Targeted temperature management after cardiac arrest. A systematic review and meta-analysis of animal studies

Abstract

Aim: Animal studies are an important knowledge base when information from clinical trials is missing or conflicting. The goal of this systematic review and meta-analysis was to investigate the effect of conventional targeted temperature management (TTM) between 32À36 C in animal cardiac arrest models, and to estimate the influence of effect modifiers on the pooled effect of TTM.Data sources: We searched Medline and Scopus from inception to May 2020 for randomised controlled animal trials assessing the effect of conventional TTM versus normothermia on neurologic outcome after cardiac arrest. We extracted data on study characteristics, study quality data, neurologic outcome, mortality, and potential effect modifiers. Results:We retrieved 1635 studies, 45 studies comprising data of 981 animals met the inclusion criteria. Risk of bias was high in 17 studies and moderate in 28 studies. We undertook random-effects meta-analyses and meta-regression analyses to calculate the pooled effect and the influence of effect modifiers. There was a strong beneficial effect of TTM as compared to normothermia on neurologic outcome (standardised mean difference of 1.4 [95% CI À1.7 to À1.1; I 2 = 75%]). Faster cooling rates, lower target temperature of TTM within the range of 32À36 C, and shorter duration of cooling were independently associated with an increasing effect size of TTM.Conclusions: This systematic review of animal cardiac arrest studies showed a consistent favourable effect of postresuscitation TTM as compared to normothermia on neurologic outcome that increased with lower target temperatures.

Hypothermia versus normothermia after out-of-hospital cardiac arrest: A systematic review and meta-analysis of randomized controlled trials

“…The plausible mechanisms for the neuroprotective effect of therapeutic hypothermia (TH) include decreased cerebral metabolism, reduced generation of free radicals, cold-induced protein, anti-inflammatory effects, and decreased excitotoxic amino acids and neurotransmitters [ [17] , [18] , [19] ]. Furthermore, beneficial effects are seen in pre-clinical animal studies [ 20 , 21 ]. However, although initial landmark trials showed a clinical benefit, adequately powered more recent trials have shown contradicting results.…”

Brain injury after cardiac arrest: pathophysiology, treatment, and prognosis

“…This usually involves core temperature measurement probes in the bladder or oesophagus and a feed-back controlled surface cooling device or intravascular catheter. In experimental literature, the neuroprotective effects of hypothermia are consistent across models [ 36 ] and species [ 37 ], but the significant heterogeneity among studies makes it difficult to conclude on the optimal timing, dosing (temperature level) and duration of treatment.…”

Targeted temperature management in adult cardiac arrest: Systematic review and meta-analysis

“…48,49 Recently, two systematic reviews on TTM in animals were published demonstrating a consistent and strong protective effect across animal species and models. 50,51 The mechanisms involved in the potential protective effect of TTM were not clear at the time of the first clinical trials, although they were partly attributed to a reduction in cerebral metabolism. 52 Subsequently, many studies have investigated the protective effects of TTM and have demonstrated an array of potential mechanistic pathways, including anti-oxidant, antiapoptotic and anti-inflammatory effects and a decrease in the accumulation or release of excitotoxic amino acids.…”