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Objectives: Anemia has been associated with an increased risk of both cardiac arrest and stroke, frequent complications of COVID-19. The effect of hemoglobin level at ICU admission on a composite outcome of cardiac arrest or stroke in an international cohort of COVID-19 patients was investigated., Design: Retrospective analysis of prospectively collected database., Setting: A registry of COVID-19 patients admitted to ICUs at over 370 international sites was reviewed for patients diagnosed with cardiac arrest or stroke up to 30 days after ICU admission. Anemia was defined as: normal (hemoglobin ≥ 12.0 g/dL for women, ≥ 13.5 g/dL for men), mild (hemoglobin 10.0-11.9 g/dL for women, 10.0-13.4 g/dL for men), moderate (hemoglobin ≥ 8.0 and < 10.0 g/dL for women and men), and severe (hemoglobin < 8.0 g/dL for women and men)., Patients: Patients older than 18 years with acute COVID-19 infection in the ICU., Interventions: None., Measurements and Main Results: Of 6926 patients (median age = 59 yr, male = 65%), 760 patients (11.0%) experienced stroke (2.0%) and/or cardiac arrest (9.4%). Cardiac arrest or stroke was more common in patients with low hemoglobin, occurring in 12.8% of patients with normal hemoglobin, 13.3% of patients with mild anemia, and 16.7% of patients with moderate/severe anemia. Time to stroke or cardiac arrest by anemia status was analyzed using Cox proportional hazards regression with death as a competing risk. Covariates selected through clinical knowledge were age, sex, comorbidities (diabetes, hypertension, obesity, and cardiac or neurologic conditions), pandemic era, country income, mechanical ventilation, and extracorporeal membrane oxygenation. Moderate/severe anemia was associated with a higher risk of cardiac arrest or stroke (hazard ratio, 1.32; 95% CI, 1.05-1.67)., Conclusions: In an international registry of ICU patients with COVID-19, moderate/severe anemia was associated with increased hazard of cardiac arrest or stroke., Competing Interests: Drs. Suen, Li Bassi, and Fraser received support for article research from the Bill and Melinda Gates Foundation. Drs. Fraser’s, Suen’s, and Li Bassi’s institutions received funding from The Bill and Melinda Gates Foundation. Dr. Suen is funded by the Advance Queensland fellowship program, Queensland Government, Australia. Dr. Li Bassi’s institution received funding from Fisher & Paykel. Dr. Li Bassi is a recipient of the Biomedical international training research programme for excellent clinician-scientists (BITRECS) fellowship; the “BITRECS” project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 754550 and from the “La Caixa” Foundation (ID 100010434), under the agreement LCF/PR/GN18/50310006. Dr. Cho received funding from Hyperfine. Dr. Arora has received honoraria from Edwards Lifesciences, HLS Therapeutics, and Bioporto as well is on the advisory board for Renibus Therapeutics for work unrelated to this article. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: Improving access to healthcare for ethnic minorities is a public health priority in many countries, yet little is known about how to incorporate information on race, ethnicity, and related social determinants of health into large international studies. Most studies of differences in treatments and outcomes of COVID-19 associated with race and ethnicity are from single cities or countries., Methods: We present the breadth of race and ethnicity reported for patients in the COVID-19 Critical Care Consortium, an international observational cohort study from 380 sites across 32 countries. Patients from the United States, Australia, and South Africa were the focus of an analysis of treatments and in-hospital mortality stratified by race and ethnicity. Inclusion criteria were admission to intensive care for acute COVID-19 between January 14th, 2020, and February 15, 2022. Measurements included demographics, comorbidities, disease severity scores, treatments for organ failure, and in-hospital mortality., Results: Seven thousand three hundred ninety-four adults met the inclusion criteria. There was a wide variety of race and ethnicity designations. In the US, American Indian or Alaska Natives frequently received dialysis and mechanical ventilation and had the highest mortality. In Australia, organ failure scores were highest for Aboriginal/First Nations persons. The South Africa cohort ethnicities were predominantly Black African (50%) and Coloured* (28%). All patients in the South Africa cohort required mechanical ventilation. Mortality was highest for South Africa (68%), lowest for Australia (15%), and 30% in the US., Conclusions: Disease severity was higher for Indigenous ethnicity groups in the US and Australia than for other ethnicities. Race and ethnicity groups with longstanding healthcare disparities were found to have high acuity from COVID-19 and high mortality. Because there is no global system of race and ethnicity classification, researchers designing case report forms for international studies should consider including related information, such as socioeconomic status or migration background. *Note: "Coloured" is an official, contemporary government census category of South Africa and is a term of self-identification of race and ethnicity of many citizens of South Africa., (© 2023. The Author(s).)

Objectives: Evidence of cerebrovascular complications in COVID-19 requiring venovenous extracorporeal membrane oxygenation (ECMO) is limited. Our study aims to characterize the prevalence and risk factors of stroke secondary to COVID-19 in patients on venovenous ECMO., Design: We analyzed prospectively collected observational data, using univariable and multivariable survival modeling to identify risk factors for stroke. Cox proportional hazards and Fine-Gray models were used, with death and discharge treated as competing risks., Setting: Three hundred eighty institutions in 53 countries in the COVID-19 Critical Care Consortium (COVID Critical) registry., Patients: Adult COVID-19 patients who were supported by venovenous ECMO., Interventions: None., Measurements and Main Results: Five hundred ninety-five patients (median age [interquartile range], 51 yr [42-59 yr]; male: 70.8%) had venovenous ECMO support. Forty-three patients (7.2%) suffered strokes, 83.7% of which were hemorrhagic. In multivariable survival analysis, obesity (adjusted hazard ratio [aHR], 2.19; 95% CI, 1.05-4.59) and use of vasopressors before ECMO (aHR, 2.37; 95% CI, 1.08-5.22) were associated with an increased risk of stroke. Forty-eight-hour post-ECMO Pa co2 -pre-ECMO Pa co2 /pre-ECMO Pa co2 (relative ΔPa co2 ) of negative 26% and 48-hour post-ECMO Pa o2 -pre-ECMO Pa o2 /pre-ECMO Pa o2 (relative ΔPa o2 ) of positive 24% at 48 hours of ECMO initiation were observed in stroke patients in comparison to relative ΔPa co2 of negative 17% and relative ΔPa o2 of positive 7% in the nonstroke group. Patients with acute stroke had a 79% in-hospital mortality compared with 45% mortality for stroke-free patients., Conclusions: Our study highlights the association of obesity and pre-ECMO vasopressor use with the development of stroke in COVID-19 patients on venovenous ECMO. Also, the importance of relative decrease in Pa co2 and moderate hyperoxia within 48 hours after ECMO initiation were additional risk factors., Competing Interests: Drs. Kelly’s, Heinsar’s, and Suen’s institutions received funding from the Bill and Melinda Gates Foundation. Drs. Kelly, Heinsar, Suen, and Fraser received support for article research from the Bill and Melinda Gates Foundation. Dr. Heinsar received funding from The Prince Charles Hospital Foundation. Dr. Suen is funded by the Advance Queensland fellowship program. Dr. Li Bassi is a recipient of the Biomedicine International training research programme for excellent clinician-scientists (BITRECS) fellowship; the “BITRECS” project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 754550 and from the “La Caixa” Foundation (identification number 100010434), under the agreement LCF/PR/GN18/50310006. Dr. Jacobs received funding from SpecialtyCare and the American Academy of Dermatology. Dr. Fraser’s institution received funding from Fisher & Paykel, Mallinckrodt Pharmaceuticals, and Lendlease; he received funding from De Motu Cordis, Philips Electronics, International Society for Heart and Lung Transplantation, and General Practice Training Queensland. Dr. Lorusso’s institution received funding from Medtronic, LivaNova, Getinge, Eurosets, Corcym, Hemocue, and Xenios. Dr. Cho received support for article research from the National Institutes of Health; he is funded by the National Heart, Lung, and Blood Institute 1K23HL157610. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Objectives: To determine the prevalence and outcomes associated with hemorrhage, disseminated intravascular coagulopathy, and thrombosis (HECTOR) complications in ICU patients with COVID-19., Design: Prospective, observational study., Setting: Two hundred twenty-nine ICUs across 32 countries., Patients: Adult patients (≥ 16 yr) admitted to participating ICUs for severe COVID-19 from January 1, 2020, to December 31, 2021., Interventions: None., Measurements and Main Results: HECTOR complications occurred in 1,732 of 11,969 study eligible patients (14%). Acute thrombosis occurred in 1,249 patients (10%), including 712 (57%) with pulmonary embolism, 413 (33%) with myocardial ischemia, 93 (7.4%) with deep vein thrombosis, and 49 (3.9%) with ischemic strokes. Hemorrhagic complications were reported in 579 patients (4.8%), including 276 (48%) with gastrointestinal hemorrhage, 83 (14%) with hemorrhagic stroke, 77 (13%) with pulmonary hemorrhage, and 68 (12%) with hemorrhage associated with extracorporeal membrane oxygenation (ECMO) cannula site. Disseminated intravascular coagulation occurred in 11 patients (0.09%). Univariate analysis showed that diabetes, cardiac and kidney diseases, and ECMO use were risk factors for HECTOR. Among survivors, ICU stay was longer (median days 19 vs 12; p < 0.001) for patients with versus without HECTOR, but the hazard of ICU mortality was similar (hazard ratio [HR] 1.01; 95% CI 0.92-1.12; p = 0.784) overall, although this hazard was identified when non-ECMO patients were considered (HR 1.13; 95% CI 1.02-1.25; p = 0.015). Hemorrhagic complications were associated with an increased hazard of ICU mortality compared to patients without HECTOR complications (HR 1.26; 95% CI 1.09-1.45; p = 0.002), whereas thrombosis complications were associated with reduced hazard (HR 0.88; 95% CI 0.79-0.99, p = 0.03)., Conclusions: HECTOR events are frequent complications of severe COVID-19 in ICU patients. Patients receiving ECMO are at particular risk of hemorrhagic complications. Hemorrhagic, but not thrombotic complications, are associated with increased ICU mortality., Competing Interests: Dr. J. P. Fanning received funding from the Australian-American Fulbright Commission and Metro North Clinical Research Fellowship, Queensland Government, Australia. Drs. Suen, Li Bassi, and Fraser received support for article research from the Bill and Melinda Gates Foundation. Dr. Cho is funded by National Heart, Lung, and Blood Institute 1K23HL157610. Dr. Rando received funding from the American Heart Association. Dr. Whitman disclosed that he is 50% owner of a patent for a medical device for GWBN, LLC and that he received funding from Cellphire/Avania as principal investigator for a national study. Dr. Arora received funding from Edwards LifeSciences and Avir Pharma. Dr. Grasselli received funding from Getinge, Fisher & Paykel, Draeger Medical, Merck Sharp and Dohme, Cook Medical, and GlaxoSmithKline. Dr. Usman received support for article research from the National Institutes of Health. Drs. Suen’s and Li Bassi’s institutions received funding from The Bill and Melinda Gates Foundation. Dr. Suen is funded by the Advance Queensland fellowship program, Queensland Government, Australia. Dr. Li Bassi’s institution received funding from Fisher & Paykel. Dr. Li Bassi is a recipient of the Biomedical international training research programme for excellent clinician-scientists (BITRECS) fellowship; the “BITRECS” project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 754550 and from the “La Caixa” Foundation (ID 100010434), under the agreement LCF/PR/GN18/50310006. Dr. Dalton received funding from extracorporeal membrane oxygenation concepts, entegrion, and hemocue. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Objectives: The study investigated the impact of prone positioning during venovenous extracorporeal membrane oxygenation support for coronavirus disease 2019 acute respiratory failure on the patient outcome., Design: An observational study of venovenous extracorporeal membrane oxygenation patients. We used a multistate survival model to compare the outcomes of patients treated with or without prone positioning during extracorporeal membrane oxygenation, which incorporates the dynamic nature of prone positioning and adjusts for potential confounders., Setting: Seventy-two international institutions participating in the Coronavirus Disease 2019 Critical Care Consortium international registry., Patients: Coronavirus disease 2019 patients who were supported by venovenous extracorporeal membrane oxygenation during the study period., Intervention: None., Measurements and Main Results: There were 232 coronavirus disease 2019 patients at 72 participating institutions who were supported with venovenous extracorporeal membrane oxygenation during the study period from February 16, 2020, to October 31, 2020. Proning was used in 176 patients (76%) before initiation of extracorporeal membrane oxygenation and in 67 patients (29%) during extracorporeal membrane oxygenation. Survival to hospital discharge was 33% in the extracorporeal membrane oxygenation prone group versus 22% in the extracorporeal membrane oxygenation supine group. Prone positioning during extracorporeal membrane oxygenation support was associated with reduced mortality (hazard ratio, 0.31; 95% CI, 0.14-0.68)., Conclusions: Our study highlights that prone positioning during venovenous extracorporeal membrane oxygenation support for refractory coronavirus disease 2019-related acute respiratory distress syndrome is associated with reduced mortality. Given the observational nature of the study, a randomized controlled trial of prone positioning on venovenous extracorporeal membrane oxygenation is needed to confirm these findings., Competing Interests: Dr. Jacobs received funding from SpecialtyCare and the American Academy of Dermatology. Dr. Heinsar received funding via PhD scholarship from the University of Queensland. Dr. Bassi’s institution received funding from Fisher & Paykel. Dr. Dalton received funding from Innovative Extracorporeal Membrane Oxygenation (ECMO) Concepts; she disclosed the off-label product use of ECMO equipment. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)