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Targeted Temperature Management after Cardiac Arrest: A Systematic Review and Meta-Analysis with Trial Sequential Analysis.

ABSTRACT: 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.

SUBMITTER: Sanfilippo F

PROVIDER: S-EPMC8432025 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Targeted Temperature Management after Cardiac Arrest: A Systematic Review and Meta-Analysis with Trial Sequential Analysis.

Sanfilippo Filippo F La Via Luigi L Lanzafame Bruno B Dezio Veronica V Busalacchi Diana D Messina Antonio A Ristagno Giuseppe G Pelosi Paolo P Astuto Marinella M

Journal of clinical medicine 20210831 17

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" ...[more]

PMID: 34501392

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Project description:BACKGROUND:Targeted temperature management (TTM) of 32 to 34 °C has been the standard treatment for out-of-hospital cardiac arrest since clinical trials in 2002 indicated benefit on survival and neurological outcome. In 2013, a clinical trial showed no difference in outcome between TTM of 33 °C and TTM of 36 °C. In this meta-analysis, we investigate the evidence for TTM in animal models of cardiac arrest. METHODS:We searched PubMed and EMBASE for adult animal studies using TTM as a treatment in different models of cardiac arrest or global brain ischemia which reported neurobehavioural outcome, brain histology or mortality. We used a random effects model to calculate estimates of efficacy and assessed risk of bias using an adapted eight-item version of the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES) quality checklist. We also used a scoring system based on the recommendations of the Stroke Treatment Academic Industry Roundtable (STAIR), to assess the scope of testing in the field. Included studies which investigated a post-ischemic induction of TTM had their treatment regimens characterized with regard to depth, duration and time to treatment and scored against the modified STAIR criteria. RESULTS:The initial and updated search generated 17809 studies after duplicate removal. One hundred eighty-one studies met the inclusion criteria, including data from 1,787, 6,495 and 2,945 animals for neurobehavioural, histological and mortality outcomes, respectively. TTM was favoured compared to control for all outcomes. TTM was beneficial using short and prolonged cooling, deep and moderate temperature reduction, and early and delayed time to treatment. Median [IQR] study quality was 4 [3 to 6]. Eighteen studies checked seven or more of the eight CAMARADES quality items. There was no clear correlation between study quality and efficacy for any outcome. STAIR analysis identified 102 studies investigating post-ischemic induction of TTM, comprising 147 different treatment regimens of TTM. Only 2 and 8 out of 147 regimens investigated comorbid and gyrencephalic animals, respectively. CONCLUSIONS:TTM is beneficial under most experimental conditions in animal models of cardiac arrest or global brain ischemia. However, research on gyrencephalic species and especially comorbid animals is uncommon and a possible translational gap. Also, low study quality suggests risk of bias within studies. Future animal research should focus on mimicking the clinical scenario and employ similar rigour in trial design to that of modern clinical trials.

Project description:BackgroundTemperature control with target temperature management (TTM) after cardiac arrest has been endorsed by expert societies and adopted in international clinical practice guidelines but recent evidence challenges the use of hypothermic TTM.MethodsSystematic review and Bayesian meta-analysis of clinical trials on adult survivors from cardiac arrest undergoing TTM for at least 12 h comparing TTM versus no TTM or with a separation > 2 °C between intervention and control groups using the PubMed/MEDLINE, EMBASE, CENTRAL databases from inception to 1 September 2021 (PROSPERO CRD42021248140). All randomised and quasi-randomised controlled trials were considered. The risk ratio and 95% confidence interval for death (primary outcome) and unfavourable neurological recovery (secondary outcome) were captured using the original study definitions censored up to 180 days after cardiac arrest. Bias was assessed using the updated Cochrane risk-of-bias for randomised trials tool and certainty of evidence assessed using the Grading of Recommendation Assessment, Development and Evaluation methodology. A hierarchical robust Bayesian model-averaged meta-analysis was performed using both minimally informative and data-driven priors and reported by mean risk ratio (RR) and its 95% credible interval (95% CrI).ResultsIn seven studies (three low bias, three intermediate bias, one high bias, very low to low certainty) recruiting 3792 patients the RR by TTM 32-34 °C was 0.95 [95% CrI 0.78-1.09] for death and RR 0.93 [95% CrI 0.84-1.02] for unfavourable neurological outcome. The posterior probability for no benefit (RR ≥ 1) by TTM 32-34 °C was 24% for death and 12% for unfavourable neurological outcome. The posterior probabilities for favourable treatment effects of TTM 32-34 °C were the highest for an absolute risk reduction of 2-4% for death (28-53% chance) and unfavourable neurological outcome (63-78% chance). Excluding four studies without active avoidance of fever in the control arm reduced the probability to achieve an absolute risk reduction > 2% for death or unfavourable neurological outcome to ≤ 50%.ConclusionsThe posterior probability distributions did not support the use of TTM at 32-34 °C compared to 36 °C also including active control of fever to reduce the risk of death and unfavourable neurological outcome at 90-180 days. Any likely benefit of hypothermic TTM is smaller than targeted in RCTs to date.

Project description:BackgroundWe sought to determine the outcome of suicidal hanging and the impact of targeted temperature management (TTM) on hanging-induced cardiac arrest (CA) through an Eastern Association for the Surgery of Trauma (EAST) multicenter retrospective study.MethodsWe analyzed hanging patient data and TTM variables from January 1992 to December 2015. Cerebral performance category score of 1 or 2 was considered good neurologic outcome, while cerebral performance category score of 3 or 4 was considered poor outcome. Classification and Regression Trees recursive partitioning was used to develop multivariate predictive models for survival and neurologic outcome.ResultsA total of 692 hanging patients from 17 centers were analyzed for this study. Their overall survival rate was 77%, and the CA survival rate was 28.6%. The CA patients had significantly higher severity of illness and worse outcome than the non-CA patients. Of the 175 CA patients who survived to hospital admission, 81 patients (46.3%) received post-CA TTM. The unadjusted survival of TTM CA patients (24.7% vs 39.4%, p < 0.05) and good neurologic outcome (19.8% vs 37.2%, p < 0.05) were worse than non-TTM CA patients. However, when subgroup analyses were performed between those with an admission Glasgow Coma Scale score of 3 to 8, the differences between TTM and non-TTM CA survival (23.8% vs 30.0%, p = 0.37) and good neurologic outcome (18.8% vs 28.7%, p = 0.14) were not significant. Targeted temperature management implementation and post-CA management varied between the participating centers. Classification and Regression Trees models identified variables predictive of favorable and poor outcome for hanging and TTM patients with excellent accuracy.ConclusionCardiac arrest hanging patients had worse outcome than non-CA patients. Targeted temperature management CA patients had worse unadjusted survival and neurologic outcome than non-TTM patients. These findings may be explained by their higher severity of illness, variable TTM implementation, and differences in post-CA management. Future prospective studies are necessary to ascertain the effect of TTM on hanging outcome and to validate our Classification and Regression Trees models.Level of evidenceTherapeutic study, level IV; prognostic study, level III.

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Targeted Temperature Management after Cardiac Arrest: A Systematic Review and Meta-Analysis with Trial Sequential Analysis.

Publications

Targeted Temperature Management after Cardiac Arrest: A Systematic Review and Meta-Analysis with Trial Sequential Analysis.

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