Rationale: Large decreases in PaCO2 that occur when initiating extracorporeal membrane oxygenation (ECMO) in patients with respiratory failure may cause cerebral vasoconstriction and compromise brain tissue perfusion. Objectives: To determine if the magnitude of PaCO2 correction upon ECMO initiation is associated with an increased incidence of neurological complications in patients with respiratory failure. Methods: We conducted a multicenter, international, retrospective cohort study using the Extracorporeal Life Support Organization Registry, including adults with respiratory failure receiving ECMO via any mode between 2012 and 2017. The relative change in PaCO2 in the first 24 hours was calculated as (24-h post-ECMO PaCO2 − pre-ECMO PaCO2)/pre-ECMO PaCO2. The primary outcome was the occurrence of neurological complications, defined as seizures, ischemic stroke, intracranial hemorrhage, or brain death. Measurements and Main Results: We included 11,972 patients, 88% of whom were supported with venovenous ECMO. The median relative change in PaCO2 was −31% (interquartile range, −46% to −12%). Neurological complications were uncommon overall (6.9%), with a low incidence of seizures (1.1%), ischemic stroke (1.9%), intracranial hemorrhage (3.5%), and brain death (1.6%). Patients with a large relative decrease in PaCO2 (>50%) had an increased incidence of neurological complications compared with those with a smaller decrease (9.8% vs. 6.4%; P < 0.001). A large relative decrease in PaCO2 was independently associated with neurological complications after controlling for previously described risk factors (odds ratio, 1.7; 95% confidence interval, 1.3 to 2.3; P < 0.001). Conclusions: In patients receiving ECMO for respiratory failure, a large relative decrease in PaCO2 in the first 24 hours after ECMO initiation is independently associated with an increased incidence of neurological complications.

Whether proton-pump inhibitors are beneficial or harmful for stress ulcer prophylaxis in critically ill patients undergoing invasive ventilation is unclear. In this international, randomized trial, we assigned critically ill adults who were undergoing invasive ventilation to receive intravenous pantoprazole (at a dose of 40 mg daily) or matching placebo. The primary efficacy outcome was clinically important upper gastrointestinal bleeding in the intensive care unit (ICU) at 90 days, and the primary safety outcome was death from any cause at 90 days. Multiplicity-adjusted key secondary outcomes were ventilator-associated pneumonia, Clostridioides difficile infection, and patient-important bleeding. A total of 4821 patients underwent randomization in 68 ICUs. Clinically important upper gastrointestinal bleeding occurred in 25 of 2385 patients (1.0%) receiving pantoprazole and in 84 of 2377 patients (3.5%) receiving placebo (hazard ratio, 0.30; 95% confidence interval [CI], 0.19 to 0.47; P<0.001). At 90 days, death was reported in 696 of 2390 patients (29.1%) in the pantoprazole group and in 734 of 2379 patients (30.9%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.85 to 1.04; P = 0.25). Patient-important bleeding was reduced with pantoprazole; all other key secondary outcomes were similar in the two groups. Among patients undergoing invasive ventilation, pantoprazole resulted in a significantly lower risk of clinically important upper gastrointestinal bleeding than placebo, with no significant effect on mortality. (Funded by the Canadian Institutes of Health Research and others; REVISE ClinicalTrials.gov number, NCT03374800.).

Purpose: Veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) can be used to restore organ perfusion in patients with cardiogenic shock until native heart recovery occurs. It may be challenging, however, to determine when patients can be weaned successfully from ECMO—surviving without requiring further mechanical support or heart transplant. We aimed to systematically review the medical literature to determine the biomarkers, hemodynamic and echocardiographic parameters associated with successful weaning of VA-ECMO in adults with cardiogenic shock and to present an evidence-based weaning algorithm incorporating key findings. Method: We systematically searched PubMed, Embase, ProQuest, Google Scholars, Web of Science and the Grey literature for pertinent original research reports. We excluded studies limited to extracorporeal cardiopulmonary resuscitation (ECPR) as the neurological prognosis may significantly alter the decision-making process surrounding the device removal in this patient population. Studies with a mixed population of VA-ECMO for cardiogenic shock or cardiac arrest were included. We excluded studies limited to patients in which ECMO was only used as a bridge to VAD or heart transplant, as such patients are, by definition, never “successfully weaned.” We used the Risk of Bias Assessment tool for Non-Randomized Studies. The study was registered on the International prospective register of systematic reviews (PROSPERO CRD42020178641). Results: We screened 14,578 records and included 47 that met our pre-specified criteria. Signs of lower initial severity of shock and myocardial injury, early recovery of systemic perfusion, left and right ventricular recovery, hemodynamic and echocardiographic stability during flow reduction trial and/or pump-controlled retrograde trial off predicted successful weaning. The most widely used parameter was the left ventricular outflow tract velocity time integral, an indicator of stroke volume. Most studies had a moderate or high risk of bias. Heterogeneity in methods, timing, and conditions of measurements precluded any meta-analysis. Conclusions: In adult patients on VA-ECMO for cardiogenic shock, multiple biomarkers, hemodynamic and echocardiographic parameters may be used to track resolution of systemic hypoperfusion and myocardial recovery in order to identify patients that can be successfully weaned. Graphical

Rationale: Extracorporeal membrane oxygenation (ECMO) use has exploded over the last decade. However, it remains invasive and associated with significant complications, including tamponade, infection, thrombosis, gas embolism and bleeding. The most dreaded complication is intracranial hemorrhage (ICH). In this article, we review the literature on the incidence, diagnosis, risk factors, pathophysiology, prognosis, prevention and management of ICH in adults on ECMO. Main findings: We found a high incidence of ICH in the literature with a poor prognosis. Important risk factors included pre-ECMO cardiac arrest, sepsis, influenza, renal failure, renal replacement therapy, hemolysis and thrombocytopenia. The optimal anticoagulation strategy is still uncertain. As platelet dysfunction and depletion appear to play an important role in the pathogenesis of ICH in patients on ECMO, a liberal platelet transfusion strategy may be advised. Prompt computed tomography (CT) diagnosis is of great importance as interventions to limit hematoma expansion and secondary neurological injury are most effective if instituted early. Transporting patients to the radiology department can be performed safely while on ECMO. A strategy combining screening CT on admission with a heparin-free period of extracorporeal support was demonstrated to be safe in VV-ECMO patients and resulted in a better prognosis compared to similar cohorts in the literature. Conclusion: Despite major technological improvements and all the experience gained in adults, ECMO remains associated with a high incidence of ICH. There are still wide gaps in our understanding of the disease. Optimal management strategies that minimize the risk of ICH and improve prognosis need to be further studied.

Patients on extracorporeal membrane oxygenation (ECMO) are often among the most severely ill in the intensive care unit. They are often receiving broad-spectrum antibiotics; they have multiple entry points for pathogens; and their immune system is impaired by blood circuit interaction. These factors are thought to predispose them to fungal infections. We thus aimed to evaluate the prevalence, risk factors, and prognosis of fungal infections in adults on ECMO. We conducted a retrospective cohort study using the Extracorporeal Life Support Organization registry, which compiles data on ECMO use from hundreds of international centers. We included all adult patients from 2006 to 2016 on any mode of ECMO with either a diagnosis of fungal infection or a positive fungal culture. Our study comprised 2129 adult patients (10.8%) with fungal colonization or infection. Aspergillus involvement (colonization or infection) was present in 272 patients (1.4%), of whom 35.7% survived to hospital discharge. There were 245 patients (1.2%) with Candida invasive bloodstream infection, with 35.9% survival. Risk factors for Aspergillus involvement included solid organ transplant (OR 1.83; p = 0.008), respiratory support (OR 2.75; p < 0.001), and influenza infection (OR 2.48; p < 0.001). Risk factors for candidemia included sepsis (OR 1.60; p = 0.005) and renal replacement therapy (OR 1.55; p = 0.007). In multivariable analysis, Aspergillus involvement (OR 0.40; p < 0.001) and candidemia (OR 0.47; p < 0.001) were both independently associated with decreased survival. The prevalence of Aspergillus involvement and Candida invasive bloodstream infection were not higher in patients on ECMO than what has been reported in the general intensive care population. Both were independently associated with a reduced survival. Aspergillus involvement was strongly associated with ECMO for respiratory support and influenza.