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Early peak temperature and mortality in critically ill patients with or without infection

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Abstract

Purpose

To determine whether fever is associated with an increased or decreased risk of death in patients admitted to an intensive care unit (ICU) with infection.

Methods

We evaluated the independent association between peak temperature in the first 24 h after ICU admission and in-hospital mortality according to whether there was an admission diagnosis of infection using a database of admissions to 129 ICUs in Australia and New Zealand (ANZ) (n = 269,078). Subsequently, we sought to confirm or refute the ANZ database findings using a validation cohort of admissions to 201 ICUs in the UK (n = 366,973).

Results

A total of 29,083/269,078 (10.8%) ANZ patients and 103,191/366,973 (28.1%) of UK patients were categorised as having an infection. In the ANZ cohort, adjusted in-hospital mortality risk progressively decreased with increasing peak temperature in patients with infection. Relative to the risk at 36.5–36.9°C, the lowest risk was at 39–39.4°C (adjusted OR 0.56; 95% CI 0.48–0.66). In patients without infection, the adjusted mortality risk progressively increased above 39.0°C (adjusted OR 2.07 at 40.0°C or above; 95% CI 1.68–2.55). In the UK cohort, findings were similar with adjusted odds ratios at corresponding temperatures of 0.77 (95% CI 0.71–0.85) and 1.94 (95% CI 1.60–2.34) for infection and non-infection groups, respectively.

Conclusions

Elevated peak temperature in the first 24 h in ICU is associated with decreased in-hospital mortality in critically ill patients with an infection; randomised trials are needed to determine whether controlling fever increases mortality in such patients.

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References

  1. Laupland KB, Shahpori R, Kirkpatrick AW, Ross T, Gregson DB, Stelfox HT (2008) Occurrence and outcome of fever in critically ill adults. Crit Care Med 36:1531–1535

    Article  PubMed  Google Scholar 

  2. Kluger MJ (1979) Fever: its biology, evolution and function. Princeton University Press, New Jersey, p 224

    Google Scholar 

  3. Mackowiak PA (1994) Fever: blessing or curse? A unifying hypothesis. Ann Intern Med 120:1037–1040

    PubMed  CAS  Google Scholar 

  4. Bennett AE, Person JP, Simmons EE (1936) Treatment of chronic meningococcic infections in artificial fever. Arch Phys Ther 17:743–748

    Google Scholar 

  5. Hench PS, Slocumb CH, Popp WC (1935) Fever therapy: results for gonorrheal arthritis, chronic infectious (atrophic) arthritis, and other forms of “rheumatism”. J Am Med Assoc 104:1779–1790

    Article  Google Scholar 

  6. Wagner-Jauregg J (1919) Uber die Einwirkung der Malaria auf die progressive Paralyse. Psychiat-Neurol Wchnschr 20:251–255

    Google Scholar 

  7. Eyers S, Weatherall M, Shirtcliffe P, Perrin K, Beasley R (2010) The effect on mortality of antipyretics in the treatment of influenza infection: systematic review and meta-analysis. J R Soc Med 103:403–411

    Article  PubMed  Google Scholar 

  8. Shann F (1995) Antipyretics in severe sepsis. Lancet 345:338

    Article  PubMed  CAS  Google Scholar 

  9. Doran T, de Angelis C, Baugardner R, Mellits E (1989) Acetaminophen: more harm than good for chickenpox? J Pediatr 114:1045–1048

    Article  PubMed  CAS  Google Scholar 

  10. Brandts CH, Ndjave M, Graninger W, Kremsner PG (1997) Effect of paracetamol on parasite clearance time in Plasmodium falciparum malaria. Lancet 350:704–709

    Article  PubMed  CAS  Google Scholar 

  11. Stanley E, Jackson G, Panusarn C, Rubenis M, Dirda V (1975) Increased virus shedding with aspirin treatment of rhinovirus infection. JAMA 231:1248–1251

    Article  PubMed  CAS  Google Scholar 

  12. Horvath SM, Spurr GB, Hutt BK, Hamilton LH (1956) Metabolic cost of shivering. J Appl Physiol 8:595–602

    PubMed  CAS  Google Scholar 

  13. Greisman SE (1997) Cardiovascular alterations during fever. In: Mackowiak PA (ed) Fever: basic mechanisms and management, 2nd edn. Lippincott-Raven, Philadelphia, pp 143–165

    Google Scholar 

  14. Bruder N, Raynal M, Pellissier D, Courtinat C, Francois G (1998) Influence of body temperature, with and without sedation, on energy expenditure in severe head injuries. Crit Care Med 26:568–572

    Article  PubMed  CAS  Google Scholar 

  15. Greer DM, Funk SE, Reaven NL, Ouzounelli M, Uman GC (2008) Impact of fever on outcome in patients with stroke and neurologic injury: a comprehensive meta-analysis. Stroke 39:3029–3035

    Article  PubMed  Google Scholar 

  16. Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, Smith K (2002) Treatment of comatose survivors of out of hospital cardiac arrest with induced hypothermia. N Engl J Med 346:557–563

    Article  PubMed  Google Scholar 

  17. Gluckman PD, Wyatt JS, Azzopardi D, Ballard R, Edwards AD, Ferriero DM, Polin RA, Robertson CM, Thoresen M, Whitelaw A, Gunn AJ (2005) Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre, randomised trial. Lancet 365:663–670

    PubMed  Google Scholar 

  18. Stow PJ, Hart GK, Higlett T, George C, Herkes R, McWilliam D, Bellomo R, for the ANZICS Database Management Committee (2006) Development and implementation of a high quality clinical database: the Australian and New Zealand Intensive Care Society Adult Patient Database. J Crit Care 21:133

    Article  PubMed  Google Scholar 

  19. Harrison DA, Brady AR, Rowan K (2005) Case mix, outcome and length of stay for admissions to adult, general critical care units in England, Wales and Northern Ireland: the Intensive Care National Audit & Research Centre Case Mix Programme Database. Crit Care 9:S1–S13

    Article  Google Scholar 

  20. Knaus WA, Wagner DP, Draper EA, Zimmerman JE, Bergner M, Bastos PG, Sirio CA, Murphy DJ, Lotring T, Damiano A et al (1991) The APACHE III prognostic system. Risk prediction of hospital mortality for critically ill hospitalised adults. Chest 100:1619–1636

    Article  PubMed  CAS  Google Scholar 

  21. Harrison DA, Parry GJ, Carpenter JR, Short A, Rowan K (2007) A new risk prediction model for critical care: the Intensive Care National Audit & Research Centre (ICNARC) model. Crit Care Med 35:1091–1098

    Article  PubMed  Google Scholar 

  22. Young JD, Goldfrad C, Rowan K, on behalf of the ICNARC Coding Method Working Group (2001) Development and testing of a hierarchical method to code the reason for admission to intensive care units: the ICNARC coding method. Brit J Anaesth 87:543–548

    Article  PubMed  CAS  Google Scholar 

  23. Diringer MN, Reaven NL, Funk SE, Uman GC (2004) Elevated body temperature independently contributes to increased length of stay in neurologic intensive care unit patients. Crit Care Med 32:1489–1495

    Article  PubMed  Google Scholar 

  24. Schulman CI, Namias N, Doherty J, Manning RJ, Li P, Elhaddad A, Lasko D, Amortegui J, Dy CJ, Dlugasch L, Baracco G, Cohn SM (2005) The effect of antipyretic therapy upon outcomes in critically ill patients: a randomized, prospective study. Surg Infect (Larchmt) 6:369–375

    Article  Google Scholar 

  25. Bernard GR, Wheeler AP, Russell JA, Schein R, Summer WR, Steinberg KP, Fulkerson WJ, Wright PE, Christman BW, Dupont WD, Higgins SB, Swindell BB (1997) The effects of ibuprofen on the physiology and survival of patients with sepsis. N Engl J Med 336:912–919

    Article  PubMed  CAS  Google Scholar 

  26. Haupt MT, Jastremski MS, Clemmer TP, Metz CA, Goris GB (1991) Effect of ibuprofen in patients with severe sepsis: a randomized, double-blind, multicenter study. The Ibuprofen Study Group. Crit Care Med 19:1339–1347

    Article  PubMed  CAS  Google Scholar 

  27. Enders J, Shaffer M (1936) Studies on natural immunity to Pneumococcus type III: I. The capacity of strains of Pneumococcus type III to grow at 40°C and their virulence for rabbits. J Exp Med 64:7–18

    Article  PubMed  CAS  Google Scholar 

  28. Chu CM, Tian SF, Ren GF, Zhang YM, Zhang LX, Liu GQ (1982) Occurrence of temperature-sensitive influenza A viruses in nature. J Virol 41:353–359

    PubMed  CAS  Google Scholar 

  29. Moench M (1926) A study of the heat sensitivity of the meningococcus in vitro within the range of therapeutic temperatures. J Lab Clin Med 57:665–676

    Google Scholar 

  30. Mackowiak PA, Marling-Cason M, Cohen RL (1982) Effects of temperature on antimicrobial susceptibility of bacteria. J Infect Dis 145:550–553

    Article  PubMed  CAS  Google Scholar 

  31. Arons MM, Wheeler AP, Bernard GR, Christman BW, Russell JA, Schein R, Summer WR, Steinberg KP, Fulkerson W, Wright P, Dupont WD, Swindell BB (1999) Effects of ibuprofen on the physiology and survival of hypothermic sepsis. Crit Care Med 27:699–707

    Article  PubMed  CAS  Google Scholar 

  32. Frank SM, Fleisher LA, Breslow MJ, Higgins MS, Olson KF, Kelly S, Beattie C (1997) Perioperative maintenance of normothermia reduces the incidence of morbid cardiac events. A randomized clinical trial. JAMA 277:1127–1134

    Article  PubMed  CAS  Google Scholar 

  33. Kurz A, Sessler DI, Lenhardt R (1996) Perioperative normothermia to reduce the incidence of surgical-wound infection and shorten hospitalization. Study of Wound Infection and Temperature Group. N Engl J Med 334:1209–1215

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We would like to thank Prof. John Kellum and Prof. Michael Reade for offering their feedback and suggestions on this manuscript. This study was funded by the Australian and New Zealand Intensive Care Research Centre, Melbourne, Australia and the Intensive Care National Audit & Research Centre, London, UK.

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Correspondence to Paul Jeffrey Young.

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Young, P.J., Saxena, M., Beasley, R. et al. Early peak temperature and mortality in critically ill patients with or without infection. Intensive Care Med 38, 437–444 (2012). https://doi.org/10.1007/s00134-012-2478-3

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  • DOI: https://doi.org/10.1007/s00134-012-2478-3

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