Hypothermia may reduce mortality and improve neurologic outcomes in adult patients treated with VA-ECMO: A systematic review and meta-analysis

Abstract

Background: VA-ECMO can greatly reduce mortality in critically ill patients, and hypothermia attenuates the deleterious effects of ischemia-reperfusion injury. We aimed to study the effects of hypothermia on mortality and neurological outcomes in VA-ECMO patients.

Methods: A systematic search of the PubMed, Embase, Web of Science, and Cochrane Library databases was performed from the earliest available date to 31 December 2022. The primary outcome was discharge or 28-day mortality and favorable neurological outcomes in VA-ECMO patients, and the secondary outcome was bleeding risk in VA-ECMO patients. The results are presented as odds ratios (ORs) and 95% confidence intervals (CIs). Based on the heterogeneity assessed by the I² statistic, meta-analyses were performed using random or fixed-effects models. GRADE methodology was used to rate the certainty in the findings.

Results: A total of 27 articles (3782 patients) were included. Hypothermia (33-35 °C) lasting at least 24 h can significantly reduce discharge or 28-day mortality (OR, 0.45; 95% CI, 0.33-0.63; I² = 41%) and significantly improve favorable neurological outcomes (OR, 2.08; 95% CI, 1.66-2.61; I² = 3%) in VA-ECMO patients. Additionally, there was no risk associated with bleeding (OR, 1.15; 95% CI, 0.86-1.53; I² = 12%). In our subgroup analysis according to in-hospital or out-of-hospital cardiac arrest, hypothermia reduced short-term mortality in both VA-ECMO-assisted in-hospital (OR, 0.30; 95% CI, 0.11-0.86; I² = 0.0%) and out-of-hospital cardiac arrest (OR, 0.41; 95% CI, 0.25-0.69; I² = 52.3%). Out-of-hospital cardiac arrest patients assisted by VA-ECMO for favorable neurological outcomes were consistent with the conclusions of this paper (OR, 2.10; 95% CI, 1.63-2.72; I² = 0.5%).

Conclusions: Our results show that mild hypothermia (33-35 °C) lasting at least 24 h can greatly reduce short-term mortality and significantly improve favorable short-term neurologic outcomes in VA-ECMO-assisted patients without bleeding-related risks. As the grade assessment indicated that the certainty of the evidence was relatively low, hypothermia as a strategy for VA-ECMO-assisted patient care may need to be treated with caution.

Keywords: Hypothermia; Mortality; Neurologic outcome; Systematic review; Veno-arterial extracorporeal membrane oxygenation (VA-ECMO); meta-analysis.