Hypothermia for neuroprotection in adults after cardiac arrest

Jasmin Arrich, Nikola Schütz, Julia Oppenauer, Janne Vendt, Michael Holzer, Christof Havel, and Harald Herkner

Published: 22 May 2023 

https://doi.org/10.1002/14651858.CD004128.pub5 

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Good neurological outcome after cardiac arrest is difficult to achieve. Interventions during the resuscitation phase and treatment within the first hours after the event are critical for a favourable prognosis. Experimental evidence suggests that therapeutic hypothermia is beneficial, and several clinical studies on this topic have been published. This review was originally published in 2009; updated versions were published in 2012 and 2016.

Objectives

To evaluate the benefits and harms of therapeutic hypothermia after cardiac arrest in adults compared to standard treatment.

Search methods

The authors used standard, extensive Cochrane search methods. The latest search date was 30 September 2022.

Selection criteria

The authors included randomised controlled trials (RCTs) and quasi‐RCTs in adults comparing therapeutic hypothermia after cardiac arrest with standard treatment (control). They included studies with adults cooled by any method, applied within six hours of cardiac arrest, to target body temperatures of 32 °C to 34 °C. Good neurological outcome was defined as no or only minor brain damage allowing people to live an independent life.

Data collection and analysis

Standard Cochrane methods were used. The primary outcome was 1. neurological recovery. Our secondary outcomes were 2. survival to hospital discharge, 3. quality of life, 4. cost‐effectiveness and 5. adverse events. We used GRADE to assess certainty.

Main results

The authors found 12 studies with 3956 participants reporting the effects of therapeutic hypothermia on neurological outcome or survival. There were some concerns about the quality of all the studies, and two studies had high risk of bias overall. When they compared conventional cooling methods versus any type of standard treatment (including a body temperature of 36 °C), they found that participants in the therapeutic hypothermia group were more likely to reach a favourable neurological outcome (risk ratio (RR) 1.41, 95% confidence interval (CI) 1.12 to 1.76; 11 studies, 3914 participants). The certainty of the evidence was low.

When therapeutic hypothermia with fever prevention or no cooling was compared, they found that participants in the therapeutic hypothermia group were more likely to reach a favourable neurological outcome (RR 1.60, 95% CI 1.15 to 2.23; 8 studies, 2870 participants). The certainty of the evidence was low.

When they compared therapeutic hypothermia methods with temperature management at 36 °C, there was no evidence of a difference between groups (RR 1.78, 95% CI 0.70 to 4.53; 3 studies; 1044 participants). The certainty of the evidence was low.

Across all studies, the incidence of pneumonia, hypokalaemia and severe arrhythmia was increased amongst participants receiving therapeutic hypothermia (pneumonia: RR 1.09, 95% CI 1.00 to 1.18; 4 trials, 3634 participants; hypokalaemia: RR 1.38, 95% CI 1.03 to 1.84; 2 trials, 975 participants; severe arrhythmia: RR 1.40, 95% CI 1.19 to 1.64; 3 trials, 2163 participants). The certainty of the evidence was low (pneumonia, severe arrhythmia) to very low (hypokalaemia). There were no differences in other reported adverse events between groups.

Authors' conclusions

Current evidence suggests that conventional cooling methods to induce therapeutic hypothermia may improve neurological outcomes after cardiac arrest. The authors obtained available evidence from studies in which the target temperature was 32 °C to 34 °C.

Link to full review