Abstract: We found six RCTs (1412 participants overall) conducted to evaluate the effects of therapeutic hypothermia - five on neurological outcome and survival, one on only neurological outcome. The quality of the included studies was generally moderate, and risk of bias was low in three out of six studies. When we compared conventional cooling methods versus no cooling (four trials; 437 participants), we found that participants in the conventional cooling group were more likely to reach a favourable neurological outcome (risk ratio (RR) 1.94, 95% confidence interval (CI) 1.18 to 3.21). The quality of the evidence was moderate. Across all studies that used conventional cooling methods rather than no cooling (three studies; 383 participants), we found a 30% survival benefit (RR 1.32, 95% CI 1.10 to 1.65). The quality of the evidence was moderate. Across all studies, the incidence of pneumonia (RR 1.15, 95% CI 1.02 to 1.30; two trials; 1205 participants) and hypokalaemia (RR 1.38, 95% CI 1.03 to 1.84; two trials; 975 participants) was slightly increased among participants receiving therapeutic hypothermia, and we observed no significant differences in reported adverse events between hypothermia and control groups. Overall the quality of the evidence was moderate (pneumonia) to low (hypokalaemia). Evidence of moderate quality suggests that conventional cooling methods provided to induce mild therapeutic hypothermia improve neurological outcome after cardiac arrest, specifically with better outcomes than occur with no temperature management. We obtained available evidence from studies in which the target temperature was 34°C or lower. This is consistent with current best medical practice as recommended by international resuscitation guidelines for hypothermia/targeted temperature management among survivors of cardiac arrest. We found insufficient evidence to show the effects of therapeutic hypothermia on participants with in-hospital cardiac arrest, asystole or non-cardiac causes of arrest.

Plain-language summary: We included in our analysis six studies (1412 people overall), four of which (437 people) examined effects of cooling the body by conventional methods after successful resuscitation for cardiac arrest. One study that used haemofiltration (cooling the blood externally - similar to dialysis) as the cooling method and one study in which cooling to 33°C was compared with temperature management at 36°C were treated separately in the review. The study that used external cooling was supported by a dialysis-related company. Of the five studies included in the main analysis, two received funding from government or non-profit organizations; three studies did not provide information on funding. When we compared people whose bodies were cooled to 32°C to 34°C after resuscitation versus those whose bodies were not cooled at all, we found that 63% of those receiving cooling would suffer no, or only minor, brain damage, while only 33% of those not cooled would suffer no, or only minor, brain damage. Cooling had an important effect on simple survival, with or without brain damage: 57% would survive if their bodies were cooled compared with 42% if their bodies were not cooled at all. No serious side effects occurred, but cooling the body was associated with increased risk of pneumonia (49% vs 42% of those studied) and increased risk of low concentrations of potassium in the blood (18% vs 13%). Some studies had quality shortcomings including small numbers of participants and use of inadequate methods to balance participants between intervention and control groups. However, when differences between studies are acknowledged (heterogeneity), it is clear that these shortcomings had no major impact on the main results.