Therapeutic Hypothermia Compared with Normothermia in Adults with Traumatic Brain Injury; Functional Outcome, Mortality, and Adverse Effects: A Systematic Review and Meta-Analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 38664327 · doi:10.1007/s12028-024-01985-5
What was done
A systematic review and meta-analysis of randomized controlled trials was conducted via MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials to compare therapeutic hypothermia (TH) with normothermia in adults with traumatic brain injury (TBI). Reviewers assessed study quality and calculated pooled risk ratios (RRs) or odds ratios with 95% confidence intervals (CIs) for mortality, functional outcomes, and adverse complications.
What was found
Across 32 studies (3,909 patients), overall pooled estimates showed lower mortality (RR 0.81, 95% CI 0.68–0.96, I² = 41%) and lower poor functional outcome (RR 0.77, 95% CI 0.67–0.88, I² = 68%) with TH. However, subgroup analysis revealed this benefit was confined only to studies with a high risk of bias. By cooling method, reduced poor functional outcome occurred with systemic surface cooling (RR 0.68, 95% CI 0.59–0.79, I² = 35%) and cranial cooling (RR 0.44, 95% CI 0.29–0.67, I² = 0%), with no difference in systemic intravenous or gastric cooling. Reduced mortality occurred only with systemic surface cooling (RR 0.63, 95% CI 0.53–0.75, I² = 0%), which consisted mostly of high-bias studies. TH was associated with higher rates of pneumonia (RR 1.24, 95% CI 1.10–1.40, I² = 32%), coagulation abnormalities (RR 1.63, 95% CI 1.09–2.44, I² = 55%), and cardiac arrhythmias (RR 1.78, 95% CI 1.05–3.01, I² = 21%), though complication differences disappeared in low-risk-of-bias studies.
Why it matters
This meta-analysis indicates that the apparent mortality and functional benefits of therapeutic hypothermia in traumatic brain injury are driven by lower-quality trials, and rigorous trials demonstrate no clear advantage over normothermia.
Limits
Key outcomes showed substantial heterogeneity (e.g., I² = 68% for functional outcome; I² = 55% for coagulation abnormalities). Primary outcomes were heavily confounded by risk of bias across included trials, with overall evidence certainty rated as moderate for mortality, functional outcomes, and pneumonia, and low for coagulation and cardiac complications.
Cited by
- supports Clinical studies of therapeutic hypothermia after traumatic brain injury have generally not shown a significant beneficial effect.