Evaluating the Clinical Safety and Efficacy of Therapeutic Hypothermia in Acute Neurotrauma Care: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

OBJECTIVES: This review aims to update the evidence on therapeutic hypothermia's safety and effectiveness in the acute phase of traumatic brain injury (TBI), ischemic stroke, or post-hemorrhagic conditions, focusing on complications, adverse effects, neurological outcomes, and mortality rates over 6 months.

METHODS: Publications up to June 9, 2023, were searched in six databases, including Ovid MEDLINE, EMBASE, and the Cochrane Central Register for international studies, and KoreaMed, the Korean Medical Database, and the Korean Education and Research Information Service for South Korean research. Only randomized controlled trials (RCTs) on therapeutic hypothermia in patients with TBI, ischemic stroke, or intracerebral hemorrhage, compared to normothermia, were included, with discrepancies resolved by consensus or third-party review. Bias was evaluated using the Cochrane Risk of Bias tool. Effect sizes were derived through the Mantel-Haenszel random-effects model as Relative Risk (RR), considering study heterogeneity. Heterogeneity was quantified using the I² statistic, with <50% indicating low and >75% high heterogeneity. Analyses were performed with R Studio 2022.12.0.

RESULTS: In our review of 35 studies with 2,639 patients, therapeutic hypothermia was associated with more complications such as pneumonia (RR 1.29, 95% CI 1.02-1.64; I²=36%), coagulopathy (RR 1.74, 95% CI 1.39-2.18; I²=18%), and electrolyte imbalances (RR 1.29, 95% CI 1.06-1.56; I²=23%) in TBI cases. However, it notably reduced mortality (RR 0.73, 95% CI 0.59-0.89; I²=29%) in TBI patients and improved neurological outcomes at 6 months in ischemic stroke cases (RR 2.04, 95% CI 1.01-4.13; I²=0%).

CONCLUSIONS: Our review supports therapeutic hypothermia in reducing mortality in TBI patients and enhancing neurological outcomes in ischemic stroke cases, despite being linked to increased complications, highlighting the need for further research.