patients with hypothermic septic patients; and to examine plasma levels of cytokines tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) and the lipid mediators thromboxane B2 (TxB2) and prostacyclin in hypothermic septic patients in comparison with febrile patients. Most importantly, we wanted to report the effect of ibuprofen treatment on vital signs, organ failure, and mortality in hypothermic sepsis. Setting: The study was performed in the intensive care units (ICUs) of seven clinical centers in the United States and Canada. Patients: Four hundred fifty-five patients admitted to the ICU who met defined criteria for severe sepsis and were suspected of having a serious infection. Intervention: Ibuprofen at a dose of 10 mg/kg (maximum 800 mg) was administered intravenously over 30 to 60 mins every 6 hrs for eight doses vs. placebo (glycine buffer vehicle). Measurements and Main Results: Forty-four (10%) septic patients met criteria for hypothermia and 409 were febrile. The mortality rate was significantly higher in hypothermic patients, 70% vs. 35% for febrile patients. At study entry, urinary metabolites of TxB2, prostacyclin, and serum levels of TNF-α and IL-6 were significantly elevated in hypothermic patients compared with febrile patients. In hypothermic patients treated with ibuprofen, there was a trend toward an increased number of days free of major organ system failures and a significant reduction in the 30-day mortality rate from 90% (18/20 placebo-treated patients) to 54% (13/24 ibuprofen-treated patients). Conclusions: Hypothermic sepsis has an incidence of ~10% and an untreated mortality twice that of severe sepsis presenting with fever. When compared with febrile patients, the hypothermic group has an amplified response with respect to cytokines TNF-α and IL-6 and lipid mediators TxB2 and prostacyclin. Treatment with ibuprofen may decrease mortality in this select group of septic patients.

Original languageEnglish
Pages (from-to)699-707
Number of pages9
JournalCritical Care Medicine
Volume27
Issue number4
DOIs
StatePublished - Jan 1 1999

Fingerprint

Ibuprofen
Sepsis
Survival
Fever
Thromboxane B2
Epoprostenol
Mortality
Interleukin-6
Tumor Necrosis Factor-alpha
Intensive Care Units
Placebos
Cytokines
Lipids
Vital Signs
Hypothermia
Glycine

Keywords

  • Cytokines
  • Eicosinoids
  • Human
  • Hypothermia
  • Ibuprofen
  • Interleukins
  • Prostaglandins
  • Sepsis
  • Thromboxane
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Arons, M. M., Wheeler, A. P., Bernard, G. R., Christman, B. W., Russell, J. A., Schein, R., ... Colvin, K. (1999). Effects of ibuprofen on the physiology and survival of hypothermic sepsis. Critical Care Medicine, 27(4), 699-707. https://doi.org/10.1097/00003246-199904000-00020

Effects of ibuprofen on the physiology and survival of hypothermic sepsis. / Arons, Murray M.; Wheeler, Arthur P.; Bernard, Gordon R.; Christman, Brian W.; Russell, James A.; Schein, Roland; Summer, Warren R.; Steinberg, Kenneth P.; Fulkerson, William; Wright, Patrick; Dupont, William D.; Swindell, Bridgett B.; Drummond, Alana; Pena, Maria; DeBoisblanc, Bennett; Everett, Brenda; Glenn, Chris; Tebbe, Denise; Carmichael, Laurence C.; Stroud, Mary J.; Higgins, Stanley B.; Jiang, Keyuan; Plummer, Walton D.; Carroll, Frank E.; Hudson, Leonard D.; Anardi, Doreen; Abernathy, Mary Jo; Mallatratt, Lee; Weston, Pat; Wright, Patrick E.; Colvin, Kelly.

In: Critical Care Medicine, Vol. 27, No. 4, 01.01.1999, p. 699-707.

Research output: Contribution to journalArticle

Arons, MM, Wheeler, AP, Bernard, GR, Christman, BW, Russell, JA, Schein, R, Summer, WR, Steinberg, KP, Fulkerson, W, Wright, P, Dupont, WD, Swindell, BB, Drummond, A, Pena, M, DeBoisblanc, B, Everett, B, Glenn, C, Tebbe, D, Carmichael, LC, Stroud, MJ, Higgins, SB, Jiang, K, Plummer, WD, Carroll, FE, Hudson, LD, Anardi, D, Abernathy, MJ, Mallatratt, L, Weston, P, Wright, PE & Colvin, K 1999, 'Effects of ibuprofen on the physiology and survival of hypothermic sepsis', Critical Care Medicine, vol. 27, no. 4, pp. 699-707. https://doi.org/10.1097/00003246-199904000-00020
Arons, Murray M. ; Wheeler, Arthur P. ; Bernard, Gordon R. ; Christman, Brian W. ; Russell, James A. ; Schein, Roland ; Summer, Warren R. ; Steinberg, Kenneth P. ; Fulkerson, William ; Wright, Patrick ; Dupont, William D. ; Swindell, Bridgett B. ; Drummond, Alana ; Pena, Maria ; DeBoisblanc, Bennett ; Everett, Brenda ; Glenn, Chris ; Tebbe, Denise ; Carmichael, Laurence C. ; Stroud, Mary J. ; Higgins, Stanley B. ; Jiang, Keyuan ; Plummer, Walton D. ; Carroll, Frank E. ; Hudson, Leonard D. ; Anardi, Doreen ; Abernathy, Mary Jo ; Mallatratt, Lee ; Weston, Pat ; Wright, Patrick E. ; Colvin, Kelly. / Effects of ibuprofen on the physiology and survival of hypothermic sepsis. In: Critical Care Medicine. 1999 ; Vol. 27, No. 4. pp. 699-707.
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abstract = "Objectives: The objective was to compare the clinical and physiologic characteristics of febrile septic patients with hypothermic septic patients; and to examine plasma levels of cytokines tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) and the lipid mediators thromboxane B2 (TxB2) and prostacyclin in hypothermic septic patients in comparison with febrile patients. Most importantly, we wanted to report the effect of ibuprofen treatment on vital signs, organ failure, and mortality in hypothermic sepsis. Setting: The study was performed in the intensive care units (ICUs) of seven clinical centers in the United States and Canada. Patients: Four hundred fifty-five patients admitted to the ICU who met defined criteria for severe sepsis and were suspected of having a serious infection. Intervention: Ibuprofen at a dose of 10 mg/kg (maximum 800 mg) was administered intravenously over 30 to 60 mins every 6 hrs for eight doses vs. placebo (glycine buffer vehicle). Measurements and Main Results: Forty-four (10{\%}) septic patients met criteria for hypothermia and 409 were febrile. The mortality rate was significantly higher in hypothermic patients, 70{\%} vs. 35{\%} for febrile patients. At study entry, urinary metabolites of TxB2, prostacyclin, and serum levels of TNF-α and IL-6 were significantly elevated in hypothermic patients compared with febrile patients. In hypothermic patients treated with ibuprofen, there was a trend toward an increased number of days free of major organ system failures and a significant reduction in the 30-day mortality rate from 90{\%} (18/20 placebo-treated patients) to 54{\%} (13/24 ibuprofen-treated patients). Conclusions: Hypothermic sepsis has an incidence of ~10{\%} and an untreated mortality twice that of severe sepsis presenting with fever. When compared with febrile patients, the hypothermic group has an amplified response with respect to cytokines TNF-α and IL-6 and lipid mediators TxB2 and prostacyclin. Treatment with ibuprofen may decrease mortality in this select group of septic patients.",
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T1 - Effects of ibuprofen on the physiology and survival of hypothermic sepsis

AU - Arons, Murray M.

AU - Wheeler, Arthur P.

AU - Bernard, Gordon R.

AU - Christman, Brian W.

AU - Russell, James A.

AU - Schein, Roland

AU - Summer, Warren R.

AU - Steinberg, Kenneth P.

AU - Fulkerson, William

AU - Wright, Patrick

AU - Dupont, William D.

AU - Swindell, Bridgett B.

AU - Drummond, Alana

AU - Pena, Maria

AU - DeBoisblanc, Bennett

AU - Everett, Brenda

AU - Glenn, Chris

AU - Tebbe, Denise

AU - Carmichael, Laurence C.

AU - Stroud, Mary J.

AU - Higgins, Stanley B.

AU - Jiang, Keyuan

AU - Plummer, Walton D.

AU - Carroll, Frank E.

AU - Hudson, Leonard D.

AU - Anardi, Doreen

AU - Abernathy, Mary Jo

AU - Mallatratt, Lee

AU - Weston, Pat

AU - Wright, Patrick E.

AU - Colvin, Kelly

PY - 1999/1/1

Y1 - 1999/1/1

N2 - Objectives: The objective was to compare the clinical and physiologic characteristics of febrile septic patients with hypothermic septic patients; and to examine plasma levels of cytokines tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) and the lipid mediators thromboxane B2 (TxB2) and prostacyclin in hypothermic septic patients in comparison with febrile patients. Most importantly, we wanted to report the effect of ibuprofen treatment on vital signs, organ failure, and mortality in hypothermic sepsis. Setting: The study was performed in the intensive care units (ICUs) of seven clinical centers in the United States and Canada. Patients: Four hundred fifty-five patients admitted to the ICU who met defined criteria for severe sepsis and were suspected of having a serious infection. Intervention: Ibuprofen at a dose of 10 mg/kg (maximum 800 mg) was administered intravenously over 30 to 60 mins every 6 hrs for eight doses vs. placebo (glycine buffer vehicle). Measurements and Main Results: Forty-four (10%) septic patients met criteria for hypothermia and 409 were febrile. The mortality rate was significantly higher in hypothermic patients, 70% vs. 35% for febrile patients. At study entry, urinary metabolites of TxB2, prostacyclin, and serum levels of TNF-α and IL-6 were significantly elevated in hypothermic patients compared with febrile patients. In hypothermic patients treated with ibuprofen, there was a trend toward an increased number of days free of major organ system failures and a significant reduction in the 30-day mortality rate from 90% (18/20 placebo-treated patients) to 54% (13/24 ibuprofen-treated patients). Conclusions: Hypothermic sepsis has an incidence of ~10% and an untreated mortality twice that of severe sepsis presenting with fever. When compared with febrile patients, the hypothermic group has an amplified response with respect to cytokines TNF-α and IL-6 and lipid mediators TxB2 and prostacyclin. Treatment with ibuprofen may decrease mortality in this select group of septic patients.

AB - Objectives: The objective was to compare the clinical and physiologic characteristics of febrile septic patients with hypothermic septic patients; and to examine plasma levels of cytokines tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) and the lipid mediators thromboxane B2 (TxB2) and prostacyclin in hypothermic septic patients in comparison with febrile patients. Most importantly, we wanted to report the effect of ibuprofen treatment on vital signs, organ failure, and mortality in hypothermic sepsis. Setting: The study was performed in the intensive care units (ICUs) of seven clinical centers in the United States and Canada. Patients: Four hundred fifty-five patients admitted to the ICU who met defined criteria for severe sepsis and were suspected of having a serious infection. Intervention: Ibuprofen at a dose of 10 mg/kg (maximum 800 mg) was administered intravenously over 30 to 60 mins every 6 hrs for eight doses vs. placebo (glycine buffer vehicle). Measurements and Main Results: Forty-four (10%) septic patients met criteria for hypothermia and 409 were febrile. The mortality rate was significantly higher in hypothermic patients, 70% vs. 35% for febrile patients. At study entry, urinary metabolites of TxB2, prostacyclin, and serum levels of TNF-α and IL-6 were significantly elevated in hypothermic patients compared with febrile patients. In hypothermic patients treated with ibuprofen, there was a trend toward an increased number of days free of major organ system failures and a significant reduction in the 30-day mortality rate from 90% (18/20 placebo-treated patients) to 54% (13/24 ibuprofen-treated patients). Conclusions: Hypothermic sepsis has an incidence of ~10% and an untreated mortality twice that of severe sepsis presenting with fever. When compared with febrile patients, the hypothermic group has an amplified response with respect to cytokines TNF-α and IL-6 and lipid mediators TxB2 and prostacyclin. Treatment with ibuprofen may decrease mortality in this select group of septic patients.

KW - Cytokines

KW - Eicosinoids

KW - Human

KW - Hypothermia

KW - Ibuprofen

KW - Interleukins

KW - Prostaglandins

KW - Sepsis

KW - Thromboxane

KW - Tumor necrosis factor

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