Cerebral Microbleeds and Intracranial Hemorrhages in Adult Patients on Extracorporeal Membrane Oxygenation—Autopsy Study

Abstract

Objectives: Current studies lack robust information on the prevalence and associated factors of cerebral microbleeds in patients who underwent extracorporeal membrane oxygenation. Design: Retrospective analysis. Setting: We reviewed patients who underwent (extracorporeal membrane oxygenation) and subsequent brain autopsy with gross and microscopic examinations from January 2009 to December 2018 from a single tertiary center. Patients: Twenty-five extracorporeal membrane oxygenation patients (median age, 53 yr; interquartile range, 36–61 yr; 17 women and 8 men) underwent brain autopsy. Interventions: Descriptive analysis of neuropathologic findings. Cerebral microbleed was defined as a small focus (< 10 mm diameter) of accumulation of blood product in the brain tissue. Macrohemorrhage was defined as any of the grossly identifiable epidural, subdural, subarachnoid, or intraparenchymal hemorrhages larger than 10 mm. Measurement and Main Results: Of 25 (22 venoarterial extracorporeal membrane oxygenation; three venovenous extracorporeal membrane oxygenation), 15 patients (60%) were found to have cerebral microbleeds, whereas 13 (52%) had macrohemorrhages, of whom five (20%) had both. Overall, 92% of brains demonstrated the presence of either cerebral microbleeds or macrohemorrhages after extracorporeal membrane oxygenation support. Of the patients with cerebral microbleeds, lobar cerebral microbleeds (80%) occurred more frequently than deep cerebral microbleeds (60%), with 40% of patients having both types. The cases of macrohemorrhages consisted of one epidural (8%), two subdural (15%), and 10 subarachnoid hemorrhages (77%). In univariate analyses, the presence of macrohemorrhages was significantly associated with the presence of cerebral microbleeds (p = 0.03) with odds ratio of 0.13 (CI, 0.02–0.82). Age, sex, extracorporeal membrane oxygenation duration, extracorporeal membrane oxygenation type, use of aspirin or dialysis during extracorporeal membrane oxygenation support, bloodstream infections, hemoglobin, platelets, and coagulopathy profiles were not associated with cerebral microbleeds. Conclusions: In patients with postmortem neuropathologic evaluation, 92% sustained acute cerebral microbleeds or macrohemorrhages after extracorporeal membrane oxygenation support. Cerebral microbleeds were commonly present in the majority of extracorporeal membrane oxygenation nonsurvivors. Further research is necessary to study the long-term sequelae, such as cognitive outcome of extracorporeal membrane oxygenation-associated cerebral microbleeds in extracorporeal membrane oxygenation survivors.

Intracranial hemorrhage in COVID-19 patients during extracorporeal membrane oxygenation for acute respiratory failure: a nationwide register study report

“…In an observational study from Northern Germany, the observation of intracranial bleeding in COVID-19 non-autopsy ECMO patients (35.4%) was higher compared to our findings. In a study from a single tertiary center on 25 non-COVID ECMO autopsy cases, 52% had intracranial macrohemorrhages [ 12 ]. However, it is possible, that due to concerns regarding occupational hazards, the omission of brain examination especially during the first pandemic wave led to an underreporting of intracranial hemorrhage at autopsy in our cohort.…”

Cerebral microbleeds in critically ill patients with respiratory failure or sepsis: a scoping review

“…Other hypothetical mechanisms for the presence of CMBs include disseminated intravascular coagulation, platelet dysfunction, and COVID-19 related endothelial inflammation. 23 Iatrogenic causes of CMBs, such as ventilation-induced cerebral venous hypertension 5 , ECMO 24 , or dialysis 25 have also been reported. In summary, hypoxemia and sepsis may result in disruption of the blood-brain barrier, coagulopathy, endothelial dysfunction, and CMBs.…”

Cerebral microbleeds in critically ill patients with respiratory failure or sepsis: a scoping review

“…Other hypothetical mechanisms for the presence of CMBs include disseminated intravascular coagulation, platelet dysfunction, and COVID-19 related endothelial in ammation. 23 Iatrogenic causes of CMBs, such as ventilation-induced cerebral venous hypertension 5 , ECMO 24 , or dialysis 25 have also been reported. In summary, hypoxemia and sepsis may result in disruption of the blood-brain barrier, coagulopathy, endothelial dysfunction, and CMBs.…”