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

Abstract

Background In severe cases, SARS-CoV-2 infection leads to acute respiratory distress syndrome (ARDS), often treated by extracorporeal membrane oxygenation (ECMO). During ECMO therapy, anticoagulation is crucial to prevent device-associated thrombosis and device failure, however, it is associated with bleeding complications. In COVID-19, additional pathologies, such as endotheliitis, may further increase the risk of bleeding complications. To assess the frequency of bleeding events, we analyzed data from the German COVID-19 autopsy registry (DeRegCOVID). Methods The electronic registry uses a web-based electronic case report form. In November 2021, the registry included N = 1129 confirmed COVID-19 autopsy cases, with data on 63 ECMO autopsy cases and 1066 non-ECMO autopsy cases, contributed from 29 German sites. Findings The registry data showed that ECMO was used in younger male patients and bleeding events occurred much more frequently in ECMO cases compared to non-ECMO cases (56% and 9%, respectively). Similarly, intracranial bleeding (ICB) was documented in 21% of ECMO cases and 3% of non-ECMO cases and was classified as the immediate or underlying cause of death in 78% of ECMO cases and 37% of non-ECMO cases. In ECMO cases, the three most common immediate causes of death were multi-organ failure, ARDS and ICB, and in non-ECMO cases ARDS, multi-organ failure and pulmonary bacterial ± fungal superinfection, ordered by descending frequency. Interpretation Our study suggests the potential value of autopsies and a joint interdisciplinary multicenter (national) approach in addressing fatal complications in COVID-19.

The authors reply

“…Second, our observation of higher than normal ICH rates in COVID-19 patients on ECMO stands not alone and has been reported by many groups around the globe, acknowledging both the critical combination of anticoagulation and a certain COVID-19–driven vascular susceptibility (4). Regarding choice of anticoagulation, UFH is used by the overwhelming majority of ECMO centers across the globe (5), whereas direct thrombin inhibitors are usually reserved for situations where UFH is contraindicated such as heparin-induced thrombocytopenia or plainly inefficient.…”

Massive airway hemorrhage in severe COVID-19 and the role endotracheal tube clamping

“…The bleeding complications of ECMO are usually related to anticoagulation and include gastrointestinal bleeding, craniocerebral hemorrhage, and airway hemorrhage. In COVID-19, in ammation, vascular endothelial injury, and coagulation disorders lead to the coexistence of thrombosis and bleeding risk; if anticoagulation is used in COVID-19 treatment, the bleeding risk may further increase [11,12]. Studies have shown that the incidence of major bleeding in patients with COVID-19 treated with ECMO is 30.9-42% [13,14], and airway bleeding accounts for 26% of the bleeding instances [14].…”

Patterns of acute ischemic stroke and intracranial hemorrhage in patients with COVID-19

“…Patients with IH were considerably younger than patients with AIS. von Stillfried et al reported the preferential use of ECMO therapy in younger patients with COVID-19 [ 22 ]. ECMO therapy is a risk factor for bleeding events and was also associated with the occurrence of IH in our study.…”