Targeted Temperature Management after Cardiac Arrest: A Systematic Review and Meta-Analysis with Trial Sequential Analysis

Target temperature management (TTM) in cardiac arrest (CA) survivors is recommended after hospital admission for its possible beneficial effects on survival and neurological outcome. Whether a lower target temperature (i.e., 32-34 degrees C) improves outcomes is unclear. We conducted a systematic review and meta-analysis on Pubmed and EMBASE to evaluate the effects on mortality and neurologic outcome of TTM at 32-34 degrees C as compared to controls (patients cared with "actively controlled" or "uncontrolled" normothermia). Results were analyzed via risk ratios (RR) and 95% confidence intervals (CI). Eight randomized controlled trials (RCTs) were included. TTM at 32-34 degrees C was compared to "actively controlled" normothermia in three RCTs and to "uncontrolled" normothermia in five RCTs. TTM at 32-34 degrees C does not improve survival as compared to normothermia (RR:1.06 (95%CI 0.94, 1.20), p = 0.36; I-2 = 39%). In the subgroup analyses, TTM at 32-34 degrees C is associated with better survival when compared to "uncontrolled" normothermia (RR: 1.31 (95%CI 1.07, 1.59), p = 0.008) but shows no beneficial effects when compared to "actively controlled" normothermia (RR: 0.97 (95%CI 0.90, 1.04), p = 0.41). TTM at 32-34 degrees C does not improve neurological outcome as compared to normothermia (RR: 1.17 (95%CI 0.97, 1.41), p = 0.10; I-2 = 60%). TTM at 32-34 degrees C increases the risk of arrhythmias (RR: 1.35 (95%CI 1.16, 1.57), p = 0.0001, I-2 = 0%). TTM at 32-34 degrees C does not improve survival nor neurological outcome after CA and increases the risk of arrhythmias.