title: Association of body temperature and antipyretic treatments with mortality of critically ill patients with and without sepsis: multi-centered prospective observational study.
abstract: BACKGROUND
  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 (MAXICU) 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 (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].
  
  
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT00940654.
authors.affiliation: Department of Anesthesiology, St. Paul’s Hospital, Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Byung Ho
authors.initials: BH
authors.lastname: Lee
authors.forename: Daisuke
authors.initials: D
authors.lastname: Inui
authors.forename: Gee Young
authors.initials: GY
authors.lastname: Suh
authors.forename: Jae Yeol
authors.initials: JY
authors.lastname: Kim
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Kwon
authors.forename: Jisook
authors.initials: J
authors.lastname: Park
authors.forename: Keiichi
authors.initials: K
authors.lastname: Tada
authors.forename: Keiji
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authors.lastname: Tanaka
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ietsugu
authors.forename: Kenji
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authors.lastname: Uehara
authors.forename: Kentaro
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authors.lastname: Dote
authors.forename: Kimitaka
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authors.lastname: Tajimi
authors.forename: Kiyoshi
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authors.lastname: Morita
authors.forename: Koichi
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authors.lastname: Matsuo
authors.forename: Koji
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authors.lastname: Hoshino
authors.forename: Koji
authors.initials: K
authors.lastname: Hosokawa
authors.forename: Kook Hyun
authors.initials: KH
authors.lastname: Lee
authors.forename: Kyoung Min
authors.initials: KM
authors.lastname: Lee
authors.forename: Makoto
authors.initials: M
authors.lastname: Takatori
authors.forename: Masaji
authors.initials: M
authors.lastname: Nishimura
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Sanui
authors.forename: Masanori
authors.initials: M
authors.lastname: Ito
authors.forename: Moritoki
authors.initials: M
authors.lastname: Egi
authors.forename: Naofumi
authors.initials: N
authors.lastname: Honda
authors.forename: Naoko
authors.initials: N
authors.lastname: Okayama
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Shime
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Tsuruta
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nogami
authors.forename: Seok-Hwa
authors.initials: SH
authors.lastname: Yoon
authors.forename: Shigeki
authors.initials: S
authors.lastname: Fujitani
authors.forename: Shin Ok
authors.initials: SO
authors.lastname: Koh
authors.forename: Shinhiro
authors.initials: S
authors.lastname: Takeda
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Saito
authors.forename: Sung Jin
authors.initials: SJ
authors.lastname: Hong
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Takuhiro
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Tomoki
authors.initials: T
authors.lastname: Nishiyama
authors.forename: Toshiko
authors.initials: T
authors.lastname: Igarashi
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kakihana
authors.forename: Younsuck
authors.initials: Y
authors.lastname: Koh
mesh_terms: D000368:Aged; D058633:Antipyretics / Q000009:adverse effects*; D001831:Body Temperature / Q000187:drug effects* / Q000502:physiology; D016638:Critical Illness / Q000401:mortality* / Q000628:therapy*; D005260:Female; D005334:Fever / Q000188:drug therapy / Q000401:mortality*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018805:Sepsis / Q000188:drug therapy / Q000401:mortality*; D016896:Treatment Outcome
chemical_list: D058633:Antipyretics