In a randomized trial, patients with out-of-hospital cardiac arrest who received extracorporeal CPR and those who received conventional CPR had similar results for survival and favorable neurologic ...outcomes.
Return of spontaneous circulation occurs in less than 10% of patients with cardiac arrest undergoing cardiopulmonary resuscitation (CPR) for more than 15 minutes. Studies suggest that extracorporeal ...life support during cardiopulmonary resuscitation (ECPR) improves survival rate in these patients. These studies, however, are hampered by their non-randomized, observational design and are mostly single-center. A multicenter, randomized controlled trial is urgently warranted to evaluate the effectiveness of ECPR.
We hypothesize that early initiation of ECPR in refractory out-of-hospital cardiac arrest (OHCA) improves the survival rate with favorable neurological status.
The INCEPTION trial is an investigator-initiated, prospective, multicenter trial that will randomly allocate 110 patients to either continued CPR or ECPR in a 1:1 ratio. Patients eligible for inclusion are adults (≤ 70 years) with witnessed OHCA presenting with an initial rhythm of ventricular fibrillation (VF) or ventricular tachycardia (VT), who received bystander basic life support and who fail to achieve sustained return of spontaneous circulation within 15 minutes of cardiopulmonary resuscitation by emergency medical services. The primary endpoint of the study is 30-day survival rate with favorable neurological status, defined as 1 or 2 on the Cerebral Performance Category score. The secondary endpoints include 3, 6 and 12-month survival rate with favorable neurological status and the cost-effectiveness of ECPR compared to CCPR.
The INCEPTION trial aims to determine the clinical benefit for the use of ECPR in patients with refractory OHCA presenting with VF/VT. Additionally, the feasibility and cost-effectiveness of ECPR will be evaluated.
Purpose of review
Extracorporeal cardiopulmonary resuscitation (ECPR) is an emerging treatment for refractory cardiac arrest. In recent years, several randomized controlled trials have been published ...that aimed to address the efficacy and effectiveness of ECPR for out-of-hospital cardiac arrest (OHCA). Despite the lack of high-quality evidence concerning clinical effectiveness and cost-effectiveness, ECPR is increasingly implemented throughout the world. In this review, we aim to provide an overview of the current status of ECPR for OHCA.
Recent findings
Randomized controlled trials showed diverging results, largely due to differences in selection criteria and study design. Single-center studies, performed in centers with extraordinary expertise and dedication consistently achieve a low-flow time of around 60 min, but such achievements are rarely reproduced outside these centers. Strict patient selection can improve outcome but simultaneously limits the caseload. Preliminary data suggest that outcome may also be improved by avoiding hyperoxia postresuscitation.
Summary
The potential of ECPR to increase survival in selected patients in highly dedicated systems seems to be proven, the question remains whether ECPR for OHCA can be widely implemented successfully and can develop into a sustainable, commonplace resource-effective treatment.
Evidence for extracorporeal cardiopulmonary resuscitation (CPR) in refractory out-of-hospital cardiac arrest (OHCA) remains inconclusive. Recently, the INCEPTION-trial, comparing extracorporeal with ...conventional CPR, found no statistically significant difference in neurologically favorable survival. Since protocol deviations were anticipated, a pre-specified per-protocol analysis was foreseen.
The per-protocol analysis of the INCEPTION trial excluded patients not meeting inclusion or exclusion criteria, amongst which time-to-cannulation of >60 minutes, and achieving a return of spontaneous circulation before hospital arrival. Crossovers were excluded as well. The primary outcome (30-day survival in a neurologically favorable condition; cerebral performance category CPC 1–2) was primarily analyzed under a frequentist statistical framework. In addition, Bayesian analysis under a minimally informative prior was performed.
Eighty-one patients were included in the per-protocol analysis (extracorporeal CPR n = 33, conventional CPR n = 48). Thirty-day survival with CPC1-2 was 15% in the extracorporeal CPR group versus 9% in the conventional CPR group (adjusted OR 1.9; 95% CI 0.4–9.3; p-value 0.393). Bayesian analysis showed an 84% posterior probability of any ECPR benefit and a 61% posterior probability of a 5% absolute risk reduction for the primary outcome.
A pre-planned, pre-specified per-protocol analysis of the INCEPTION-trial, found a higher survival with favorable neurological in patients undergoing ECPR versus CCPR for refractory shockable OHCA. This difference did not reach statistical significance, but results should be interpreted with care, in the light of the small remaining sample size.
Ethics of ECPR research Suverein, Martje M.; Shaw, David; Lorusso, Roberto ...
Resuscitation,
December 2021, 2021-12-00, 20211201, Letnik:
169
Journal Article
Recenzirano
Odprti dostop
The design of emergency medicine trials can raise several ethical concerns – risks may be greater, and randomisation may have to occur before consent. Research in emergency medicine is thus an ...illuminating context to explore the interplay between risk and randomisation, and the consequences for consent. Using a currently running trial, we describe possible concerns, considerations, and solutions to reconcile the conflicting interests of scientific inquiry, ethical principles, and clinical reality in emergency medicine research.
Extracorporeal cardiopulmonary resuscitation (ECPR), has demonstrated promise in the management of refractory out-of-hospital cardiac arrest (OHCA). However, evidence from observational studies and ...clinical trials are conflicting and the factors influencing outcome have not been well established.
We conducted a systematic review and meta-analysis summarizing the association between pre-ECPR prognostic factors and likelihood of good functional outcome among adult patients requiring ECPR for OHCA. We searched Medline and Embase databases from inception to February 28, 2023 and screened studies with two independent reviewers. We performed meta-analyses of unadjusted and adjusted odds ratios, adjusted hazard ratios and mean differences separately. We assessed risk of bias using the QUIPS tool and certainty of evidence using the GRADE approach.
We included 29 observational and randomized studies involving 7,397 patients. Factors with moderate or high certainty of association with increased survival with favourable functional outcome include pre-arrest patient factors, such as younger age (odds ratio (OR) 2.13, 95% CI 1.52 to 2.99) and female sex (OR 1.37, 95% CI 1.11 to 1.70), as well as intra-arrest factors, such as shockable rhythm (OR 2.79, 95% CI 2.04 to 3.80), witnessed arrest (OR 1.68 (95% CI 1.16 to 2.42), bystander CPR (OR 1.55, 95% CI 1.19 to 2.01), return of spontaneous circulation (OR 2.81, 95% CI 2.19 to 3.61) and shorter time to cannulation (OR 1.14, 95% CI 1.17 to 1.69 per 10 minutes).
The findings of this review confirm several clinical concepts wellestablished in the cardiac arrest literature and their applicability to the patient for whom ECPR is considered - that is, the impact of pre-existing patient factors, the benefit of timely and effective CPR, as well as the prognostic importance of minimizing low-flow time. We advocate for the thoughtful consideration of these prognostic factors as part of a risk stratification framework when evaluating a patient's potential candidacy for ECPR.
Abstract Background The outcomes of several randomized trials on extracorporeal cardiopulmonary resuscitation (ECPR) in patients with refractory out-of-hospital cardiac arrest were examined using ...frequentist methods, resulting in a dichotomous interpretation of results based on p-values rather than in the probability of clinically relevant treatment effects. To determine such a probability of a clinically relevant ECPR-based treatment effect on neurological outcomes, the authors of these trials performed a Bayesian meta-analysis of the totality of randomized ECPR evidence. Methods A systematic search was applied to three electronic databases. Randomized trials that compared ECPR-based treatment with conventional CPR for refractory out-of-hospital cardiac arrest were included. The study was preregistered in INPLASY (INPLASY2023120060). The primary Bayesian hierarchical meta-analysis estimated the difference in 6-month neurologically favorable survival in patients with all rhythms, and a secondary analysis assessed this difference in patients with shockable rhythms (Bayesian hierarchical random-effects model). Primary Bayesian analyses were performed under vague priors. Outcomes were formulated as estimated median relative risks, mean absolute risk differences, and numbers needed to treat with corresponding 95% credible intervals (CrIs). The posterior probabilities of various clinically relevant absolute risk difference thresholds were estimated. Results Three randomized trials were included in the analysis (ECPR, n = 209 patients; conventional CPR, n = 211 patients). The estimated median relative risk of ECPR for 6-month neurologically favorable survival was 1.47 (95%CrI 0.73–3.32) with a mean absolute risk difference of 8.7% (− 5.0; 42.7%) in patients with all rhythms, and the median relative risk was 1.54 (95%CrI 0.79–3.71) with a mean absolute risk difference of 10.8% (95%CrI − 4.2; 73.9%) in patients with shockable rhythms. The posterior probabilities of an absolute risk difference > 0% and > 5% were 91.0% and 71.1% in patients with all rhythms and 92.4% and 75.8% in patients with shockable rhythms, respectively. Conclusion The current Bayesian meta-analysis found a 71.1% and 75.8% posterior probability of a clinically relevant ECPR-based treatment effect on 6-month neurologically favorable survival in patients with all rhythms and shockable rhythms. These results must be interpreted within the context of the reported credible intervals and varying designs of the randomized trials. Registration INPLASY (INPLASY2023120060, December 14th, 2023, https://doi.org/10.37766/inplasy2023.12.0060 ).
Prospective, trial-based data comparing health-related quality of life (HRQoL) in patients surviving out-of-hospital cardiac arrest (OHCA) through extracorporeal cardiopulmonary resuscitation (ECPR) ...or conventional CPR (CCPR) are scarce. We aimed to determine HRQoL during 1-year after refractory OHCA in patients treated with ECPR and CCPR.
We present a secondary analysis of the multicenter INCEPTION-trial, which studied the effectiveness of ECPR versus CCPR in patients with refractory OHCA. HRQoL was prospectively assessed using the EQ-5D-5L questionnaire. Poor HRQoL was pragmatically defined as an EQ-5D-5L health utility index (HUI) > 1 SD below the age-adjusted norm. We used mixed linear models to assess the difference in HRQoL over time and univariable analyses to assess factors potentially associated with poor HRQoL.
A total of 134 patients were enrolled, and hospital survival was 20% (27 patients). EQ-5D-5L data were available for 25 patients (5 ECPR and 20 CCPR). One year after OHCA, the estimated mean HUI was 0.73 (0.05) in all patients, 0.84 (0.12) in ECPR survivors, and 0.71 (0.05) in CCPR survivors (p-value 0.31). Eight (32%) survivors had a poor HRQoL. HRQoL was good in 17 (68%) patients, with 100% in ECPR survivors versus 60% in CCPR survivors (p-value 0.14).
One year after refractory OHCA, 68% of the survivors had a good HRQoL. We found no statistically significant difference in HRQoL one year after OHCA in patients treated with ECPR compared to CCPR. However, numerical differences may be clinically relevant in favor of ECPR.
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