Early Extracorporeal CPR for Refractory Out-of-Hospital Cardiac Arrest.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (CPR) restores perfusion and oxygenation in a patient who does not have spontaneous circulation. The evidence with regard to the effect of extracorporeal CPR on survival with a favorable neurologic outcome in refractory out-of-hospital cardiac arrest is inconclusive. METHODS: In this multicenter, randomized, controlled trial conducted in the Netherlands, we assigned patients with an out-of-hospital cardiac arrest to receive extracorporeal CPR or conventional CPR (standard advanced cardiac life support). Eligible patients were between 18 and 70 years of age, had received bystander CPR, had an initial ventricular arrhythmia, and did not have a return of spontaneous circulation within 15 minutes after CPR had been initiated. The primary outcome was survival with a favorable neurologic outcome, defined as a Cerebral Performance Category score of 1 or 2 (range, 1 to 5, with higher scores indicating more severe disability) at 30 days. Analyses were performed on an intention-to-treat basis. RESULTS: Of the 160 patients who underwent randomization, 70 were assigned to receive extracorporeal CPR and 64 to receive conventional CPR; 26 patients who did not meet the inclusion criteria at hospital admission were excluded. At 30 days, 14 patients (20%) in the extracorporeal-CPR group were alive with a favorable neurologic outcome, as compared with 10 patients (16%) in the conventional-CPR group (odds ratio, 1.4; 95% confidence interval, 0.5 to 3.5; P = 0.52). The number of serious adverse events per patient was similar in the two groups. CONCLUSIONS: In patients with refractory out-of-hospital cardiac arrest, extracorporeal CPR and conventional CPR had similar effects on survival with a favorable neurologic outcome. (Funded by the Netherlands Organization for Health Research and Development and Maquet Cardiopulmonary [Getinge]; INCEPTION ClinicalTrials.gov number, NCT03101787.).

Extracorporeal cardiopulmonary resuscitation versus standard treatment for refractory out-of-hospital cardiac arrest: a Bayesian meta-analysis.

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 ).

Transfusion of red blood cells in venoarterial extracorporeal membrane oxygenation: A multicenter retrospective observational cohort study.

BACKGROUND: Evidence-based recommendations for transfusion in patients with venoarterial extracorporeal membrane oxygenation (VA ECMO) are scarce. The current literature is limited to single-center studies with small sample sizes, therefore complicating generalizability. This study aims to create an overview of red blood cell (RBC) transfusion in VA ECMO patients. METHODS: This international mixed-method study combined a survey with a retrospective observational study in 16 centers. The survey inventoried local transfusion guidelines. Additionally, retrospective data of all adult patients with a VA ECMO run >24 h (January 2018 until July 2019) was collected of patient, ECMO, outcome, and daily transfusion parameters. All patients that received VA ECMO for primary cardiac support were included, including surgical (i.e., post-cardiotomy) and non-surgical (i.e., myocardial infarction) indications. The primary outcome was the number of RBC transfusions per day and in total. Univariable logistic regressions and a generalized linear mixed model (GLMM) were performed to assess factors associated with RBC transfusion. RESULTS: Out of 419 patients, 374 (89%) received one or more RBC transfusions. During a median ECMO run of 5 days (1st-3rd quartile 3-8), patients received a median total of eight RBC units (1st-3rd quartile 3-17). A lower hemoglobin (Hb) prior to ECMO, longer ECMO-run duration, and hemorrhage were associated with RBC transfusion. After correcting for duration and hemorrhage using a GLMM, a different transfusion trend was found among the regimens. No unadjusted differences were found in overall survival between either transfusion status or the different regimens, which remained after adjustment for potential confounders. CONCLUSION: RBC transfusion in patients on VA ECMO is very common. The sum of RBC transfusions increases rapidly after ECMO initiation, and is dependent on the Hb threshold applied. This study supports the rationale for prospective studies focusing on indications and thresholds for RBC transfusion.

The interaction of thrombocytopenia, hemorrhage, and platelet transfusion in venoarterial extracorporeal membrane oxygenation: a multicenter observational study.

BACKGROUND: Thrombocytopenia, hemorrhage and platelet transfusion are common in patients supported with venoarterial extracorporeal membrane oxygenation (VA ECMO). However, current literature is limited to small single-center experiences with high degrees of heterogeneity. Therefore, we aimed to ascertain in a multicenter study the course and occurrence rate of thrombocytopenia, and to assess the association between thrombocytopenia, hemorrhage and platelet transfusion during VA ECMO. METHODS: This was a sub-study of a multicenter (N = 16) study on transfusion practices in patients on VA ECMO, in which a retrospective cohort (Jan-2018-Jul-2019) focusing on platelets was selected. The primary outcome was thrombocytopenia during VA ECMO, defined as mild (100-150·109/L), moderate (50-100·109/L) and severe (< 50·109/L). Secondary outcomes included the occurrence rate of platelet transfusion, and the association between thrombocytopenia, hemorrhage and platelet transfusion, assessed through mixed-effect models. RESULTS: Of the 419 patients included, median platelet count at admission was 179·109/L. During VA ECMO, almost all (N = 398, 95%) patients developed a thrombocytopenia, of which a significant part severe (N = 179, 45%). One or more platelet transfusions were administered in 226 patients (54%), whereas 207 patients (49%) suffered a hemorrhagic event during VA ECMO. In non-bleeding patients, still one in three patients received a platelet transfusion. The strongest association to receive a platelet transfusion was found in the presence of severe thrombocytopenia (adjusted OR 31.8, 95% CI 17.9-56.5). After including an interaction term of hemorrhage and thrombocytopenia, this even increased up to an OR of 110 (95% CI 34-360). CONCLUSIONS: Thrombocytopenia has a higher occurrence than is currently recognized. Severe thrombocytopenia is strongly associated with platelet transfusion. Future studies should focus on the etiology of severe thrombocytopenia during ECMO, as well as identifying indications and platelet thresholds for transfusion in the absence of bleeding. TRIAL REGISTRATION: This study was registered at the Netherlands Trial Registry at February 26th, 2020 with number NL8413 and can currently be found at https://trialsearch.who.int/Trial2.aspx?TrialID=NL8413.

Coronary Angiography after Cardiac Arrest without ST-Segment Elevation.

BACKGROUND: Ischemic heart disease is a major cause of out-of-hospital cardiac arrest. The role of immediate coronary angiography and percutaneous coronary intervention (PCI) in the treatment of patients who have been successfully resuscitated after cardiac arrest in the absence of ST-segment elevation myocardial infarction (STEMI) remains uncertain. METHODS: In this multicenter trial, we randomly assigned 552 patients who had cardiac arrest without signs of STEMI to undergo immediate coronary angiography or coronary angiography that was delayed until after neurologic recovery. All patients underwent PCI if indicated. The primary end point was survival at 90 days. Secondary end points included survival at 90 days with good cerebral performance or mild or moderate disability, myocardial injury, duration of catecholamine support, markers of shock, recurrence of ventricular tachycardia, duration of mechanical ventilation, major bleeding, occurrence of acute kidney injury, need for renal-replacement therapy, time to target temperature, and neurologic status at discharge from the intensive care unit. RESULTS: At 90 days, 176 of 273 patients (64.5%) in the immediate angiography group and 178 of 265 patients (67.2%) in the delayed angiography group were alive (odds ratio, 0.89; 95% confidence interval [CI], 0.62 to 1.27; P = 0.51). The median time to target temperature was 5.4 hours in the immediate angiography group and 4.7 hours in the delayed angiography group (ratio of geometric means, 1.19; 95% CI, 1.04 to 1.36). No significant differences between the groups were found in the remaining secondary end points. CONCLUSIONS: Among patients who had been successfully resuscitated after out-of-hospital cardiac arrest and had no signs of STEMI, a strategy of immediate angiography was not found to be better than a strategy of delayed angiography with respect to overall survival at 90 days. (Funded by the Netherlands Heart Institute and others; COACT Netherlands Trial Register number, NTR4973.).

RBC Transfusion in Venovenous Extracorporeal Membrane Oxygenation: A Multicenter Cohort Study.

OBJECTIVES: In the general critical care patient population, restrictive transfusion regimen of RBCs has been shown to be safe and is yet implemented worldwide. However, in patients on venovenous extracorporeal membrane oxygenation, guidelines suggest liberal thresholds, and a clear overview of RBC transfusion practice is lacking. This study aims to create an overview of RBC transfusion in venovenous extracorporeal membrane oxygenation. DESIGN: Mixed method approach combining multicenter retrospective study and survey. SETTING: Sixteen ICUs worldwide. PATIENTS: Patients receiving venovenous extracorporeal membrane oxygenation between January 2018 and July 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the proportion receiving RBC, the amount of RBC units given daily and in total. Furthermore, the course of hemoglobin over time during extracorporeal membrane oxygenation was assessed. Demographics, extracorporeal membrane oxygenation characteristics, and patient outcome were collected. Two-hundred eight patients received venovenous extracorporeal membrane oxygenation, 63% male, with an age of 55 years (45-62 yr), mainly for acute respiratory distress syndrome. Extracorporeal membrane oxygenation duration was 9 days (5-14 d). Prior to extracorporeal membrane oxygenation, hemoglobin was 10.8 g/dL (8.9-13.0 g/dL), decreasing to 8.7 g/dL (7.7-9.8 g/dL) during extracorporeal membrane oxygenation. Nadir hemoglobin was lower on days when a transfusion was administered (8.1 g/dL [7.4-9.3 g/dL]). A vast majority of 88% patients received greater than or equal to 1 RBC transfusion, consisting of 1.6 U (1.3-2.3 U) on transfusion days. This high transfusion occurrence rate was also found in nonbleeding patients (81%). Patients with a liberal transfusion threshold (hemoglobin > 9 g/dL) received more RBC in total per transfusion day and extracorporeal membrane oxygenation day. No differences in survival, hemorrhagic and thrombotic complication rates were found between different transfusion thresholds. Also, 28-day mortality was equal in transfused and nontransfused patients. CONCLUSIONS: Transfusion of RBC has a high occurrence rate in patients on venovenous extracorporeal membrane oxygenation, even in nonbleeding patients. There is a need for future studies to find optimal transfusion thresholds and triggers in patients on extracorporeal membrane oxygenation.

Targeted Temperature Management in Out-of-Hospital Cardiac Arrest With Shockable Rhythm: A Post Hoc Analysis of the Coronary Angiography After Cardiac Arrest Trial.

OBJECTIVES: The optimal targeted temperature in patients with shockable rhythm is unclear, and current guidelines recommend targeted temperature management with a correspondingly wide range between 32°C and 36°C. Our aim was to study survival and neurologic outcome associated with targeted temperature management strategy in postarrest patients with initial shockable rhythm. DESIGN: Observational substudy of the Coronary Angiography after Cardiac Arrest without ST-segment Elevation trial. SETTING: Nineteen hospitals in The Netherlands. PATIENTS: The Coronary Angiography after Cardiac Arrest trial randomized successfully resuscitated patients with shockable rhythm and absence of ST-segment elevation to a strategy of immediate or delayed coronary angiography. In this substudy, 459 patients treated with mild therapeutic hypothermia (32.0-34.0°C) or targeted normothermia (36.0-37.0°C) were included. Allocation to targeted temperature management strategy was at the discretion of the physician. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After 90 days, 171 patients (63.6%) in the mild therapeutic hypothermia group and 129 (67.9%) in the targeted normothermia group were alive (hazard ratio, 0.86 [95% CI, 0.62-1.18]; log-rank p = 0.35; adjusted odds ratio, 0.89; 95% CI, 0.45-1.72). Patients in the mild therapeutic hypothermia group had longer ICU stay (4 d [3-7 d] vs 3 d [2-5 d]; ratio of geometric means, 1.32; 95% CI, 1.15-1.51), lower blood pressures, higher lactate levels, and increased need for inotropic support. Cerebral Performance Category scores at ICU discharge and 90-day follow-up and patient-reported Mental and Physical Health Scores at 1 year were similar in the two groups. CONCLUSIONS: In the context of out-of-hospital cardiac arrest with shockable rhythm and no ST-elevation, treatment with mild therapeutic hypothermia was not associated with improved 90-day survival compared with targeted normothermia. Neurologic outcomes at 90 days as well as patient-reported Mental and Physical Health Scores at 1 year did not differ between the groups.

Temporary mechanical circulatory support for COVID-19 patients: A systematic review of literature.

OBJECTIVE: Myocardial damage occurs in up to 25% of coronavirus disease 2019 (COVID-19) cases. While veno-venous extracorporeal life support (V-V ECLS) is used as respiratory support, mechanical circulatory support (MCS) may be required for severe cardiac dysfunction. This systematic review summarizes the available literature regarding MCS use rates, disease drivers for MCS initiation, and MCS outcomes in COVID-19 patients. METHODS: PubMed/EMBASE were searched until October 14, 2021. Articles including adults receiving ECLS for COVID-19 were included. The primary outcome was the rate of MCS use. Secondary outcomes included mortality at follow-up, ECLS conversion rate, intubation-to-cannulation time, time on ECLS, cardiac diseases, use of inotropes, and vasopressors. RESULTS: Twenty-eight observational studies (comprising both ECLS-only populations and ECLS patients as part of larger populations) included 4218 COVID-19 patients (females: 28.8%; median age: 54.3 years, 95%CI: 50.7-57.8) of whom 2774 (65.8%) required ECLS with the majority (92.7%) on V-V ECLS, 4.7% on veno-arterial ECLS and/or Impella, and 2.6% on other ECLS. Acute heart failure, cardiogenic shock, and cardiac arrest were reported in 7.8%, 9.7%, and 6.6% of patients, respectively. Vasopressors were used in 37.2%. Overall, 3.1% of patients required an ECLS change from V-V ECLS to MCS for heart failure, myocarditis, or myocardial infarction. The median ECLS duration was 15.9 days (95%CI: 13.9-16.3), with an overall survival of 54.6% and 28.1% in V-V ECLS and MCS patients. One study reported 61.1% survival with oxy-right ventricular assist device. CONCLUSION: MCS use for cardiocirculatory compromise has been reported in 7.3% of COVID-19 patients requiring ECLS, which is a lower percentage compared to the incidence of any severe cardiocirculatory complication. Based on the poor survival rates, further investigations are warranted to establish the most appropriated indications and timing for MCS in COVID-19.

Extracorporeal Membrane Oxygenation in Patients With COVID-19: An International Multicenter Cohort Study.

BACKGROUND: To report and compare the characteristics and outcomes of COVID-19 patients on extracorporeal membrane oxygenation (ECMO) to non-COVID-19 acute respiratory distress syndrome (ARDS) patients on ECMO. METHODS: We performed an international retrospective study of COVID-19 patients on ECMO from 13 intensive care units from March 1 to April 30, 2020. Demographic data, ECMO characteristics and clinical outcomes were collected. The primary outcome was to assess the complication rate and 28-day mortality; the secondary outcome was to compare patient and ECMO characteristics between COVID-19 patients on ECMO and non-COVID-19 related ARDS patients on ECMO (non-COVID-19; January 1, 2018 until July 31, 2019). RESULTS: During the study period 71 COVID-19 patients received ECMO, mostly veno-venous, for a median duration of 13 days (IQR 7-20). ECMO was initiated at 5 days (IQR 3-10) following invasive mechanical ventilation. Median PaO2/FiO2 ratio prior to initiation of ECMO was similar in COVID-19 patients (58 mmHg [IQR 46-76]) and non-COVID-19 patients (53 mmHg [IQR 44-66]), the latter consisting of 48 patients. 28-day mortality was 37% in COVID-19 patients and 27% in non-COVID-19 patients. However, Kaplan-Meier curves showed that after a 100-day follow-up this non-significant difference resolves. Non-surviving COVID-19 patients were more acidotic prior to initiation ECMO, had a shorter ECMO run and fewer received muscle paralysis compared to survivors. CONCLUSIONS: No significant differences in outcomes were found between COVID-19 patients on ECMO and non-COVID-19 ARDS patients on ECMO. This suggests that ECMO could be considered as a supportive therapy in case of refractory respiratory failure in COVID-19.

Nitric Oxide Ventilation Improves Recirculation and Right Ventricular Function During Veno-Venous Extracorporeal Membrane Oxygenation in a COVID-19 Patient.

Patients with coronavirus disease 2019 (COVID-19) are prone to pulmonary artery hypertension (PAH) and right ventricular pressure overload due to severe bilateral infiltrates, high ventilation pressures, persistent hypoxemia, pulmonary fibrosis, and/or pulmonary embolism. In patients on extracorporeal membrane oxygenation (ECMO), this potentially leads to increased recirculation. In the current report, the authors present a case in which continuous inhaled nitric oxide (iNO)-enriched ventilation was effective in terms of PAH and recirculation reduction in a COVID-19 patient on veno-venous ECMO.

Early initiation of extracorporeal life support in refractory out-of-hospital cardiac arrest: Design and rationale of the INCEPTION trial.

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. HYPOTHESIS: We hypothesize that early initiation of ECPR in refractory out-of-hospital cardiac arrest (OHCA) improves the survival rate with favorable neurological status. STUDY DESIGN: 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. SUMMARY: 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.

Extracorporeal cardiopulmonary resuscitation for refractory ventricular fibrillation. A rescue bridge to reperfusion.

Accumulating evidence suggests benefit of extracorporeal cardiopulmonary resuscitation (E-CPR) in patients with refractory cardiac arrest by using venoarterial extracorporeal membrane oxygenation. Appropriate patient selection for E-CPR is cumbersome and still debated. We describe a 56-year-old male who developed refractory ventricular fibrillation upon arrival at the emergency department and was successfully treated by urgent E-CPR. Patient selection, complications and the need to adapt the chain of survival are discussed.

Extracorporeal life support in cardiac arrest: a post hoc Bayesian re-analysis of the INCEPTION trial.

AIMS: Previously, we performed the multicentre INCEPTION trial, randomizing patients with refractory out-of-hospital cardiac arrest (OHCA) to extracorporeal cardiopulmonary resuscitation (ECPR) or conventional cardiopulmonary resuscitation (CCPR). Frequentist analysis showed no statistically significant treatment effect for the primary outcome; 30-day survival with a favourable neurologic outcome (cerebral performance category score of 1-2). To facilitate a probabilistic interpretation of the results, we present a Bayesian re-analysis of the INCEPTION trial. METHODS AND RESULTS: We analysed survival with a favourable neurologic outcome at 30 days and 6 months under a minimally informative prior in the intention-to-treat population. Effect sizes are presented as absolute risk differences (ARDs) and relative risks (RRs), with 95% credible intervals (CrIs). We estimated posterior probabilities at various thresholds, including the minimal clinically important difference (MCID) (5% ARD), based on expert consensus, and performed sensitivity analyses under sceptical and literature-based priors. The mean ARD for 30-day survival with a favourable neurologic outcome was 3.6% (95% CrI -9.5-16.7%), favouring ECPR, with a median RR of 1.22 (95% CrI 0.59-2.51). The posterior probability of an MCID was 42% at 30 days and 42% at 6 months, in favour of ECPR. CONCLUSION: Bayesian re-analysis of the INCEPTION trial estimated a 42% probability of an MCID between ECPR and CCPR in refractory OHCA in terms of 30-day survival with a favourable neurologic outcome. TRIAL REGISTRATION: Clinicaltrials.gov (NCT03101787, registered 5 April 2017).

Early extracorporeal CPR for refractory out-of-hospital cardiac arrest - A pre-planned per-protocol analysis of the INCEPTION-trial.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Cost-effectiveness of extracorporeal cardiopulmonary resuscitation vs. conventional cardiopulmonary resuscitation in out-of-hospital cardiac arrest: a pre-planned, trial-based economic evaluation.

AIMS: When out-of-hospital cardiac arrest (OHCA) becomes refractory, extracorporeal cardiopulmonary resuscitation (ECPR) is a potential option to restore circulation and improve the patient's outcome. However, ECPR requires specific materials and highly skilled personnel, and it is unclear whether increased survival and health-related quality of life (HRQOL) justify these costs. METHODS AND RESULTS: This cost-effectiveness study was part of the INCEPTION study, a multi-centre, pragmatic randomized trial comparing hospital-based ECPR to conventional CPR (CCPR) in patients with refractory OHCA in 10 cardiosurgical centres in the Netherlands. We analysed healthcare costs in the first year and measured HRQOL using the EQ-5D-5L at 1, 3, 6, and 12 months. Incremental cost-effectiveness ratios (ICERs), cost-effectiveness planes, and acceptability curves were calculated. Sensitivity analyses were performed for per-protocol and as-treated subgroups as well as imputed productivity loss in deceased patients. In total, 132 patients were enrolled: 62 in the CCPR and 70 in the ECPR group. The difference in mean costs after 1 year was €5109 (95% confidence interval -7264 to 15 764). Mean quality-adjusted life year (QALY) after 1 year was 0.15 in the ECPR group and 0.11 in the CCPR group, resulting in an ICER of €121 643 per additional QALY gained. The acceptability curve shows that at a willingness-to-pay threshold of €80.000, the probability of ECPR being cost-effective compared with CCPR is 36%. Sensitivity analysis showed increasing ICER in the per-protocol and as-treated groups and lower probabilities of acceptance. CONCLUSION: Hospital-based ECPR in refractory OHCA has a low probability of being cost-effective in a trial-based economic evaluation.

Health-related quality of life one year after refractory cardiac arrest treated with conventional or extracorporeal CPR; a secondary analysis of the INCEPTION-trial.

Background: 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. Methods: 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. Results: 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). Conclusion: 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.

Favorable resuscitation characteristics in patients undergoing extracorporeal cardiopulmonary resuscitation: A secondary analysis of the INCEPTION-trial.

Introduction: Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly used as a supportive treatment for refractory out-of-hospital cardiac arrest (OHCA). Still, there is a paucity of data evaluating favorable and unfavorable prognostic characteristics in patients considered for ECPR. Methods: We performed a previously unplanned post-hoc analysis of the multicenter randomized controlled INCEPTION-trial. The study group consisted of patients receiving ECPR, irrespective of initial group randomization. The patients were divided into favorable survivors (cerebral performance category [CPC] 1-2) and unfavorable or non-survivors (CPC 3-5). Results: In the initial INCEPTION-trial, 134 patients were randomized. ECPR treatment was started in 46 (66%) of 70 patients in the ECPR treatment arm and 3 (4%) of 74 patients in the conventional treatment arm. No statistically significant differences in baseline characteristics, medical history, or causes of arrest were observed between survivors (n = 5) and non-survivors (n = 44). More patients in the surviving group had a shockable rhythm at the time of cannulation (60% vs. 14%, p = 0.037), underwent more defibrillation attempts (13 vs. 6, p = 0.002), and received higher dosages of amiodarone (450 mg vs 375 mg, p = 0.047) despite similar durations of resuscitation maneuvers. Furthermore, non-survivors more frequently had post-ECPR implantation adverse events. Conclusion: The persistence of ventricular arrhythmia is a favorable prognostic factor in patients with refractory OHCA undergoing an ECPR-based treatment. Future studies are warranted to confirm this finding and to establish additional prognostic factors.Clinical trial Registration:clinicaltrials.gov registration number NCT03101787.

Extracorporeal cardiopulmonary resuscitation for refractory OHCA: lessons from three randomized controlled trials-the trialists' view.

Extracorporeal cardiopulmonary resuscitation is a promising treatment for refractory out-of-hospital cardiac arrest. Three recent randomized trials (ARREST trial, Prague OHCA study, and INCEPTION trial) that addressed the clinical benefit of extracorporeal cardiopulmonary resuscitation in out-of-hospital cardiac arrest yielded seemingly diverging results. The evidence for extracorporeal cardiopulmonary resuscitation in out-of-hospital cardiac arrest, derived from three recent randomized controlled trials, is not contradictory but rather complementary. Excellent results can be achieved with a very high level of dedication, provided that strict selection criteria are applied. However, pragmatic implementation of extracorporeal cardiopulmonary resuscitation does not necessarily lead to improved outcome of refractory out-of-hospital cardiac arrest. Centres that are performing extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest or aspire to do so should critically evaluate whether they are able to meet the pre-requisites that are needed to conduct an effective extracorporeal cardiopulmonary resuscitation programme.

Plasma Transfusion and Procoagulant Product Administration in Extracorporeal Membrane Oxygenation: A Secondary Analysis of an International Observational Study on Current Practices.

OBJECTIVES: To achieve optimal hemostatic balance in patients on extracorporeal membrane oxygenation (ECMO), a liberal transfusion practice is currently applied despite clear evidence. We aimed to give an overview of the current use of plasma, fibrinogen concentrate, tranexamic acid (TXA), and prothrombin complex concentrate (PCC) in patients on ECMO. DESIGN: A prespecified subanalysis of a multicenter retrospective study. Venovenous (VV)-ECMO and venoarterial (VA)-ECMO are analyzed as separate populations, comparing patients with and without bleeding and with and without thrombotic complications. SETTING: Sixteen international ICUs. PATIENTS: Adult patients on VA-ECMO or VV-ECMO. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 420 VA-ECMO patients, 59% (n = 247) received plasma, 20% (n = 82) received fibrinogen concentrate, 17% (n = 70) received TXA, and 7% of patients (n = 28) received PCC. Fifty percent of patients (n = 208) suffered bleeding complications and 27% (n = 112) suffered thrombotic complications. More patients with bleeding complications than patients without bleeding complications received plasma (77% vs. 41%, p < 0.001), fibrinogen concentrate (28% vs 11%, p < 0.001), and TXA (23% vs 10%, p < 0.001). More patients with than without thrombotic complications received TXA (24% vs 14%, p = 0.02, odds ratio 1.75) in VA-ECMO, where no difference was seen in VV-ECMO. Of 205 VV-ECMO patients, 40% (n = 81) received plasma, 6% (n = 12) fibrinogen concentrate, 7% (n = 14) TXA, and 5% (n = 10) PCC. Thirty-nine percent (n = 80) of VV-ECMO patients suffered bleeding complications and 23% (n = 48) of patients suffered thrombotic complications. More patients with than without bleeding complications received plasma (58% vs 28%, p < 0.001), fibrinogen concentrate (13% vs 2%, p < 0.01), and TXA (11% vs 2%, p < 0.01). CONCLUSIONS: The majority of patients on ECMO receive transfusions of plasma, procoagulant products, or antifibrinolytics. In a significant part of the plasma transfused patients, this was in the absence of bleeding or prolonged international normalized ratio. This poses the question if these plasma transfusions were administered for another indication or could have been avoided.