Risk Factors of Ischemic and Hemorrhagic Strokes During Venovenous Extracorporeal Membrane Oxygenation: Analysis of Data From the Extracorporeal Life Support Organization Registry

Abstract

OBJECTIVES: Stroke is commonly reported in patients receiving venovenous extracorporeal membrane oxygenation, but risk factors are not well described. We sought to determine preextracorporeal membrane oxygenation and on-extracorporeal membrane oxygenation risk factors for both ischemic and hemorrhagic strokes in patients with venovenous extracorporeal membrane oxygenation support. DESIGN: Retrospective analysis. SETTING: Data reported to the Extracorporeal Life Support Organization by 366 extracorporeal membrane oxygenation centers from 2013 to 2019. PATIENTS: Patients older than 18 years supported with a single run of venovenous extracorporeal membrane oxygenation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 15,872 venovenous extracorporeal membrane oxygenation patients, 812 (5.1%) had at least one type of acute brain injury, defined as ischemic stroke, hemorrhagic stroke, or brain death. Overall, 215 (1.4%) experienced ischemic stroke and 484 (3.1%) experienced hemorrhagic stroke. Overall inhospital mortality was 36%, but rates were higher in those with ischemic or hemorrhagic stroke (68% and 73%, respectively). In multivariable analysis, preextracorporeal membrane oxygenation pH (adjusted odds ratio = 0.10; 95% CI, 0.03–0.35; p < 0.001), hemolysis (adjusted odds ratio = 2.27; 95% CI, 1.22–4.24; p = 0.010), gastrointestinal hemorrhage (adjusted odds ratio = 2.01; 95% CI 1.12–3.59; p = 0.019), and disseminated intravascular coagulation (adjusted odds ratio = 3.61; 95% CI, 1.51–8.66; p = 0.004) were independently associated with ischemic stroke. Pre-extracorporeal membrane oxygenation pH (adjusted odds ratio = 0.28; 95% CI, 0.12–0.65; p = 0.003), preextracorporeal membrane oxygenation Po 2 (adjusted odds ratio = 0.96; 95% CI, 0.93–0.99; p = 0.021), gastrointestinal hemorrhage (adjusted odds ratio = 1.70; 95% CI, 1.15–2.51; p = 0.008), and renal replacement therapy (adjusted odds ratio=1.57; 95% CI, 1.22–2.02; p < 0.001) were independently associated with hemorrhagic stroke. CONCLUSIONS: Among venovenous extracorporeal membrane oxygenation patients in the Extracorporeal Life Support Organization registry, approximately 5% had acute brain injury. Mortality rates increased two-fold when ischemic or hemorrhagic strokes occurred. Risk factors such as lower pH and hypoxemia during the pericannulation period and markers of coagulation disturbances were associated with acute brain injury. Further research on understanding preextracorporeal membrane oxygenation and on-extracorporeal membrane oxygenation risk factors and the timing of acute brain injury is necessary to develop appropriate prevention and management strategies.

Neurological Complications in COVID-19 Patients With ECMO Support: A Systematic Review and Meta-Analysis

“…Our meta-analysis showed an overall mortality of 36%, and this increased to 92% in patients with neurological events. A previous study, including 15,872 VV-ECMO patients (non COVID-19), showed a similar overall mortality (34%) and 73% mortality for patients with ICH, which is consistent with the findings from our study [11]. While it is not surprising that the presence of neurological events increased the risk of mortality, it is essential to emphasise the importance of a standardised neuromonitoring protocol and frequent neurological assessment for ECMO patients regardless of COVID-19 status [22].…”

“…We demonstrated an overall prevalence of 5.9% for ICHs, 1.1% for ischaemic stroke and 0.3% for HIBI among 1,322 COVID-19 patients requiring ECMO support. Previously, a large cohort study using the Extracorporeal Life Support Organization registry database demonstrated that patients with VV-ECMO support for acute respiratory failure, without COVID-19, had 3.1% ICHs and 1.4% ischaemic strokes [11]. Similarly, a recent meta-analysis, pooling ECMO patient data from 1992-2015, showed a 7.1% overall prevalence of neurological events, with 3.6% of patients with ICH and 1.7% with ischaemic stroke [12].…”

Diagnosis of Suspected Small Bowel Bleeding by Capsule Endoscopy in Patients with COVID-19

“…It should be noted that the use of ECMO and a ventilator in critical COVID-19 patients may result in gastrointestinal bleeding. The bleeding in EMCO-supported patients may be due in part to the required high doses of heparin, mechanically high blood flow rates and circuit-induced coagulopathy (30)(31)(32). These patients may have a high incidence of bleeding despite the use of acid-suppressing agents.…”

Brain injury in extracorporeal cardiopulmonary resuscitation: translational to clinical research

“…In addition to HIBIs, acute ischemic stroke (AIS) and intracranial hemorrhage (ICH) are major complications that increase mortality in patients supported with ECMO [76,84,85]. In patients treated with VA-ECMO, the prevalence of AIS is 3.3% and may be as high as 16% on autopsy [86,87].…”