ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19

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Modifiable Risk Factors and Mortality From Ischemic and Hemorrhagic Strokes in Patients Receiving Venoarterial Extracorporeal Membrane Oxygenation:Results From the Extracorporeal Life Support Organization Registry

OBJECTIVES: Although acute brain injury (ABI) is common in patients receiving extracorporeal membrane oxygenation (ECMO), little is known regarding the mechanism and predictors of ischemic and hemorrhagic stroke. We aimed to determine the risk factors and outcomes of each ischemic and hemorrhagic stroke in patients with venoarterial (VA)-ECMO support. DESIGN: Retrospective analysis. SETTING: Data reported to the Extracorporeal Life Support Organization by 310 extracorporeal membrane oxygenation centers from 2013 to 2017. PATIENTS: Patients more than 18 years old supported with a single run of VA-ECMO. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 10,342 V-A ECMO patients, 401 (3.9%) experienced ischemic stroke and 229 (2.2%) experienced hemorrhagic stroke. Reported ABI during V-A ECMO decreased from 10% to 6% in 5 years. Overall in-hospital mortality was 56%, but rates were higher when ischemic stroke and hemorrhagic stroke were present (76% and 86%, respectively). In multivariable analysis, lower pre-ECMO pH (adjusted odds ratio [aOR], 0.21; 95%CI, 0.09–0.49; p<0.001), higher PO(2) on first day of ECMO (aOR, 1.01; 95%CI, 1.00–1.02; p=0.009), higher rates of ECMO circuit mechanical failure (aOR, 1.33; 95%CI, 1.02–1.74; p=0.03), and renal replacement therapy (aOR, 1.49; 95%CI, 1.14–1.94; p=0.004) were independently associated with ischemic stroke. Female sex (aOR, 1.61; 95%CI, 1.16–2.22; p=0.004), ECMO duration (aOR, 1.01; 95%CI, 1.00–1.03; p=0.02), renal replacement therapy (aOR, 1.81; 95%CI, 1.30–2.52; p<0.001), and hemolysis (aOR, 1.87; 95%CI, 1.11–3.16; p=0.02) were independently associated with hemorrhagic stroke. CONCLUSIONS: Despite a decrease in the incidence of ABI in recent years, mortality rates remain high when ischemic and hemorrhagic strokes are present. Future research is necessary on understanding the timing of associated risk factors to promote prevention and management strategy

Racial and ethnical discrepancy in hypoxemia detection in patients on extracorporeal membrane oxygenationCentral MessagePerspective

Objective: To determine whether there is racial/ethnical discrepancy between pulse oximetry (SpO2) and oxygen saturation (SaO2) in patients receiving extracorporeal membrane oxygenation (ECMO). Methods: This was a retrospective observational study at a tertiary academic ECMO center with adults (>18 years) on venoarterial (VA) or venovenous (VV) ECMO. Datapoints were excluded if oxygen saturation ≤70% or SpO2–SaO2 pairs were not measured within 10 minutes. The primary outcome was the presence of a SpO2–SaO2 discrepancy between different races/ethnicities. Bland–Altman analyses and linear mixed-effects modeling, adjusting for prespecified covariates, were used to assess the SpO2–SaO2 discrepancy between races/ethnicities. Occult hypoxemia was defined as SaO2 <88% with a time-matched SpO2 ≥92%. Results: Of 139 patients receiving VA-ECMO and 57 patients receiving VV-ECMO, we examined 16,252 SpO2–SaO2 pairs. The SpO2–SaO2 discrepancy was greater in VV-ECMO (1.4%) versus VA-ECMO (0.15%). In VA-ECMO, SpO2 overestimated SaO2 in Asian (0.2%), Black (0.94%), and Hispanic (0.03%) patients and underestimated SaO2 in White (−0.06%) and nonspecified race (−0.80%) patients. The proportion of SpO2–SaO2 measurements considered occult hypoxemia was 70% from Black compared to 27% from White patients (P < .0001). In VV-ECMO, SpO2 overestimated SaO2 in Asian (1.0%), Black (2.9%), Hispanic (1.1%), and White (0.50%) patients and underestimated SaO2 in nonspecified race patients (−0.53%). In linear mixed-effects modeling, SpO2 overestimated SaO2 by 0.19% in Black patients (95% confidence interval, 0.045%-0.33%, P = .023). The proportion of SpO2–SaO2 measurements considered occult hypoxemia was 66% from Black compared with 16% from White patients (P < .0001). Conclusions: SpO2 overestimates SaO2 in Asian, Black, and Hispanic versus White patients, and this discrepancy was greater in VV-ECMO versus VA-ECMO, suggesting the need for physiological studies

Management of Anticoagulation Therapy in ECMO-Associated Ischemic Stroke and Intracranial Hemorrhage

Objective: Despite the common occurrence of extracorporeal membrane oxygenation (ECMO)–associated acute ischemic stroke (AIS) and intracranial hemorrhage (ICH), there are little data to guide optimal anticoagulation management. We sought to describe antithrombotic therapy management after stroke and outcomes. Methods: A retrospective analysis was conducted of venoarterial (VA) and venovenous (VV) ECMO patients treated at a tertiary care center from June 2016 to February 2021. Patients with image-confirmed diagnosis of AIS or ICH while receiving ECMO were included for study with data collected regarding anticoagulation management and clinical outcomes. Results: Overall, 216 patients (153 VA-ECMO, 63 VV-ECMO) were included in this study. Of the 153 patients on VA-ECMO, 13 (8.4%) had AIS and 6 (3.9%) had ICH. Of the 63 patients on VV-ECMO, none had AIS and 5 (7.9%) had ICH. One patient (9%) received anticoagulation reversal after ICH. Anticoagulation was discontinued and later resumed in all 5 ICH survivors (median cessation time, 30 h) and 1 of 2 (50%) AIS survivors (median cessation time, 96 h). While off anticoagulation, 2 of 11 patients (18%) had thromboembolic events and none had new AIS. Upon resumption, there were no cases of hemorrhagic transformation of AIS or ICH expansion. There was no difference in in-hospital mortality between patients with ICH and those without in both the VA-ECMO and VV-ECMO cohorts nor between VA-ECMO patients with AIS and those without. Conclusions: Early cessation and judicious resumption of anticoagulation appeared feasible in the cohort of patients with ECMO-associated AIS and ICH. </jats:sec

Resting Energy Expenditure of Patients on Venovenous Extracorporeal Membrane Oxygenation for Adult Respiratory Distress Syndrome: A Pilot Study

OBJECTIVES:. The objectives of this study were to 1) in patients without pulmonary function, determine resting energy expenditure (REE) in venovenous extracorporeal membrane oxygenation (ECMO) acute respiratory distress syndrome (ARDS) patients by paralysis status and 2) determine the threshold tidal volume (TV) associated with meaningful gas exchange as determined by measurable end-tidal carbon dioxide elimination (etV̇co2). DESIGN:. Retrospective observational study. SETTING:. A tertiary high ECMO volume academic institution. PATIENTS/SUBJECTS:. Ten adult ARDS patients on venovenous ECMO. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. The modified Weir equation, Fick principle, Henderson-Hasselbalch equation, ECMO flow, hemoglobin, and pre and post oxygenator blood gases were used to determine ECMO carbon dioxide production (V̇co2), ECMO oxygen consumption, and REE. REE values were matched to patients’ paralysis status based on medication flowsheets and compared using a paired t test. Linear regression was performed to determine the threshold TV normalized to ideal body weight (IBW) associated with measurable ventilator etV̇co2, above which meaningful ventilation occurs. When lungs were not functioning, patients had significantly lower mean REE when paralyzed (23.4 ± 2.8 kcal/kg/d) than when not paralyzed (29.2 ± 5.8 kcal/kg/d) (p = 0.02). Furthermore, mean REE was not similar between patients and varied as much as 1.7 times between patients when paralyzed and as much as 1.4 times when not paralyzed. Linear regression showed that ventilator V̇co2 was measurable and increased linearly when TV was greater than or equal to 0.7 mL/kg. CONCLUSIONS:. REE is patient-specific and varies significantly with and without patient paralysis. When TV exceeds 0.7 mL/kg IBW, ventilator V̇co2 increases measurably and must be considered in determining total REE

An appraisal of respiratory system compliance in mechanically ventilated covid-19 patients

International audienceAbstract Background Heterogeneous respiratory system static compliance ( C RS ) values and levels of hypoxemia in patients with novel coronavirus disease (COVID-19) requiring mechanical ventilation have been reported in previous small-case series or studies conducted at a national level. Methods We designed a retrospective observational cohort study with rapid data gathering from the international COVID-19 Critical Care Consortium study to comprehensively describe C RS —calculated as: tidal volume/[airway plateau pressure-positive end-expiratory pressure (PEEP)]—and its association with ventilatory management and outcomes of COVID-19 patients on mechanical ventilation (MV), admitted to intensive care units (ICU) worldwide. Results We studied 745 patients from 22 countries, who required admission to the ICU and MV from January 14 to December 31, 2020, and presented at least one value of C RS within the first seven days of MV. Median (IQR) age was 62 (52–71), patients were predominantly males (68%) and from Europe/North and South America (88%). C RS , within 48 h from endotracheal intubation, was available in 649 patients and was neither associated with the duration from onset of symptoms to commencement of MV ( p = 0.417) nor with PaO 2 /FiO 2 ( p = 0.100). Females presented lower C RS than males (95% CI of C RS difference between females-males: − 11.8 to − 7.4 mL/cmH 2 O p < 0.001), and although females presented higher body mass index (BMI), association of BMI with C RS was marginal ( p = 0.139). Ventilatory management varied across C RS range, resulting in a significant association between C RS and driving pressure (estimated decrease − 0.31 cmH 2 O/L per mL/cmH 2 0 of C RS , 95% CI − 0.48 to − 0.14, p < 0.001). Overall, 28-day ICU mortality, accounting for the competing risk of being discharged within the period, was 35.6% (SE 1.7). Cox proportional hazard analysis demonstrated that C RS (+ 10 mL/cm H 2 O) was only associated with being discharge from the ICU within 28 days (HR 1.14, 95% CI 1.02–1.28, p = 0.018). Conclusions This multicentre report provides a comprehensive account of C RS in COVID-19 patients on MV. C RS measured within 48 h from commencement of MV has marginal predictive value for 28-day mortality, but was associated with being discharged from ICU within the same period. Trial documentation: Available at https://www.covid-critical.com/study . Trial registration : ACTRN12620000421932

An appraisal of respiratory system compliance in mechanically ventilated covid-19 patients

Abstract Background Heterogeneous respiratory system static compliance (CRS) values and levels of hypoxemia in patients with novel coronavirus disease (COVID-19) requiring mechanical ventilation have been reported in previous small-case series or studies conducted at a national level. Methods We designed a retrospective observational cohort study with rapid data gathering from the international COVID-19 Critical Care Consortium study to comprehensively describe CRS—calculated as: tidal volume/[airway plateau pressure-positive end-expiratory pressure (PEEP)]—and its association with ventilatory management and outcomes of COVID-19 patients on mechanical ventilation (MV), admitted to intensive care units (ICU) worldwide. Results We studied 745 patients from 22 countries, who required admission to the ICU and MV from January 14 to December 31, 2020, and presented at least one value of CRS within the first seven days of MV. Median (IQR) age was 62 (52–71), patients were predominantly males (68%) and from Europe/North and South America (88%). CRS, within 48 h from endotracheal intubation, was available in 649 patients and was neither associated with the duration from onset of symptoms to commencement of MV (p = 0.417) nor with PaO2/FiO2 (p = 0.100). Females presented lower CRS than males (95% CI of CRS difference between females-males: − 11.8 to − 7.4 mL/cmH2O p &lt; 0.001), and although females presented higher body mass index (BMI), association of BMI with CRS was marginal (p = 0.139). Ventilatory management varied across CRS range, resulting in a significant association between CRS and driving pressure (estimated decrease − 0.31 cmH2O/L per mL/cmH20 of CRS, 95% CI − 0.48 to − 0.14, p &lt; 0.001). Overall, 28-day ICU mortality, accounting for the competing risk of being discharged within the period, was 35.6% (SE 1.7). Cox proportional hazard analysis demonstrated that CRS (+ 10 mL/cm H2O) was only associated with being discharge from the ICU within 28 days (HR 1.14, 95% CI 1.02–1.28, p = 0.018). Conclusions This multicentre report provides a comprehensive account of CRS in COVID-19 patients on MV. CRS measured within 48 h from commencement of MV has marginal predictive value for 28-day mortality, but was associated with being discharged from ICU within the same period. Trial documentation: Available at https://www.covid-critical.com/study. Trial registration: ACTRN12620000421932. </jats:sec

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Abstract Background The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men. </jats:sec