In-hospital and 6-month outcomes in patients with COVID-19 supported with extracorporeal membrane oxygenation (EuroECMO-COVID): a multicentre, prospective observational study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been widely used in patients with COVID-19, but uncertainty remains about the determinants of in-hospital mortality and data on post-discharge outcomes are scarce. The aims of this study were to investigate the variables associated with in-hospital outcomes in patients who received ECMO during the first wave of COVID-19 and to describe the status of patients 6 months after ECMO initiation. METHODS: EuroECMO-COVID is a prospective, multicentre, observational study developed by the European Extracorporeal Life Support Organization. This study was based on data from patients aged 16 years or older who received ECMO support for refractory COVID-19 during the first wave of the pandemic-from March 1 to Sept 13, 2020-at 133 centres in 21 countries. In-hospital mortality and mortality 6 months after ECMO initiation were the primary outcomes. Mixed-Cox proportional hazards models were used to investigate associations between patient and management-related variables (eg, patient demographics, comorbidities, pre-ECMO status, and ECMO characteristics and complications) and in-hospital deaths. Survival status at 6 months was established through patient contact or institutional charts review. This study is registered with ClinicalTrials.gov, NCT04366921, and is ongoing. FINDINGS: Between March 1 and Sept 13, 2020, 1215 patients (942 [78%] men and 267 [22%] women; median age 53 years [IQR 46-60]) were included in the study. Median ECMO duration was 15 days (IQR 8-27). 602 (50%) of 1215 patients died in hospital, and 852 (74%) patients had at least one complication. Multiorgan failure was the leading cause of death (192 [36%] of 528 patients who died with available data). In mixed-Cox analyses, age of 60 years or older, use of inotropes and vasopressors before ECMO initiation, chronic renal failure, and time from intubation to ECMO initiation of 4 days or more were associated with higher in-hospital mortality. 613 patients did not die in hospital, and 547 (95%) of 577 patients for whom data were available were alive at 6 months. 102 (24%) of 431 patients had returned to full-time work at 6 months, and 57 (13%) of 428 patients had returned to part-time work. At 6 months, respiratory rehabilitation was required in 88 (17%) of 522 patients with available data, and the most common residual symptoms included dyspnoea (185 [35%] of 523 patients) and cardiac (52 [10%] of 514 patients) or neurocognitive (66 [13%] of 512 patients) symptoms. INTERPRETATION: Patient's age, timing of cannulation (<4 days vs ≥4 days from intubation), and use of inotropes and vasopressors are essential factors to consider when analysing the outcomes of patients receiving ECMO for COVID-19. Despite post-discharge survival being favourable, persisting long-term symptoms suggest that dedicated post-ECMO follow-up programmes are required. FUNDING: None.

Outcomes of the NHS England National Extracorporeal Membrane Oxygenation Service for adults with respiratory failure: a multicentre observational cohort study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly used to support adults with severe respiratory failure refractory to conventional measures. In 2011, NHS England commissioned a national service to provide ECMO to adults with refractory acute respiratory failure. Our aims were to characterise the patients admitted to the service, report their outcomes, and highlight characteristics potentially associated with survival. METHODS: An observational cohort study was conducted of all patients treated by the NHS England commissioned ECMO service between December 1, 2011 and December 31, 2017. Analysis was conducted according to a prespecified protocol (NCT: 03979222). Data are presented as median [inter-quartile range, IQR]. RESULTS: A total of 1205 patients were supported with ECMO during the study period; the majority (n=1150; 95%) had veno-venous ECMO alone. The survival rate at ECMO ICU discharge was 74% (n=887). Survivors had a lower median age (43 yr [32-52]), compared with non-survivors (49 y [39-60]). Increased severity of hypoxaemia at time of decision-to-cannulate was associated with a lower probability of survival: survivors had a median Sao2 of 90% (84-93%; median Pao2/Fio2, 9.4 kPa [7.7-12.6]), compared with non-survivors (Sao2 88% [80-92%]; Pao2/Fio2 ratio: 8.5 kPa [7.1-11.5]). Patients requiring ECMO because of asthma were more likely to survive (95% survival rate (95% CI, 91-99%), compared with a survival of 71% (95% CI, 69-74%) in patients with respiratory failure attributable to other diagnoses. CONCLUSION: A national ECMO service can achieve good short-term outcomes for patients with undifferentiated respiratory failure refractory to conventional management. CLINICAL TRIAL REGISTRATION: NCT03979222.

Venoarterial extracorporeal membrane oxygenation for postcardiotomy cardiogenic shock-A six-year service evaluation.

Only a small number of English hospitals provide postcardiotomy venoarterial extracorporeal membrane oxygenation (VA-ECMO) and there are doubts about its efficacy and safety. The aim of this service evaluation was to determine local survival rates and report on patient demographics. This was a retrospective service evaluation of prospectively recorded routine clinical data from a tertiary cardiothoracic center in the United Kingdom offering services including cardiac and thoracic surgery, heart and lung transplantation, venovenous extracorporeal membrane oxygenation (VV-ECMO) for respiratory failure, and all types of mechanical circulatory support. In six years, 39 patients were supported with VA-ECMO for refractory postcardiotomy cardiogenic shock (PCCS). We analyzed survival data and looked for associations between survival rates and patient characteristics. The intervention was venoarterial-ECMO in patients with PCCS either following weaning from cardiopulmonary bypass or following a trial of inotropes and intra-aortic balloon counterpulsation on the intensive care unit. 30-day, hospital discharge, 1-year and 2-year survivals were 51.3%, 41%, 37.5%, and 38.5%, respectively. The median (IQR [range]) duration of support was 6 (4-9 [1-35]) days. Nonsurvival was associated with advanced age, shorter intensive care length of stay, and the requirement for postoperative hemofiltration. Reasonable survival rates can be achieved in selected patients who may have been expected to have a worse mortality without VA-ECMO. We suggest postoperative VA-ECMO should be available to all patients undergoing cardiac surgery be it in their own center or through an established pathway to a specialist center.

Perioperative Extracorporeal Cardiopulmonary Resuscitation: The Defibrillator of the 21st Century?: A Case Report.

Veno-arterial-extracorporeal membrane oxygenation (ECMO) for cardiopulmonary resuscitation (ECMO-CPR) has been recommended by new resuscitation guidelines in the United Kingdom. Our recently established yet unfunded ECMO-CPR service has thus far treated 6 patients, with 3 making a good recovery. One patient suffered a catastrophic perioperative complication through glycine absorption and we are in no doubt that she would not have survived without ECMO. We argue for a pragmatic approach to funding of ECMO-CPR because observational evidence suggests superiority over traditional resuscitation and there exists major methodological and ethical barriers to randomized controlled studies. We also call for high-quality observational evidence in the perioperative setting.

Extracorporeal membrane oxygenation in severe respiratory failure resulting from burns and smoke inhalation injury.

Extracorporeal membrane oxygenation (ECMO) is one of the most frequent forms of extracorporeal life support (ECLS) and can be used as rescue therapy in patients with severe respiratory failure resulting from burns and/or smoke inhalation injury. Experience and literature on this treatment option is still very limited, consequently results are varied. We report a retrospective analysis of our experience with veno-venous (VV) ECMO in burn patients. All five patients, three male and two female (age: 28-37 years) had flame type burns and smoke inhalation injury. Their Murray scores ranged between 3.25 and 3.75, and their revised Baux scores between 62 and 102. The mean pre-ECMO conventional ventilation time was 7.4days (3-13). The mean ECMO duration was 18days (8-35). Three patients were cannulated with dual lumen, two with separate cannulae. One oxygenator had to be changed due to technical issues and two patients needed two parallel oxygenators. Four patients had renal replacement therapy. All patients needed vasoconstrictor support, antibiotics and packed red blood cells (5-62 units). Three had steroid treatment. All five patients were successfully weaned from ECMO. One patient died later from multi-organ failure in the ICU, the other four patients survived. VV-ECMO is a useful rescue intervention in patients with burns related severe respiratory failure. Patients in our institution benefit from having both burns and ECMO centres with major expertise in the field under one roof. The results from this small cohort are encouraging, although more cases are needed to draw more robust conclusions.

The role of thoracic surgery in extracorporeal membrane oxygenation services.

Background Recent evidence surrounding the use of venovenous extracorporeal membrane oxygenation in treating acute respiratory failure has led to the expansion of extracorporeal membrane oxygenation services worldwide. The high rate of complications related to venovenous extracorporeal membrane oxygenation often requires intervention by specialist thoracic surgeons. This study aimed to investigate the role of specialist thoracic surgeons within the multidisciplinary team managing these high-risk patients. Methods We retrospectively reviewed 90 patients who received venovenous extracorporeal membrane oxygenation at our tertiary referral center between December 2011 and May 2015. Four patients who underwent lung transplantation were excluded. Results We found that 29.1% (25/86) of patients on venovenous extracorporeal membrane oxygenation had undergone a thoracic intervention. A total of 82 interventions were performed: 11 thoracotomies, 49 chest drains, 13 rigid bronchoscopies, 4 flexible bronchoscopies, 4 temporary endobronchial blockers, and 1 sternotomy. Of the 11 thoracotomies, 3 were reexplorations. Survival to discharge for patients who underwent thoracic surgical interventions was 72% (18/25). Conclusions Our experience has demonstrated that a large proportion of patients receiving venovenous extracorporeal membrane oxygenation require a thoracic intervention, many of which are major intraoperative procedures. Patients on venovenous extracorporeal membrane oxygenation have benefited from rapid on-site access to thoracic surgical services to manage these challenging life-threatening complications.

Postcardiotomy VA-ECMO for refractory cardiogenic shock.

Postcardiotomy cardiogenic shock (PCCS) is a rare but catastrophic syndrome that can occur following separation from cardiopulmonary bypass or at any time during the immediate postoperative course. The management of PCCS varies between clinicians, institutions and countries. The available evidence to guide this practice is limited. In their systematic review and meta-analysis, Khorsandi and colleagues report a synthesis of case-series pertinent to the use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) for PCCS. Whilst we acknowledge the potential survival benefit for carefully selected patients for what is ordinarily a condition with high mortality, we wish to comment on several aspects of the study in the context of its application to clinical practice.

The effect of veno-venous ECMO on the pharmacokinetics of Ritonavir, Darunavir, Tenofovir and Lamivudine.

INTRODUCTION: To our knowledge, there is no published data on the pharmacokinetic (PK) profile of antiretroviral (ART) drugs on patients undergoing extracorporeal membrane oxygenation (ECMO) therapy. We present PK analyses of Ritonavir, Darunavir, Lamivudine and Tenofovir in a patient with HIV who required veno-venous ECMO (VV ECMO). METHODS: Plasma concentrations for Ritonavir, Darunavir, Tenofovir and Lamivudine were obtained while the patient was on ECMO following pre-emptive dose adjustments. Published population PK models were used to simulate plasma concentration profiles for the drugs. The population prediction and the observed plasma concentrations were then overlaid with the expected drug profiles using the individual Bayesian post-hoc parameter estimates. RESULTS: Following dose adjustments, the PK profiles of Ritonavir, Darunavir and Tenofovir fell within the expected range and appeared similar to the population prediction, although slightly different for Ritonavir. The observed data for Lamivudine and its PK profile were completely different from the data available in the literature. CONCLUSIONS: To our knowledge, this is the first study reporting the PK profile of ART drugs during ECMO therapy. Based on our results, dose adjustment of ART drugs while on VV ECMO may be advisable. Further study of the PK profile of Lamivudine is required.

Intra-abdominal hypertension complicating pancreatitis-induced acute respiratory distress syndrome in three patients on extracorporeal membrane oxygenation.

BACKGROUND: Severe acute pancreatitis is associated with sever multiorgan failure from 15 to 50%, depending on the series. In some of these patients, conventional methods of ventilation and respiratory support will fail, demanding the use of extracorporeal membrane oxygenation (ECMO). Abdominal compartment syndrome is potentially harmful in this cohort of patients. We describe the successful treatment of three patients with severe acute pancreatitis who underwent respiratory ECMO and where intra abdominal pressure was monitored regularly. METHODS: Retrospective review of case notes. RESULTS: Three patients with severe acute pancreatitis requiring ECMO suffered from increased intra abdominal pressure during their ICU stay. No surgical interventions were taken to relieve abdominal compartment syndrome. Survival to hospital discharge was 100%. CONCLUSIONS: Monitoring intraabdominal pressure is a valuable adjunct to decision making while caring for these high-risk critically ill patients.

Chronic mould exposure as a risk factor for severe community acquired pneumonia in a patient requiring extra corporeal membrane oxygenation.

A previously fit and well man developed acute respiratory failure due to environmental mould exposure from living in damp rental accommodation. Despite aggressive intensive care management he rapidly deteriorated and required respiratory and cardiac Extracorporeal Membrane Oxygenation. We hypothesize that poor domiciliary conditions may make an underestimated contribution to community respiratory disease. These conditions may present as acute and severe illness with non-typical pathogens identified.

Prophylaxis against atrial fibrillation after cardiac surgery: effective, but not routinely used--a survey of cardiothoracic units in the United kingdom.

OBJECTIVE: To establish whether international recommendations on chemoprophylaxis against postoperative atrial fibrillation in cardiac surgery patients are implemented locally in cardiothoracic units in the United Kingdom; to determine which drugs are being used, how long they are given, and whether outcomes are monitored. DESIGN: Survey of local cardiothoracic center guidelines. SETTING: Postal and telephone survey. PARTICIPANTS: Senior anesthesiologists and critical care staff in all 37 public cardiothoracic units in the United Kingdom. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Results were obtained from all contacted cardiothoracic units. Five units (14%) have local guidelines for chemoprophylaxis against atrial fibrillation in place. All use ß-antagonists as their primary prophylactic drugs; only one unit uses amiodarone as a secondary prophylactic drug. Duration of prophylactic treatment varies, from 5 days to 6 weeks postoperatively. Thirty-two units (86%) have no local guidelines for chemoprophylaxis in place. CONCLUSION: Chemoprophylaxis against postoperative atrial fibrillation in cardiac surgery patients remains underused, despite its effectiveness and recommendations for its routine use by several international organizations. Departmental guidelines help to ensure routine use, but this survey shows that so far only a minority of cardiothoracic units in the United Kingdom have implemented such guidelines. Awareness of the advantages of routine prophylaxis against atrial fibrillation should be improved and departmental prescribing policies encouraged.

The effects of protamine overdose on coagulation parameters as measured by the thrombelastograph.

BACKGROUND AND OBJECTIVE: Protamine is routinely administered following cardiopulmonary bypass in order to neutralize the effects of heparin. An excess of protamine can contribute to coagulopathy, hence predisposing to bleeding with associated morbidity and mortality. Thromboelastography (TEG) is recognized as an invaluable bedside tool to detect coagulation parameters; however, the effects of protamine overdose on TEG parameters have not been fully established. METHODS: Forty-six patients undergoing cardiac surgery using cardiopulmonary bypass were recruited in the study. Following heparinization, the patient's blood heparin level was measured using Hepcon HMS. Incremental doses of protamine [at a protamine-to-Hepcon-derived heparin ratio (PHR) of 1:1, 2:1 and 3:1] were added to patients' blood samples in vitro and four TEG coagulation parameters, including R (time to clot initiation), K (clot kinetics), alpha (clot kinetics) and maximum amplitude (ultimate clot strength), were monitored. Statistical analysis was performed using NCSS software. RESULTS: Protamine caused dose-dependent worsening of coagulation parameters on TEG; K was significantly elevated, whereas alpha and maximum amplitude showed significant reduction (P < 0.001) compared with baseline at a PHR of 2:1 and 3:1, respectively. R was significantly prolonged compared with baseline (P < 0.001) at a PHR of 3:1. CONCLUSION: Protamine adversely affects clot initiation time, clot kinetics and platelet function in a dose-dependent manner, which can predispose to bleeding.