Optimal Time of Collapse to Return of Spontaneous Circulation to Apply Targeted Temperature Management for Cardiac Arrest: A Bayesian Network Meta-Analysis

Background: Both the American Heart Association (AHA) and European Resuscitation Council (ERC) have strongly recommended targeted temperature management (TTM) for patients who remain in coma after return of spontaneous circulation (ROSC). However, the role of TTM, especially hypothermia, in cardiac arrest patients after TTM2 trials has become much uncertain.Methods: We searched four online databases (PubMed, Embase, CENTRAL, and Web of Science) and conducted a Bayesian network meta-analysis. Based on the time of collapse to ROSC and whether the patient received TTM or not, we divided this analysis into eight groups (<20 min + TTM, <20 min, 20–39 min + TTM, 20–39 min, 40–59 min + TTM, 40–59 min, ≥60 min + TTM and ≥60 min) to compare their 30-day and at-discharge survival and neurologic outcomes.Results: From an initial search of 3,023 articles, a total of 9,005 patients from 42 trials were eligible and were included in this network meta-analysis. Compared with other groups, patients in the <20 min + TTM group were more likely to have better survival and good neurologic outcomes (probability = 46.1 and 52.5%, respectively). In comparing the same time groups with and without TTM, only the survival and neurologic outcome of the 20–39 min + TTM group was significantly better than that of the 20–39 min group [odds ratio = 1.41, 95% confidence interval (1.04–1.91); OR = 1.46, 95% CI (1.07–2.00) respectively]. Applying TTM with <20 min or more than 40 min of collapse to ROSC did not improve survival or neurologic outcome [ <20 min vs. <20 min + TTM: OR = 1.02, 95% CI (0.61–1.71)/OR = 1.03, 95% CI (0.61–1.75); 40–59 min vs. 40–59 min + TTM: OR = 1.50, 95% CI (0.97–2.32)/OR = 1.40, 95% CI (0.81–2.44); ≧60 min vs. ≧60 min + TTM: OR = 2.09, 95% CI (0.70–6.24)/OR = 4.14, 95% CI (0.91–18.74), respectively]. Both survival and good neurologic outcome were closely related to the time from collapse to ROSC.Conclusion: Survival and good neurologic outcome are closely associated with the time of collapse to ROSC. These findings supported that 20–40 min of collapse to ROSC should be a more suitable indication for TTM for cardiac arrest patients. Moreover, the future trials should pay more attention to these patients who suffer from moderate injury.Systematic Review Registration: [https://inplasy.com/?s=202180027], identifier [INPLASY202180027]

Impact of Cardiac Arrest Centers on the Survival of Patients With Nontraumatic Out‐of‐Hospital Cardiac Arrest: A Systematic Review and Meta‐Analysis

Background The role of cardiac arrest centers (CACs) in out‐of‐hospital cardiac arrest care systems is continuously evolving. Interpretation of existing literature is limited by heterogeneity in CAC characteristics and types of patients transported to CACs. This study assesses the impact of CACs on survival in out‐of‐hospital cardiac arrest according to varying definitions of CAC and prespecified subgroups. Methods and Results Electronic databases were searched from inception to March 9, 2021 for relevant studies. Centers were considered CACs if self‐declared by study authors and capable of relevant interventions. Main outcomes were survival and neurologically favorable survival at hospital discharge or 30 days. Meta‐analyses were performed for adjusted odds ratio (aOR) and crude odds ratios. Thirty‐six studies were analyzed. Survival with favorable neurological outcome significantly improved with treatment at CACs (aOR, 1.85 [95% CI, 1.52–2.26]), even when including high‐volume centers (aOR, 1.50 [95% CI, 1.18–1.91]) or including improved‐care centers (aOR, 2.13 [95% CI, 1.75–2.59]) as CACs. Survival significantly increased with treatment at CACs (aOR, 1.92 [95% CI, 1.59–2.32]), even when including high‐volume centers (aOR, 1.74 [95% CI, 1.38–2.18]) or when including improved‐care centers (aOR, 1.97 [95% CI, 1.71–2.26]) as CACs. The treatment effect was more pronounced among patients with shockable rhythm ( P =0.006) and without prehospital return of spontaneous circulation ( P =0.005). Conclusions were robust to sensitivity analyses, with no publication bias detected. Conclusions Care at CACs was associated with improved survival and neurological outcomes for patients with nontraumatic out‐of‐hospital cardiac arrest regardless of varying CAC definitions. Patients with shockable rhythms and those without prehospital return of spontaneous circulation benefited more from CACs. Evidence for bypassing hospitals or interhospital transfer remains inconclusive.

Cardiac Arrest in Pigs With 48 hours of Post‐Resuscitation Care Induced by 2 Methods of Myocardial Infarction: A Methodological Description

Background Systematic reviews have disclosed a lack of clinically relevant cardiac arrest animal models. The aim of this study was to develop a cardiac arrest model in pigs encompassing relevant cardiac arrest characteristics and clinically relevant post‐resuscitation care. Methods and Results We used 2 methods of myocardial infarction in conjunction with cardiac arrest. One group (n=7) had a continuous coronary occlusion, while another group (n=11) underwent balloon‐deflation during arrest and resuscitation with re‐inflation after return of spontaneous circulation. A sham group was included (n=6). All groups underwent 48 hours of intensive care including 24 hours of targeted temperature management. Pigs underwent invasive hemodynamic monitoring. Left ventricular function was assessed by pressure‐volume measurements. The proportion of pigs with return of spontaneous circulation was 43% in the continuous infarction group and 64% in the deflation‐reinflation group. In the continuous infarction group 29% survived the entire protocol while 55% survived in the deflation‐reinflation group. Both cardiac arrest groups needed vasopressor and inotropic support and pressure‐volume measurements showed cardiac dysfunction. During rewarming, systemic vascular resistance decreased in both cardiac arrest groups. Median [25%;75%] troponin‐I 48 hours after return of spontaneous circulation, was 88 973 ng/L [53 124;99 740] in the continuous infarction group, 19 661 ng/L [10 871;23 209] in the deflation‐reinflation group, and 1973 ng/L [1117;1995] in the sham group. Conclusions This article describes a cardiac arrest pig model with myocardial infarction, targeted temperature management, and clinically relevant post‐cardiac arrest care. We demonstrate 2 methods of inducing myocardial ischemia with cardiac arrest resulting in post‐cardiac arrest organ injury including cardiac dysfunction and cerebral injury.

Efficacy of vasopressin, steroid, and epinephrine protocol for in-hospital cardiac arrest resuscitation: A systematic review and meta-analysis of randomized controlled trials with trial sequential analysis

Aim: To assess the effect of vasopressin, steroid and epinephrine (VSE) combination therapy on return of spontaneous circulation (ROSC) after in-hospital cardiac arrest (IHCA), and test the conclusiveness of evidence using trial sequential analysis (TSA). Methods: The systematic search included PubMed, EMBASE, Scopus, and Cochrane Central Register of Controlled Trials. Randomized controlled trials that included adult patients with in-hospital cardiac arrest, with at least one group receiving combined vasopressin, epinephrine and steroid therapy were selected. Data was extracted independently by two reviewers. The main outcome of interest was ROSC. Other outcomes included survival to hospital discharge with good neurological outcomes and survival to 30 and 90 days with good neurological outcomes. Results: We included a total of three randomized controlled trials (n=869 patients). Results showed that Vasopressin, steroid and epinephrine combination therapy increased return of spontaneous circulation (risk ratio, 1.32; 95% CI, 1.18-1.47) as compared to placebo. Trial sequential analysis demonstrated that the existing evidence is conclusive. This was also validated by the alpha-spending adjusted relative risk (1.32 [1.16, 1.49], p<0.0001). Other outcomes could not be meta-analysed due to differences in timeframe in the included studies. Conclusions: VSE combination therapy administered in cardiopulmonary resuscitation led to improved rates of return of spontaneous circulation. Future trials of vasopressin, steroid and epinephrine combination therapy should evaluate survival to hospital discharge, neurological function and long-term survival. Keywords: cardiac arrest; cardiopulmonary resuscitation; meta-analysis; vasopressin; steroid; epinephrine