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.

Keywords: Autopsy; Bleeding events; COVID-19; ECMO; Intracranial bleeding; Registry.

Fig. 1

a Number of COVID-19 autopsy cases and percentage of COVID-19 autopsies after ECMO therapy by postal code of the deceased person (1 value missing of ECMO cases, 17 values missing of non-ECMO cases). b Number of COVID-19 autopsy cases and percentage of COVID-19 autopsies after ECMO therapy by postal code of the contributing center. c Individual disease duration (orange bars) or death date (black boxes, when no data on symptom onset/ first positive SARS-CoV-2 test was available) in N = 63 ECMO COVID-19 autopsy cases. d Age and sex distribution in COVID-19 autopsies after ECMO therapy (N = 63). e Age and sex distribution in COVID-19 autopsies without ECMO therapy (N = 1065, 1 value missing). f Age and sex distribution in COVID-19 autopsies as a percentage of respective age group. g Intracranial bleeding (ICB) and other hemorrhages in ECMO and non-ECMO COVID-19 cases. The associations between the variables ECMO and ICB and ECMO and any bleeding event were significant (both p value < 0.0001 Fisher’s exact test, two-tailed). Note that the number of bleeding events exceeds the number of patients, because in N = 3 non-ECMO, and N = 3 ECMO autopsies, both ICB and other bleeding events were present at the autopsy, respectively. h ECMO cases (violet) and non-ECMO cases (dark yellow) with any bleeding event. The number of extracranial bleeding events is higher compared to h, because, in N = 4 ECMO cases, two different extracranial bleeding events were documented. ICB, intracranial bleeding