Clinical paperPost-hypothermia fever is associated with increased mortality after out-of-hospital cardiac arrest☆
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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Therapeutic Hypothermia Following Cardiac Arrest After the TTM2 trial – More Questions Raised Than Answered
2023, Current Problems in CardiologyCitation Excerpt :The trial was definitely larger than the ones before and more rigorous according to current demands on trial design. The reason for controlled normothermia was the increased body temperature observed in the previous trials’ control groups potentially being responsible for the observed difference between groups as post-arrest fever had been described as a negative confounder in post-arrest trials and registries.14 In contrast to the earlier smaller trials, TTM1 did not show a benefit of hypothermia despite a comparably high rate of mortality of 48%-50%.20
Recent developments and controversies in therapeutic hypothermia after cardiopulmonary resuscitation: A narrative review
2023, American Journal of Emergency MedicineERC-ESICM guidelines on temperature control after cardiac arrest in adults
2022, ResuscitationA Chilling Conclusion to the Hypothermia Debate?: November 2021 Annals of Emergency Medicine Journal Club
2021, Annals of Emergency MedicineCitation Excerpt :Although temperature management at 33 °C is sometimes considered labor intensive, it should be noted that the control group in this trial received an intensive strategy to avoid fevers and still involved aggressive temperature monitoring and intervention. Fever is associated with unfavorable neurologic outcomes after cardiac arrest, although it is unclear whether there is a direct causal relationship between the 2.9,16-18 Although the benefits of hypothermia are being discussed as a result of the TTM2 trial, there are no data that suggest that allowing fever in patients is beneficial.
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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.