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 °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 °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 °C was compared to "actively controlled" normothermia in three RCTs and to "uncontrolled" normothermia in five RCTs. TTM at 32-34 °C does not improve survival as compared to normothermia (RR:1.06 (95%CI 0.94, 1.20), p = 0.36; I2 = 39%). In the subgroup analyses, TTM at 32-34 °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 °C does not improve neurological outcome as compared to normothermia (RR: 1.17 (95%CI 0.97, 1.41), p = 0.10; I2 = 60%). TTM at 32-34 °C increases the risk of arrhythmias (RR: 1.35 (95%CI 1.16, 1.57), p = 0.0001, I2 = 0%). TTM at 32-34 °C does not improve survival nor neurological outcome after CA and increases the risk of arrhythmias.

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.