Restrictive versus Liberal Transfusion Thresholds

Clinical guidelines have concluded that there are insufficient data to provide recommendations for the hemoglobin threshold for the use of red cell transfusion in patients with acute myocardial infarction (MI) and anemia. After the recent publication of the Myocardial Infarction and Transfusion (MINT) trial, we performed an individual patient-level data meta-analysis to evaluate the effect of restrictive versus liberal blood transfusion strategies. We conducted searches in major databases. Eligible trials randomly assigned patients with MI and anemia to either a restrictive (i.e., transfusion threshold of 7-8 g/dl) or liberal (i.e., transfusion threshold of 10 g/dl) red cell transfusion strategy. We used individual patient data from each trial. The primary outcome was a composite of 30-day mortality or MI. We included 4311 patients from four trials. The primary outcome occurred in 334 patients (15.4%) in the restrictive strategy and 296 patients (13.8%) in the liberal strategy (relative risk [RR] 1.13, 95% confidence interval [CI], 0.97 to 1.30). Death at 30 days occurred in 9.3% of patients in the restrictive strategy and in 8.1% of patients in the liberal strategy (RR 1.15, 95% CI, 0.95 to 1.39). Cardiac death at 30 days occurred in 5.5% of patients in the restrictive strategy and in 3.7% of patients in the liberal strategy (RR 1.47, 95% CI, 1.11 to 1.94). Heart failure (RR 0.89, 95% CI, 0.70 to 1.13) was similar in the transfusion strategies. All-cause mortality at 6 months occurred in 20.5% of patients in the restrictive strategy compared with 19.1% of patients in the liberal strategy (hazard ratio 1.08, 95% CI, 1.05 to 1.11). Pooling individual patient data from four trials did not find a definitive difference in our primary composite outcome of MI or death at 30 days. At 6 months, a restrictive transfusion strategy was associated with increased all-cause mortality. (Partially funded by a grant from the U.S. National Heart, Lung, and Blood Institute [R01HL171977].).

The hemoglobin threshold at which postoperative red-cell transfusion is warranted is controversial. We conducted a randomized trial to determine whether a higher threshold for blood transfusion would improve recovery in patients who had undergone surgery for hip fracture. We enrolled 2016 patients who were 50 years of age or older, who had either a history of or risk factors for cardiovascular disease, and whose hemoglobin level was below 10 g per deciliter after hip-fracture surgery. We randomly assigned patients to a liberal transfusion strategy (a hemoglobin threshold of 10 g per deciliter) or a restrictive transfusion strategy (symptoms of anemia or at physician discretion for a hemoglobin level of <8 g per deciliter). The primary outcome was death or an inability to walk across a room without human assistance on 60-day follow-up. A median of 2 units of red cells were transfused in the liberal-strategy group and none in the restrictive-strategy group. The rates of the primary outcome were 35.2% in the liberal-strategy group and 34.7% in the restrictive-strategy group (odds ratio in the liberal-strategy group, 1.01; 95% confidence interval [CI], 0.84 to 1.22), for an absolute risk difference of 0.5 percentage points (95% CI, -3.7 to 4.7). The rates of in-hospital acute coronary syndrome or death were 4.3% and 5.2%, respectively (absolute risk difference, -0.9%; 99% CI, -3.3 to 1.6), and rates of death on 60-day follow-up were 7.6% and 6.6%, respectively (absolute risk difference, 1.0%; 99% CI, -1.9 to 4.0). The rates of other complications were similar in the two groups. A liberal transfusion strategy, as compared with a restrictive strategy, did not reduce rates of death or inability to walk independently on 60-day follow-up or reduce in-hospital morbidity in elderly patients at high cardiovascular risk. (Funded by the National Heart, Lung, and Blood Institute; FOCUS ClinicalTrials.gov number, NCT00071032.).

To determine whether a restrictive strategy of red-cell transfusion and a liberal strategy produced equivalent results in critically ill patients, we compared the rates of death from all causes at 30 days and the severity of organ dysfunction. We enrolled 838 critically ill patients with euvolemia after initial treatment who had hemoglobin concentrations of less than 9.0 g per deciliter within 72 hours after admission to the intensive care unit and randomly assigned 418 patients to a restrictive strategy of transfusion, in which red cells were transfused if the hemoglobin concentration dropped below 7.0 g per deciliter and hemoglobin concentrations were maintained at 7.0 to 9.0 g per deciliter, and 420 patients to a liberal strategy, in which transfusions were given when the hemoglobin concentration fell below 10.0 g per deciliter and hemoglobin concentrations were maintained at 10.0 to 12.0 g per deciliter. Overall, 30-day mortality was similar in the two groups (18.7 percent vs. 23.3 percent, P= 0.11). However, the rates were significantly lower with the restrictive transfusion strategy among patients who were less acutely ill -- those with an Acute Physiology and Chronic Health Evaluation II score of < or =20 (8.7 percent in the restrictive-strategy group and 16.1 percent in the liberal-strategy group; P=0.03) -- and among patients who were less than 55 years of age (5.7 percent and 13.0 percent, respectively; P=0.02), but not among patients with clinically significant cardiac disease (20.5 percent and 22.9 percent, respectively; P=0.69). The mortality rate during hospitalization was significantly lower in the restrictive-strategy group (22.3 percent vs. 28.1 percent, P=0.05). A restrictive strategy of red-cell transfusion is at least as effective as and possibly superior to a liberal transfusion strategy in critically ill patients, with the possible exception of patients with acute myocardial infarction and unstable angina.

The decision-making process for red blood cell transfusion (RBCT) in critically ill patients in the intensive care unit (ICU) remains primarily guided by hemoglobin-based thresholds. However, as a component of personalized medicine, innovative and individualized criteria should be developed to optimize RBCT decisions. This study aims to assess the impact of RBCTs on oxygenation parameters and patient outcomes, with a specific focus on the oxygen extraction ratio (O2ER). This prospective observational study included 77 critically ill patients receiving RBCTs according to ICU transfusion protocols. The primary hypothesis is that patients with an O2ER&#x2009;>&#x2009;0.30 will benefit most from RBCTs. To investigate this, patients receiving RBCTs were divided into two groups: those with O2ER&#x2009;>&#x2009;0.30 (RBCTs appropriate) and those with O2ER&#x2009;&#x2264;&#x2009;0.30 (RBCTs appropriateness questionable). The two groups were compared in terms of primarily O2ER, other oxygenation parameters, and clinical outcomes. The primary outcome was the change in O2ER following RBCTs, while secondary outcomes encompassed other oxygenation parameter changes. The O2ER&#x2009;>&#x2009;0.30 group showed significant improvement in O2ER (0.38&#x2009;&#xb1;&#x2009;0.04 vs. 0.32&#x2009;&#xb1;&#x2009;0.05; p&#x2009;<&#x2009;.001), whereas no such improvement was observed in the O2ER&#x2009;&#x2264;&#x2009;0.30 group (0.26&#x2009;&#xb1;&#x2009;0.03 vs. 0.28&#x2009;&#xb1;&#x2009;0.05; p: .017). Additionally, the O2ER&#x2009;>&#x2009;0.30 group exhibited improvements in central venous oxygen saturation (ScvO2) following RBCTs, which were not seen in the O2ER&#x2009;&#x2264;&#x2009;0.30 group. Our study reveals promising insights into the impact of RBCTs on O2ER; however, these physiological changes did not result in significant clinical improvements. Hence, this study provides a rational basis for the feasibility of implementing a personalized strategy focused on physiological triggers for RBCTs. NCT05798130 (https://clinicaltrials.gov/study/NCT05798130).

There is a willingness to move towards a more personalised medicine; however, the red blood cells' (RBC) transfusion decision-making process remains a one-size-fits-all practice in most non-bleeding critically ill patients. This narrative review describes the limitations of a transfusion decision-making process based only on haemoglobin (Hb) threshold and the potential physiological triggers of RBC transfusion with the clinical evidence investigating their implementation in routine. Hb does not reflect tissue oxygenation and anaemia tolerance, and applying the same Hb threshold throughout the ICU stay neither prevents unnecessary transfusion nor insufficient transfusion. Central venous oxygen saturation (ScvO2) and oxygen extraction ratio (O2ER) are accessible at the bedside and display significant changes after RBC transfusion when in abnormal ranges. Although they have been prospectively investigated in the transfusion decision process, there is a need for more evidence to definitely implement them in routine. The arterial-venous difference in oxygen (A-VO2diff) might be another useful bedside RBC transfusion trigger. Microcirculatory markers are also promising candidates for physiological determinants for RBC transfusion. There is a need for additional determinants in the RBC transfusion decision process to offset the limitations of RBC transfusion based only on Hb level in non-bleeding critically ill patients. A multimodal strategy, including comorbidities, underlying diseases, clinical signs, ECG changes, biochemical markers, and microcirculatory assessment, may optimise transfusion timing and avoid unnecessary red blood cell administration. However, further research is warranted to determine the potential benefit of integrating tissue oxygenation and microcirculatory parameters in the transfusion decision-making process.

Optimal transfusion strategies for patients with acute myocardial infarction (AMI) are uncertain. The aim of this guideline is to provide recommendations for red blood cell transfusion in patients with AMI. These guidelines are based on evidence from randomized controlled trials of patients presenting with AMI and assigned to 2 different transfusion strategies (restrictive or liberal) based on hemoglobin concentrations or hematocrit levels before receipt of a transfusion. A meta-analysis of eligible trials was performed using Cochrane methods. The international panel followed GRADE (Grading of Recommendations Assessment, Development and Evaluation) methods to summarize evidence and formulate recommendations. This guideline's primary perspective is that of the patient, including medical, financial, and psychological effects, with secondary consideration of health care system issues, particularly conservation of the limited and costly blood supply. For hospitalized patients with AMI, the panel suggests a liberal red cell transfusion strategy when the hemoglobin concentration is less than 10 g/dL (conditional recommendation, low-certainty evidence). A restrictive strategy of 7 to 8 g/dL may result in increased mortality in patients with AMI. The direction of the recommendation for the liberal strategy was based on the great importance of mortality for patients. The conditional recommendation was based on the low certainty of evidence and the competing consideration of blood supply conservation. Clinicians should adopt mitigation strategies to reduce potential adverse events associated with a liberal transfusion strategy, and all transfusion decisions should incorporate the clinical context rather than solely the hemoglobin concentration.

To determine whether a restrictive strategy of red blood cell (RBC) transfusion at lower haemoglobin concentrations is inferior to a liberal strategy of RBC transfusion at higher haemoglobin concentrations in patients undergoing cardiac surgery. We conducted a systematic review, meta-analysis, and trial sequential analysis of randomized controlled trials of the effect of restrictive and liberal RBC transfusion strategies on mortality within 30&#x2009;days of surgery as the primary outcome. Secondary outcomes were those potentially resulting from anaemia-induced tissue hypoxia and transfusion outcomes. We searched the electronic databases MEDLINE, EMBASE, and the Cochrane Library until 17 November 2017. Thirteen trials were included. The risk ratio (RR) of mortality derived from 4545 patients assigned to a restrictive strategy when compared with 4547 transfused according to a liberal strategy was 0.96 [95% confidence interval (CI) 0.76-1.21, I2&#x2009;=&#x2009;0]. A restrictive strategy did not have a statistically significant effect on the risk of myocardial infarction (RR 1.01, 95% CI 0.81-1.26; I2=0), stroke (RR 0.93, 95% CI 0.68-1.27, I2&#x2009;=&#x2009;0), renal failure (RR 0.96, 95% CI 0.76-1.20, I2&#x2009;=&#x2009;0), or infection (RR 1.12, 95% CI 0.98-1.29, I2&#x2009;=&#x2009;0). Subgroup analysis of adult and paediatric trials did not show a significant interaction. At approximately 70% of the critical information size, the meta-analysis of mortality crossed the futility boundary for inferiority of the restrictive strategy. The current evidence does not support the notion that restrictive RBC transfusion strategies are inferior to liberal RBC strategies in patients undergoing cardiac surgery.