Daily Anesthesiology Research Analysis

BACKGROUND: Adult intensive care unit (ICU) patients receive many interventions, but few are supported by high-certainty evidence. Randomised clinical trials (RCTs) are essential for trustworthy comparisons of intervention effects, but conventional RCTs are costly, cumbersome, inflexible, and often turn out inconclusive. Adaptive platform trials may mitigate these issues and have higher probabilities of obtaining conclusive results faster and at lower costs per participant. METHODS: The Intensive Care Platform Trial (INCEPT) is an investigator-initiated, pragmatic, randomised, embedded, multifactorial, international, adaptive platform trial including adults acutely admitted to ICUs. INCEPT will assess comparable groups of interventions (primarily commonly used interventions with clinical uncertainty and practice variation) nested in domains. Interventions may be either open-label or masked. New domains will continuously be added to the platform. INCEPT assesses multiple core outcomes selected following substantial stakeholder involvement: mortality, days alive without life support/out of hospital/free of delirium, health-related quality of life, cognitive function, and safety outcomes. Each domain will use one of these core outcomes as the primary outcome. INCEPT primarily uses Bayesian statistical methods with neutral, minimally informative or sceptical priors, adjustment for important prognostic baseline variables, and calculation of absolute and relative differences in the intention-to-treat populations. Domains and intervention arms may be stopped for superiority/inferiority, practical equivalence, or futility according to pre-specified adaptation rules evaluated using statistical simulation or at pre-specified maximum sample sizes. Domains may use response-adaptive randomisation, meaning that more participants will be allocated to interventions with higher probabilities of being superior. CONCLUSIONS: INCEPT provides an efficient, pragmatic, and flexible platform for comparing the effects of many interventions used in adult ICU patients. The adaptive design enables the trial to use accumulating data to improve the treatment of future participants. INCEPT will provide high-certainty, conclusive evidence for many interventions, directly inform clinical practice, and thus improve patient-important outcomes.

BACKGROUND: Patient blood management (PBM) is a set of evidence-based practices that reduces the need for blood transfusions. However, its impact on relevant clinical outcomes remains unclear. The authors evaluated the association between adherence to guideline-recommended PBM care and 30-day postoperative complications in patients undergoing primary total knee and hip arthroplasty. Secondary outcomes included the length of hospital stay and erythrocyte utilization. METHODS: This was a retrospective, multicenter cohort study including patients from 43 hospitals. The PBM clinical pathway comprised nine major guideline-recommended interventions, and adherence was assessed using a composite quality indicator. Multilevel multivariable regression models were used to evaluate the associations between PBM adherence and outcomes at the patient level while accounting for hospital characteristics and hospital variation. RESULTS: A total of 30,926 patients who underwent primary total knee or hip arthroplasty between 2016 and 2022 at 43 hospitals were included. Of these, 1,335 (4.3%) had 30-day postoperative complications. The median adherence to the PBM clinical pathway was 60.0%. Higher PBM adherence was associated with fewer 30-day postoperative complications (adjusted odds ratio, 0.43; 95% CI, 0.32 to 0.58; P < 0.001), including 65% lower odds of major adverse cardiac events and 45% lower odds of infection. Additionally, higher adherence was associated with shorter hospital stays (adjusted incidence rate ratio, 0.77; 95% CI, 0.76 to 0.79; P < 0.001) and reduced transfusion rates (adjusted odds ratio, 0.11; 95% CI, 0.09 to 0.14; P < 0.001). Sensitivity analyses confirmed these associations. CONCLUSIONS: Adherence to the PBM clinical pathway was associated with improved outcomes. While causality cannot be established, these findings support the potential effectiveness of PBM in reducing postoperative complications and its efficiency in shortening hospital stays, beyond minimizing blood transfusions, in patients undergoing knee and hip arthroplasty.

BACKGROUND: Bleeding is a common and sometimes fatal complication of venovenous extracorporeal membrane oxygenation (ECMO). Whether lowering the intensity of anticoagulation during venovenous ECMO is safe or effective is unknown. RESEARCH QUESTION: Is a large, multicenter randomized trial of low-intensity vs moderate-intensity anticoagulation during venovenous ECMO feasible? STUDY DESIGN AND METHODS: In a multicenter, parallel-group, randomized pilot trial conducted at 3 centers across the United States, we randomly assigned critically ill adults undergoing venovenous ECMO to low-intensity or moderate-intensity anticoagulation. Feasibility was assessed by enrollment rate and adherence to the assigned anticoagulation strategy. The primary efficacy outcome was major bleeding, and the primary safety outcome was thromboembolic events, both assessed between enrollment and 24 hours after decannulation. RESULTS: All of the 26 patients enrolled received the assigned intensity of anticoagulation. A major bleeding event occurred in 1 of 12 patients (8.3%) in the low-intensity anticoagulation group and in 4 of 14 patients (28.6%) in the moderate-intensity anticoagulation group (absolute risk difference, -20.2 percentage points; 95% CI, -48.6 to 8.1; P = .33). One patient experienced a thromboembolic event (8.3%) in the low-intensity anticoagulation group compared with none in the moderate-intensity group (difference, 8.3 percentage points; 95% CI, -7.3 to 24.0; P = .46). No patients died before discharge in the low-intensity anticoagulation group, compared with 2 patients (14.3%) in the moderate-intensity group, both of whom experienced major bleeding events. No patients died before discharge in the low-intensity anticoagulation group, compared with 2 patients (14.3%) in the moderate-intensity group, both of whom experienced major bleeding events. INTERPRETATION: Our results indicate that enrollment and separation between groups are feasible in a multicenter randomized trial of low-intensity vs moderate-intensity anticoagulation for critically ill adults receiving venovenous ECMO. A large, multicenter, randomized trial is needed and seems to be feasible. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04997265; URL: www. CLINICALTRIALS: gov.