Abstract Body: Introduction: Rewarming after targeted temperature management (TTM) in cardiac arrest triggers complex physiological changes that may affect neurological recovery. Current guidelines recommend controlled rewarming at 0.25-0.5°C/hour based on expert consensus, but clinical practice varies widely, with some centers using rates as slow as 1°C/day. Evidence supporting optimal rewarming strategies remains limited.

Hypothesis: We hypothesized that slower rewarming rates would be associated with improved neurological outcomes and reduced post-rewarming fever incidence in cardiac arrest survivors treated with TTM.

Methods: We searched MEDLINE, Embase, Cochrane CENTRAL, and Web of Science from January 2002 to May 2025 for studies of adult cardiac arrest survivors treated with TTM at ≤34°C reporting rewarming rates and neurological outcomes. The primary outcome was good neurological outcome (CPC 1-2 or equivalent). We performed random-effects meta-analysis and meta-regression to examine the relationship between rewarming rate and outcomes.
Results: Nine studies (3 RCTs, 6 observational) including 906 patients were analyzed. Rewarming rates ranged from 0.045 to 0.4°C/h. The pooled proportion of good neurological outcomes was 52% (95% CI: 42-61%), with substantial heterogeneity (I(sq)=79.8%). Slow rewarming (<0.25°C/hour; 4 studies, n=420) achieved 48.3% good outcomes (95% CI: 37.0-59.8%) vs. 54.3% (95% CI: 38.7-69.2%) for moderate rewarming (0.25-0.5°C/hour; 5 studies, n=486). Meta-regression found no significant association between rewarming rate and neurological outcomes (β=0.27 per 0.1°C/h increase, 95% CI: -3.33 to 3.86, p=0.88). Rewarming rate explained none of the observed heterogeneity (R(sq)=0%). Only one study reported post-rewarming fever incidence (76%).

Conclusions: Current evidence does not support slower rewarming rates to improve neurological outcomes after cardiac arrest. The high heterogeneity despite similar rewarming rates suggests other factors are more important determinants of outcome. Guideline recommendations of 0.25-0.5°C/h appear appropriate based on available evidence.