The effect of a liberal transfusion strategy as compared with a restrictive strategy on outcomes in critically ill patients with traumatic brain injury is unclear. We randomly assigned adults with moderate or severe traumatic brain injury and anemia to receive transfusion of red cells according to a liberal strategy (transfusions initiated at a hemoglobin level of ≤10 g per deciliter) or a restrictive strategy (transfusions initiated at ≤7 g per deciliter). The primary outcome was an unfavorable outcome as assessed by the score on the Glasgow Outcome Scale-Extended at 6 months, which we categorized with the use of a sliding dichotomy that was based on the prognosis of each patient at baseline. Secondary outcomes included mortality, functional independence, quality of life, and depression at 6 months. A total of 742 patients underwent randomization, with 371 assigned to each group. The analysis of the primary outcome included 722 patients. The median hemoglobin level in the intensive care unit was 10.8 g per deciliter in the group assigned to the liberal strategy and 8.8 g per deciliter in the group assigned to the restrictive strategy. An unfavorable outcome occurred in 249 of 364 patients (68.4%) in the liberal-strategy group and in 263 of 358 (73.5%) in the restrictive-strategy group (adjusted absolute difference, restrictive strategy vs. liberal strategy, 5.4 percentage points; 95% confidence interval, -2.9 to 13.7). Among survivors, a liberal strategy was associated with higher scores on some but not all the scales assessing functional independence and quality of life. No association was observed between the transfusion strategy and mortality or depression. Venous thromboembolic events occurred in 8.4% of the patients in each group, and acute respiratory distress syndrome occurred in 3.3% and 0.8% of patients in the liberal-strategy and restrictive-strategy groups, respectively. In critically ill patients with traumatic brain injury and anemia, a liberal transfusion strategy did not reduce the risk of an unfavorable neurologic outcome at 6 months. (Funded by the Canadian Institutes of Health Research and others; HEMOTION ClinicalTrials.gov number, NCT03260478.).

Rationale: Spontaneous breathing trials (SBTs) are designed to simulate conditions after extubation, and it is essential to understand the physiologic impact of different methods. Objectives: We conducted a systematic review and pooled measures reflecting patient respiratory effort among studies comparing SBT methods in a meta-analysis. Methods: We searched Medline, Excerpta Medica Database, and Web of Science from inception to January 2016 to identify randomized and nonrandomized clinical trials reporting physiologic measurements of respiratory effort (pressure–time product) or work of breathing during at least two SBT techniques. Secondary outcomes included the rapid shallow breathing index (RSBI), and effort measured before and after extubation. The quality of physiologic measurement and research design was appraised for each study. Outcomes were analyzed using ratio of means. Measurements and Main Results: Among 4,138 citations, 16 studies (n = 239) were included. Compared with T-piece, pressure support ventilation significantly reduced work by 30% (ratio of means [RoM], 0.70; 95% confidence interval [CI], 0.57–0.86), effort by 30% (RoM, 0.70; 95% CI, 0.60–0.82), and RSBI by 20% (RoM, 0.80; 95% CI, 0.75–0.86). Continuous positive airway pressure had significantly lower pressure-time product by 18% (RoM, 0.82; 95% CI, 0.68–0.999) compared with T-piece, and reduced RSBI by 16% (RoM, 0.84; 95% CI, 0.74–0.95). Studies comparing SBTs with the postextubation period demonstrated that pressure support induced significantly lower effort and RSBI; T-piece reduced effort, but not the work, compared with postextubation. Work, effort, and RSBI measured while intubated on the ventilator with continuous positive airway pressure of 0 cm H2O were no different than extubation. Conclusions: Pressure support reduces respiratory effort compared with T-piece. Continuous positive airway pressure of 0 cm H2O and T-piece more accurately reflect the physiologic conditions after extubation.

Invasive mechanical ventilation (IMV) is a defining feature of critical illness. In epidemiologic studies conducted in the US between 2002 and 2010, the incidence of IMV ranged from 270 to 314 cases per 100 000 population,^1,2 and this incidence is expected to increase in the future.³ IMV increases the complexity and costs of health care.⁴ Quiz Ref ID Cumulative exposure to IMV has been associated with potentially harmful cointerventions (eg, sedation), increased morbidity (eg, ventilator-related complications [such as pneumonia]),⁵ and long-term functional sequelae and cognitive impairment.⁶ Thus, limiting the duration of IMV has been identified as a priority area for research.⁷

Introduction: The objective of this systematic review and meta-analysis was to determine the effect of renal replacement therapy (RRT), delivered as hemofiltration vs. hemodialysis, on clinical outcomes in patients with acute kidney injury (AKI). Methods: MEDLINE, EMBASE and CENTRAL databases and conference abstracts were searched to June 2012 for parallel-group or crossover randomized and quasi-randomized controlled trials (RCTs) evaluating hemofiltration vs. hemodialysis in patients with AKI. Two authors independently selected studies and abstracted data on study quality and outcomes. Additional information was obtained from trial authors. We pooled data using random-effects models. Results: Of 6,657 citations, 19 RCTs (10 parallel-group and 9 crossover) met inclusion criteria. Sixteen trials used continuous RRT. Study quality was variable. The primary analysis included three parallel-group trials comparing similar doses of hemofiltration and hemodialysis; sensitivity analyses included trials comparing combined hemofiltration-hemodialysis or dissimilar doses. We found no effect of hemofiltration on mortality (risk ratio (RR) 0.96, 95% confidence interval (CI) 0.73 to 1.25, P = 0.76; three trials, n = 121 (primary analysis); RR 1.10, 95% CI 0.88 to 1.38, P = 0.38; eight trials, n = 540 (sensitivity analysis)) or other clinical outcomes (RRT dependence in survivors, vasopressor use, organ dysfunction) compared to hemodialysis. Hemofiltration appeared to shorten time to filter failure (mean difference (MD) -7 hours, 95% CI (-19,+5), P = 0.24; two trials, n = 50 (primary analysis); MD -5 hours, 95% CI (-10, -1), P = 0.01; three trials, n = 113 (including combined hemofiltration-hemodialysis trials comparing similar doses); MD -6 hours, 95% CI (-10, -1), P = 0.02; five trials, n = 383 (sensitivity analysis)). Data primarily from crossover RCTs suggested that hemofiltration increased clearance of medium to larger molecules, including inflammatory cytokines, compared to hemodialysis, although almost no studies measured changes in serum concentrations. Meta-analyses were based on very limited data. Conclusions: Data from small RCTs do not suggest beneficial clinical outcomes from hemofiltration, but confidence intervals were wide. Hemofiltration may increase clearance of medium to larger molecules. Larger trials are required to evaluate effects on clinical outcomes.