• Byung Ho Lee, Daisuke Inui, Gee Young Suh, Jae Yeol Kim, Jae Young Kwon, Jisook Park, Keiichi Tada, Keiji Tanaka, Kenichi Ietsugu, Kenji Uehara, Kentaro Dote, Kimitaka Tajimi, Kiyoshi Morita, Koichi Matsuo, Koji Hoshino, Koji Hosokawa, Kook Hyun Lee, Kyoung Min Lee, Makoto Takatori, Masaji Nishimura, Masamitsu Sanui, Masanori Ito, Moritoki Egi, Naofumi Honda, Naoko Okayama, Nobuaki Shime, Ryosuke Tsuruta, Satoshi Nogami, Seok-Hwa Yoon, Shigeki Fujitani, Shin Ok Koh, Shinhiro Takeda, Shinsuke Saito, Sung Jin Hong, Takeshi Yamamoto, Takeshi Yokoyama, Takuhiro Yamaguchi, Tomoki Nishiyama, Toshiko Igarashi, Yasuyuki Kakihana, Younsuck Koh, and Fever and Antipyretic in Critically ill patients Evaluation (FACE) Study Group.
• Department of Anesthesiology, St. Paul’s Hospital, Catholic University of Korea, Seoul, Republic of Korea.
• Crit Care. 2012 Jan 1;16(1):R33.

IntroductionFever 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.MethodsWe 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 (MAXICU) and the use of antipyretic treatments with 28-day mortality.ResultsWe 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 (MAXICU ≥ 39.5°C increased risk of 28-day mortality in non-septic patients (adjusted odds ratio 8.14, P=0.01), but not in septic patients (adjusted odds ratio 0.47, P=0.11) [corrected].ConclusionsIn 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 RegistrationClinicalTrials.gov: NCT00940654.

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