In patients undergoing cardiac surgery who were at moderate-to-high risk for death, a restrictive strategy regarding red-cell transfusion was noninferior to a liberal strategy with respect to the composite outcome of death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis, with less blood transfused. (Funded by the Canadian Institutes of Health Research and others; TRICS III ClinicalTrials.gov number, NCT02042898 .).

Writing Committee for the REMAP-CAP Investigators IMPORTANCE The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive.OBJECTIVE To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19. DESIGN, SETTING, AND PARTICIPANTSThe ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) enrolled and randomized 4763 adults with suspected or confirmed COVID-19 between March 9, 2020, and January 18, 2021, within at least 1 domain; 2011 critically ill adults were randomized to open-label interventions in the immunoglobulin domain at 129 sites in 4 countries. Follow-up ended on April 19, 2021. INTERVENTIONSThe immunoglobulin domain randomized participants to receive 2 units of high-titer, ABO-compatible convalescent plasma (total volume of 550 mL ± 150 mL) within 48 hours of randomization (n = 1084) or no convalescent plasma (n = 916). MAIN OUTCOMES AND MEASURESThe primary ordinal end point was organ support-free days (days alive and free of intensive care unit-based organ support) up to day 21 (range, −1 to 21 days; patients who died were assigned -1 day). The primary analysis was an adjusted bayesian cumulative logistic model. Superiority was defined as the posterior probability of an odds ratio (OR) greater than 1 (threshold for trial conclusion of superiority >99%). Futility was defined as the posterior probability of an OR less than 1.2 (threshold for trial conclusion of futility >95%). An OR greater than 1 represented improved survival, more organ support-free days, or both. The prespecified secondary outcomes included in-hospital survival; 28-day survival; 90-day survival; respiratory support-free days; cardiovascular support-free days; progression to invasive mechanical ventilation, extracorporeal mechanical oxygenation, or death; intensive care unit length of stay; hospital length of stay; World Health Organization ordinal scale score at day 14; venous thromboembolic events at 90 days; and serious adverse events. RESULTS Among the 2011 participants who were randomized (median age, 61 [IQR, 52 to 70] years and 645/1998 [32.3%] women), 1990 (99%) completed the trial. The convalescent plasma intervention was stopped after the prespecified criterion for futility was met. The median number of organ support-free days was 0 (IQR, -1 to 16) in the convalescent plasma group and 3 (IQR, -1 to 16) in the no convalescent plasma group. The in-hospital mortality rate was 37.3% (401/1075) for the convalescent plasma group and 38.4% (347/904) for the no convalescent plasma group and the median number of days alive and free of organ support was 14 (IQR, 3 to 18) and 14 (IQR, 7 to 18), respectively. The median-adjusted OR was 0.97 (95% credible interval, 0.83 to 1.15) and the posterior probability of futility (OR <1.2) was 99.4% for the convalescent plasma group compared with the no convalescent plasma group. The treatment effects were consistent across the primary outcome and the 11...

In patients undergoing cardiac surgery who were at moderate-to-high risk for death, a restrictive strategy for red-cell transfusion was noninferior to a liberal strategy with respect to the composite outcome of death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis at 6 months after surgery. (Funded by the Canadian Institutes of Health Research and others; TRICS III ClinicalTrials.gov number, NCT02042898 .).

Purpose A consensus group recently proposed epidural analgesia as the optimal analgesic modality for patients with multiple traumatic rib fractures. However, its beneficial effects are not consistently recognized in the literature. We performed a systematic review and a meta-analysis of randomized controlled trials (RCT) of epidural analgesia in adult patients with traumatic rib fractures. Methods A systematic search strategy was applied to MEDLINE, EMBASE, the Cochrane Library and to the annual meeting of relevant societies (up to July 2008). All randomized controlled trials comparing epidural analgesia with other analgesic modalities in adult patients with traumatic rib fractures were included. Primary outcomes were mortality, ICU length of stay (LOS), hospital LOS and duration of mechanical ventilation. Results Eight studies (232 patients) met eligibility criteria. Epidural analgesia did not significantly affect mortality (odds ratio [OR] 1.6, 95% CI, 0.3, 9.3, 3 studies, n = 89), ICU LOS (weighted mean difference [WMD] -3.7 days, 95% CI, -11.4, 4.0, 4 studies, n = 135), hospital LOS (WMD -6.7, 95% CI, -19.8, 6.4, 4 studies, n = 140) or duration of mechanical ventilation (WMD -7.5, 95% CI, -16.3, 1.2, 3 studies, n = 101). Duration of mechanical ventilation was decreased when only studies using thoracic epidural analgesia with local anesthetics were evaluated (WMD -4.2, 95% CI, -5.5, -2.9, 2 studies, n = 73). However, hypotension was significantly associated with the use of thoracic epidural analgesia with local anesthetics (OR 13.76, 95% CI, 2.89, 65.51, 3 studies, n = 99).Abstract presentation: Presented in part at the Residents' Competition at the 62nd Annual Meeting of the Canadian Anesthesiologists' Society,

Background: The role of remdesivir inThe primary outcome was in-hospital 24.8% and 28.2%, respectively (95% CI the treatment of patients in hospital mortality. Secondary outcomes 0.72 to 1.07). For patients not mechanwith COVID-19 remains ill defined in a included changes in clinical severity, ically ventilated at baseline, the need for global context. The World Health Organ-oxygen-and ventilator-free days (at mechanical ventilation was 8.0% in those ization Solidarity randomized controlled 28 d), incidence of new oxygen or assigned remdesivir, and 15.0% in those trial (RCT) evaluated remdesivir in mechanical ventilation use, duration of receiving standard of care (RR 0.53, 95% CI patients across many countries, with hospital stay, and adverse event rates. 0.38 to 0.75). Mean oxygen-free and Canada enrolling patients using anWe performed a priori subgroup analy-ventilator-free days at day 28 were 15.9 expanded data collection format in the ses according to duration of symptoms (± standard deviation [SD] 10.5) and 21.4 Canadian Treatments for COVID-19 before enrolment, age, sex and severity (± SD 11.3) in those receiving remdesivir (CATCO) trial. We report on the Canad-of symptoms on presentation. and 14.2 (± SD 11) and 19.5 (± SD 12.3) in ian findings, with additional demo-those receiving standard of care (p = 0.006 graphics, characteristics and clinical Results: Across 52 Canadian hospitals, and 0.007, respectively). There was no difoutcomes, to explore the potential for we randomized 1282 patients between ference in safety events of new dialysis, differential effects across different Aug. 14, 2020, and Apr. 1, 2021, to remde-change in creatinine, or new hepatic dyshealth care systems.sivir (n = 634) or standard of care (n = function between the 2 groups. 648). Of these, 15 withdrew consent or Methods: We performed an open-label, were still in hospital, for a total sample of Interpretation: Remdesivir, when compragmatic RCT in Canadian hospitals, in 1267 patients. Among patients assigned pared with standard of care, has a modest conjunction with the Solidarity trial. We to receive remdesivir, in-hospital mortal-but significant efect on outcomes imporrandomized patients to 10 days of rem-ity was 18.7%, compared with 22.6% in tant to patients and health systems, such desivir (200 mg intravenously [IV] on day the standard-of-care arm (relative risk as the need for mechanical ventilation. 0, followed by 100 mg IV daily), plus[RR] 0.83 (95% confidence interval [CI] Trial registration: ClinicalTrials.gov, no. standard care, or standard care alone. 0.67 to 1.03), and 60-day mortality was NCT04330690.

To study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients with coronavirus disease 2019 .Methods: Critically ill adults with COVID-19 were randomized to receive lopinavir-ritonavir, hydroxychloroquine, combination therapy of lopinavir-ritonavir and hydroxychloroquine or no antiviral therapy (control). The primary endpoint was an ordinal scale of organ support-free days. Analyses used a Bayesian cumulative logistic model and expressed treatment effects as an adjusted odds ratio (OR) where an OR > 1 is favorable. Results:We randomized 694 patients to receive lopinavir-ritonavir (n = 255), hydroxychloroquine (n = 50), combination therapy (n = 27) or control (n = 362). The median organ support-free days among patients in lopinavir-ritonavir, hydroxychloroquine, and combination therapy groups was 4 (-1 to 15), 0 (-1 to 9) and-1 (-1 to 7), respectively,

IMPORTANCEThe efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain.OBJECTIVE To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19. DESIGN, SETTING, AND PARTICIPANTSIn an ongoing adaptive platform trial (REMAP-CAP) testing multiple interventions within multiple therapeutic domains, 1557 critically ill adult patients with COVID-19 were enrolled between October 30, 2020, and June 23, 2021, from 105 sites in 8 countries and followed up for 90 days (final follow-up date: July 26, 2021).INTERVENTIONS Patients were randomized to receive either open-label aspirin (n = 565), a P2Y12 inhibitor (n = 455), or no antiplatelet therapy (control; n = 529). Interventions were continued in the hospital for a maximum of 14 days and were in addition to anticoagulation thromboprophylaxis. MAIN OUTCOMES AND MEASURESThe primary end point was organ support-free days (days alive and free of intensive care unit-based respiratory or cardiovascular organ support) within 21 days, ranging from −1 for any death in hospital (censored at 90 days) to 22 for survivors with no organ support. There were 13 secondary outcomes, including survival to discharge and major bleeding to 14 days. The primary analysis was a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented improved survival, more organ support-free days, or both. Efficacy was defined as greater than 99% posterior probability of an OR greater than 1. Futility was defined as greater than 95% posterior probability of an OR less than 1.2 vs control. Intervention equivalence was defined as greater than 90% probability that the OR (compared with each other) was between 1/1.2 and 1.2 for 2 noncontrol interventions. RESULTSThe aspirin and P2Y12 inhibitor groups met the predefined criteria for equivalence at an adaptive analysis and were statistically pooled for further analysis. Enrollment was discontinued after the prespecified criterion for futility was met for the pooled antiplatelet group compared with control. Among the 1557 critically ill patients randomized, 8 patients withdrew consent and 1549 completed the trial (median age, 57 years; 521 [33.6%] female). The median for organ support-free days was 7 (IQR, −1 to 16) in both the antiplatelet and control groups (median-adjusted OR, 1.02 [95% credible interval {CrI}, 0.86-1.23]; 95.7% posterior probability of futility). The proportions of patients surviving to hospital discharge were 71.5% (723/1011) and 67.9% (354/521) in the antiplatelet and control groups, respectively (median-adjusted OR, 1.27 [95% CrI, 0.99-1.62]; adjusted absolute difference, 5% [95% CrI, −0.2% to 9.5%]; 97% posterior probability of efficacy). Among survivors, the median for organ support-free days was 14 in both groups. Major bleeding occurred in 2.1% and 0.4% of patients in the antiplatelet and control groups (adjusted OR, 2.97 [95% CrI,; adjusted absolute risk increase, 0.8% [95% CrI, 0.1%-2.7%]; 99.4% probability of harm).CONCLUSIONS AND RELEVANCE Among crit...

A chief concern over the first months of the coronavirus disease 2019 (COVID-19) pandemic was the capacity to provide care for acutely ill patients in hospitals and intensive care units (ICUs). The variability in outcomes of patients with COVID-19 internationally has been striking, with some reports describing ICU mortality in ranges between 40 and 90%. 1-3 Systematic reviews including Characteristics and outcomes of patients with COVID-19 admitted to hospital and intensive care in the first phase of the pandemic in Canada: a national cohort study