Hemorrhagic, coagulopathic, and thrombotic (HECTOR) complications among critically-ill patients with COVID-19: An International COVID-19 critical care consortium study

Background: Hemorrhage, coagulopathy and thrombosis (HECTOR) are reported complications of coronavirus disease 2019 (COVID-19) however, more information is needed on the prevalence of these complications and their associated outcomes in intensive care unit (ICU) settings. Aim(s): To determine the prevalence and outcomes of HECTOR complications in ICU patients with COVID-19. Method(s): Observational cohort study spanning 229 ICUs across 32 countries. Patients >=16 years admitted for severe COVID-19 from 1st January 2020, through 31st December 2021 were included. Patient characteristics and clinical data were collected. Survival analysis estimated the instantaneous impact of HECTOR complications on ICU-mortality and discharge. Result(s): HECTOR complications occurred in 1,735 (14%) of 11,972 study-eligible patients. Acute thrombosis occurred in 1,249 (10%) patients, including 712 (57%) with pulmonary embolism, 413 (33%) with myocardial infarction, 93 (7.4%) with deep vein thrombosis, and 49 (3.9%) with ischemic stroke. Hemorrhagic complications were reported in 582 (4.9%) patients, including 276 (48%) with gastrointestinal hemorrhage, 83 (14%) with hemorrhagic stroke, and 77 (13%) with pulmonary hemorrhage. Disseminated intravascular coagulation occurred in 11 (0.09%) patients. Univariate analysis identified diabetes, hypertension, cardiac and kidney disease and ECMO as statistically-significant risk factors for HECTOR complications. Patients with versus without HECTOR complications suffered higher ICU-mortality at 28 days (25%vs.13%, p < 0.001), 90 days (32%vs.15%, p < 0.0001) and overall (44%vs.36%, p < 0.001). Among ICU survivors, the ICU stay was longer (median days 19vs.12, p < 0.001). ICU mortality was similar between patients with and without HECTOR complications (HR = 1.01, 95%CI 0.92-1.12, p = 0.783) where an increased hazard of ICU mortality with hemorrhage (HR = 1.26, 1.09-1.45, p = 0.002) was balanced by a reduced hazard of thrombosis (HR = 0.88, 0.79-0.99, p = 0.03). Kaplan-Meier curves are presented in the Figure. Conclusion(s): HECTOR events are frequent complications of severe COVID-19 in ICU patients. Hemorrhagic, but not thrombotic complications are associated with increased ICU-mortality.

The Impact of Morbid Obesity on Patients with COVID-19 who Develop Respiratory Failure requiring Extracorporeal Membrane Oxygenation

Background: In patients with COVID-19 and respiratory failure, class 3 obesity (body mass index > 40 kg/m2) has been associated with worse survival. Obese patients on mechanical ventilation with progressively more severe acute respiratory syndrome (ARDS) may be offered venovenous (VV) extracorporeal membrane oxygenation (ECMO) therapy. The impact of morbid obesity on the outcome of COVID-19 patients supported with VV ECMO has been underexplored. Methods: This is a multicenter, retrospective observational cohort analysis of critically ill adults with COVID-19 ARDS requiring advanced mechanical ventilation with or without VV ECMO. Data was collected from 236 international institutions forming the COVID-19 Critical Care Consortium international registry. Patients were admitted between January 2020 to December 2021. Included patients were stratified by ECMO status and a BMI threshold at 40 kg/m2. Median values with interquartile range (IQR) were used to summarize continuous variables and multi-state analysis was used to explore the effect of Class 3 obesity on the study endpoints of patient survival to discharge or death. Results: Complete data was available on 8851 of 9059 patients on mechanical ventilation, of which 767 patients required VV ECMO. For the entire study group, older age and male gender were associated with an increased risk of death. The demographics and comorbidities of the higher BMI (H >40 kg/m2) and lower BMI (L ≤40 kg/m2) cohorts were similar with the exception of age and weight. Patients with a higher BMI were younger. The median age of the H, non-ECMO cohort was 56 years (46-64), and the H, ECMO cohort was 41 years (35-51) versus the L, non-ECMO cohort of 64 years(55-71), and the L, ECMO cohort of 53years (45-60). Patients requiring VV ECMO had higher SOFA scores, experienced longer ICU and hospital lengths of stay, and a longer duration of total mechanical ventilation. Table The median time to intubation was longer in the mechanical ventilation only group (2 versus 0 days). Predictors for requiring ECMO included younger age, higher BMI and male gender. Risk factors for death included advancing age (every 10 years), male gender and increasing BMI (every 5kg/m2). The association between BMI and a higher rate of death was reduced in the mechanical ventilation only group (HR 0.92, 95% confidence interval 0.85 to 0.99). Conclusion: In patients with severe ARDS due to COVID-19 requiring mechanical ventilation, the likelihood of progressing to VV ECMO therapy or experiencing death is impacted by age, gender and higher BMI. The cohort of COVID-19 patients that ultimately required ECMO appear to be sicker at time hospital admission owing to the shorter time until mechanical ventilation. It appears the association between increasing BMI and death differs among the ECMO and mechanical ventilation alone cohorts. We would advocate for a prospective study to determine the benefit of VVECMO for the obese patient requiring VV-ECMO for COVID-19 ARDS. (Figure Presented).

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

Rationale 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 smallcase 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 the impact of CRS on the ventilatory management and outcomes of COVID-19 patients on mechanical ventilation (MV), admitted to intensive care units (ICU) worldwide.Results We enrolled 318 COVID-19 patients enrolled into the study from January 14th through September 31th, 2020 in 19 countries and stratified into two CRS groups. CRS was calculated as: tidal volume/[airway plateau pressure-positive endexpiratory pressure (PEEP)] and available within 48h from commencement of MV in 318 patients. Patients were mean±SD of 58.0±12.2, predominantly from Europe (54%) and males (68%). Median CRS (IQR) was 34.1 mL/cmH2O (26.5-45.5) and PaO2/FiO2 was 119 mmHg (87.1-164) and was not correlated with CRS. Female sex presented lower CRS than in males (95% CI:-13.8 to-8.5 P<0.001) and higher body mass index (34.7±10.9 vs 29.1±6.0, p<0.001). Median (IQR) PEEP was 12 cmH2O (10-15), throughout the range of CRS, while median (IQR) driving pressure was 12.3 (10-15) cmH2O and significantly decreased as CRS improved (p<0.001). No differences were found in comorbidities and clinical management between CRS strata. In addition, 28-day ICU mortality and hospital mortality did not differ between CRSgroups.Conclusions This multicentre report provides a comprehensive account of CRS in COVID-19 patients on MV-predominantly males or overweight females, in their late 50s-admitted to ICU during the first international outbreaks. Phenotypes associated with different CRS upon commencement of MV could not be identified.

Neuromuscular blocking agents in critically-ill COVID-19 patients requiring mechanical ventilation

RATIONALE. Neuromuscular blocking agents (NMBA) are used in patients with moderate to severe acute respiratory distress syndrome. NMBA have also been used in COVID-19 patients who required mechanical ventilation (MV), but their benefit-to-risk ratio remains uncertain.METHODS. We investigated the effects associated with the use of NMBA in COVID-19 patients who required MV from January 1, 2020 to October 31, 2020 in 153 hospitals across 6 continents, comprising the COVID-19 Critical Care Consortium. Cox proportional hazards analysis was conducted to study the impact of NMBA on 28-day intensive care unit (ICU) mortality. Hospital/ICU lengths of stay were appraised. We performed a propensity score (PS) matching analysis to control confounding factors.RESULTS. 1227 patients were eligible for analysis, among those 598 (48.7%) received NMBA for 2 days or longer, with a median time from ICU admission to commencement of NMBA therapy of 0 day (IQR 0-1 days). The median duration of NMBA therapy was 2 days (N=789, IQR 1-5). In comparison with standard of care, treatment with NMBA was more frequent in obese (31% vs. 39%, P = 0.03) and diabetic patients (2% vs. 8%, P <0.01) and less frequent in patients with hypertension (52% vs. 46%, P =0.04) or cardiac diseases (21% vs. 14%, P =0.003). Upon commencement of MV, patients who underwent NMBA therapy vs those who did not presented a PaO2/FiO2 of 136.1±69.2 vs. 162.7 ±125.8 (p<0.01), required more often ECMO (10% vs 5.2%, p <0.01) and prone position (25.1% vs 6.2%, p <0.01). Unadjusted 28-day all-cause mortality was similar (58.2% vs. 62.4%, P =0.134) between patients without or with NMBA therapy, respectively, but length of MV (3 days [2-5] vs. 6 [3-12] P <0.01) and ICU stay (8 days [4-14] vs. 13 [7-19] P <0.01) were prolonged. After PS matching, NMBA therapy was strongly associated with 28-day ICU mortality (adjusted HR 3.18, 95% CI 2.65-3.81, P <0.01). CONCLUSION. Use of NMBA in COVID-19 patients requiring MV is associated with increased 28-day mortality, delayed discontinuation of MV and prolonged ICU stay.

Factors associated with mortality in patients with COVID-19 requiring mechanical ventilation: An international cohort study from 139 intensive care unit across 6 continents

Rationale: Patients with COVID-19 commonly develop severe hypoxemic respiratory failure and require invasive mechanical ventilation (MV). The disease burden and predictors of mortality in this population remain uncertain. Methods: Prospective observational cohort study from 139 intensive care units of the international COVID-19 Critical Care Consortium. Patients enrolled from January 14th through November 31st 2020 were included in the analysis. Patient's characteristics and clinical data were assessed. Multivariable Cox proportional hazards analysis was conducted to identify indipendent predictors of mortality within 28 days from commencement of MV. Results: 1578 patients on MV were included into the analysis. Mean±SD age was 59 years±13 and patients were predominantly males (66%). 542 Patients (34.4%) died within 28 days from commencement of MV. Nonsurvivors were slightly older (mean age±SD 62±13 vs. 59±13) and presented more frequently hypertension, chronic cardiac disease and diabetes. Median (IQR) PaO2/FiO2 upon commencement of MV was 96 (68-135) and 111 (81-173) in patients who did not survive vs. survivors, respectively (p=0.04). ECMO (13% vs 25%, p<0.01), inhaled nitric oxide (11% vs 15%, p=0.02) and recruitment manoeauvres (26% vs 31%, p<0.01) were used less frequently in patients who did not survive. Independent risk factors associated with 28-day mortality included age older than 70 years (hazard ratio [HR], 2.83;95% CI, 1.32-6.07), higher creatinine levels upon ICU admission (HR, 1.20;95% CI, 1.03-1.40), and lower pH within 24h from commencement of MV (HR, 0.12;95% CI, 0.02-0.62), while a shorter period (day) from early symptoms to hospitalisation reduced mortality risks (HR, 0.96;95% CI, 0.93-0.99). Conclusions: Our findings from a large international cohort of critically-ill COVID-19 patients on mechanical ventilation emphasises that elderly patients, not promptly admitted to the hospital, and who present higher creatinine levels and acidosis are at higher risk of mortality.