Flow capabilities of arterial and drainage cannulae during venoarterial extracorporeal membrane oxygenation: A simulation model.

BACKGROUND: Large cannulae can increase cannula-related complications during venoarterial extracorporeal membrane oxygenation (VA ECMO). Conversely, the ability for small cannulae to provide adequate support is poorly understood. Therefore, we aimed to evaluate a range of cannula sizes and VA ECMO flow rates in a simulated patient under various disease states. METHODS: Arterial cannulae sizes between 13 and 21 Fr and drainage cannula sizes between 21 and 25 Fr were tested in a VA ECMO circuit connected to a mock circulation loop simulating a patient with severe left ventricular failure. Systemic and pulmonary hypertension, physiologically normal, and hypotension were simulated by varying systemic and pulmonary vascular resistances (SVR and PVR, respectively). All cannula combinations were evaluated against all combinations of SVR, PVR, and VA ECMO flow rates. RESULTS: A 15 Fr arterial cannula combined with a 21 Fr drainage cannula could provide >4 L/min of total flow and a mean arterial pressure of 81.1 mmHg. Changes in SVR produced marked changes to all measured parameters, while changes to PVR had minimal effect. Larger drainage cannulae only increased maximum circuit flow rates when combined with larger arterial cannulae. CONCLUSION: Smaller cannulae and lower flow rates could sufficiently support the simulated patient under various disease states. We found arterial cannula size and SVR to be key factors in determining the flow-delivering capabilities for any given VA ECMO circuit. Overall, our results challenge the notion that larger cannulae and high flows must be used to achieve adequate ECMO support.

Current and future strategies to monitor and manage coagulation in ECMO patients.

Extracorporeal membrane oxygenation (ECMO) can provide life-saving support for critically ill patients suffering severe respiratory and/or cardiac failure. However, thrombosis and bleeding remain common and complex problems to manage. Key causes of thrombosis in ECMO patients include blood contact to pro-thrombotic and non-physiological surfaces, as well as high shearing forces in the pump and membrane oxygenator. On the other hand, adverse effects of anticoagulant, thrombocytopenia, platelet dysfunction, acquired von Willebrand syndrome, and hyperfibrinolysis are all established as causes of bleeding. Finding safe and effective anticoagulants that balance thrombosis and bleeding risk remains challenging. This review highlights commonly used anticoagulants in ECMO, including their mechanism of action, monitoring methods, strengths and limitations. It further elaborates on existing anticoagulant monitoring strategies, indicating their target range, benefits and drawbacks. Finally, it introduces several highly novel approaches to real-time anticoagulation monitoring methods including sound, optical, fluorescent, and electrical measurement as well as their working principles and future directions for research.

Clinical characteristics and outcomes of critically ill patients with one, two and three doses of vaccination against COVID-19 in Australia.

BACKGROUND: Vaccination has been shown to be highly effective in preventing death and severe disease from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Currently, few studies have directly compared vaccinated and unvaccinated patients with severe COVID-19 in the intensive care unit (ICU). AIMS: To compare the clinical characteristics and outcomes of vaccine recipients and unvaccinated patients with SARS-CoV-2 infection admitted to the ICU in a nationwide setting. METHODS: Data were extracted from the Short PeRiod IncideNce sTudy of Severe Acute Respiratory Infection Australia, in 57 ICU during Delta and Omicron predominant periods of the COVID-19 pandemic. The primary outcome was inhospital mortality. Secondary outcomes included duration of mechanical ventilation, ICU length of stay, hospital length of stay and ICU mortality. RESULTS: There were 2970 patients admitted to ICU across participating sites from 26 June 2021 to 8 February 2022; 1134 (38.2%) patients were vaccine recipients, and 1836 (61.8%) patients were unvaccinated. Vaccine recipients were older, more comorbid and less likely to require organ support. Unadjusted inhospital mortality was greater in the vaccinated cohort. After adjusting for age, gender and comorbid status, no statistically significant association between inhospital or ICU mortality, and vaccination status, was apparent. CONCLUSION: We found COVID-19 infection can cause severe disease and death in vaccine recipients, though comorbid status and older age were significant contributors to mortality. Organ support requirements and the number of deaths were highest in the unvaccinated cohort.

Diabetes mellitus, glycaemic control, and severe COVID-19 in the Australian critical care setting: A nested cohort study.

BACKGROUND: Internationally, diabetes mellitus is recognised as a risk factor for severe COVID-19. The relationship between diabetes mellitus and severe COVID-19 has not been reported in the Australian population. OBJECTIVE: The objective of this study was to determine the prevalence of and outcomes for patients with diabetes admitted to Australian intensive care units (ICUs) with COVID-19. METHODS: This is a nested cohort study of four ICUs in Melbourne participating in the Short Period Incidence Study of Severe Acute Respiratory Infection (SPRINT-SARI) Australia project. All adult patients admitted to the ICU with COVID-19 from 20 February 2020 to 27 February 2021 were included. Blood glucose and glycated haemoglobin (HbA1c) data were retrospectively collected. Diabetes was diagnosed from medical history or an HbA1c ≥6.5% (48 mmol/mol). Hospital mortality was assessed using logistic regression. RESULTS: There were 136 patients with median age 58 years [48-68] and median Acute Physiology and Chronic Health Evaluation II (APACHE II) score of 14 [11-19]. Fifty-eight patients had diabetes (43%), 46 patients had stress-induced hyperglycaemia (34%), and 32 patients had normoglycaemia (23%). Patients with diabetes were older, were with higher APACHE II scores, had greater glycaemic variability than patients with normoglycaemia, and had longer hospital length of stay. Overall hospital mortality was 16% (22/136), including nine patients with diabetes, nine patients with stress-induced hyperglycaemia, and two patients with normoglycaemia. CONCLUSION: Diabetes is prevalent in patients admitted to Australian ICUs with severe COVID-19, highlighting the need for prevention strategies in this vulnerable population.

Hemodynamics of small arterial return cannulae for venoarterial extracorporeal membrane oxygenation.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (ECMO) provides mechanical support for critically ill patients with cardiogenic shock. Typically, the size of the arterial return cannula is chosen to maximize flow. However, smaller arterial cannulae may reduce cannula-related complications and be easier to insert. This in vitro study quantified the hemodynamic effect of different arterial return cannula sizes in a simulated acute heart failure patient. METHODS: Baseline support levels were simulated with a 17 Fr arterial cannula in an ECMO circuit attached to a cardiovascular simulator with targeted partial (2.0 L/min ECMO flow, 60-65 mm Hg mean aortic pressure-MAP) and targeted full ECMO support (3.5 L/min ECMO flow and 70-75 mm Hg MAP). Return cannula size was varied (13-21 Fr), and hemodynamics were recorded while keeping ECMO pump speed constant and adjusting pump speed to restore desired support levels. RESULTS: Minimal differences in hemodynamics were found between cannula sizes in partial support mode. A maximum pump speed change of +600 rpm was required to reach the support target, and arterial cannula inlet pressure varied from 79 (21 Fr) to 224 mm Hg (13 Fr). The 15 Fr arterial cannula could provide the target full ECMO support at the targeted hemodynamics; however, the 13 Fr cannula could not due to the high resistance associated with the small diameter. CONCLUSIONS: A 15 Fr arterial return cannula provided targeted partial and full ECMO support to a simulated acute heart failure patient. Balancing reduced cannula size and ECMO support level may improve patient outcomes by reducing cannula-related adverse events.

A Core Outcome Set for Research in Patients on Extracorporeal Membrane Oxygenation.

OBJECTIVES: A core set of outcomes have been identified and published, which are essential to include in all clinical research evaluating the use of extracorporeal membrane oxygenation in critically ill patients, particularly regarding safety and adverse events. The purpose of this international modified Delphi study was to determine which measurement tools and the timing of measurement should be selected for the core outcome set for research evaluating patients receiving extracorporeal membrane oxygenation. DESIGN: This was a two-round international, multidisciplinary web-based, modified Delphi study. PATIENTS: Participants were identified from the International Extracorporeal Membrane Oxygenation Network and the Extracorporeal Life Support Organization, including consumers, multidisciplinary clinicians, researchers and industry partners. MEASUREMENTS: Measurement tools and the timing of measurement were identified from a systematic review of the literature and clinical trials registrations. The primary outcome was the percentage of respondents who completed each survey and indicated that a measurement tool as well as the timing of the measurement should "always" be included in a core outcome set. MAIN RESULTS: Participant response rates were 46 of 65 (71%) and 40 of 46 (87%) for rounds one and two, respectively, with participants representing, researchers, consumers, and industry partners from 15 countries over five continents. Seven measurement tools were identified for the core outcome set of patients on extracorporeal membrane oxygenation. CONCLUSIONS: This study has identified appropriate measurement instruments and the timing of measurement to include in the core outcome set for research evaluating patients receiving extracorporeal membrane oxygenation. This was an important final step to standardize and synthesize research efforts internationally.

Association Between Arterial Carbon Dioxide Tension and Clinical Outcomes in Venoarterial Extracorporeal Membrane Oxygenation.

OBJECTIVES: The manipulation of arterial carbon dioxide tension is associated with differential mortality and neurologic injury in intensive care and cardiac arrest patients; however, few studies have investigated this relationship in patients on venoarterial extracorporeal membrane oxygenation. We investigated the association between the initial arterial carbon dioxide tension and change over 24 hours on mortality and neurologic injury in patients undergoing venoarterial extracorporeal membrane oxygenation for cardiac arrest and refractory cardiogenic shock. DESIGN: Retrospective cohort analysis of adult patients recorded in the international Extracorporeal Life Support Organization Registry. SETTING: Data reported to the Extracorporeal Life Support Organization from all international extracorporeal membrane oxygenation centers during 2003-2016. PATIENTS: Adult patients (≥ 18 yr old) supported with venoarterial extracorporeal membrane oxygenation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 7,168 patients had sufficient data for analysis at the initiation of venoarterial extracorporeal membrane oxygenation, 4,918 of these patients had arterial carbon dioxide tension data available at 24 hours on support. The overall in-hospital mortality rate was 59.9%. A U-shaped relationship between arterial carbon dioxide tension tension at extracorporeal membrane oxygenation initiation and in-hospital mortality was observed. Increased mortality was observed with a arterial carbon dioxide tension less than 30 mm Hg (odds ratio, 1.26; 95% CI, 1.08-1.47; p = 0.003) and greater than 60 mm Hg (odds ratio, 1.28; 95% CI, 1.10-1.50; p = 0.002). Large reductions (> 20 mm Hg) in arterial carbon dioxide tension over 24 hours were associated with important neurologic complications: intracranial hemorrhage, ischemic stroke, and/or brain death, as a composite outcome (odds ratio, 1.63; 95% CI, 1.03-2.59; p = 0.04), independent of the initial arterial carbon dioxide tension. CONCLUSIONS: Initial arterial carbon dioxide tension tension was independently associated with mortality in this cohort of venoarterial extracorporeal membrane oxygenation patients. Reductions in arterial carbon dioxide tension (> 20 mm Hg) from the initiation of extracorporeal membrane oxygenation were associated with neurologic complications. Further prospective studies testing these associations are warranted.

The effect of hyperoxia on inflammation and platelet responses in an ex vivo extracorporeal membrane oxygenation circuit.

Use of extracorporeal membrane oxygenation (ECMO) is expanding, however, it is still associated with significant morbidity and mortality. Activation of inflammatory and innate immune responses and hemostatic alterations contribute to complications. Hyperoxia may play a role in exacerbating these responses. Nine ex vivo ECMO circuits were tested using fresh healthy human whole blood, with two oxygen levels: 21% inspired fraction of oxygen (FiO2 ; mild hyperoxia; n = 5) and 100% FiO2 (severe hyperoxia; n = 4). Serial blood samples were taken for analysis of platelet aggregometry, leukocyte activation, inflammatory, and oxidative stress markers. ECMO resulted in reduced adenosine diphosphate- (P < .05) and thrombin receptor activating peptide-induced (P < .05) platelet aggregation, as well as increasing levels of the neutrophil activation marker, neutrophil elastase (P = .013). Additionally, levels of the inflammatory chemokine interleukin-8 were elevated (P < .05) and the activity of superoxide dismutase, a marker of oxidative stress, was increased (P = .002). Hyperoxia did not augment these responses, with no significant differences detected between mild and severe hyperoxia. Our ex vivo model of ECMO revealed that the circuit itself triggers a pro-inflammatory and oxidative stress response, however, exposure to supra-physiologic oxygen does not amplify that response. Extended-duration studies and inclusion of an endothelial component could be beneficial in characterizing longer term changes.

Core Outcome Measures for Research in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation for Acute Respiratory or Cardiac Failure: An International, Multidisciplinary, Modified Delphi Consensus Study.

OBJECTIVES: Research evaluating outcomes in critically ill patients with acute respiratory and cardiac failure supported with extracorporeal membrane oxygenation has increased significantly. The objective was to identify a core set of outcomes that are essential to include in all clinical research evaluating the use of either venoarterial or venovenous extracorporeal membrane oxygenation in critically ill patients, particularly regarding safety and adverse events. DESIGN: A three-round modified Delphi process. SUBJECTS: Patients, caregivers, multidisciplinary clinicians, researchers, industry partners, and research funders were included. SETTING: Participants represented key extracorporeal membrane oxygenation organizations, including the Extracorporeal Life Support Organization, the International Extracorporeal Membrane Oxygenation Network, clinicians from high volume extracorporeal membrane oxygenation centers, and extracorporeal membrane oxygenation researchers or former extracorporeal membrane oxygenation patients from five continents. INTERVENTIONS: We used recommended standards for the development of a core outcome set. Outcome measures identified from systematic reviews of the literature and from qualitative studies of survivors were mapped to the domains identified by the Core Outcome Measures in Effectiveness Trials initiative separately for venovenous extracorporeal membrane oxygenation and venoarterial extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS: Participant response rates were 40 of 47 (85%), 35 of 37 (95%), and 64 of 69 (93%) for survey rounds 1, 2, and 3, respectively, with participants representing 10 different countries on five continents. After the third round survey, 8 outcome measures met consensus for both venovenous extracorporeal membrane oxygenation and venoarterial extracorporeal membrane oxygenation. CONCLUSIONS: This study identified core outcomes to assess in all research evaluating the use of extracorporeal membrane oxygenation, including adverse events specific to this intervention, permitting standardization of outcome reporting for the first time. Identifying appropriate measurement instruments to evaluate these outcomes is an important next step to enable synthesis of extracorporeal membrane oxygenation research.

Retrieval of Adult Patients on Extracorporeal Membrane Oxygenation by an Intensive Care Physician Model.

The optimal staffing model during the inter-hospital transfer of patients on extracorporeal membrane oxygenation (ECMO) is not known. We report the complications and outcomes of patients who were commenced on ECMO at a referring hospital by intensive care physicians and compare these findings with patients who had ECMO established at an ECMO center in Australia. This was a single center, retrospective observational study based on a prospectively collected ECMO database from Melbourne, Australia. Patients with severe cardiac and/or respiratory failure failing conventional supportive treatment between 2007-2013 were placed on ECMO via a physician-led model of ECMO retrieval, including two intensivists in a four person team, using percutaneous ECMO cannulation. Patients (198) underwent ECMO over the study period, of which 31% were retrieved. Veno-venous (VV)-ECMO and veno-arterial (VA)-ECMO accounted for 27 and 73% respectively. The VA-ECMO patients had more intra-transport interventions compared with VV-ECMO transported patients, but none resulting in serious morbidity or death. There was no overall difference in survival at 6 months between retrieved and ECMO center patients: VV-ECMO (75 vs. 70%, P = 0.690) versus VA-ECMO (70 vs. 68%, P = 1.000). An intensive care physician-led team was able to safely place all critically ill patients on ECMO and retrieve them to an ECMO center. This may be an appropriate staffing model for ECMO retrieval.

Flow characterization of Maquet and Bio-Medicus multi-stage drainage cannulae during venoarterial extracorporeal membrane oxygenation.

BACKGROUND: Drainage cannulae extract blood from a patient during venoarterial extracorporeal membrane oxygenation (VA ECMO), a treatment that temporarily supports patients undergoing severe heart and/or lung dysfunction. Currently, the two most commonly used multi-stage drainage cannulae are manufactured by Maquet and Bio-Medicus, but their designs vary in many aspects which impacts the generated flow dynamics. Therefore, this study aimed to use computational fluid dynamics (CFD) to explore the flow characteristics of the aforementioned cannulae and their impact on complications such as thrombosis. METHODS: The Maquet and Bio-Medicus cannulae were 3D modelled within a patient-specific geometry of the venous vasculature taken from a computed tomography scan of a patient undergoing VA ECMO. A drainage flow rate of 4 L/min was assigned to each cannula. Lastly, a stress blended eddy simulation turbulence model was employed to resolve bulk flow turbulence. RESULTS: The proximal row of side holes in both cannulae generated high intensity counter-rotating vortices, thus generating supraphysiological shear. These proximal rows were also responsible for the majority of flow extraction in both cannulae (>1.6 L/min). Despite identical simulation settings, each cannulae had differing impacts on global flow dynamics. For instance, the Bio-Medicus model produced a total stagnant blood volume of 25.6 ml, compared to 17.8 ml the Maquet cannula, thereby increasing the risk of thrombosis. CONCLUSIONS: Overall, our results demonstrate that differences in design clearly impact flow dynamics and risk of complications. Therefore, further work in optimizing cannula design may be beneficial to prevent harmful flow characteristics.

The Hematological Effects of Extracorporeal Membrane Oxygenator Exchange.

Membrane oxygenator failure during venovenous (V-V) extracorporeal membrane oxygenation (ECMO) can lead to life-threatening hypoxia, high replacement costs, and may be associated with a hyperfibrinolytic state and bleeding. The current understanding of the underlying mechanisms that drive this is limited. The primary aim of this study therefore is to investigate the hematological changes that occur before and after membrane oxygenator and circuit exchanges (ECMO circuit exchange) in patients with severe respiratory failure managed on V-V ECMO. We analyzed 100 consecutive V-V ECMO patients using linear mixed-effects modeling to evaluate hematological markers in the 72 hours before and 72 hours after ECMO circuit exchange. A total of 44 ECMO circuit exchanges occurred in 31 of 100 patients. The greatest change from baseline to peak were seen in plasma-free hemoglobin (42-fold increase p < 0.01) and the D-dimer:fibrinogen ratio (1.6-fold increase p = 0.03). Bilirubin, carboxyhemoglobin, D-dimer, fibrinogen, and platelets also showed statistically significant changes ( p < 0.01), whereas lactate dehydrogenase did not ( p = 0.93). Progressively deranged hematological markers normalize more than 72 hours after ECMO circuit exchange, with an associated reduction in membrane oxygenator resistance. This supports the biologic plausibility that ECMO circuit exchange may prevent further complications such as hyperfibrinolysis, membrane failure, and clinical bleeding.

The effect of arterial cannula tip position on differential hypoxemia during venoarterial extracorporeal membrane oxygenation.

Interaction between native ventricular output and venoarterial extracorporeal membrane oxygenation (VA ECMO) flow may hinder oxygenated blood flow to the aortic arch branches, resulting in differential hypoxemia. Typically, the arterial cannula tip is placed in the iliac artery or abdominal aorta. However, the hemodynamics of a more proximal arterial cannula tip have not been studied before. This study investigated the effect of arterial cannula tip position on VA ECMO blood flow to the upper extremities using computational fluid dynamics simulations. Four arterial cannula tip positions (P1. common iliac, P2. abdominal aorta, P3. descending aorta and P4. aortic arch) were compared with different degrees of cardiac dysfunction and VA ECMO support (50%, 80% and 90% support). P4 was able to supply oxygenated blood to the arch vessels at all support levels, while P1 to P3 only supplied the arch vessels during the highest level (90%) of VA ECMO support. Even during the highest level of support, P1 to P3 could only provide oxygenated VA-ECMO flow at 0.11 L/min to the brachiocephalic artery, compared with 0.5 L/min at P4. This study suggests that cerebral perfusion of VA ECMO flow can be increased by advancing the arterial cannula tip towards the aortic arch.

COVID-19 related ICU admissions in paediatric and young adult patients in Australia: a national case series 2020-2022.

Background: COVID-19 pandemic research efforts have focused on disease phenotypes in adults. A distinct spectrum of illness has been documented in paediatric populations. We aimed to review paediatric intensive care unit (ICU) admissions in Australia, across differing variant predominant phases of the pandemic. Methods: Data reported to the Short PeRiod IncideNce sTudy of Severe Acute Respiratory Infection (SPRINT-SARI) Australia, across 49 ICUs from February 2020 to June 2022 were extracted. We defined 'child' as patients aged <12 years, 'adolescent' as patients aged 12-17 years, and 'young adult' as patients aged 18-25 years. Findings: We identified 226 paediatric ICU admissions with COVID-19, representing 3.9% of ICU admissions across the study period. Comorbidity was present in 34.6% of children, 51.4% of adolescents, and 48.7% of young adults. The need for respiratory support was highest in young adults. While 28.3% of patients <18 years required invasive ventilation, in-hospital mortality in paediatric patients was 3.6%. During the Omicron period, there was an increase in the annualised incidence of age-specific COVID-19 ICU admissions per 100,000 population, albeit a decrease in the incidence per 1000 SARS-CoV-2 notifications. Interpretation: This study demonstrated an appreciable burden of COVID-19 in paediatric patients. Adolescent patients presented phenotypically similar to young adults, however, illness severity was lower in younger cohorts. The Omicron phase of the pandemic demonstrated an increased age-specific population incidence of COVID-19 ICU admissions, albeit a reduced incidence when based on SARS-CoV-2 notifications. Funding: SPRINT-SARI Australia is supported by the Department of Health, Commonwealth of Australia [Standing Deed SON60002733].

The effect of restrictive versus liberal selection criteria on survival in ECPR: a retrospective analysis of a multi-regional dataset.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) is an established rescue therapy for both out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA). However, there remains significant heterogeneity in populations and outcomes across different studies. The primary aim of this study was to compare commonly used selection criteria and their effect on survival and utilisation in an Australian ECPR cohort. METHODS: We performed a retrospective, observational study of three established ECPR centres in Australia, including cases from 1 January 2013 to 31 December 2020 to establish the baseline cohort. We applied five commonly used ECPR selection criteria, ranging from restrictive to liberal. RESULTS: The baseline cohort included 199 ECPR cases: 95 OHCA and 104 IHCA patients. Survival to hospital discharge was 20% for OHCA and 41.4% for IHCA. For OHCA patients, strictly applying the most restrictive criteria would have resulted in the highest survival rate 7/16 (43.8%) compared to the most liberal criteria 16/73 (21.9%). However, only 16/95 (16.8%) in our cohort strictly met the most restrictive criteria versus 73/95 (76.8%) with the most liberal criteria. Similarly, in IHCA, the most restrictive criteria would have resulted in a higher survival rate in eligible patients 10/15 (66.7%) compared to 27/59 (45.8%) with the most liberal criteria. With all criteria a large portion of survivors in IHCA would not have been eligible for ECMO if strictly applying criteria, 33/43 (77%) with restrictive and 16/43 (37%) with the most liberal criteria. CONCLUSIONS: Adherence to different selection criteria impacts both the ECPR survival rate and the total number of survivors. Commonly used selection criteria may be unsuitable to select IHCA ECPR patients.

Implementation of Recommendations on the Use of Corticosteroids in Severe COVID-19.

Importance: Research diversity and representativeness are paramount in building trust, generating valid biomedical knowledge, and possibly in implementing clinical guidelines. Objectives: To compare variations over time and across World Health Organization (WHO) geographic regions of corticosteroid use for treatment of severe COVID-19; secondary objectives were to evaluate the association between the timing of publication of the RECOVERY (Randomised Evaluation of COVID-19 Therapy) trial (June 2020) and the WHO guidelines for corticosteroids (September 2020) and the temporal trends observed in corticosteroid use by region and to describe the geographic distribution of the recruitment in clinical trials that informed the WHO recommendation. Design, Setting, and Participants: This prospective cohort study of 434 851 patients was conducted between January 31, 2020, and September 2, 2022, in 63 countries worldwide. The data were collected under the auspices of the International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC)-WHO Clinical Characterisation Protocol for Severe Emerging Infections. Analyses were restricted to patients hospitalized for severe COVID-19 (a subset of the ISARIC data set). Exposure: Corticosteroid use as reported to the ISARIC-WHO Clinical Characterisation Protocol for Severe Emerging Infections. Main Outcomes and Measures: Number and percentage of patients hospitalized with severe COVID-19 who received corticosteroids by time period and by WHO geographic region. Results: Among 434 851 patients with confirmed severe or critical COVID-19 for whom receipt of corticosteroids could be ascertained (median [IQR] age, 61.0 [48.0-74.0] years; 53.0% male), 174 307 (40.1%) received corticosteroids during the study period. Of the participants in clinical trials that informed the guideline, 91.6% were recruited from the United Kingdom. In all regions, corticosteroid use for severe COVID-19 increased, but this increase corresponded to the timing of the RECOVERY trial (time-interruption coefficient 1.0 [95% CI, 0.9-1.2]) and WHO guideline (time-interruption coefficient 1.9 [95% CI, 1.7-2.0]) publications only in Europe. At the end of the study period, corticosteroid use for treatment of severe COVID-19 was highest in the Americas (5421 of 6095 [88.9%]; 95% CI, 87.7-90.2) and lowest in Africa (31 588 of 185 191 [17.1%]; 95% CI, 16.8-17.3). Conclusions and Relevance: The results of this cohort study showed that implementation of the guidelines for use of corticosteroids in the treatment of severe COVID-19 varied geographically. Uptake of corticosteroid treatment was lower in regions with limited clinical trial involvement. Improving research diversity and representativeness may facilitate timely knowledge uptake and guideline implementation.