Position paper for the organization of extracorporeal membrane oxygenation programs for acute respiratory failure in adult patients.

The use of extracorporeal membrane oxygenation (ECMO) for severe acute respiratory failure (ARF) in adults is growing rapidly given recent advances in technology, even though there is controversy regarding the evidence justifying its use. Because ECMO is a complex, high-risk, and costly modality, at present it should be conducted in centers with sufficient experience, volume, and expertise to ensure it is used safely. This position paper represents the consensus opinion of an international group of physicians and associated health-care workers who have expertise in therapeutic modalities used in the treatment of patients with severe ARF, with a focus on ECMO. The aim of this paper is to provide physicians, ECMO center directors and coordinators, hospital directors, health-care organizations, and regional, national, and international policy makers a description of the optimal approach to organizing ECMO programs for ARF in adult patients. Importantly, this will help ensure that ECMO is delivered safely and proficiently, such that future observational and randomized clinical trials assessing this technique may be performed by experienced centers under homogeneous and optimal conditions. Given the need for further evidence, we encourage restraint in the widespread use of ECMO until we have a better appreciation for both the potential clinical applications and the optimal techniques for performing ECMO.

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.].

Factors associated with outcomes of patients on extracorporeal membrane oxygenation support: a 5-year cohort study.

INTRODUCTION: Mortality of patients on extracorporeal membrane oxygenation (ECMO) remains high. The objectives of this study were to assess the factors associated with outcome of patients undergoing ECMO in a large ECMO referral centre and to compare veno-arterial ECMO (VA ECMO) with veno-venous ECMO (VV ECMO). METHODS: We reviewed a prospectively obtained ECMO database and patients' medical records between January 2005 and June 2011. Demographic characteristics, illness severity at admission, ECMO indication, organ failure scores before ECMO and the ECMO mode and configuration were recorded. Bleeding, neurological, vascular and infectious complications that occurred on ECMO were also collected. Demographic, illness, ECMO support descriptors and complications associated with hospital mortality were analysed. RESULTS: ECMO was initiated 158 times in 151 patients. VA ECMO (66.5%) was twice as common as VV ECMO (33.5%) with a median duration significantly shorter than for VV ECMO (7 days (first and third quartiles: 5; 10 days) versus 10 days (first and third quartiles: 6; 16 days)). The most frequent complications during ECMO support were bleeding and bloodstream infections regardless of ECMO type. More than 70% of the ECMO episodes were successfully weaned in each ECMO group. The overall mortality was 37.3% (37.1% for the patients who underwent VA ECMO, and 37.7% for the patients who underwent VV ECMO). Haemorrhagic events, assessed by the total of red blood cell units received during ECMO, were associated with hospital mortality for both ECMO types. CONCLUSIONS: Among neurologic, vascular, infectious and bleeding events that occurred on ECMO, bleeding was the most frequent and had a significant impact on mortality. Further studies are needed to better investigate bleeding and coagulopathy in these patients. Interventions that reduce these complications may improve outcome.

Aspergillus sp. isolated in critically ill patients with extracorporeal membrane oxygenation support.

This study reports Aspergillus isolation in critically ill patients who underwent extracorporeal membrane oxygenation (ECMO) and highlights the difficulty in establishing a diagnosis of aspergillosis in this population. The diagnosis of Aspergillus infection or colonization was retrospectively performed using the proposed modified criteria of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group (EORTC/MSG) adapted to critically ill patients. Between 2005 and 2011, 11 of 151 patients (7.2%) who underwent ECMO had Aspergillus sp. isolates, 10 in a pulmonary sample and 1 in a mediastinal wound sample. Five patients did not have any classical risk factors for aspergillosis. One patient had a proven invasive pulmonary aspergillosis (IPA), 2 had a putative IPA, and 1 patient had a possible Aspergillus mediastinitis, whilst in 7 patients this was considered colonization. However, the clinical relevance of Aspergillus isolation was based on an algorithm not validated in patients undergoing ECMO. Our data support the need to implement non-invasive diagnostic procedures for aspergillosis in this population.

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.

Institution of extracorporeal membrane oxygenation late after lung transplantation - a futile exercise?

The use of and indications for extracorporeal membrane oxygenation (ECMO) are expanding as its reliability improves with widely varying results reported. A retrospective review of 24 lung transplant recipients who required ECMO support postoperatively was performed with 13 patients requiring ECMO within the first 48 h ("early" group) and 11 requiring ECMO after seven d postoperatively ("late" group). The majority of early ECMO group had primary graft failure patients and the late ECMO group comprised patients with infection or non-specific graft failure. There were significant differences in outcomes between groups, with 10/13 in the early group and 4/11 in the late group successfully weaned from ECMO (p = 0.045). Six of the 13 patients in the early group and none of the late group survived to hospital discharge (p = 0.009). The late ECMO group had a much higher incidence of death owing to complications existing prior to institution of ECMO (essentially uncontrolled infection or organ failure). There were no differences in complications arising during ECMO between groups. Late institution of ECMO in lung transplant recipients for causes other than primary graft failure is associated with such poor survival that its use should be considered only in very select cases.

Extracorporeal membrane oxygenation for respiratory failure in adults.

PURPOSE OF REVIEW: This article reviews case series and trials that evaluated extracorporeal membrane oxygenation (ECMO) for respiratory failure and describes patient and circuit management in the modern era of ECMO support. RECENT FINDINGS: In recent years, pivotal progress has been made in the conception and construction of ECMO circuits. They are now simpler, safer, require less anticoagulation and are associated with fewer bleeding complications. The encouraging results of the efficacy and economic assessment of conventional ventilatory support versus ECMO for severe adult respiratory failure (CESAR) trial performed in the United Kingdom and good outcomes of patients who received ECMO as rescue therapy during the recent H1N1 influenza pandemic, in which the latest generation of ECMO technology was used, reignited interest in ECMO for severe acute respiratory distress syndrome (ARDS). SUMMARY: The latest generation of ECMO systems is more biocompatible, better performing and longer lasting. Although recent studies suggested that veno-venous ECMO might improve the outcomes of patients with ARDS, indications for ECMO use remain uncertain. Future trials of ECMO for severe ARDS should strictly control for standard-of-care mechanical ventilation strategies in the control group and early transportation on ECMO for patients in the intervention arm.

Extracorporeal membrane oxygenation for 2009 influenza A (H1N1)-associated acute respiratory distress syndrome.

The 2009 novel swine-origin influenza A (H1N1) virus was identified in April 2009 in Mexico, and the World Health Organization declared the first phase 6 global influenza pandemic of the century on June 11, 2009. The pandemic spread worldwide in just a few weeks. Most patients diagnosed with H1N1-2009 virus had a self-limited respiratory illness. However, among patients admitted to hospitals, 20 to 33% were hospitalized in intensive care units (ICUs) because of influenza-associated pneumonia and acute respiratory distress syndrome (ARDS). Mortality in patients admitted to the ICU with respiratory failure varied between 17 and 28% and was associated with greater illness severity scores and the need for mechanical ventilation on admission as well as the presence of comorbid conditions and older age. Despite attempts to optimize ventilator settings, some patients developed refractory hypoxemia or hypercapnia and received extracorporeal membrane oxygenation (ECMO) as a rescue therapy. In most of these cases, patients were retrieved from outside major cities and safely transported under ECMO to experienced tertiary centers through semiformal referral networks. However, whether the 25 to 50% mortality observed in the reported ECMO series was affected by the recourse to this technique could not be established.

Infections acquired by adults who receive extracorporeal membrane oxygenation: risk factors and outcome.

OBJECTIVES: To analyze infectious complications that occur in patients who receive extracorporeal membrane oxygenation (ECMO), associated risk factors, and consequences on patient outcome. DESIGN: Retrospective observational survey from 2005 through 2011. PARTICIPANTS AND SETTING: Patients who required ECMO in an Australian referral center. METHODS: Cases of bloodstream infection (BSI), catheter-associated urinary tract infection (CAUTI), and ventilator-associated pneumonia (VAP) that occurred in patients who received ECMO were analyzed. RESULTS: A total of 146 ECMO procedures were performed for more than 48 hours in 139 patients, and 36 patients had a total of 46 infections (30.1 infectious episodes per 1,000 days of ECMO). They included 24 cases of BSI, 6 of them secondary to VAP; 23 cases of VAP; and 5 cases of CAUTI. The most frequent pathogens were Enterobacteriaceae (found in 16 of 46 cases), and Candida was the most common cause of BSI (in 9 of 24 cases). The Sequential Organ Failure Assessment score before ECMO initiation and the number of days of support were independently associated with a risk of BSI, with odds ratios of 1.23 (95% confidence interval [CI], 1.03-1.47; [Formula: see text]) and 1.08 (95% CI, 1.03-1.19]; [Formula: see text]), respectively. Infected patients did not have a significantly higher mortality compared with uninfected patients (41.7% vs 32%; [Formula: see text]), but intensive care unit length of stay (16 days [interquartile range, 8-26 days] vs 11 days [IQR, 4-19 days]; [Formula: see text]) and hospital length of stay (33.5 days [interquartile range, 15.5-55.5] vs 24 days [interquartile range, 9-42 days]; [Formula: see text]) were longer. CONCLUSION: The probability of infection increased with the duration of support and the severity of illness before initiation of ECMO. Infections affected length of stay but did not have an impact on mortality.

Extracorporeal membrane oxygenation in primary graft failure after heart transplantation.

BACKGROUND: The aim of this review was to analyze our results with extracorporeal membrane oxygenation (ECMO) support for primary graft failure (PGF) in heart transplant recipients. METHODS: A retrospective review of 239 consecutive patients who underwent heart transplantation between January 2000 and August 2009 was performed. Orthotopic, heterotopic, and heart lung transplants were included in this analysis. Over that time period, 54 patients developed PGF, of whom 39 patients required ECMO support. These 39 patients form the basis of this review. RESULTS: Thirty-four patients (87%) were successfully weaned from ECMO and 29 (74.3%) survived to hospital discharge. There were no significant differences in wean rates or complications between central and peripheral ECMO. Comparison of survival in the 39 ECMO patients to the non-PGF patients (n = 185) showed a significantly worse survival in the ECMO group (p = 0.007). When those patients who died in the first 30 days were excluded, there was no difference in overall survival between groups (p = 0.73). CONCLUSIONS: Extracorporeal membrane oxygenation provides excellent circulatory support for patients with PGF after heart transplantation with good wean and survival to discharge rates.

Aprotinin in lung transplantation is associated with an increased incidence of primary graft dysfunction.

OBJECTIVE: Aprotinin has been widely used to reduce bleeding and transfusion requirements in cardiac surgery and in lung transplantation. A recent study found a significant reduction in severe (grade III) primary graft dysfunction (PGD) in lung transplantation where aprotinin had been used. However, recently, concerns regarding the safety of aprotinin have been raised, and the future use of aprotinin is uncertain. In our institution, aprotinin has been widely used in cardiac surgery and transplantation. We decided to review our lung transplant caseload to investigate the impact of aprotinin on PGD and mortality and to guide our future clinical use of this antifibrinolytic. METHODS: A retrospective review of prospectively collected data on 213 consecutive patients who underwent single- or double-lung transplantation was performed. Ninety-nine patients, who received aprotinin, were compared with 114 patients who did not. The main outcome variables analysed were development of primary graft dysfunction, renal impairment and mortality. RESULTS: Aprotinin was associated with a significantly increased risk of PGD in the first 48 h postoperatively (p=0.01). CONCLUSIONS: In conclusion, although the benefits of aprotinin on blood loss are well established, this study does not provide support for the use of aprotinin to reduce PGD in lung transplantation and indicates that aprotinin may in fact have a detrimental effect.