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In patients with myocardial infarction and anemia, a liberal transfusion strategy led to fewer deaths and heart attacks than a restricted transfusion strategy, but the difference was of borderline significance.

Objective To compare the benefit and harm of restrictive versus liberal transfusion strategies to guide red blood cell transfusions.Design Systematic review with meta-analyses and trial sequential analyses of randomised clinical trials.Data sources Cochrane central register of controlled trials, SilverPlatter Medline (1950 to date), SilverPlatter Embase (1980 to date), and Science Citation Index Expanded (1900 to present). Reference lists of identified trials and other systematic reviews were assessed, and authors and experts in transfusion were contacted to identify additional trials.Trial selection Published and unpublished randomised clinical trials that evaluated a restrictive compared with a liberal transfusion strategy in adults or children, irrespective of language, blinding procedure, publication status, or sample size.Data extraction Two authors independently screened titles and abstracts of trials identified, and relevant trials were evaluated in full text for eligibility. Two reviewers then independently extracted data on methods, interventions, outcomes, and risk of bias from included trials. random effects models were used to estimate risk ratios and mean differences with 95% confidence intervals.Results 31 trials totalling 9813 randomised patients were included. The proportion of patients receiving red blood cells (relative risk 0.54, 95% confidence interval 0.47 to 0.63, 8923 patients, 24 trials) and the number of red blood cell units transfused (mean difference −1.43, 95% confidence interval −2.01 to −0.86) were lower with the restrictive compared with liberal transfusion strategies. Restrictive compared with liberal transfusion strategies were not associated with risk of death (0.86, 0.74 to 1.01, 5707 patients, nine lower risk of bias trials), overall morbidity (0.98, 0.85 to 1.12, 4517 patients, six lower risk of bias trials), or fatal or non-fatal myocardial infarction (1.28, 0.66 to 2.49, 4730 patients, seven lower risk of bias trials). Results were not affected by the inclusion of trials with unclear or high risk of bias. Using trial sequential analyses on mortality and myocardial infarction, the required information size was not reached, but a 15% relative risk reduction or increase in overall morbidity with restrictive transfusion strategies could be excluded.Conclusions Compared with liberal strategies, restrictive transfusion strategies were associated with a reduction in the number of red blood cell units transfused and number of patients being transfused, but mortality, overall morbidity, and myocardial infarction seemed to be unaltered. Restrictive transfusion strategies are safe in most clinical settings. Liberal transfusion strategies have not been shown to convey any benefit to patients.Trial registration PROSPERO CRD42013004272.

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.).

A randomized clinical trial shows that among patients with upper GI bleeding, withholding transfusion until the hemoglobin level falls below 7 g per deciliter results in better outcomes than using 9 g per deciliter as the trigger for transfusion. Acute upper gastrointestinal bleeding is a common emergency condition associated with high morbidity and mortality. 1 It is a frequent indication for red-cell transfusion, because acute blood loss can decrease tissue perfusion and the delivery of oxygen to tissues. Transfusion may be lifesaving in patients with massive exsanguinating bleeding. However, in most cases hemorrhage is not so severe, and in such circumstances the safest and most effective transfusion strategy is controversial. 2 , 3 Restricted transfusion strategies may be appropriate in some settings. Controlled trials have shown that for critically ill patients, a restrictive transfusion strategy is at least as effective as a . . .

In a trial involving nearly 1100 patients undergoing cardiac surgery, there were no significant differences in outcomes among patients receiving transfusions of red cells stored for 10 days or less as compared with outcomes in those receiving red cells stored for 21 days or more. The objective of red-cell transfusion is to increase oxygen delivery and improve clinical outcomes. However, in the United States, storage systems are licensed for up to 42 days on the basis of the estimated in vivo recovery of transfused red cells rather than on the basis of the clinical effectiveness of the transfusion. 1 During storage, red cells undergo numerous changes. 2 , 3 Some laboratory data suggest that red cells stored for longer periods may not traverse the microcirculation or deliver oxygen as effectively as those stored for shorter periods. 4 , 5 Several observational studies have assessed the association between the duration of . . .

In a trial involving patients with subarachnoid hemorrhage and anemia, liberal transfusion of red cells did not result in a lower risk of an unfavorable neurologic outcome than a more restrictive strategy.

In a trial involving more than 2400 critically ill patients, 90-day mortality was similar among patients receiving blood donated on average 6 days earlier and those receiving blood donated 22 days earlier. The age of the transfused blood did not influence outcomes. Blood transfusions are administered frequently and may have unintended consequences in critically ill patients. 1 – 4 Current regulations permit the storage of red cells for up to 42 days, but prolonged storage has been associated with changes that may render red cells ineffective as oxygen carriers and that lead to the accumulation of substances that have untoward biologic effects. 5 – 8 A systematic review of 18 observational studies involving a total of 409,840 patients and three randomized, controlled trials involving a total of 126 patients suggested that the transfusion of older red cells, as compared with newer red cells, was associated with . . .

A large Scandinavian randomized trial showed no important outcome differences between hemoglobin levels of 7 g per deciliter and 9 g per deciliter as transfusion thresholds in patients with septic shock. Blood transfusions are frequently given to patients with septic shock. 1 – 4 Some of these transfusions are given to patients who are bleeding, but many nonbleeding patients also undergo transfusion. 5 The recommendations of the Surviving Sepsis Campaign regarding blood transfusion in patients with septic shock are complex and include a recommendation for transfusion to maintain a hematocrit of more than 30% in the presence of hypoperfusion in the first 6 hours. 6 After that, the transfusion threshold should be a hemoglobin level of less than 7 g per deciliter, aiming at levels between 7 g and 9 g per deciliter in patients . . .

In this open, randomized, multicenter trial involving extremely-low-birth-weight preterm infants, the use of a higher hemoglobin threshold for red-cell transfusion did not improve survival without neurodevelopmental impairment at 22 to 26 months of age, corrected for prematurity.

Patients undergoing cardiac surgery often receive red-cell transfusions, along with the associated risks and costs. Early intraoperative normovolemic hemodilution (i.e., acute normovolemic hemodilution [ANH]) is a blood-conservation technique that entails autologous blood collection before initiation of cardiopulmonary bypass and reinfusion of the collected blood after bypass weaning. More data are needed on whether ANH reduces the number of patients receiving allogeneic red-cell transfusion. In a multinational, single-blind trial, we randomly assigned adults from 32 centers and 11 countries who were undergoing cardiac surgery with cardiopulmonary bypass to receive ANH (withdrawal of ≥650 ml of whole blood with crystalloids replacement if needed) or usual care. The primary outcome was the transfusion of at least one unit of allogeneic red cells during the hospital stay. Secondary outcomes were death from any cause within 30 days after surgery or during the hospitalization for surgery, bleeding complications, ischemic complications, and acute kidney injury. A total of 2010 patients underwent randomization; 1010 were assigned to ANH and 1000 to usual care. Among patients with available data, 274 of 1005 (27.3%) in the ANH group and 291 of 997 (29.2%) in the usual-care group received at least one allogeneic red-cell transfusion (relative risk, 0.93; 95% confidence interval, 0.81 to 1.07; P = 0.34). Surgery for postoperative bleeding was performed in 38 of 1004 patients (3.8%) in the ANH group and 26 of 995 patients (2.6%) in the usual-care group. Death within 30 days or during hospitalization occurred in 14 of 1008 patients (1.4%) in the ANH group and 16 of 997 patients (1.6%) in the usual-care group. Safety outcomes were similar in the two groups. Among adults undergoing cardiac surgery, ANH did not reduce the number of patients receiving allogeneic red-cell transfusion. (Funded by the Italian Ministry of Health; ANH ClinicalTrials.gov number, NCT03913481.).