Conservative or liberal oxygen targets in patients on venoarterial extracorporeal membrane oxygenation.

PURPOSE: Patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) frequently develop arterial hyperoxaemia, which may be harmful. However, lower oxygen saturation targets may also lead to harmful episodes of hypoxaemia. METHODS: In this registry-embedded, multicentre trial, we randomly assigned adult patients receiving VA-ECMO in an intensive care unit (ICU) to either a conservative (target SaO2 92-96%) or to a liberal oxygen strategy (target SaO2 97-100%) through controlled oxygen administration via the ventilator and ECMO gas blender. The primary outcome was the number of ICU-free days to day 28. Secondary outcomes included ICU-free days to day 60, mortality, ECMO and ventilation duration, ICU and hospital lengths of stay, and functional outcomes at 6 months. RESULTS: From September 2019 through June 2023, 934 patients who received VA-ECMO were reported to the EXCEL registry, of whom 300 (192 cardiogenic shock, 108 refractory cardiac arrest) were recruited. We randomised 149 to a conservative and 151 to a liberal oxygen strategy. The median number of ICU-free days to day 28 was similar in both groups (conservative: 0 days [interquartile range (IQR) 0-13.7] versus liberal: 0 days [IQR 0-13.7], median treatment effect: 0 days [95% confidence interval (CI) - 3.1 to 3.1]). Mortality at day 28 (59/159 [39.6%] vs 59/151 [39.1%]) and at day 60 (64/149 [43%] vs 62/151 [41.1%] were similar in conservative and liberal groups, as were all other secondary outcomes and adverse events. The conservative group experienced 44 (29.5%) major protocol deviations compared to 2 (1.3%) in the liberal oxygen group (P < 0.001). CONCLUSIONS: In adults receiving VA-ECMO in ICU, a conservative compared to a liberal oxygen strategy, did not affect the number of ICU-free days to day 28.

Neurologic complications in patients receiving aortic versus subclavian versus femoral arterial cannulation for post-cardiotomy extracorporeal life support: results of the PELS observational multicenter study.

BACKGROUND: Cerebral perfusion may change depending on arterial cannulation site and may affect the incidence of neurologic adverse events in post-cardiotomy extracorporeal life support (ECLS). The current study compares patients' neurologic outcomes with three commonly used arterial cannulation strategies (aortic vs. subclavian/axillary vs. femoral artery) to evaluate if each ECLS configuration is associated with different rates of neurologic complications. METHODS: This retrospective, multicenter (34 centers), observational study included adults requiring post-cardiotomy ECLS between January 2000 and December 2020 present in the Post-Cardiotomy Extracorporeal Life Support (PELS) Study database. Patients with Aortic, Subclavian/Axillary and Femoral cannulation were compared on the incidence of a composite neurological end-point (ischemic stroke, cerebral hemorrhage, brain edema). Secondary outcomes were overall in-hospital mortality, neurologic complications as cause of in-hospital death, and post-operative minor neurologic complications (seizures). Association between cannulation and neurological outcomes were investigated through linear mixed-effects models. RESULTS: This study included 1897 patients comprising 26.5% Aortic (n = 503), 20.9% Subclavian/Axillary (n = 397) and 52.6% Femoral (n = 997) cannulations. The Subclavian/Axillary group featured a more frequent history of hypertension, smoking, diabetes, previous myocardial infarction, dialysis, peripheral artery disease and previous stroke. Neuro-monitoring was used infrequently in all groups. Major neurologic complications were more frequent in Subclavian/Axillary (Aortic: n = 79, 15.8%; Subclavian/Axillary: n = 78, 19.6%; Femoral: n = 118, 11.9%; p < 0.001) also after mixed-effects model adjustment (OR 1.53 [95% CI 1.02-2.31], p = 0.041). Seizures were more common in Subclavian/Axillary (n = 13, 3.4%) than Aortic (n = 9, 1.8%) and Femoral cannulation (n = 12, 1.3%, p = 0.036). In-hospital mortality was higher after Aortic cannulation (Aortic: n = 344, 68.4%, Subclavian/Axillary: n = 223, 56.2%, Femoral: n = 587, 58.9%, p < 0.001), as shown by Kaplan-Meier curves. Anyhow, neurologic cause of death (Aortic: n = 12, 3.9%, Subclavian/Axillary: n = 14, 6.6%, Femoral: n = 28, 5.0%, p = 0.433) was similar. CONCLUSIONS: In this analysis of the PELS Study, Subclavian/Axillary cannulation was associated with higher rates of major neurologic complications and seizures. In-hospital mortality was higher after Aortic cannulation, despite no significant differences in incidence of neurological cause of death in these patients. These results encourage vigilance for neurologic complications and neuromonitoring use in patients on ECLS, especially with Subclavian/Axillary cannulation.

Post-cardiotomy extracorporeal life support: A cohort of cannulation in the general ward.

OBJECTIVES: Post-cardiotomy extracorporeal life support (ECLS) cannulation might occur in a general post-operative ward due to emergent conditions. Its characteristics have been poorly reported and investigated This study investigates the characteristics and outcomes of adult patients receiving ECLS cannulation in a general post-operative cardiac ward. METHODS: The Post-cardiotomy Extracorporeal Life Support (PELS) is a retrospective (2000-2020), multicenter (34 centers), observational study including adult patients who required ECLS for post-cardiotomy shock. This PELS sub-analysis analyzed patients´ characteristics, in-hospital outcomes, and long-term survival in patients cannulated for veno-arterial ECLS in the general ward, and further compared in-hospital survivors and non-survivors. RESULTS: The PELS study included 2058 patients of whom 39 (1.9%) were cannulated in the general ward. Most patients underwent isolated coronary bypass grafting (CABG, n = 15, 38.5%) or isolated non-CABG operations (n = 20, 51.3%). The main indications to initiate ECLS included cardiac arrest (n = 17, 44.7%) and cardiogenic shock (n = 14, 35.9%). ECLS cannulation occurred after a median time of 4 (2-7) days post-operatively. Most patients' courses were complicated by acute kidney injury (n = 23, 59%), arrhythmias (n = 19, 48.7%), and postoperative bleeding (n = 20, 51.3%). In-hospital mortality was 84.6% (n = 33) with persistent heart failure (n = 11, 28.2%) as the most common cause of death. No peculiar differences were observed between in-hospital survivors and nonsurvivors. CONCLUSIONS: This study demonstrates that ECLS cannulation due to post-cardiotomy emergent adverse events in the general ward is rare, mainly occurring in preoperative low-risk patients and after a postoperative cardiac arrest. High complication rates and low in-hospital survival require further investigations to identify patients at risk for such a complication, optimize resources, enhance intervention, and improve outcomes.

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.

Corrigendum to "Blend to Limit OxygEN in ECMO: A RanDomised ControllEd Registry (BLENDER) trial: Study protocol and statistical analysis plan" [Crit Care Resuscit 25 (2023) 118-125].

[This corrects the article DOI: 10.1016/j.ccrj.2023.06.001.].

Features and outcomes of female and male patients requiring postcardiotomy extracorporeal life support.

OBJECTIVES: Although cardiogenic shock requiring extracorporeal life support after cardiac surgery is associated with high mortality, the impact of sex on outcomes of postcardiotomy extracorporeal life support remains unclear with conflicting results in the literature. We compare patient characteristics, in-hospital outcomes, and overall survival between females and males requiring postcardiotomy extracorporeal life support. METHODS: This retrospective, multicenter (34 centers), observational study included adults requiring postcardiotomy extracorporeal life support between 2000 and 2020. Preoperative, procedural, and extracorporeal life support characteristics, complications, and survival were compared between females and males. Association between sex and in-hospital survival was investigated through mixed Cox proportional hazard models. RESULTS: This analysis included 1823 patients (female: 40.8%; median age: 66.0 years [interquartile range, 56.2-73.0 years]). Females underwent more mitral valve surgery (females: 38.4%, males: 33.1%, P = .019) and tricuspid valve surgery (feamales: 18%, males: 12.4%, P < .001), whereas males underwent more coronary artery surgery (females: 45.9%, males: 52.4%, P = .007). Extracorporeal life support implantation was more common intraoperatively in feamales (females: 64.1%, females: 59.1%) and postoperatively in males (females: 35.9%, males: 40.9%, P = .036). Ventricular unloading (females: 25.1%, males: 36.2%, P < .001) and intra-aortic balloon pumps (females: 25.8%, males: 36.8%, P < .001) were most frequently used in males. Females had more postoperative right ventricular failure (females: 24.1%, males: 19.1%, P = .016) and limb ischemia (females: 12.3%, males: 8.8%, P = .23). In-hospital mortality was 64.9% in females and 61.9% in males (P = .199) with no differences in 5-year survival (females: 20%, 95% CI, 17-23; males: 24%, 95% CI, 21-28; P = .069). Crude hazard ratio for in-hospital mortality in females was 1.12 (95% CI, 0.99-1.27; P = .069) and did not change after adjustments. CONCLUSIONS: This study demonstrates that female and male patients requiring postcardiotomy extracorporeal life support have different preoperative and extracorporeal life support characteristics, as well as complications, without a statistical difference in in-hospital and 5-year survivals.

Anticoagulation and Bleeding during Veno-Venous Extracorporeal Membrane Oxygenation: Insights from the PROTECMO Study.

Rationale: Definitive guidelines for anticoagulation management during veno-venous extracorporeal membrane oxygenation (VV ECMO) are lacking, whereas bleeding complications continue to pose major challenges. Objectives: To describe anticoagulation modalities and bleeding events in adults receiving VV ECMO. Methods: This was an international prospective observational study in 41 centers, from December 2018 to February 2021. Anticoagulation was recorded daily in terms of type, dosage, and monitoring strategy. Bleeding events were reported according to site, severity, and impact on mortality. Measurements and Main Results: The study cohort included 652 patients, and 8,471 days on ECMO were analyzed. Unfractionated heparin was the initial anticoagulant in 77% of patients, and the most frequently used anticoagulant during the ECMO course (6,221 d; 73%). Activated partial thromboplastin time (aPTT) was the most common test for monitoring coagulation (86% of days): the median value was 52 seconds (interquartile range, 39 to 61 s) but dropped by 5.3 seconds after the first bleeding event (95% confidence interval, -7.4 to -3.2; P < 0.01). Bleeding occurred on 1,202 days (16.5%). Overall, 342 patients (52.5%) experienced at least one bleeding event (one episode every 215 h on ECMO), of which 10 (1.6%) were fatal. In a multiple penalized Cox proportional hazard model, higher aPTT was a potentially modifiable risk factor for the first episode of bleeding (for 20-s increase; hazard ratio, 1.07). Conclusions: Anticoagulation during VV ECMO was a dynamic process, with frequent stopping in cases of bleeding and restart according to the clinical picture. Future studies might explore lower aPTT targets to reduce the risk of bleeding.

Population pharmacokinetics of fluconazole in critically ill patients receiving extracorporeal membrane oxygenation and continuous renal replacement therapy: an ASAP ECMO study.

This multicenter study describes the population pharmacokinetics (PK) of fluconazole in critically ill patients receiving concomitant extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) and includes an evaluation of different fluconazole dosing regimens for achievement of target exposure associated with maximal efficacy. Serial blood samples were obtained from critically ill patients on ECMO and CRRT receiving fluconazole. Total fluconazole concentrations were measured in plasma using a validated chromatographic assay. A population PK model was developed and Monte Carlo dosing simulations were performed using Pmetrics in R. The probability of target attainment (PTA) of various dosing regimens to achieve fluconazole area under the curve to minimal inhibitory concentration ratio (AUC0-24/MIC) >100 was estimated. Eight critically ill patients receiving concomitant ECMO and CRRT were included. A two-compartment model including total body weight as a covariate on clearance adequately described the data. The mean (±standard deviation, SD) clearance and volume of distribution were 2.87 ± 0.63 L/h and 15.90 ± 13.29 L, respectively. Dosing simulations showed that current guidelines (initial loading dose of 12 mg/kg then 6 mg/kg q24h) achieved >90% of PTA for a MIC up to 1 mg/L. None of the tested dosing regimens achieved 90% of PTA for MIC above 2 mg/L. Current fluconazole dosing regimen guidelines achieved >90% PTA only for Candida species with MIC <1 mg/L and thus should be only used for Candida-documented infections in critically ill patients receiving concomitant ECMO and CRRT. Total body weight should be considered for fluconazole dose.

Detecting Oxygenator Thrombosis in ECMO: A Review of Current Techniques and an Exploration of Future Directions.

Extracorporeal membrane oxygenation (ECMO) is a life-support technique used to treat cardiac and pulmonary failure, including severe cases of COVID-19 (coronavirus disease 2019) involving acute respiratory distress syndrome. Blood clot formation in the circuit is one of the most common complications in ECMO, having potentially harmful and even fatal consequences. It is therefore essential to regularly monitor for clots within the circuit and take appropriate measures to prevent or treat them. A review of the various methods used by hospital units for detecting blood clots is presented. The benefits and limitations of each method are discussed, specifically concerning detecting blood clots in the oxygenator, as it is concluded that this is the most critical and challenging ECMO component to assess. We investigate the feasibility of solutions proposed in the surrounding literature and explore two areas that hold promise for future research: the analysis of small-scale pressure fluctuations in the circuit, and real-time imaging of the oxygenator. It is concluded that the current methods of detecting blood clots cannot reliably predict clot volume, and their inability to predict clot location puts patients at risk of thromboembolism. It is posited that a more in-depth analysis of pressure readings using machine learning could better provide this information, and that purpose-built imaging could allow for accurate, real-time clotting analysis in ECMO components.

A randomized trial of expedited intra-arrest transfer versus more extended on-scene resuscitation for refractory out of hospital cardiac arrest: Rationale and design of the EVIDENCE trial.

BACKGROUND: Refractory Out of Hospital Cardiac Arrest (r-OHCA) is common and the benefit versus harm of intra-arrest transport of patients to hospital is not clear. OBJECTIVE: To assess the rate of survival to hospital discharge in adult patients with r-OHCA, initial rhythm pulseless ventricular tachycardia (VT)/ventricular fibrillation (VF) or Pulseless Electrical Activity (PEA) treated with 1 of 2 locally accepted standards of care:1 expedited transport from scene; or2 ongoing advanced life support (ALS) resuscitation on-scene. HYPOTHESIS: We hypothesize that expedited transport from scene in r-OHCA improves survival with favorable neurological status/outcome. METHODS/DESIGN: Phase III, multi-center, partially blinded, prospective, intention-to-treat, safety and efficacy clinical trial with contemporaneous registry of patient ineligible for the clinical trial. Eligible patients for inclusion are adults with witnessed r-OHCA; estimated age 18 to 70, assumed medical cause with immediate bystander cardiopulmonary resuscitation (CPR); initial rhythm of VF/pulseless VT, or PEA; no return of spontaneous circulation following 3 shocks and/or 15 minutes of professional on-scene resuscitation; with mechanical CPR available. Two hundred patients will be randomized in a 1:1 ratio to either expedited transport from scene or ongoing ALS at the scene of cardiac arrest. SETTING: Two urban regions in NSW Australia. OUTCOMES: Primary: survival to hospital discharge with cerebral performance category (CPC) 1 or 2. Secondary: safety, survival, prognostic factors, use of ECMO supported CPR and functional assessment at hospital discharge and 4 weeks and 6 months, quality of life, healthcare use and cost-effectiveness. CONCLUSIONS: The EVIDENCE trial will determine the potential risks and benefits of an expedited transport from scene of cardiac arrest.

The effect of restrictive versus liberal selection criteria on survival in ECPR: a retrospective analysis of a multi-regional dataset.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) is an established rescue therapy for both out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA). However, there remains significant heterogeneity in populations and outcomes across different studies. The primary aim of this study was to compare commonly used selection criteria and their effect on survival and utilisation in an Australian ECPR cohort. METHODS: We performed a retrospective, observational study of three established ECPR centres in Australia, including cases from 1 January 2013 to 31 December 2020 to establish the baseline cohort. We applied five commonly used ECPR selection criteria, ranging from restrictive to liberal. RESULTS: The baseline cohort included 199 ECPR cases: 95 OHCA and 104 IHCA patients. Survival to hospital discharge was 20% for OHCA and 41.4% for IHCA. For OHCA patients, strictly applying the most restrictive criteria would have resulted in the highest survival rate 7/16 (43.8%) compared to the most liberal criteria 16/73 (21.9%). However, only 16/95 (16.8%) in our cohort strictly met the most restrictive criteria versus 73/95 (76.8%) with the most liberal criteria. Similarly, in IHCA, the most restrictive criteria would have resulted in a higher survival rate in eligible patients 10/15 (66.7%) compared to 27/59 (45.8%) with the most liberal criteria. With all criteria a large portion of survivors in IHCA would not have been eligible for ECMO if strictly applying criteria, 33/43 (77%) with restrictive and 16/43 (37%) with the most liberal criteria. CONCLUSIONS: Adherence to different selection criteria impacts both the ECPR survival rate and the total number of survivors. Commonly used selection criteria may be unsuitable to select IHCA ECPR patients.

Fulminant myocarditis proven by early biopsy and outcomes.

BACKGROUND AND AIMS: While endomyocardial biopsy (EMB) is recommended in adult patients with fulminant myocarditis, the clinical impact of its timing is still unclear. METHODS: Data were collected from 419 adult patients with clinically suspected fulminant myocarditis admitted to intensive care units across 36 tertiary centres in 15 countries worldwide. The diagnosis of myocarditis was histologically proven in 210 (50%) patients, either by EMB (n = 183, 44%) or by autopsy/explanted heart examination (n = 27, 6%), and clinically suspected cardiac magnetic resonance imaging confirmed in 96 (23%) patients. The primary outcome of survival free of heart transplantation (HTx) or left ventricular assist device (LVAD) at 1 year was specifically compared between patients with early EMB (within 2 days after intensive care unit admission, n = 103) and delayed EMB (n = 80). A propensity score-weighted analysis was done to control for confounders. RESULTS: Median age on admission was 40 (29-52) years, and 322 (77%) patients received temporary mechanical circulatory support. A total of 273 (65%) patients survived without HTx/LVAD. The primary outcome was significantly different between patients with early and delayed EMB (70% vs. 49%, P = .004). After propensity score weighting, the early EMB group still significantly differed from the delayed EMB group in terms of survival free of HTx/LVAD (63% vs. 40%, P = .021). Moreover, early EMB was independently associated with a lower rate of death or HTx/LVAD at 1 year (odds ratio of 0.44; 95% confidence interval: 0.22-0.86; P = .016). CONCLUSIONS: Endomyocardial biopsy should be broadly and promptly used in patients admitted to the intensive care unit for clinically suspected fulminant myocarditis.

Expert consensus on training and accreditation for extracorporeal cardiopulmonary resuscitation an international, multidisciplinary modified Delphi Study.

BACKGROUND: A multidisciplinary group of stakeholders were used to identify: (1) the core competencies of a training program required to perform in-hospital ECPR initiation (2) additional competencies required to perform pre-hospital ECPR initiation and; (3) the optimal training method and maintenance protocol for delivering an ECPR program. METHODS: A modified Delphi process was undertaken utilising two web based survey rounds and one virtual meeting. Experts rated the importance of different aspects of ECPR training, competency and governance on a 9-point Likert scale. A diverse, representative group was targeted. Consensus was achieved when greater than 70% respondents rated a domain as critical (> or = 7 on the 9 point Likert scale). RESULTS: 35 international ECPR experts from 9 countries formed the expert panel, with a median number of 14 years of ECMO practice (interquartile range 11-38). Participant response rates were 97% (survey round one), 63% (virtual meeting) and 100% (survey round two). After the second round of the survey, 47 consensus statements were formed outlining a core set of competencies required for ECPR provision. We identified key elements required to safely train and perform ECPR including skill pre-requisites, surrogate skill identification, the importance of competency-based assessment over volume of practice and competency requirements for successful ECPR practice and skill maintenance. CONCLUSIONS: We present a series of core competencies, training requirements and ongoing governance protocols to guide safe ECPR implementation. These findings can be used to develop training syllabus and guide minimum standards for competency as the growth of ECPR practitioners continues.

Blend to Limit OxygEN in ECMO: A RanDomised ControllEd Registry (BLENDER) Trial: Study Protocol and Statistical Analysis Plan.

Introduction: Critically ill patients supported with venoarterial extracorporeal membrane oxygenation (VA ECMO) are at risk of developing severe arterial hyperoxia, which has been associated with increased mortality. Lower saturation targets in this population may lead to deleterious episodes of severe hypoxia. This manuscript describes the protocol and statistical analysis plan for the Blend to Limit OxygEN in ECMO: A RanDomised ControllEd Registry (BLENDER) Trial. Design: The BLENDER trial is a pragmatic, multicentre, registry-embedded, randomised clinical trial., registered at ClinicalTrials.gov (NCT03841084) and approved by The Alfred Hospital Ethics Committee project ID HREC/50486/Alfred-2019. Participants and setting: Patients supported by VA ECMO for cardiogenic shock or cardiac arrest who are enrolled in the Australian national ECMO registry. Intervention: The study compares a conservative oxygenation strategy (target arterial saturations 92-96%) with a liberal oxygenation strategy (target 97-100%). Main Outcome Measures: The primary outcome is the number of intensive care unit (ICU)-free days for patients alive at day 60. Secondary outcomes include duration of mechanical ventilation, ICU and hospital mortality, the number of hypoxic episodes, neurocognitive outcomes, and health economic analyses. The 300-patient sample size enables us to detect a 3-day difference in ICU-free days at day 60, assuming a mean ICU-free days of 11 days, with a risk of type 1 error of 5% and power of 80%. Data will be analysed according to a predefined analysis plan. Findings will be disseminated in peer-reviewed publications. Conclusions: This paper details the protocol and statistical analysis plan for the BLENDER trial, a registry-embedded, multicentre interventional trial comparing liberal and conservative oxygenation strategies in VA ECMO.

On-Support and Postweaning Mortality in Postcardiotomy Extracorporeal Membrane Oxygenation.

BACKGROUND: Postcardiotomy venoarterial extracorporeal membrane oxygenation (VA ECMO) is characterized by discrepancies between weaning and survival-to-discharge rates. This study analyzes the differences between postcardiotomy VA ECMO patients who survived, died on ECMO, or died after ECMO weaning. Causes of death and variables associated with mortality at different time points are investigated. METHODS: The retrospective, multicenter, observational Postcardiotomy Extracorporeal Life Support Study (PELS) includes adults requiring postcardiotomy VA ECMO between 2000 and 2020. Variables associated with on-ECMO mortality and postweaning mortality were modeled using mixed Cox proportional hazards, including random effects for center and year. RESULTS: In 2058 patients (men, 59%; median age, 65 years; interquartile range [IQR], 55-72 years), weaning rate was 62.7%, and survival to discharge was 39.6%. Patients who died (n = 1244) included 754 on-ECMO deaths (36.6%; median support time, 79 hours; IQR, 24-192 hours), and 476 postweaning deaths (23.1%; median support time, 146 hours; IQR, 96-235.5 hours). Multiorgan (n = 431 of 1158 [37.2%]) and persistent heart failure (n = 423 of 1158 [36.5%]) were the main causes of death, followed by bleeding (n = 56 of 754 [7.4%]) for on-ECMO mortality and sepsis (n = 61 of 401 [15.4%]) for postweaning mortality. On-ECMO death was associated with emergency surgery, preoperative cardiac arrest, cardiogenic shock, right ventricular failure, cardiopulmonary bypass time, and ECMO implantation timing. Diabetes, postoperative bleeding, cardiac arrest, bowel ischemia, acute kidney injury, and septic shock were associated with postweaning mortality. CONCLUSIONS: A discrepancy exists between weaning and discharge rate in postcardiotomy ECMO. Deaths occurred during ECMO support in 36.6% of patients, mostly associated with unstable preoperative hemodynamics. Another 23.1% of patients died after weaning in association with severe complications. This underscores the importance of postweaning care for postcardiotomy VA ECMO patients.

Patient and Management Variables Associated With Survival After Postcardiotomy Extracorporeal Membrane Oxygenation in Adults: The PELS-1 Multicenter Cohort Study.

Background Extracorporeal membrane oxygenation (ECMO) has been increasingly used for postcardiotomy cardiogenic shock, but without a concomitant reduction in observed in-hospital mortality. Long-term outcomes are unknown. This study describes patients' characteristics, in-hospital outcome, and 10-year survival after postcardiotomy ECMO. Variables associated with in-hospital and postdischarge mortality are investigated and reported. Methods and Results The retrospective international multicenter observational PELS-1 (Postcardiotomy Extracorporeal Life Support) study includes data on adults requiring ECMO for postcardiotomy cardiogenic shock between 2000 and 2020 from 34 centers. Variables associated with mortality were estimated preoperatively, intraoperatively, during ECMO, and after the occurrence of any complications, and then analyzed at different time points during a patient's clinical course, through mixed Cox proportional hazards models containing fixed and random effects. Follow-up was established by institutional chart review or contacting patients. This analysis included 2058 patients (59% were men; median [interquartile range] age, 65.0 [55.0-72.0] years). In-hospital mortality was 60.5%. Independent variables associated with in-hospital mortality were age (hazard ratio [HR], 1.02 [95% CI, 1.01-1.02]) and preoperative cardiac arrest (HR, 1.41 [95% CI, 1.15-1.73]). In the subgroup of hospital survivors, the overall 1-, 2-, 5-, and 10-year survival rates were 89.5% (95% CI, 87.0%-92.0%), 85.4% (95% CI, 82.5%-88.3%), 76.4% (95% CI, 72.5%-80.5%), and 65.9% (95% CI, 60.3%-72.0%), respectively. Variables associated with postdischarge mortality included older age, atrial fibrillation, emergency surgery, type of surgery, postoperative acute kidney injury, and postoperative septic shock. Conclusions In adults, in-hospital mortality after postcardiotomy ECMO remains high; however, two-thirds of those who are discharged from hospital survive up to 10 years. Patient selection, intraoperative decisions, and ECMO management remain key variables associated with survival in this cohort. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03857217.

The importance of timing in postcardiotomy venoarterial extracorporeal membrane oxygenation: A descriptive multicenter observational study.

OBJECTIVES: Postcardiotomy extracorporeal membrane oxygenation (ECMO) can be initiated intraoperatively or postoperatively based on indications, settings, patient profile, and conditions. The topic of implantation timing only recently gained attention from the clinical community. We compare patient characteristics as well as in-hospital and long-term survival between intraoperative and postoperative ECMO. METHODS: The retrospective, multicenter, observational Postcardiotomy Extracorporeal Life Support (PELS-1) study includes adults who required ECMO due to postcardiotomy shock between 2000 and 2020. We compared patients who received ECMO in the operating theater (intraoperative) with those in the intensive care unit (postoperative) on in-hospital and postdischarge outcomes. RESULTS: We studied 2003 patients (women: 41.1%; median age: 65 years; interquartile range [IQR], 55.0-72.0). Intraoperative ECMO patients (n = 1287) compared with postoperative ECMO patients (n = 716) had worse preoperative risk profiles. Cardiogenic shock (45.3%), right ventricular failure (15.9%), and cardiac arrest (14.3%) were the main indications for postoperative ECMO initiation, with cannulation occurring after (median) 1 day (IQR, 1-3 days). Compared with intraoperative application, patients who received postoperative ECMO showed more complications, cardiac reoperations (intraoperative: 19.7%; postoperative: 24.8%, P = .011), percutaneous coronary interventions (intraoperative: 1.8%; postoperative: 3.6%, P = .026), and had greater in-hospital mortality (intraoperative: 57.5%; postoperative: 64.5%, P = .002). Among hospital survivors, ECMO duration was shorter after intraoperative ECMO (median, 104; IQR, 67.8-164.2 hours) compared with postoperative ECMO (median, 139.7; IQR, 95.8-192 hours, P < .001), whereas postdischarge long-term survival was similar between the 2 groups (P = .86). CONCLUSIONS: Intraoperative and postoperative ECMO implantations are associated with different patient characteristics and outcomes, with greater complications and in-hospital mortality after postoperative ECMO. Strategies to identify the optimal location and timing of postcardiotomy ECMO in relation to specific patient characteristics are warranted to optimize in-hospital outcomes.

Association of early mobility with the incidence of deep-vein thrombosis and mortality among critically ill patients: a post hoc analysis of PREVENT trial.

BACKGROUND: This study assessed the mobility levels among critically ill patients and the association of early mobility with incident proximal lower-limb deep-vein thrombosis and 90-day mortality. METHODS: This was a post hoc analysis of the multicenter PREVENT trial, which evaluated adjunctive intermittent pneumatic compression in critically ill patients receiving pharmacologic thromboprophylaxis with an expected ICU stay ≥ 72 h and found no effect on the primary outcome of incident proximal lower-limb deep-vein thrombosis. Mobility levels were documented daily up to day 28 in the ICU using a tool with an 8-point ordinal scale. We categorized patients according to mobility levels within the first 3 ICU days into three groups: early mobility level 4-7 (at least active standing), 1-3 (passive transfer from bed to chair or active sitting), and 0 (passive range of motion). We evaluated the association of early mobility and incident lower-limb deep-vein thrombosis and 90-day mortality by Cox proportional models adjusting for randomization and other co-variables. RESULTS: Of 1708 patients, only 85 (5.0%) had early mobility level 4-7 and 356 (20.8%) level 1-3, while 1267 (74.2%) had early mobility level 0. Patients with early mobility levels 4-7 and 1-3 had less illness severity, femoral central venous catheters, and organ support compared to patients with mobility level 0. Incident proximal lower-limb deep-vein thrombosis occurred in 1/85 (1.3%) patients in the early mobility 4-7 group, 7/348 (2.0%) patients in mobility 1-3 group, and 50/1230 (4.1%) patients in mobility 0 group. Compared with early mobility group 0, mobility groups 4-7 and 1-3 were not associated with differences in incident proximal lower-limb deep-vein thrombosis (adjusted hazard ratio [aHR] 1.19, 95% confidence interval [CI] 0.16, 8.90; p = 0.87 and 0.91, 95% CI 0.39, 2.12; p = 0.83, respectively). However, early mobility groups 4-7 and 1-3 had lower 90-day mortality (aHR 0.47, 95% CI 0.22, 1.01; p = 0.052, and 0.43, 95% CI 0.30, 0.62; p < 0.0001, respectively). CONCLUSIONS: Only a small proportion of critically ill patients with an expected ICU stay ≥ 72 h were mobilized early. Early mobility was associated with reduced mortality, but not with different incidence of deep-vein thrombosis. This association does not establish causality, and randomized controlled trials are required to assess whether and to what extent this association is modifiable. TRIAL REGISTRATION: The PREVENT trial is registered at ClinicalTrials.gov, ID: NCT02040103 (registered on 3 November 2013) and Current controlled trials, ID: ISRCTN44653506 (registered on 30 October 2013).