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.).

Characteristics and Outcomes of Prolonged Venoarterial Extracorporeal Membrane Oxygenation After Cardiac Surgery: The Post-Cardiotomy Extracorporeal Life Support (PELS-1) Cohort Study.

OBJECTIVES: Most post-cardiotomy (PC) extracorporeal membrane oxygenation (ECMO) runs last less than 7 days. Studies on the outcomes of longer runs have provided conflicting results. This study investigates patient characteristics and short- and long-term outcomes in relation to PC ECMO duration, with a focus on prolonged (> 7 d) ECMO. DESIGN: Retrospective observational cohort study. SETTING: Thirty-four centers from 16 countries between January 2000 and December 2020. PATIENTS: Adults requiring post PC ECMO between 2000 and 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Characteristics, in-hospital, and post-discharge outcomes were compared among patients categorized by ECMO duration. Survivors and nonsurvivors were compared in the subgroup of patients with ECMO duration greater than 7 days. The primary outcome was in-hospital mortality. Two thousand twenty-one patients were included who required PC ECMO for 0-3 days (n = 649 [32.1%]), 4-7 days (n = 776 [38.3%]), 8-10 days (n = 263 [13.0%]), and greater than 10 days (n = 333 [16.5%]). There were no major differences in the investigated preoperative and procedural characteristics among ECMO duration groups. However, the longer ECMO duration category was associated with multiple complications including bleeding, acute kidney injury, arrhythmias, and sepsis. Hospital mortality followed a U-shape curve, with lowest mortality in patients with ECMO duration of 4-7 days (n = 394, 50.8%) and highest in patients with greater than 10 days ECMO support (n = 242, 72.7%). There was no significant difference in post-discharge survival between ECMO duration groups. In patients with ECMO duration greater than 7 days, age, comorbidities, valvular diseases, and complex procedures were associated with nonsurvival. CONCLUSIONS: Nearly 30% of PC ECMO patients were supported for greater than 7 days. In-hospital mortality increased after 7 days of support, especially in patients undergoing valvular and complex surgery, or who had complications, although the long-term post-discharge prognosis was comparable to PC ECMO patients with shorter support duration.

Extracorporeal cardiopulmonary resuscitation for refractory cardiac arrest: an overview of current practice and evidence.

Cardiac arrest (CA) is a common and potentially avoidable cause of death, while constituting a substantial public health burden. Although survival rates for out-of-hospital cardiac arrest (OHCA) have improved in recent decades, the prognosis for refractory OHCA remains poor. The use of veno-arterial extracorporeal membrane oxygenation during cardiopulmonary resuscitation (ECPR) is increasingly being considered to support rescue measures when conventional cardiopulmonary resuscitation (CPR) fails. ECPR enables immediate haemodynamic and respiratory stabilisation of patients with CA who are refractory to conventional CPR and thereby reduces the low-flow time, promoting favourable neurological outcomes. In the case of refractory OHCA, multiple studies have shown beneficial effects in specific patient categories. However, ECPR might be more effective if it is implemented in the pre-hospital setting to reduce the low-flow time, thereby limiting permanent brain damage. The ongoing ON-SCENE trial might provide a definitive answer regarding the effectiveness of ECPR. The aim of this narrative review is to present the most recent literature available on ECPR and its current developments.

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.

Higher mean cerebral oxygen saturation shortly after extracorporeal cardiopulmonary resuscitation in patients who regain consciousness.

INTRODUCTION: In cardiac arrest, cerebral ischemia and reperfusion injury mainly determine the neurological outcome. The aim of this study was to investigate the relation between the course of cerebral oxygenation and regain of consciousness in patients treated with extracorporeal cardiopulmonary resuscitation (ECPR). We hypothesized that rapid cerebral oxygenation increase causes unfavorable outcomes. METHODS: This prospective observational study was conducted in three European hospitals. We included adult ECPR patients between October 2018 and March 2020, in whom cerebral regional oxygen saturation (rSO2 ) measurements were started minutes before ECPR initiation until 3 h after. The primary outcome was regain of consciousness, defined as following commands, analyzed using binary logistic regression. RESULTS: The sample consisted of 26 ECPR patients (23% women, Agemean 46 years). We found no significant differences in rSO2 values at baseline (49.1% versus 49.3% for regain versus no regain of consciousness). Mean cerebral rSO2 values in the first 30 min after ECPR initiation were higher in patients who regained consciousness (38%) than in patients who did not regain consciousness (62%, odds ratio 1.23, 95% confidence interval 1.01-1.50). CONCLUSION: Higher mean cerebral rSO2 values in the first 30 min after initiation of ECPR were found in patients who regained consciousness.

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.

Neurological outcome after extracorporeal cardiopulmonary resuscitation for in-hospital cardiac arrest: a systematic review and meta-analysis.

BACKGROUND: In-hospital cardiac arrest (IHCA) is a major adverse event with a high mortality rate if not treated appropriately. Extracorporeal cardiopulmonary resuscitation (ECPR), as adjunct to conventional cardiopulmonary resuscitation (CCPR), is a promising technique for IHCA treatment. Evidence pertaining to neurological outcomes after ECPR is still scarce. METHODS: We performed a comprehensive systematic search of all studies up to December 20, 2019. Our primary outcome was neurological outcome after ECPR at any moment after hospital discharge, defined by the Cerebral Performance Category (CPC) score. A score of 1 or 2 was defined as favourable outcome. Our secondary outcome was post-discharge mortality. A fixed-effects meta-analysis was performed. RESULTS: Our search yielded 1215 results, of which 19 studies were included in this systematic review. The average survival rate was 30% (95% CI 28-33%, I2 = 0%, p = 0.24). In the surviving patients, the pooled percentage of favourable neurological outcome was 84% (95% CI 80-88%, I2 = 24%, p = 0.90). CONCLUSION: ECPR as treatment for in-hospital cardiac arrest is associated with a large proportion of patients with good neurological outcome. The large proportion of favourable outcome could potentially be explained by the selection of patients for treatment using ECPR. Moreover, survival is higher than described in the conventional CPR literature. As indications for ECPR might extend to older or more fragile patient populations in the future, research should focus on increasing survival, while maintaining optimal neurological outcome.

Cost-effectiveness in extracorporeal life support in critically ill adults in the Netherlands.

BACKGROUND: Extracorporeal life support (ECLS) is used to support the cardiorespiratory function in case of severe cardiac and/or respiratory failure in critically ill patients. According to the ELSO guidelines ECLS should be considered when estimated mortality risk approximates 80%. ECLS seems an efficient therapy in terms of survival benefit, but no undisputed evidence is delivered yet. The aim of the study is to assess the health-related quality of life after ECLS treatment and its cost effectiveness. METHODS: We will perform a prospective observational cohort study. All adult patients who receive ECLS in the participating centers will be included. Exclusion criteria are patients in whom the ECLS is only used to bridge a procedure (like a high risk percutaneous coronary intervention or surgery) or the absence of informed consent. Data collection includes patient characteristics and data specific for ECLS treatment. Severity of illness and mortality risk is measured as precisely as possible using measurements for the appropriate age group and organ failure. For analyses on survival patients will act as their own control as we compare the actual survival with the estimated mortality on initiation of ECLS if conservative treatment would have been continued. Survivors are asked to complete validated questionnaires on health related quality of life (EQ5D-5 L) and on medical consumption and productivity losses (iMTA/iPCQ) at 6 and 12 months. Also the health related quality of life 1 month prior to ECLS initiation will be obtained by a questionnaire, if needed provided by relatives. With an estimated overall survival of 62% 210 patients need to be recruited to make a statement on cost effectiveness for all ECLS indications. DISCUSSION: If our hypothesis that ECLS treatment is cost-effective is confirmed by this prospective study this could lead to an even broader use of ECLS treatment. TRIAL REGISTRATION: The trial is registered at ( NCT02837419 ) registration date July 19, 2016 and with the Dutch trial register, http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6599.

Functional evaluation of sublingual microcirculation indicates successful weaning from VA-ECMO in cardiogenic shock.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly adopted for the treatment of cardiogenic shock (CS). However, a marker of successful weaning remains largely unknown. Our hypothesis was that successful weaning is associated with sustained microcirculatory function during ECMO flow reduction. Therefore, we sought to test the usefulness of microcirculatory imaging in the same sublingual spot, using incident dark field (IDF) imaging in assessing successful weaning from VA-ECMO and compare IDF imaging with echocardiographic parameters. METHODS: Weaning was performed by decreasing the VA-ECMO flow to 50% (F50) from the baseline. The endpoint of the study was successful VA-ECMO explantation within 48 hours after weaning. The response of sublingual microcirculation to a weaning attempt (WA) was evaluated. Microcirculation was measured in one sublingual area (single spot (ss)) using CytoCam IDF imaging during WA. Total vessel density (TVDss) and perfused vessel density (PVDss) of the sublingual area were evaluated before and during 50% flow reduction (TVDssF50, PVDssF50) after a WA and compared to conventional echocardiographic parameters as indicators of the success or failure of the WA. RESULTS: Patients (n = 13) aged 49 ± 18 years, who received VA-ECMO for the treatment of refractory CS due to pulmonary embolism (n = 5), post cardiotomy (n = 3), acute coronary syndrome (n = 2), myocarditis (n = 2) and drug intoxication (n = 1), were included. TVDssF50 (21.9 vs 12.9 mm/mm2, p = 0.001), PVDssF50 (19.7 vs 12.4 mm/mm2, p = 0.01) and aortic velocity-time integral (VTI) at 50% flow reduction (VTIF50) were higher in patients successfully weaned vs not successfully weaned. The area under the curve (AUC) was 0.99 vs 0.93 vs 0.85 for TVDssF50 (small vessels) >12.2 mm/mm2, left ventricular ejection fraction (LVEF) >15% and aortic VTI >11 cm. Likewise, the AUC was 0.91 vs 0.93 vs 0.85 for the PVDssF50 (all vessels) >14.8 mm/mm2, LVEF >15% and aortic VTI >11 cm. CONCLUSION: This study identified sublingual microcirculation as a novel potential marker for identifying successful weaning from VA-ECMO. Sustained values of TVDssF50 and PVDssF50 were found to be specific and sensitive indicators of successful weaning from VA-ECMO as compared to echocardiographic parameters.

Microcirculatory assessment of patients under VA-ECMO.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is an effective technique for providing emergency mechanical circulatory support for patients with cardiogenic shock. VA-ECMO enables a rapid restoration of global systemic organ perfusion, but it has not been found to always show a parallel improvement in the microcirculation. We hypothesized in this study that the response of the microcirculation to the initiation of VA-ECMO might identify patients with increased chances of intensive care unit (ICU) survival. METHODS: Twenty-four patients were included in this study. Sublingual microcirculation measurements were performed using the CytoCam-IDF (incident dark field) imaging device. Microcirculatory measurements were performed at baseline, after VA-ECMO insertion (T1), 48-72 h after initiation of VA-ECMO (T2), 5-6 days after (T3), 9-10 days after (T4), and within 24 h of VA-ECMO removal. RESULTS: Of the 24 patients included in the study population, 15 survived and 9 died while on VA-ECMO. There was no significant difference between the systemic global hemodynamic variables at initiation of VA-ECMO between the survivors and non-survivors. There was, however, a significant difference in the microcirculatory parameters of both small and large vessels at all time points between the survivors and non-survivors. Perfused vessel density (PVD) at baseline (survivor versus non-survivor, 19.21 versus 13.78 mm/mm2, p = 0.001) was able to predict ICU survival on initiation of VA-ECMO; the area under the receiver operating characteristic curve (ROC) was 0.908 (95 % confidence interval 0.772-1.0). CONCLUSION: PVD of the sublingual microcirculation at initiation of VA-ECMO can be used to predict ICU mortality in patients with cardiogenic shock.

Successful prehospital ECMO in drowning resuscitation after prolonged submersion.

An 18-year-old drowning victim was successfully resuscitated using prehospital veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Despite 24 min of submersion in water with a surface temperature of 15 °C, the patient was cannulated on-scene and transported to a trauma center. After ICU admission on VA-ECMO, he was decannulated and extubated by day 5. He was transferred to a peripheral hospital on day 6 and discharged home after 3.5 weeks with favorable neurological outcome of a Cerebral Performance Categories (CPC) score of 1 out of 5. This case underscores the potential of prehospital ECMO in drowning cases within a well-equipped emergency response system.

Eligibility of cardiac arrest patients for extracorporeal cardiopulmonary resuscitation and their clinical characteristics: a retrospective two-centre study.

BACKGROUND AND IMPORTANCE: Sudden cardiac arrest has a high incidence and often leads to death. A treatment option that might improve the outcomes in refractory cardiac arrest is Extracorporeal Cardiopulmonary Resuscitation (ECPR). OBJECTIVES: This study investigates the number of in-hospital cardiac arrest (IHCA) and out-of-hospital cardiac arrest (OHCA) patients eligible to ECPR and identifies clinical characteristics that may help to identify which patients benefit the most from ECPR. DESIGN, SETTINGS AND PARTICIPANTS: A retrospective two-centre study was conducted in Rotterdam, the Netherlands. All IHCA and OHCA patients between 1 January 2017 and 1 January 2020 were screened for eligibility to ECPR. The primary outcome was the percentage of patients eligible to ECPR and patients treated with ECPR. The secondary outcome was the comparison of the clinical characteristics and outcomes of patients eligible to ECPR treated with conventional Cardiopulmonary Resuscitation (CCPR) vs. those of patients treated with ECPR. MAIN RESULTS: Out of 1246 included patients, 412 were IHCA patients and 834 were OHCA patients. Of the IHCA patients, 41 (10.0%) were eligible to ECPR, of whom 20 (48.8%) patients were actually treated with ECPR. Of the OHCA patients, 83 (9.6%) were eligible to ECPR, of whom 23 (27.7%) were actually treated with ECPR. In the group IHCA patients eligible to ECPR, no statistically significant difference in survival was found between patients treated with CCPR and patients treated with ECPR (hospital survival 19.0% vs. 15.0% respectively, 4.0% survival difference 95% confidence interval -21.3 to 28.7%). In the group OHCA patients eligible to ECPR, no statistically significant difference in-hospital survival was found between patients treated with CCPR and patients treated with ECPR (13.3% vs. 21.7% respectively, 8.4% survival difference 95% confidence interval -30.3 to 10.2%). CONCLUSION: This retrospective study shows that around 10% of cardiac arrest patients are eligible to ECPR. Less than half of these patients eligible to ECPR were actually treated with ECPR in both IHCA and OHCA.

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.

A national multi centre pre-hospital ECPR stepped wedge study; design and rationale of the ON-SCENE study.

BACKGROUND: The likelihood of return of spontaneous circulation with conventional advanced life support is known to have an exponential decline and therefore neurological outcome after 20 min in patients with a cardiac arrest is poor. Initiation of venoarterial ExtraCorporeal Membrane Oxygenation (ECMO) during resuscitation might improve outcomes if used in time and in a selected patient category. However, previous studies have failed to significantly reduce the time from cardiac arrest to ECMO flow to less than 60 min. We hypothesize that the initiation of Extracorporeal Cardiopulmonary Resuscitation (ECPR) by a Helicopter Emergency Medical Services System (HEMS) will reduce the low flow time and improve outcomes in refractory Out of Hospital Cardiac Arrest (OHCA) patients. METHODS: The ON-SCENE study will use a non-randomised stepped wedge design to implement ECPR in patients with witnessed OHCA between the ages of 18-50 years old, with an initial presentation of shockable rhythm or pulseless electrical activity with a high suspicion of pulmonary embolism, lasting more than 20, but less than 45 min. Patients will be treated by the ambulance crew and HEMS with prehospital ECPR capabilities and will be compared with treatment by ambulance crew and HEMS without prehospital ECPR capabilities. The primary outcome measure will be survival at hospital discharge. The secondary outcome measure will be good neurological outcome defined as a cerebral performance categories scale score of 1 or 2 at 6 and 12 months. DISCUSSION: The ON-SCENE study focuses on initiating ECPR at the scene of OHCA using HEMS. The current in-hospital ECPR for OHCA obstacles encompassing low survival rates in refractory arrests, extended low-flow durations during transportation, and the critical time sensitivity of initiating ECPR, which could potentially be addressed through the implementation of the HEMS system. When successful, implementing on-scene ECPR could significantly enhance survival rates and minimize neurological impairment. TRIAL REGISTRATION: Clinicaltyrials.gov under NCT04620070, registration date 3 November 2020.

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.

Feasibility of HEMS performed prehospital extracorporeal-cardiopulmonary resuscitation in paediatric cardiac arrests; two case reports.

INTRODUCTION: A broad range of pathophysiologic conditions can lead to cardiopulmonary arrest in children. Some of these children suffer from refractory cardiac arrest, not responding to basic and advanced life support. Extracorporeal-Cardiopulmonary Resuscitation (E-CPR) might be a life-saving option for this group. Currently this therapy is only performed in-hospital, often necessitating long transport times, thereby negatively impacting eligibility and chances of survival. We present the first two cases of prehospital E-CPR in children performed by regular Helicopter Emergency Medical Services (HEMS). CASE PRESENTATIONS: The first patient was a previously healthy 7 year old boy who was feeling unwell for a couple of days due to influenza. His course deteriorated into a witnessed collapse. Direct bystander CPR and subsequent ambulance advanced life support was unsuccessful in establishing a perfusing rhythm. While doing chest compressions, the patient was seen moving both his arms and making spontaneous breathing efforts. Echocardiography however revealed a severe left ventricular impairment (near standstill). The second patient was a 15 year old girl, known with bronchial asthma and poor medication compliance. She suffered yet another asthmatic attack, so severe that she progressed into cardiac arrest in front of the attending ambulance and HEMS crews. Despite maximum bronchodilator therapy, intubation and the exclusion of tension pneumothoraxes and dynamic hyperinflation, no cardiac output was achieved. INTERVENTION: After consultation with the nearest paediatric E-CPR facilities, both patients were on-scene cannulated by regular HEMS. The femoral artery and vein were cannulated (15-17Fr and 21Fr respectively) under direct ultrasound guidance using an out-of-plane Seldinger approach. Extracorporeal Life Support flow of 2.1 and 3.8 l/min was established in 20 and 16 min respectively (including preparation and cannulation). Both patients were transported uneventfully to the nearest paediatric intensive care with spontaneous breathing efforts and reactive pupils during transport. CONCLUSION: This case-series shows that a properly trained regular HEMS crew of only two health care professionals (doctor and flight nurse) can establish E-CPR on-scene in (older) children. Ambulance transport with ongoing CPR is challenging, even more so in children since transportation times tend to be longer compared to adults and automatic chest compression devices are often unsuitable and/or unapproved for children. Prehospital cannulation of susceptible E-CPR candidates has the potential to reduce low-flow time and offer E-CPR therapy to a wider group of children suffering refractory cardiac arrest.

Treatment of Refractory Cardiac Arrest by Controlled Reperfusion of the Whole Body: A Multicenter, Prospective Observational Study.

Background: Survival following cardiac arrest (CA) remains poor after conventional cardiopulmonary resuscitation (CCPR) (6-26%), and the outcomes after extracorporeal cardiopulmonary resuscitation (ECPR) are often inconsistent. Poor survival is a consequence of CA, low-flow states during CCPR, multi-organ injury, insufficient monitoring, and delayed treatment of the causative condition. We developed a new strategy to address these issues. Methods: This all-comers, multicenter, prospective observational study (69 patients with in- and out-of-hospital CA (IHCA and OHCA) after prolonged refractory CCPR) focused on extracorporeal cardiopulmonary support, comprehensive monitoring, multi-organ repair, and the potential for out-of-hospital cannulation and treatment. Result: The overall survival rate at hospital discharge was 42.0%, and a favorable neurological outcome (CPC 1+2) at 90 days was achieved for 79.3% of survivors (CPC 1+2 survival 33%). IHCA survival was very favorable (51.7%), as was CPC 1+2 survival at 90 days (41%). Survival of OHCA patients was 35% and CPC 1+2 survival at 90 days was 28%. The subgroup of OHCA patients with pre-hospital cannulation showed a superior survival rate of 57.1%. Conclusions: This new strategy focusing on repairing damage to multiple organs appears to improve outcomes after CA, and these findings should provide a sound basis for further research in this area.

Systematic review and meta-analysis comparing low-flow duration of extracorporeal and conventional cardiopulmonary resuscitation.

OBJECTIVES: After cardiac arrest, a key factor determining survival outcomes is low-flow duration. Our aims were to determine the relation of survival and low-flow duration of extracorporeal cardiopulmonary resuscitation (ECPR) and conventional cardiopulmonary resuscitation (CCPR) and if these 2 therapies have different short-term survival curves in relation to low-flow duration. METHODS: We searched Embase, Medline, Web of Science and Google Scholar from inception up to April 2021. A linear mixed-effect model was used to describe the course of survival over time, based on study-specific and time-specific aggregated survival data. RESULTS: We included 42 observational studies reporting on 1689 ECPR and 375 751 CCPR procedures. Of the included studies, 25 included adults, 13 included children and 4 included both. In adults, survival curves decline rapidly over time (ECPR 37.2%, 29.8%, 23.8% and 19.1% versus CCPR-shockable 36.8%, 7.2%, 1.4% and 0.3% for 15, 30, 45 and 60 min low-flow, respectively). ECPR was associated with a statistically significant slower decline in survival than CCPR with initial shockable rhythms (CCPR-shockable). In children, survival curves decline rapidly over time (ECPR 43.6%, 41.7%, 39.8% and 38.0% versus CCPR-shockable 48.6%, 20.5%, 8.6% and 3.6% for 15, 30, 45 and 60 min low-flow, respectively). ECPR was associated with a statistically significant slower decline in survival than CCPR-shockable. CONCLUSIONS: The short-term survival of ECPR and CCPR-shockable patients both decline rapidly over time, in adults as well as in children. This decline of short-term survival in relation to low-flow duration in ECPR was slower than in conventional cardiopulmonary resuscitation. TRIAL REGISTRATION: Prospero: CRD42020212480, 2 October 2020.