Double external defibrillation for shock-refractory ventricular fibrillation cardiac arrest: A step towards standardization.

Double (or dual) external defibrillation (DED) has increasingly been used in the last few years by a number of emergency medical services (EMS) as a last resort to terminate ventricular fibrillation and pulseless ventricular tachycardia in adult patients who remain refractory to standard defibrillation. However, no randomized controlled trials comparing DED with standard defibrillation focusing on patient-oriented outcomes as the primary objective have been published to date. Selection criteria, procedure techniques, and protocol are not clearly defined and vary across observational studies. The terms and/or nomenclature used to describe DED are confusing and vary throughout the literature. Despite increased use of DED, many questions remain as to which patients will derive the most benefit from DED, when to implement DED, and the optimal form of delivering DED. The present paper provides a brief overview of the background, procedure techniques, pad placement, and factors affecting how DED is delivered. A further objective of this paper is to offer a proposal for a uniform nomenclature and a standardized protocol in the form of a flowchart for EMS agencies to guide further clinical trials and best practices. This paper should not only help give background on novel definitions and clarify nomenclature for this practice, but more importantly should help institutions lay the groundwork for performing EMS-based large trials to further investigate the effectiveness of DED.

A review of pre-hospital case series among those with time to double external defibrillation and neurologic outcomes.

BACKGROUND: Double external defibrillation (DED) has been used as a final effort to terminate refractory ventricular fibrillation/pulseless ventricular tachycardiac (rVF/pVT). Data surrounding time to DED and patient-centered outcomes remains limited. OBJECTIVES: This study summarizes patient-level data from case-series of observed survival and neurologic outcomes following the use of DED for rVF/pVT among those with data regarding time to DED. METHODS: We conducted a literature search of PubMed, MEDLINE (OVID interface), and Scopus from January 1, 2000, through January 5, 2020. The literature was screened according to inclusion and exclusion criteria. Two investigators independently conducted the literature search, study selection, and data extraction. RESULTS: Our database search identified 3139 records. Of these, 1660 studies were eliminated following inspection of the titles and 22 studies underwent full-text screening, three included in the final analysis, describing a total of 29 cases. All studies were considered to have critical risk of bias. For the critical outcomes of survival to discharge and neurologically intact survival we identified that patients who received DED before 30 min from collapse compared to those who received DED after 30 min had better survival to discharge (33.3% [5/15] vs. 7.1% [1/14]) and neurologically intact survival (20.0% [3/15] vs. 7.1% [1/14]). Overall, 20.6% of patients survived to discharge, 13.8% with neurologically intact survival. It is noteworthy that the patients who were discharged with a CPC of 1 received two, four, five, and three standard shocks before receiving DED, and the time between their onset of cardiac arrest to their first DED attempt was recorded to be 15, 26, 26, and 32 min, respectively. CONCLUSION: We would like to indicate that there is not enough evidence to suggest that early use of pre-hospital DED is associated with improved outcomes. Further research should strive to address these issues before conclusions can be drawn.

The evolving role of novel treatment techniques in the management of patients with refractory VF/pVT out-of-hospital cardiac arrest.

STUDY OBJECTIVES: The purpose of this review is to provide a brief overview of new life-saving interventions and novel techniques that have been proposed as viable treatment options for patients presenting with refractory ventricular fibrillation/pulseless ventricular tachycardia (VF/pVT) out-of-hospital cardiac arrest (OHCA). METHODS: We conducted a comprehensive literature search of PubMed recent, Medline and Embase databases via the Ovid interface and Google Scholar from inception to July 2019. Eligible studies were observational in nature reporting outcomes of extracorporeal membrane oxygenation (ECMO), esmolol, double sequential defibrillation (DSD), and stellate ganglion block (SGB). Two investigators conducted the literature search, study selection, and data extraction. Any disagreements were resolved by consensus. RESULTS: Our database search identified 5331 records. We included in our review 23 articles that met our inclusion criteria. The selected studies included 16 observational studies on ECMO, 2 observational studies on esmolol, and 5 observational studies on DSD. CONCLUSION: We would like to suggest that there is not enough evidence in the existing literature to support at large-scale the effects of these techniques in the treatment of refractory VF/pVT OHCA. Randomized studies are warranted to evaluate the significant effects of these approaches against the best current standard of care.

Esmolol in the management of pre-hospital refractory ventricular fibrillation: A systematic review and meta-analysis.

BACKGROUND: Esmolol has been proposed as a viable adjunctive therapy for pre-hospital refractory ventricular fibrillation/pulseless ventricular tachycardia (VF/pVT). OBJECTIVES: We performed a systematic review and meta-analysis to assess the effectiveness of esmolol on pre-hospital refractory VF/pVT, compared with standard of care. METHODS: MEDLINE, Embase, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched for eligible studies. Two investigators independently extracted relevant data and assessed the methodological quality of each included study using the ROBINS-I tool. The quality of evidence for summary estimates was assessed according to GRADE guidelines. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) for each outcome of interest were calculated. RESULTS: The search yielded 3253 unique records, of which two studies were found to be in accordance with the research purpose, totaling 66 patients, of whom 33.3% (n = 22) received esmolol. Additional evidence was provided in the paper but was not relevant to the analysis and was therefore not included. Esmolol was likely associated with an increased rate of survival to discharge (RR 2.82, 95% CI 1.01-7.93, p = 0.05) (GRADE: Very low) and survival with favorable neurological outcome (RR 3.44, 95% CI 1.11-10.67, p = 0.03) (GRADE: Very low). Similar results were found for return of spontaneous circulation (ROSC) (RR 2.63, 95% CI 1.37-5.07, p = 0.004) (GRADE: Very low) and survival to intensive care unit (ICU)/hospital admission (RR 2.63, 95% CI 1.37-5.07, p = 0.004) (GRADE: Very low). CONCLUSION: The effectiveness of esmolol for refractory VF/pVT remains unclear. Trial sequential analysis (TSA) indicates that the evidence is inconclusive and that further trials are required in order to reach a conclusion. Therefore, it is imperative to continue to accumulate evidence in order to obtain a higher level of scientific evidence.

Double sequential defibrillation for out-of-hospital refractory ventricular fibrillation: A scoping review.

BACKGROUND: Double sequential defibrillation (DSD) has been proposed as a viable treatment option for patients in refractory ventricular fibrillation/pulseless ventricular tachycardia (VF/pVT) out-of-hospital cardiac arrests (OHCA). However, currently there is insufficient evidence to support a widespread implementation of this therapy. STUDY OBJECTIVES: The aim of this scoping review was to summarize the current available evidence of DSD for patients with refractory VF/pVT OHCA as well as to identify gaps in the literature that may require further research. METHODS: We conducted a comprehensive literature search of MEDLINE via PubMed, Embase via Ovid, and Scopus on August 19, 2019. We also checked reference lists of relevant papers to identify additional studies. Any controlled clinical study design (randomized controlled trials and non-randomized controlled trials), and observational studies (cohort studies and case-control studies) providing information on resuscitative parameters, survival rates and neurological outcomes in adults (≥ 18 years old) treated with DSD for refractory VF/pVT OHCA were included. Two investigators independently conducted the literature search, study selection, and data extraction. RESULTS: The search yielded 1612 unique records, of which 4 peer-reviewed articles were found relating to the research purpose, totaling 1061 patients of who 20.5% (n = 217) received DSD. Most studies evaluated if pre-hospital DSD was associated with improved survival to discharge after refractory VF/pVT. No randomized controlled trials were identified. CONCLUSION: To date, it is difficult to conclude the real benefit of DSD for patients in refractory VF based on the available evidence. The findings of this scoping review suggest there is limited evidence to support at large-scale the use of DSD for refractory VF/pVT OHCA. Further research is needed to better characterize and understand the use of DSD for refractory VF/pVT, in order to implement best practices to maximize the effectiveness and efficiency of care.

Double Defibrillation for Refractory In- and Out-of-Hospital Cardiac Arrest: A Systematic Review and Meta-Analysis.

BACKGROUND: Double/dual defibrillation (DD) has been proposed as an alternative treatment for refractory ventricular fibrillation (VF). This topic has been poorly researched and data on survival rates are limited. OBJECTIVE: This systematic review and meta-analysis evaluates whether DD improves outcomes among patients with refractory VF in- and out-of-hospital cardiac arrest compared with standard defibrillation. METHODS: A literature search was conducted on July 20, 2019 using MEDLINE via PubMed, Embase, Scopus, and the Cochrane Database of Systematic Reviews. We gave all results as a pooled odds ratio (OR) and 95% confidence interval (CI). Heterogeneity was assessed by calculating the I2 statistic and was deemed significant for a p value of < 0.10 or I2 ≥ 50%. The quality of evidence was evaluated according to Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. RESULTS: We included 27 records, of which 4 cohort studies totaling 1061 patients were included in the quantitative analysis. Of these, 20.5% (n = 217) received the intervention. DD had no effect on return of spontaneous circulation (OR 0.68; 95% CI 0.44-1.04; I2 = 41%, p = 0.08) (GRADE: Very low), survival to admission (OR 0.77; 95% CI 0.51-1.17; I2 = 18%, p = 0.22) (GRADE: Very low), or survival to discharge (OR 0.66; 95% CI 0.38-1.15; I2 = 0%, p = 0.14) (GRADE: Very low). CONCLUSIONS: DD did not improve any outcomes of interest. Therefore, it is imperative that a well-designed study in this area be conducted. Ideally, conducting a randomized controlled trial in this population should be attempted to obtain a higher level of scientific evidence.

Extracorporeal cardiopulmonary resuscitation for adults with shock-refractory cardiac arrest.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation has increasingly emerged as a feasible treatment to mitigate the progressive multiorgan dysfunction that occurs during cardiac arrest, in support of further resuscitation efforts. OBJECTIVES: Because the recent systematic review commissioned in 2018 by the International Liaison Committee on Resuscitation Advanced Life Support task did not include studies without a control group, our objective was to conduct a review incorporating these studies to increase available evidence supporting the use of extracorporeal cardiopulmonary resuscitation (ECPR) for cardiac arrest patients, while waiting for high-quality evidence from randomized controlled trials (RCTs). METHODS: MEDLINE, Embase, and Science Citation Index (Web of Science) were searched for eligible studies from database inception to July 20, 2020. The population of interest was adult patients who had suffered cardiac arrest in any setting. We included all cohort studies with 1 exposure/1 group and descriptive studies (ie, case series studies). We excluded RCTs, non-RCTs, and observational analytic studies with a control group. Outcomes included short-term survival and favorable neurological outcome. Short-term outcomes (ie, hospital discharge, 30 days, and 1 month) were combined into a single category. RESULTS: Our searches of databases and other sources yielded a total of 4302 citations. Sixty-two eligible studies were included (including a combined total of 3638 participants). Six studies were of in-hospital cardiac arrest, 34 studies were of out-of-hospital cardiac arrest, and 22 studies included both in-hospital and out-of-hospital cardiac arrest. Seven hundred and sixty-eight patients of 3352 (23%) had short-term survival; whereas, 602 of 3366 (18%) survived with favorable neurological outcome, defined as a cerebral performance category score of 1 or 2. CONCLUSIONS: Current clinical evidence is mostly drawn from observational studies, with their potential for confounding selection bias. Although studies without controls cannot supplant case-control or cohort studies, several ECPR studies without a control group show successful resuscitation with impressive results that may provide valuable information to inform a comparison.

Extracorporeal cardiopulmonary resuscitation for refractory cardiac arrest: a scoping review.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) is an emerging concept in cardiac arrest and cardiopulmonary resuscitation. Recent research has documented a significant improvement in favorable outcomes, notable survival to discharge, and neurologically intact survival. OBJECTIVES: The present study undertakes a scoping review to summarize the available evidence by assessing the use of ECPR, compared with no ECPR or the standard of care, for adult patients who sustain cardiac arrest in any setting, in studies which record survival and neurologic outcomes. METHODS: This review followed the PRISMA extension for scoping reviews (PRISMA-ScR) guidelines. Four online databases were used to identify papers published from database inception to July 12, 2020. We selected 23 observational studies from Asia, Europe, and North America that used survival to discharge or neurologically intact survival as a primary or secondary endpoint variable in patients with cardiac arrest refractory to standard treatment. RESULTS: Twenty-three observational studies were included in the review. Eleven studies were of out-of-hospital cardiac arrest, 7 studies were of in-hospital cardiac arrest, and 5 studies included mixed populations. Ten studies reported long-term favorable neurological outcomes (ie, Cerebral Performance Category score of 1 - 2 at 3 months [n = 3], 6 months [n = 3], and 1 year [n = 4]), of which only 4 had statistical significance at 5% significance levels. Current knowledge is mostly drawn from single-center observations, with most of the evidence coming from case series and cohort studies, hence is prone to publication bias. No randomized control trials were included. CONCLUSIONS: This scoping review highlights the need for high-quality studies to increase the level of evidence and reduce knowledge gaps to change the paradigm of care for patients with shock-refractory cardiac arrest.

Prehospital Double Defibrillation for Refractory Ventricular Fibrillation: A Scoping Review Protocol.

Double defibrillation (DD) has been proposed as an alternative treatment for patients with refractory ventricular fibrillation/pulseless ventricular tachycardia (VF/pVT) out-of-hospital cardiac arrest (OHCA) nonresponsive to the best current standard of care. Treatment results are promising, but the efficacy and safety of the procedure remain unclear. Currently, there is a paucity of evidence in the literature on DD suggesting the optimal strategy for treating this challenging patient population. Thus, we aim to perform a scoping review to explore the current literature addressing resuscitative parameters, survival rates, and neurological outcomes in refractory VF/pVT OHCA patients treated with DD as well as to identify gaps in the literature that may require further research. Here, we discuss the anticipated study protocol.

The Evolving Role of Esmolol in Management of Pre-Hospital Refractory Ventricular Fibrillation; a Scoping Review.

INTRODUCTION: Few studies have described their experience using esmolol, an ultra-short acting ß-adrenergic antagonist, in the emergency department (ED) as a feasible adjuvant therapy for the treatment of refractory ventricular fibrillation/pulseless ventricular tachycardia (VF/pVT) out-of-hospital cardiac arrest. However, there is currently insufficient evidence to support the widespread implementation of this therapy. The aim of this scoping review was to summarize the current available evidence on the use of esmolol as an adjuvant therapy for refractory VF/pVT out-of-hospital cardiac arrest, as well as to identify gaps within the literature that may require further research. METHODS: We conducted a comprehensive literature search of MEDLINE via PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL) on July 5, 2019. The search was restricted to articles that were published from January 2000 to July 2019. Google Scholar was searched and reference lists of relevant papers were examined to identify additional studies. We included any controlled clinical study design (randomized controlled trials and non-randomized controlled trials) and observational studies (cohort studies and case-control studies) in adults providing information on the use of esmolol as an adjuvant therapy for refractory VF/pVT out-of-hospital cardiac arrest. RESULTS: The search yielded 2817 unique records, out of which 2 peer-reviewed articles were found relating to the research purpose totaling 66 patients 33.3% (n = 22) of which received esmolol. These studies found that sustained return of spontaneous circulation (ROSC) was significantly more common in the patients that received esmolol compared to the control group. However, no statistically significant outcomes were found regarding survival to discharge and favorable neurological outcome. No randomized controlled trials were identified. CONCLUSION: To date, it is difficult to conclude the real benefit of esmolol as an adjuvant therapy for refractory VF/pVT out-of-hospital cardiac arrest based on the available evidence. The findings of this scoping review suggest that there is a paucity of research and limited evidence to support this therapy.

Extracorporeal cardiopulmonary resuscitation for in- and out-of-hospital cardiac arrest: systematic review and meta-analysis of propensity score-matched cohort studies.

INTRODUCTION: In this systematic review and meta-analysis of propensity score-matched cohort studies, we quantitatively summarize whether venoarterial extracorporeal membrane oxygenation (VA-ECMO) used as extracorporeal cardiopulmonary resuscitation (ECPR), compared with conventional cardiopulmonary resuscitation (CCPR), is associated with improved rates of 30-day and long-term favorable neurological outcomes and survival in patients resuscitated from in- and out-of-hospital cardiac arrest. METHODS: We searched MEDLINE via PubMed, Embase, Scopus, and Google Scholar for eligible studies on January 14, 2019. All searches were limited to studies published between January 2000 and January 2019. Two investigators independently evaluated the quality (or certainty) of evidence according to GRADE guidelines. Pooled results are presented as relative risks (RRs) with 95% confidence intervals (CIs). RESULTS: Six cohort studies using propensity score-matched analysis were included, totaling 1108 matched patients. Pooled analyses showed that ECPR was likely associated with improved 30-day and long-term favorable neurological outcome in adults compared to CCPR for in- and out-of-hospital cardiac arrest (RR = 2.02, 95% CI = 1.29-3.16; I2 = 20%, P = 0.002; very low-quality evidence) and (RR = 2.86, 95% CI = 1.64-5.01; I2 = 0%, P = 0.0002; moderate-quality evidence), respectively. When we analyzed in- and out-of-hospital cardiac arrest separately, ECPR was likely associated with improved 30-day favorable neurological outcome compared to CCPR for in-hospital cardiac arrest (RR = 2.18, 95% CI = 1.24-3.81; I2 = 9%, P = 0.006; very low-quality evidence), but not for out-of-hospital cardiac arrest (RR = 2.61, 95% CI = 0.56-12.20; I2 = 59%, P = 0.22; very low-quality evidence). ECPR was also likely associated with improved long-term favorable neurological outcome compared to CCPR for in-hospital cardiac arrest (RR = 2.50, 95% CI = 1.33-4.71; I2 = 0%, P = 0.005; moderate-quality evidence) and out-of-hospital cardiac arrest (RR = 4.64, 95% CI = 1.41-15.25; I2 = 0%, P = 0.01; moderate-quality evidence). CONCLUSIONS: Our analysis suggests that VA-ECMO used as ECPR may improve long-term favorable neurological outcomes and survival when compared to the best standard of care in a selected patient population. Therefore, it is imperative for well-designed randomized clinical trials to obtain a higher level of scientific evidence to ensure optimal outcomes for cardiac arrest patients.

Long-term neurologically intact survival after extracorporeal cardiopulmonary resuscitation for in-hospital or out-of-hospital cardiac arrest: A systematic review and meta-analysis.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has been used as extracorporeal cardiopulmonary resuscitation (ECPR) to support further resuscitation efforts in patients with cardiac arrest, yet its clinical effectiveness remains uncertain. OBJECTIVES: This study reviews the role of ECPR in contemporary resuscitation care compared to no ECPR and/or standard care, e.g. conventional CPR, and quantitatively summarize the rates of long-term neurologically intact survival after adult in-hospital cardiac arrest (IHCA) or out-of-hospital cardiac arrest (OHCA). METHODS: We searched the following databases on January 31 st, 2020: CENTRAL, MEDLINE, Embase, and Web of Science. We followed PRISMA guidelines and used PICO format to summarize the research questions. Risk of bias was assessed using the ROBINS-I tool. Pooled risk ratios (RRs) for each outcome of interest were calculated. Quality of evidence was evaluated according to GRADE guidelines. RESULTS: Six cohort studies were included, totaling 1750 patients. Of these, 530 (30.3%) received the intervention, and 91 (17.2%) survived with long-term neurologically intact survival. ECPR compared to no ECPR is likely associated with improved long-term neurologically intact survival after cardiac arrest in any setting (risk ratio [RR] 3.11, 95% confidence interval [CI] 2.06-4.69; p < 0.00001) (GRADE: Very low quality). Similar results were found for long-term neurologically intact survival after IHCA (RR 3.21, 95% CI 1.74-5.94; p < 0.0002) (GRADE: Very low quality) and OHCA (RR 3.11, 95% CI 1.50-6.47; p < 0.002) (GRADE: Very low quality). Long-term time frames for neurologically intact survival (three months to two years) were combined into a single category, defined a priori as a Glasgow-Pittsburgh cerebral performance category (CPC) of 1 or 2. CONCLUSIONS: VA-ECMO used as ECPR is likely associated with improved long-term neurologically intact survival after cardiac arrest. Future evidence from randomized trials is very likely to have an important impact on the estimated effect of this intervention and will further define optimal clinical practice. Review registration: PROSPERO CRD42020171945.