Does Time to Achieve a Targeted Body Temperature Matter for Survivors of Cardiac Arrest? A Systematic Review and Meta-Analysis

OBJECTIVES: To identify the impact of early hypothermic temperature control (HTC) initiation and achievement on neurologic outcomes after cardiac arrest. Secondary endpoints assessed: 1) overall survival, 2) body temperature at hospital admission, 3) time taken to reach targeted temperature, and 4) adverse events. Subgroup analyses assessed: 1) HTC induction method, 2) presenting rhythms (shockable vs. nonshockable), and 3) timing of HTC initiation (during cardiopulmonary resuscitation CPR vs. post-return of spontaneous circulation ROSC). DATA SOURCES: PubMed, Cochrane Library, U.S. National Library of Medicine, MedRxiv, BioRxiv. STUDY SELECTION: Prospective randomized controlled trials enrolling comatose adult cardiac arrest patients that assessed the efficacy of early cooling (defined by initiation of HTC within 30 min of ROSC) against late cooling. DATA EXTRACTION: Two reviewers independently conducted study selection, data extraction, and assessment of evidence quality. Full texts were jointly reviewed, with discrepancies resolved by a third reviewer through discussion and consensus. DATA SYNTHESIS: Of 7269 citations, 11 met the inclusion criteria. Early cooling did not improve neurologic outcomes (risk ratio RR, 1.01; 95% CI, 0.94-1.14) nor survival (RR, 1.01; 95% CI, 0.92-1.11). Nasal evaporative cooling initiated during resuscitation may benefit patients with shockable rhythms (RR, 1.40; 95% CI, 1.00-1.96), while administering cold fluid during CPR was associated with a higher risk of rearrest. Cooling was initiated in the prehospital phase in ten studies, nine of which failed to achieve target temperature (32-34°C) by hospital admission. The median time to reach target temperature ranged from 38 to 360 minutes. CONCLUSIONS: Early HTC showed no neurologic nor survival benefit in cardiac arrest survivors. Nasal evaporative cooling during CPR may benefit those with shockable rhythms. Delays in reaching the target temperature may underlie the failure of HTC. Future studies should evaluate whether achieving target temperature, for example, within 30 minutes, rapidly improves outcomes.