Association of body temperature and antipyretic treatments with mortality of critically ill patients with and without sepsis: Multi-centered prospective observational study

Byung H. Lee, Daisuke Inui, Gee Y. Suh, Jae Y. Kim, Jae Y. Kwon, Jisook Park, Keiichi Tada, Keiji Tanaka, Kenichi Ietsugu, Kenji Uehara, Kentaro Dote, Kimitaka Tajimi, Kiyoshi Morita, Koichi Matsuo, Koji Hoshino, Koji Hosokawa, Kook H. Lee, Kyoung M. Lee, Makoto Takatori, Masaji NishimuraMasamitsu Sanui, Masanori Ito, Moritoki Egi, Naofumi Honda, Naoko Okayama, Nobuaki Shime, Ryosuke Tsuruta, Satoshi Nogami, Seok Hwa Yoon, Shigeki Fujitani, Shin O. Koh, Shinhiro Takeda, Shinsuke Saito, Sung J. Hong, Takeshi Yamamoto, Takeshi Yokoyama, Takuhiro Yamaguchi, Tomoki Nishiyama, Toshiko Igarashi, Yasuyuki Kakihana, Younsuck Koh

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Abstract

Introduction: Fever is frequently observed in critically ill patients. An independent association of fever with increased mortality has been observed in non-neurological critically ill patients with mixed febrile etiology. The association of fever and antipyretics with mortality, however, may be different between infective and non-infective illness.Methods: We designed a prospective observational study to investigate the independent association of fever and the use of antipyretic treatments with mortality in critically ill patients with and without sepsis. We included 1,425 consecutive adult critically ill patients (without neurological injury) requiring > 48 hours intensive care admitted in 25 ICUs. We recorded four-hourly body temperature and all antipyretic treatments until ICU discharge or 28 days after ICU admission, whichever occurred first. For septic and non-septic patients, we separately assessed the association of maximum body temperature during ICU stay (MAX ICU) and the use of antipyretic treatments with 28-day mortality.Results: We recorded body temperature 63,441 times. Antipyretic treatment was given 4,863 times to 737 patients (51.7%). We found that treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen independently increased 28-day mortality for septic patients (adjusted odds ratio: NSAIDs: 2.61, P = 0.028, acetaminophen: 2.05, P = 0.01), but not for non-septic patients (adjusted odds ratio: NSAIDs: 0.22, P = 0.15, acetaminophen: 0.58, P = 0.63). Application of physical cooling did not associate with mortality in either group. Relative to the reference range (MAX ICU 36.5°C to 37.4°C), MAX ICU ≥ 39.5°C increased risk of 28-day mortality in septic patients (adjusted odds ratio 8.14, P = 0.01), but not in non-septic patients (adjusted odds ratio 0.47, P = 0.11).Conclusions: In non-septic patients, high fever (≥ 39.5°C) independently associated with mortality, without association of administration of NSAIDs or acetaminophen with mortality. In contrast, in septic patients, administration of NSAIDs or acetaminophen independently associated with 28-day mortality, without association of fever with mortality. These findings suggest that fever and antipyretics may have different biological or clinical or both implications for patients with and without sepsis.Trial registration: ClinicalTrials.gov: NCT00940654.

Original languageEnglish
Article numberR33
JournalCritical Care
Volume16
Issue number1
DOIs
Publication statusPublished - 2012 Feb 28

Keywords

  • Antipyretic
  • Body temperature
  • Critical illness
  • Fever
  • Mortality

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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