Elsevier

Resuscitation

Volume 84, Issue 12, December 2013, Pages 1734-1740
Resuscitation

Clinical paper
Post-hypothermia fever is associated with increased mortality after out-of-hospital cardiac arrest

https://doi.org/10.1016/j.resuscitation.2013.07.023Get rights and content

Abstract

Objective

Post-cardiac arrest fever has been associated with adverse outcome before implementation of therapeutic hypothermia (TH), however the prognostic implications of post-hypothermia fever (PHF) in the era of modern post-resuscitation care including TH has not been thoroughly investigated.

The aim of the study was to assess the prognostic implication of PHF in a large consecutive cohort of comatose survivors after out-of-hospital cardiac arrest (OHCA) treated with TH.

Methods

In the period 2004–2010, a total of 270 patients resuscitated after OHCA and surviving a 24-h protocol of TH with a target temperature of 32–34 °C were included. The population was stratified in two groups by median peak temperature (≥38.5 °C) within 36 h after rewarming: PHF and no-PHF. Primary endpoint was 30-days mortality and secondary endpoint was neurological outcome assessed by Cerebral Performance Category (CPC) at hospital discharge.

Results

PHF (≥38.5 °C) was associated with a 36% 30-days mortality rate compared to 22% in patients without PHF, plog-rank = 0.02, corresponding to an adjusted hazard rate (HR) of 1.8 (95% CI: 1.1–2.7), p = 0.02). The maximum temperature (HR = 2.0 per °C above 36.5 °C (95% CI: 1.4–3.0), p = 0.0005) and the duration of PHF (HR = 1.6 per 8 h (95% CI: 1.3–2.0), p < 0.0001) were also independent predictors of 30-days mortality in multivariable models. Good neurological outcome (CPC1-2) versus unfavourable outcome (CPC3-5) at hospital discharge was found in 61% vs. 39% in the PHF group compared to 75% vs. 25% in the No PHF group, p = 0.02.

Conclusions

Post-hypothermia fever ≥38.5 °C is associated with increased 30-days mortality, even after controlling for potential confounding factors. Avoidance of PHF as a therapeutic target should be evaluated in prospective randomized trials.

Introduction

Therapeutic hypothermia (TH) plays a central role in post-resuscitation care after out-of-hospital cardiac arrest (OHCA) and is recommended in patients remaining comatose after return of spontaneous circulation (ROSC).1 TH is induced to attenuate neurological injuries and may act through a variety of mechanisms; e.g. inhibition of apoptosis, reducing cerebral metabolism and oxidative stress, which may all contribute to the beneficial effects of TH.2, 3 A recent Cochrane review evaluated TH as a strategy to improve outcome after OHCA and suggested that the neuro-protective effects of TH may at least partly be due to an antipyretic effect.4 Development of fever is most frequently an adaptive response to cell damage, activation of inflammatory cascades or infections.5 Development of fever after cardiac arrest is frequent and has previously been found to be associated with unfavourable outcome.6, 7, 8 However, these studies reported fever as a prognostic marker in relatively small series of cardiac arrest patients before implementation of TH. Prior studies regarding prognostic implications of post-cardiac arrest fever in patients treated with TH are thus limited and the findings have been ambiguous.9, 10

This study reports a tertiary single centre experience on the association between post-hypothermia fever (PHF) and outcome in consecutive comatose survivors of OHCA admitted for post-resuscitation care with TH.

Section snippets

Setting and study population

We performed a prospective observational cohort study enrolling consecutive comatose patients resuscitated from OHCA and admitted to the Copenhagen University Hospital Rigshospitalet in the period 1st June 2004 to 31th October 2010.

The physician staffed mobile emergency care unit covers the central Copenhagen with approximately 600,000 resident inhabitants increasing during daytime by 20% and the greater area of Copenhagen (population 1,200,000). Patients suffering OHCA are referred to the

Patient population

In the 6-year period from June 1st 2004 to October 31st 2010, a total of 403 consecutive comatose patients with suspected cardiac cause of OHCA were admitted to the ICU of Copenhagen University Hospital, Rigshospitalet. A total of 270 comatose (77% with an initial GCS = 3, range 3–8) patients undergoing a full 24 h protocol of TH were available for analyses after exclusions (Fig. 1). Baseline demographic data showed no significant differences between patients developing PHF and patients not

Discussion

In this large cohort of comatose consecutive OHCA patients treated with TH we found an association between development of fever in the post-hypothermia period and increased 30-days mortality. PHF was common in the post-hypothermia period as the median peak temperature in the post-hypothermia period was 38.5 °C. The causal relationship of PHF and outcome, in particular in relation to anoxic neurological injuries should be investigated in future trials, to further establish an upper temperature

Conclusion

In this large cohort of consecutive patients undergoing a full 24 h TH protocol, development of PHF (≥38.5 °C) was frequent and associated with increased 30-days mortality and unfavourable neurological outcome, even after adjustment for known potential confounding factors.

Conflict of interest statement

All authors have reported that they have no financial relationships relevant to the contents of this paper to disclose.

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    A Spanish translated version of the summary of this article appears as Appendix in the final online version at http://dx.doi.org/10.1016/j.resuscitation.2013.07.023.

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