Clinical Effect of Rebound Hyperthermia After Cooling Postcardiac Arrest: A Meta-Analysis

Abstract

Rebound hyperthermia (RH) is frequently seen after completion of targeted temperature management (TTM) in comatose survivors of cardiac arrest. However, its clinical significance is not well understood. Previous studies analyzing the association of RH with clinical outcome have reported conflicting results. The purpose of this meta-analysis is to examine the impact of RH after completion of TTM in patients postcardiac arrest. We reviewed six studies that evaluated the incidence of RH (T > 38°C) with documentation of outcome based on the presence of hyperthermia. We reviewed all six articles and extracted the data for mortality and neurological outcome. A total of 729 patients were analyzed for neurological outcome and 950 patients were analyzed for mortality. RH was found to be associated with a significantly worse neurological outcome (odds ratio [OR] 1.55; 95% confidence interval [CI] 1.13-2.14). RH was not significantly associated with a higher mortality (OR 1.31; 95% CI 1.00-1.72). We also analyzed three studies totaling 206 patients for neurological outcomes and mortality that included patients with severe RH (T > 38.5°C). Severe RH was found to be associated with significantly worse neurological outcome (OR 1.92, 95% CI 1.28-1.90) and significantly worse mortality (OR 2.22, 95% CI 1.50-3.29). RH is common after completion of TTM in comatose patients because of cardiac arrest and is associated with poor neurological outcomes. The clinical impact of RH is likely proportional to the magnitude of RH.

European Resuscitation Council and European Society of Intensive Care Medicine 2015 guidelines for post-resuscitation care

“…Fever following TTM (i.e. induction of hypothermia at 32-36 °C) is also called rebound hyperthermia and is associated with worse outcomes, in particular with high temperatures [211,212]. Whether fever contributes to poor neurological outcome or is just a marker of severe brain injury remains unknown.…”

Factors Associated With Rebound Hyperthermia After Targeted Temperature Management in Out-of-Hospital Cardiac Arrest Patients: An Explorative Substudy of the Time-Differentiated Therapeutic Hypothermia in Out-of-Hospital Cardiac Arrest Survivors Trial

“…In a meta-analysis by Makker et al ( 2 ), in which RH was defined as greater than 38°C and severe RH defined as greater than 38.5°C, both were significantly associated with worse FOs, and the authors speculated that the clinical impact of RH is likely proportional to the magnitude of RH. Indeed, in our study, RH was significantly associated with worse outcomes only with higher temperatures.…”

“…The treating clinician could select to rewarm the patient to 36°C if the patient experienced severe complications. We defined RH as the occurrence of temperature exceeding 38.5°C after rewarming during ICU stay ( 2 , 10 , 12 ).…”

“…Previous studies have reported diverse definitions for RH and have failed to demonstrate an unambiguous threshold value of temperature at which the risk of unfavorable outcome would be the highest ( 1 – 3 , 10 , 12 ). In addition, it is currently unknown whether certain patients are more likely to develop RH than others, even though the magnitude and timing of RH has been associated with FO in some studies ( 2 , 3 , 6 , 10 – 14 ).…”

Retrospective Analysis of Esophageal Heat Transfer for Active Temperature Management in Post-cardiac Arrest, Refractory Fever, and Burn Patients

“…In cooling protocols, and especially in post-cardiac arrest patients, rebound hyperthermia is a significant concern. 25 To counteract this phenomenon, patients are rewarmed slowly (AHA guidelines recommend a rate of 0.25°C−0.5°C 5 ) over a 12-h period. In neurogenic and central fever cases, temperature spikes can be unpredictable and may occur for several weeks.…”