Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2012 Feb 28;16(1):R33.
doi: 10.1186/cc11211.

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

Byung Ho Lee  1 , 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; Fever and Antipyretic in Critically ill patients Evaluation (FACE) Study Group
Affiliations
Clinical Trial

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

Byung Ho Lee et al. Crit Care. .

Erratum in

  • Crit Care. 2012;16(1):450

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 (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.

Trial registration: ClinicalTrials.gov: NCT00940654.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Flow chart showing current study. ICU, intensive care units.
Figure 2
Figure 2
Mean peak daily temperature of patients with and without sepsis. The white circles indicate the mean peak daily temperature in patients with sepsis. The black circles indicate the mean peak daily temperature in patients without sepsis. For the first seven days after admission, peak body temperature of patients with sepsis was significantly higher than of patients without sepsis. CI, confidential interval; ICU, intensive care unit.
Figure 3
Figure 3
Maximum body temperature during ICU stay and survival of patients with and without sepsis. This figure shows Kaplan-Meier estimates for the probability of survival, which at 28 days was greater in non-septic patients with MAXICU 38.5°C to 39.4°C and ≥ 39.5°C than those with 36.5°C to 37.4°C. In septic patients, there were no significant differences of provability of survival in each category compared with patients of MAXICU with 36.5°C to 37.4°C. *, significantly different probability of survival at 28 days after ICU admission than patients with 36.5°C to 37.4°C.
Figure 4
Figure 4
Administration of pharmacological antipyretic treatments (NSAIDs and/or acetaminophen) in each MAXICU category. Data show patients categorized in subgroups according to MAXICU value range: 37.5°C to 38.4°C, 38.5°C to 39.4°C and ≥ 39.5°C. White bar, patients given NSAIDs; black bar, patients given acetaminophen; gray bar, patients given both NSAIDs and acetaminophen. For the subgroup with MAXICU of 37.5°C to 38.4°C, the proportion of patients received pharmacological antipyretic treatments was significantly higher in non-septic patients (P = 0.007). For the rest of the subgroups, it was not significantly different between patients with and without sepsis (38.5°C to 39.4°C, P = 0.62; ≥ 39.5°C, P = 0.25). Acetaminophen was used more frequently for patients with sepsis, and NSAIDs for patients without sepsis in each MAXCAT subgroup (P < 0.001). MAXICU, maximum body temperature recorded during ICU stay; NSAIDs: non-steroid anti-inflammatory drugs.
Figure 5
Figure 5
Use of physical cooling in each MAXICU category of patients with and without sepsis. Data show patients categorized in subgroups according to MAXICU value range: 37.5°C to 38.4°C, 38.5°C to 39.4°C, and ≥ 39.5°C. *statistically significant difference between patients with and without sepsis. MAXICU, maximum body temperature recorded during ICU stay.
See this image and copyright information in PMC

Comment in

  • Good and bad fever.
    Cavaillon JM. Cavaillon JM. Crit Care. 2012 Dec 12;16(2):119. doi: 10.1186/cc11237. Crit Care. 2012. PMID: 22436665 Free PMC article.

References

    1. Laupland KB, Shahpori R, Kirkpatrick AW, Ross T, Gregson DB, Stelfox HT. Occurrence and outcome of fever in critically ill adults. Crit Care Med. 2008;36:1531–1535. doi: 10.1097/CCM.0b013e318170efd3. - DOI - PubMed
    1. O'Grady NP, Barie PS, Bartlett JG, Bleck T, Carroll K, Kalil AC, Linden P, Maki DG, Nierman D, Pasculle W, Masur H. American College of Critical Care Medicine; Infectious Diseases Society of America. Guidelines for evaluation of new fever in critically ill adult patients: 2008 update from the American College of Critical Care Medicine and the Infectious Diseases Society of America. Crit Care Med. 2008;36:1330–1349. doi: 10.1097/CCM.0b013e318169eda9. - DOI - PubMed
    1. Hawksworth JS, Leeser D, Jindal RM, Falta E, Tadaki D, Elster EA. New directions for induction immunosuppression strategy in solid organ transplantation. Am J Surg. 2009;197:515–524. doi: 10.1016/j.amjsurg.2008.04.025. - DOI - PubMed
    1. Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL. International Surviving Sepsis Campaign Guidelines Committee; American Association of Critical-Care Nurses; American College of Chest Physicians; American College of Emergency Physicians; Canadian Critical Care Society; European Society of Clinical Microbiology and Infectious Diseases; European Society of Intensive Care Medicine; European Respiratory Society; International Sepsis Forum; Japanese Association for Acute Medicine; Japanese Society of Intensive Care Medicine; Society of Critical Care Medicine; Society of Hospital Medicine; Surgical Infection Society; World Federation of Societies of Intensive and Critical Care Medicine. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008;36:296–327. doi: 10.1097/01.CCM.0000298158.12101.41. Erratum in: Crit Care Med 2008, 36:1394-1396. - DOI - PubMed
    1. Manthous CA, Hall JB, Olson D, Singh M, Chatila W, Pohlman A, Kushner R, Schmidt GA, Wood LD. Effect of cooling on oxygen consumption in febrile critically ill patients. Am J Respir Crit Care Med. 1995;151:10–14. - PubMed

Associated data