Liberal Transfusion Thresholds Research Articles

Perioperative Transfusion Associated With Increased Morbidity and Mortality in Geriatric Patients Undergoing Hip Fracture Surgery.

Introduction:Both conservative and liberal transfusion thresholds, in regard to hematocrit and hemoglobin levels, have been widely studied with varying outcomes. The aim of this study was to evaluate if transfusion administered peri- (anytime during the admission), pre-, intra-, or postoperatively an its association with morbidity and mortality in the geriatric population undergoing hip surgery.Methods:This study was an institutional review board approved retrospective analysis of data collected from 841 patients at a single urban institution who underwent surgical repairs for hip fractures from 2008 to 2010.Results:Our analysis included data from 841 surgical patients. Mean patient age was 83, 74% were female, 48% received spinal anesthesia while 52% underwent general anesthesia. Out of 841 patients, 425 were transfused during the perioperative period. Most transfusions occurred postoperatively. Perioperative, intraoperative and postoperative transfusion was associated with an increase in post-operative AKI. Intraoperative blood transfusion was associated with an increase in morbidity (11.6% increased to 22.2%) by 1.9 fold, AKI (3.9% increased to 11.1%) by 2.8 fold, as well as an increase in mortality (5.2 increased to 15.6%) within 60 days by 3 fold.Conclusions:This may suggest that patients transfused prior to surgery, despite having met a specific trigger hemoglobin level earlier, may have been treated before deteriorating to a point that would cause future systemic implications.

Effects of Liberal vs Restrictive Transfusion Thresholds on Survival and Neurocognitive Outcomes in Extremely Low-Birth-Weight Infants

Red blood cell transfusions are commonly administered to infants weighing less than 1000 g at birth. Evidence-based transfusion thresholds have not been established. Previous studies have suggested higher rates of cognitive impairment with restrictive transfusion thresholds. To compare the effect of liberal vs restrictive red blood cell transfusion strategies on death or disability. Randomized clinical trial conducted in 36 level III/IV neonatal intensive care units in Europe among 1013 infants with birth weights of 400 g to 999 g at less than 72 hours after birth; enrollment took place between July 14, 2011, and November 14, 2014, and follow-up was completed by January 15, 2018. Infants were randomly assigned to liberal (n = 492) or restrictive (n = 521) red blood cell transfusion thresholds based on infants' postnatal age and current health state. The primary outcome, measured at 24 months of corrected age, was death or disability, defined as any of cognitive deficit, cerebral palsy, or severe visual or hearing impairment. Secondary outcome measures included individual components of the primary outcome, complications of prematurity, and growth. Among 1013 patients randomized (median gestational age at birth, 26.3 [interquartile range {IQR}, 24.9-27.6] weeks; 509 [50.2%] females), 928 (91.6%) completed the trial. Among infants in the liberal vs restrictive transfusion thresholds groups, respectively, incidence of any transfusion was 400/492 (81.3%) vs 315/521 (60.5%); median volume transfused was 40 mL (IQR, 16-73 mL) vs 19 mL (IQR, 0-46 mL); and weekly mean hematocrit was 3 percentage points higher with liberal thresholds. Among infants in the liberal vs restrictive thresholds groups, the primary outcome occurred in 200/450 (44.4%) vs 205/478 (42.9%), respectively, for a difference of 1.6% (95% CI, -4.8% to 7.9%; P = .72). Death by 24 months occurred in 38/460 (8.3%) vs 44/491 (9.0%), for a difference of -0.7% (95% CI, -4.3% to 2.9%; P = .70), cognitive deficit was observed in 154/410 (37.6%) vs 148/430 (34.4%), for a difference of 3.2% (95% CI, -3.3% to 9.6%; P = .47), and cerebral palsy occurred in 18/419 (4.3%) vs 25/443 (5.6%), for a difference of -1.3% (95% CI, -4.2% to 1.5%; P = .37), in the liberal vs the restrictive thresholds groups, respectively. In the liberal vs restrictive thresholds groups, necrotizing enterocolitis requiring surgical intervention occurred in 20/492 (4.1%) vs 28/518 (5.4%); bronchopulmonary dysplasia occurred in 130/458 (28.4%) vs 126/485 (26.0%); and treatment for retinopathy of prematurity was required in 41/472 (8.7%) vs 38/492 (7.7%). Growth at follow-up was also not significantly different between groups. Among infants with birth weights of less than 1000 g, a strategy of liberal blood transfusions compared with restrictive transfusions did not reduce the likelihood of death or disability at 24 months of corrected age. ClinicalTrials.gov Identifier: NCT01393496.

Changes to hepatic tissue oxygenation, abdominal perfusion and its association with enteral feeding with liberal transfusion threshold in anaemic preterm infants: A prospective cohort study.

In anaemic preterm infants who receive packed red blood cell (PRBC) transfusions, changes to mesenteric tissue oxygenation and perfusion have been reported using a restrictive haemoglobin (Hb)-based threshold. We aimed to investigate changes to hepatic tissue oxygenation and abdominal blood flow after PRBC transfusion and its association with enteral feeding using a liberal Hb threshold (as shown inTable1). [Table: see text] MATERIAL AND METHODS: We prospectively studied a cohort of preterm infants born at < 32 weeks' gestation who received at least one PRBC transfusion and monitored them immediately before (Time 1), immediately after (Time 2) and 24hours after transfusion (Time 3). Data obtained included physiological parameters, the hepatic tissue oxygenation index and pulsed Doppler ultrasound measurements in the abdominal arterial circulation. Additionally, the effects of withholding enteral feeds were investigated. We monitored 50 PRBC transfusion episodes in 40 preterm infants, in whom the mean gestational age was 26.72 weeks (±1.6weeks) and the mean birth weight was 855.25g (±190.7g). We observed significant changes to pulsed Doppler measurements in abdominal arterial circulation (coeliac artery mean peak systolic velocity Time 2 [75.08 cm/sec] versus Time 3 [71.13 cm/sec]; mean end-diastolic velocity Time 2 [15.71 cm/sec] versus Time 3 [13.76 cm/sec]; mean resistive index Time 2 0.78 versus Time 3 0.80, right renal artery mean peak systolic velocity Time 1 58.28 cm/sec versus Time 2 50.97 cm/sec, left renal artery mean peak systolic velocity Time 1 49.20 cm/sec versus Time 2 45.40 cm/sec), but not to hepatic tissue oxygenation after PRBC transfusion (Time 1 mean 53.66 [SD, 13.34]; Time 2 mean 54.93 [SD, 9.3]; Time 3 mean 55.64 [SD, 12.86]). There were no changes to hepatic tissue oxygenation or mesenteric blood flow from withholding enteral feeds during PRBC transfusion. There were no local adverse effects from hepatic tissue oxygenation monitoring. In mildly anaemic preterm infants, when allowing a liberal Hb threshold-based trigger for PRBC transfusion, changes in abdominal arterial circulation were present, but not in hepatic tissue oxygenation. Withholding enteral feeds during PRBC transfusion had no impact on hepatic tissue oxygenation or mesenteric flows.

Sublingual microcirculation does not reflect red blood cell transfusion thresholds in the intensive care unit\u2014a prospective observational study in the intensive care unit

PurposeHemoglobin (Hb) transfusion thresholds are established in intensive care units. A restrictive transfusion threshold (Hb 70–75 g/l) is recommended in septic patients, and a liberal transfusion threshold (Hb 90 g/l) for cardiogenic shock. It is unclear whether these historically adopted transfusion thresholds meet the challenges of individual patients.MethodsWe evaluated microvascular flow index (MFI) and proportion of perfused vessels (PPV) in the sublingual microcirculation with CytoCam-IDF microscopy and near-infrared spectroscopy (NIRS). A study team-independent, treating intensivist assigned a total of 64 patients to 1 of 2 two transfusion thresholds, 43 patients to the Hb 75 g/l threshold and 21 patients to the Hb 90 g/l threshold, at a surgical intensive care unit. We performed microcirculatory measurements 1 h before and 1 h after transfusion of 1 unit of red blood cells.ResultsMicrocirculatory flow variables correlated negatively with pre-transfusion flow variables (ΔMFI: ρ = − 0.821, p < 0.001; ΔPPV: ρ = − 0.778, p < 0.001). Patients with good initial microcirculation (cutoffs: MFI > 2.84, PPV > 88%) showed a deteriorated microcirculation after red blood cell transfusion. An impaired microcirculation improved after transfusion. At both transfusion thresholds, approximately one third of the patients showed an initially impaired microcirculation. In contrast, one third in every group had good microcirculation above the cutoff variables and did not profit from the transfusion.ConclusionThe data suggest that the established transfusion thresholds and other hemodynamic variables do not reflect microcirculatory perfusion of patients. Blood transfusion at both thresholds 75 g/l and 90 g/l hemoglobin can either improve or harm the microcirculatory blood flow, questioning the concept of arbitrary transfusion thresholds.

Long-term outcome of brain structure in female preterm infants: possible associations of liberal versus restrictive red blood cell transfusions

Background Preterm infants who receive differential red blood cell (RBC) transfusions at birth may show brain structure differences across development, including abnormalities in white matter (WM) structure and organization. This study investigated long-term outcomes of brain structure in female infants born preterm, at an average age of 13 years old, who received red blood cell (RBC) transfusions in the neonatal period according to a liberal or restrictive approach. Results from this study will increase understanding of the effects of transfusion on the developing brain. Study design and methods This follow-up study included female preterm infants who participated in a clinical trial and had been randomized at birth to either a liberal or restrictive hematocrit threshold. Brain structures were measured in childhood using structural magnetic resonance imaging (MRI) scans. Due to the low number of females in the restrictive transfusion group at follow-up, additional females were recruited for inclusion. Main outcome measures included cerebral and subcortical brain region volumes. Results Total intracranial volume was significantly decreased in females who were randomized to higher average hematocrit levels at birth. Infants in the liberal transfusion group had proportionately smaller volumes in all measures of regional cerebral WM and subcortical brain volumes, reaching significance for temporal lobe WM and caudate volumes. Conclusion Female premature infants who received a liberal transfusion threshold at birth had decreased WM volumes, which suggests the potential long-term neurodevelopmental risks associated with liberal transfusion practices.

Restrictive versus liberal strategy for red blood-cell transfusion in hip fracture patients: A systematic review and meta-analysis.

Background:Most clinical guidelines recommend a restrictive red-blood-cell (RBC) transfusion threshold. However, indications for transfusion in patients with a hip fracture have not been definitively evaluated or remain controversial. We compared the pros and cons of restrictive versus liberal transfusion strategies in patients undergoing hip fracture surgery.Methods:Electronic databases were searched to identify randomized controlled trials (RCTs) and retrospective cohort studies (RCSs) to investigate the effects of a restrictive strategy versus its liberal counterpart in patients undergoing hip fracture surgery. The main clinical outcomes included delirium, mortality, infections, cardiogenic complications, thromboembolic events, cerebrovascular accidents, and length of hospital stay. The meta-analysis program of the Cochrane Collaboration (RevMan version 5.3.0) was used for data analysis. Statistical heterogeneity was assessed by both Cochran chi-squared test (Q test) and I2 test. Both Begg and Egger tests were used to assess potential publication bias.Results:We identified 7 eligible RCTs and 2 eligible RCSs, involving 3,575 patients in total. In patients undergoing hip fracture surgery, we found no differences in frequency of delirium, mortality, the incidence rates of all infections, pneumonia, wound infection, all cardiovascular events, congestive heart failure, thromboembolic events or length of hospital stay between restrictive and liberal thresholds for RBC transfusion (P >.05). However, we found that the use of restrictive transfusion thresholds is associated with higher rates of acute coronary syndrome (P <.05) while liberal transfusion thresholds increase the risk of cerebrovascular accidents (P <.05).Conclusion:In patients undergoing hip fracture surgery, clinicians should evaluate the patient's condition in detail and adopt different transfusion strategies according to the patient's specific situation rather than merely using a certain transfusion strategy.

Review of available evidence supporting different transfusion thresholds in different patient groups with anemia

In patients with anemia, transfusion of red blood cells (RBCs) can save lives and improve quality of life. The choice to transfuse should be cautiously made owing to risks of transfusion, economic costs, and limitations on the blood supply. Until the 1980s, the decision for RBC transfusion was guided by Hb threshold, with the aim of maintaining the patient's blood Hb level over 100 grams per liter. Since then, multiple randomized controlled trials and key systematic reviews have provided evidence-based guidelines as to appropriate transfusion thresholds in a number of clinical settings. Here, we aimed to address the outcome of defining different anemia criteria in specific clinical populations exclusively on the basis of the need for RBC transfusion based on Hb concentration. We focused on the patient populations, where there were the most available data on differing transfusion thresholds, which looked at transfusing to a higher or liberal transfusion threshold in comparison with a lower or restrictive transfusion threshold. These included patients in intensive care with or without septic shock, hip fracture surgery, cardiovascular surgery, and upper gastrointestinal bleeding, the pediatric population, and also those with malaria, by reviewing key randomized controlled trials and systematic reviews. Twenty-four randomized controlled studies and 12 systematic reviews have been included, and these are discussed below.

44 Inhalation Injury Does Not Increase Blood Transfusion Requirements Following Burn Injury in Adults

Patients with major burns receive numerous red blood cell (RBC) transfusions for many indications, but it is not known whether an accompanying inhalation injury (INHI) influences the amount of blood transfused. The purpose of this study was to examine the effect of INHI on RBC transfusion in burned adults. This was a secondary analysis of a multi-center prospective randomized controlled trial that compared a liberal and restrictive blood transfusion threshold in adults with burns ≥ 20% TBSA. We compared 25 response variables between patients with and without INHI but here focus on the total number of RBC transfusions per patient (nRBC), the number of RBC transfusions per day (RBC/day), and the number of RBC transfusions/%TBSA burn (RBC/%). Generalized estimating equations (GEE) were used to account for clustering by facility. P values for response variable tests were adjusted for multiple comparisons. Multiple regression with GEE was used to identify variables that determined RBC/day. Values are shown as mean ± SD or median [25th,75th Q] as appropriate. Of 345 patients (age 42.9 +/- 16.8 years, %TBSA burn 38.0 +/- 17.6, 20.9% female, and admission APACHE 18.4 +/- 8.1) there were 78 (23%) with INHI. The table compares patients with and without INHI. The regression found that %TBSA burn (p<0.001), age (p=0.004), and requiring at least one day of mechanical ventilation(MV) (p < 0.0001) were significant determinants of RBC/day whereas INHI (p=0.251), and presence of at least one blood stream infection (p=0.107) were not. While patients with INHI tended to get more blood transfusions, this appears to have been determined by burn extent and requiring MV rather than the INHI itself. Presence of an INHI does not independently increase the need for RBC transfusions following a major burn injury. Table a P-values were not adjusted for multiple testing. Table a P-values were not adjusted for multiple testing.

Red blood cell transfusion threshold after pediatric cardiac surgery: A systematic review and meta-analysis.

Background:Restrictive red blood cell transfusion strategy is implemented to minimize risk following allogeneic blood transfusion in adult cardiac surgery. However, it is still unclear if it can be applied to pediatric cardiac patients. The purpose of this systematic review and meta-analysis was to determine the effect of postoperative restrictive transfusion thresholds on clinical outcomes based on up-to-date results of randomized controlled trials (RCTs) and observational studies in pediatric cardiac surgery.Method:We searched for RCTs and observational studies in the following databases: the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and ClinicalTrials.gov from their inception to October 26, 2017. We also searched reference lists of published guidelines, reviews, and relevant articles, as well as conference proceedings. No language restrictions were applied and no observational study met the inclusion criteria.Results:Four RCTs on cardiac surgery involving 454 patients were included. There were no differences in the pooled fixed effects of intensive care unit (ICU) stay between the liberal and restrictive transfusion thresholds (standardized mean difference SMD, 0.007; 95% confidence interval CI, −0.18–0.19; P = .94). There were also no differences in the length of hospital stay (SMD, −0.062; 95% CI, −0.28−0.15; P = .57), ventilation duration (SMD, −0.015; 95% CI, −0.25–0.22; P = .90), mean arterial lactate level (SMD, 0.071; 95% CI, −0.22–0.36; P = .63), and mortality (risk ratio, 0.49; 95% CI, 0.13–1.94; P = .31). There was no inter-trial heterogeneity for any pooled analysis. Publication bias was tested using Egger, Begg, or the trim-and-fill test, and the results indicated no significant publication bias.Conclusion:Evidence from RCTs in pediatric cardiac surgery, though limited, showed non-inferiority of restrictive thresholds over liberal thresholds in length of ICU stay and other outcomes following red blood cell transfusion. Further high-quality RCTs are necessary to confirm the findings.

How current transfusion practices in geriatric patients with hip fracture still differ from current guidelines and the effects on outcome: A retrospective observational study.

Transfusion guidelines have become increasingly restrictive. We investigated actual transfusion practices in geriatric hip fracture patients, why they differ from current guidelines and how this affects outcome. The primary aim was to examine transfusion timing, evaluate how many red blood cell (RBC) transfusions are in keeping with guidelines and how this affects morbidity (infection, cardiac events and delirium), mortality and length of stay (LOS). Our secondary aim was to test the hypothesis that guidelines were more likely to be deviated from shortly before discharge and with consecutive transfusions. A retrospective observational study. The Luzerner Kantonsspital, a major trauma centre, over a 12-month period from 1 February 2015 to 31 January 2016. All patients over 70 years of age admitted to the Luzerner Kantonsspital with hip fractures over a 12-month period in 2015 to 2016 were included. 156 patients were included, to which 141 units of RBCs were transfused. All pre and intra-operative transfusions were according to guidelines; 110 transfusions were postoperative and 37 of these were not according to guidelines. Patients who were transfused had longer LOS in hospital (P = 0.002) and an odds ratio (OR) of 2.7 of contracting an infection (P = 0.04) in comparison with patients who were not transfused. No significant differences in mortality, LOS or morbidity were found between patients transfused according to guidelines and more liberal thresholds. Guidelines were more likely to be deviated from within the last 2 days before discharge than prior to this (58 vs. 24%, P = 0.03). Furthermore, 24 stable patients received two consecutive RBC units resulting in posttransfusion haemoglobin values of between 83 and 124 g l. Most RBC transfusions occur postoperatively, many still according to liberal transfusion thresholds, in particular shortly before discharge and as part of consecutive transfusions. Transfused patients had longer LOS and more infections than patients not transfused, but there was no difference in mortality, LOS or morbidity between patients transfused according to current guidelines and those where guidelines were deviated from.

Introduction of national guidelines for restrictive blood transfusion threshold for hip fracture patients\u2013\u2013a consecutive cohort study based on complete follow-up in national databases

BackgroundRandomized controlled trials have demonstrated that a restrictive red blood cell (RBC) transfusion strategy lowers transfusion frequency without affecting mortality. However, the external validity of these trials has not been tested in a large cohort. The purpose was to estimate the effect of introducing a National Clinical Guideline (NCG) for a restrictive hemoglobin transfusion threshold on transfusion frequency and mortality in hip fracture patients > 65 years old.MethodsA consecutive cohort study of hip fracture patients > 65 years old residing in the southern region of Denmark was conducted using prospectively gathered data from registers during two separate 1-year time periods. The first period from October 1, 2012, to September 30, 2013, included 1494 patients and used a liberal transfusion threshold, whereas the second period from October 1, 2015, to September 30, 2016, including 1414 participants used a restrictive threshold from the NCG. Participant data for age, sex, body mass index, Charlson Comorbidity Index, time to surgery, and death were retrieved from the Danish Interdisciplinary Registry of Hip Fractures and were merged with RBC transfusion and medication data extracted from the Danish Transfusion and Odense Pharmacoepidemiological Databases, respectively. Cox proportional hazards models were used to test relative mortality risk for the restrictive group compared with the liberal group at 30 and 90 days.ResultsOverall RBC transfusions decreased from 42 to 30% (p < 0.001). The 30-day mortality rate (95% CI) was 9% (8;11) in the restrictive group and 13% (11;14) in the liberal group (p < 0.008), whereas the adjusted relative mortality risk was 0.72 (0.57;0.91). The 90-day mortality rate was 15% (13;17) in the restrictive group and 19% (17;21) in the liberal group, whereas the adjusted relative mortality risk was 0.78 (0.65;0.94).ConclusionThese data suggest that the introduction of an NCG on restrictive blood transfusion leads to lower transfusion frequency in hip fracture patients > 65 years old. Even though this reduction is associated with decreased mortality at both 30 and 90 days, it may be explained by other issues than restrictive transfusion strategy. There has been an improvement in the mortality of hip fracture patients in Denmark, and we suggest that a restrictive transfusion strategy does not lead to increased mortality.

5 Does the Storage Age of Blood Transfused to Burn Patients Matter?

Patients with major burns require multiple red blood cell (RBC) transfusions. Blood banks store blood up to 42 days and issue the oldest blood 1st to avoid wasting blood. Longer storage leads to potentially unfavourable degenerative changes in a RBC unit but it is not known if this has any important effects when this blood is transfused to an immunosuppressed burn patient. The purpose of this study was to determine if the storage age of transfused blood affects outcomes in burn patients. Data on storage age of transfused RBCs was collected in a multi-center prospective randomized controlled trial involving 345 patients that compared a liberal and restrictive transfusion threshold. The mean storage age of all blood transfused to each patient (AgeRBC) and the proportion of “very-old” transfused units stored ≥ 35 days (Prop35) were the measures of blood storage age. Outcomes were severity of multiple organ dysfunction, time to wound healing, duration of ventilation (DurVent), and mortality. Multivariate regression analyses adjusting for patient age, sex, burn size, inhalation injury, admission APACHE score, and number of RBC units transfused was performed. Values are shown as median [25th,75th Q] unless otherwise noted. A total of 303 subjects received ≥ 1 RBC transfusion (age 42 [30, 55.5] years, TBSA burn 33% [26, 48.5], 23.1% female, 22.8% with inhalation injury, admission APACHE 18 [13, 24]). These subjects received 13 [6, 27] RBC units (mean 23.4 ± 31.2, range 1–219). Of the 6768 RBC transfusions available for analysis the overall storage age was 26 [17,42] days (mean 25.6 ± 10.2 days). The proportion of RBC units ≥ 35 days old was 24%. Only 225 RBC units (3.3%) were “very fresh” (≤ 8 days old). AgeRBC was not significantly related to the number of transfusions in each patient. Blood transfused in the operating room (30.5% of all transfusions) had a significantly lower Prop35 than blood given in the burn unit (p<0.0001). Severity of multiple organ dysfunction, time to wound healing, 30-day mortality, and in-hospital mortality were not significantly related to either AgeRBC or Prop35. However, DurVent (n=165 transfused while ventilated) was significantly related to the number of RBC transfusions as well as AgeRBC (p=0.02) and Prop35 (p=0.01). The storage age of blood transfused to patients with major burns does not appear to have any clinically meaningful effect on multiple organ dysfunction, time to wound healing, or survival. Although statistically significant, the relationships between DurVent and AgeRBC and Prop35 were weak and investigation in a larger sample would be needed to clarify any interaction between use of older blood and longer mechanical ventilation. Presently, transfusion of “fresher” or “younger”blood in burn patients is not warranted.

Evidence-Based Red Blood Cell Transfusion Practices in Cardiac Surgery.

Cardiac surgical patients are among the highest consumers of allogeneic red blood cells (RBCs) due to the prevalence of anemia and bleeding. Up until recently, there was a paucity of high-quality evidence informing transfusion decisions in this patient group which led to wide variability in transfusion decision making. The article reviews and critically analyzes the available evidence for RBC transfusion in cardiac surgery, focusing on trials of transfusion triggers and age of blood, and provides suggestions for future research. Observational studies analyzing outcomes in patients transfused vs those not transfused have consistently shown RBC transfusion to be associated with adverse outcomes. However, multiple sources of bias in these studies invalidate their conclusions. The best available evidence comes from randomized controlled trials which compare liberal vs restrictive transfusion thresholds. To date, 6 randomized controlled trials have been reported in cardiac surgical patients, and pooled analyses have shown no differences in clinical outcomes between the 2 strategies. Similarly, research into age of RBCs and adverse outcomes has failed to demonstrate a pathological effect attributable to the storage lesion; the recent multicenter Red Cell Storage Duration Study (RECESS) trial has demonstrated no difference in outcomes between patients receiving fresh or old RBCs. Future research needs to identify what a safe transfusion threshold may be, and how this differs for different patient groups and different stages of the perioperative journey. There is also a need to evaluate other physiological parameters which, coupled with hemoglobin concentration, can better inform those patients who need an RBC transfusion.

Guidelines on transfusion for fetuses, neonates and older children.

Guidelines on transfusion for fetuses, neonates and older children.

Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion.

There is considerable uncertainty regarding the optimal haemoglobin threshold for the use of red blood cell (RBC) transfusions in anaemic patients. Blood is a scarce resource, and in some countries, transfusions are less safe than others because of a lack of testing for viral pathogens. Therefore, reducing the number and volume of transfusions would benefit patients. The aim of this review was to compare 30-day mortality and other clinical outcomes in participants randomized to restrictive versus liberal red blood cell (RBC) transfusion thresholds (triggers) for all conditions. The restrictive transfusion threshold uses a lower haemoglobin level to trigger transfusion (most commonly 7 g/dL or 8 g/dL), and the liberal transfusion threshold uses a higher haemoglobin level to trigger transfusion (most commonly 9 g/dL to 10 g/dL). We identified trials by searching CENTRAL (2016, Issue 4), MEDLINE (1946 to May 2016), Embase (1974 to May 2016), the Transfusion Evidence Library (1950 to May 2016), the Web of Science Conference Proceedings Citation Index (1990 to May 2016), and ongoing trial registries (27 May 2016). We also checked reference lists of other published reviews and relevant papers to identify any additional trials. We included randomized trials where intervention groups were assigned on the basis of a clear transfusion 'trigger', described as a haemoglobin (Hb) or haematocrit (Hct) level below which a red blood cell (RBC) transfusion was to be administered. We pooled risk ratios of clinical outcomes across trials using a random-effects model. Two people extracted the data and assessed the risk of bias. We conducted predefined analyses by clinical subgroups. We defined participants randomly allocated to the lower transfusion threshold as 'restrictive transfusion' and to the higher transfusion threshold as 'liberal transfusion'. A total of 31 trials, involving 12,587 participants, across a range of clinical specialities (e.g. surgery, critical care) met the eligibility criteria. The trial interventions were split fairly equally with regard to the haemoglobin concentration used to define the restrictive transfusion group. About half of them used a 7 g/dL threshold, and the other half used a restrictive transfusion threshold of 8 g/dL to 9 g/dL. The trials were generally at low risk of bias .Some items of methodological quality were unclear, including definitions and blinding for secondary outcomes.Restrictive transfusion strategies reduced the risk of receiving a RBC transfusion by 43% across a broad range of clinical specialties (risk ratio (RR) 0.57, 95% confidence interval (CI) 0.49 to 0.65; 12,587 participants, 31 trials; high-quality evidence), with a large amount of heterogeneity between trials (I² = 97%). Overall, restrictive transfusion strategies did not increase or decrease the risk of 30-day mortality compared with liberal transfusion strategies (RR 0.97, 95% CI 0.81 to 1.16, I² = 37%; N = 10,537; 23 trials; moderate-quality evidence) or any of the other outcomes assessed (i.e. cardiac events (low-quality evidence), myocardial infarction, stroke, thromboembolism (high-quality evidence)). Liberal transfusion did not affect the risk of infection (pneumonia, wound, or bacteraemia). Transfusing at a restrictive haemoglobin concentration of between 7 g/dL to 8 g/dL decreased the proportion of participants exposed to RBC transfusion by 43% across a broad range of clinical specialities. There was no evidence that a restrictive transfusion strategy impacts 30-day mortality or morbidity (i.e. mortality at other points, cardiac events, myocardial infarction, stroke, pneumonia, thromboembolism, infection) compared with a liberal transfusion strategy. There were insufficient data to inform the safety of transfusion policies in certain clinical subgroups, including acute coronary syndrome, myocardial infarction, neurological injury/traumatic brain injury, acute neurological disorders, stroke, thrombocytopenia, cancer, haematological malignancies, and bone marrow failure. The findings provide good evidence that transfusions with allogeneic RBCs can be avoided in most patients with haemoglobin thresholds above 7 g/dL to 8 g/dL.

Restrictive vs. Liberal Transfusion: A Meta-Analysis Based on Clinical Context

Some randomized trials have shown that so-called “restrictive” blood transfusion (i.e., allowing hemoglobin level to drop to <7 or <8 g/dL before transfusing) can lower transfusion rates safely. However, the effect of withholding blood transfusion might vary, depending on clinical context. In this meta-analysis, researchers identified 27 randomized trials in which restrictive and liberal blood transfusion thresholds were compared in …

Red blood cell transfusion triggers in acute leukemia: a randomized pilot study.

Red blood cell (RBC) transfusion thresholds have yet to be examined in large randomized trials in hematologic malignancies. This pilot study in acute leukemia uses a restrictive compared to a liberal transfusion strategy. A randomized (2:1) study was conducted of restrictive (LOW) hemoglobin (Hb) trigger (7 g/dL) compared to higher (HIGH) Hb trigger (8 g/dL). The primary outcome was feasibility of conducting a larger trial. The four requirements for success required that more than 50% of the eligible patients could be consented, more than 75% of the patients randomized to the LOW arm tolerated the transfusion trigger, fewer than 15% of patients crossed over from the LOW arm to the HIGH arm, and no indication for the need to pause the study for safety concerns. Secondary outcomes included fatigue, bleeding, and RBCs and platelets transfused. Ninety patients were consented and randomly assigned to LOW to HIGH. The four criteria for the primary objective of feasibility were met. When the number of units transfused was compared, adjusting for baseline Hb, the LOW arm was transfused on average 8.0 (95% confidence interval [CI], 6.9-9.1) units/patient while the HIGH arm received 11.7 (95% CI, 10.1-13.2) units (p = 0.0003). There was no significant difference in bleeding events or neutropenic fevers between study arms. This study establishes feasibility for trial of Hb thresholds in leukemia through demonstration of success in all primary outcome metrics and a favorable safety profile. This population requires further study to evaluate the equivalence of liberal and restrictive transfusion thresholds in this unique clinical setting.

Effect of restrictive versus liberal transfusion strategies on outcomes in patients with cardiovascular disease in a non-cardiac surgery setting: systematic review and meta-analysis

Objective To compare patient outcomes of restrictive versus liberal blood transfusion strategies in patients with cardiovascular disease not undergoing cardiac surgery. Design Systematic review and meta-analysis. Data sources Randomised controlled...

Blood Transfusion and 30-Day Mortality in Patients With Coronary Artery Disease and Anemia Following Noncardiac Surgery.

Although liberal blood transfusion thresholds have not been beneficial following noncardiac surgery, it is unclear whether higher thresholds are appropriate for patients who develop postoperative myocardial infarction (MI). To evaluate the association between postoperative blood transfusion and mortality in patients with coronary artery disease and postoperative MI following noncardiac surgery. Retrospective cohort study involving Veterans Affairs facilities from January 1, 2000, to December 31, 2012. A total of 7361 patients with coronary artery disease who underwent inpatient noncardiac surgery and had a nadir postoperative hematocrit between 20% and 30%. Patients with significant bleeding, including any preoperative blood transfusion or transfusion of greater than 4 units during the intraoperative or postoperative setting, were excluded. Mortality rates were compared using both logistic regression and propensity score matching. Patients were stratified by postoperative nadir hematocrit and the presence of postoperative MI. Initial postoperative blood transfusion. The 30-day postoperative mortality rate. Of the 7361 patients, 2027 patients (27.5%) received at least 1 postoperative blood transfusion. Postoperative mortality occurred in 267 (3.6%), and MI occurred in 271 (3.7%). Among the 5334 patients without postoperative blood transfusion, lower nadir hematocrit was associated with an increased risk for mortality (hematocrit of 20% to <24%: 7.3%; 24% to <27%: 3.7%; and 27% to 30%: 1.6%; P < .01). In patients with postoperative MI, blood transfusion was associated with lower mortality, for those with hematocrit of 20% to 24% (odds ratio, 0.28; 95% CI, 0.13-0.64). In patients without postoperative MI, transfusion was associated with significantly higher mortality for those with hematocrit of 27% to 30% (odds ratio, 3.21; 95% CI, 1.85-5.60). These findings support a restrictive postoperative transfusion strategy in patients with stable coronary artery disease following noncardiac surgery. However, interventional studies are needed to evaluate the use of a more liberal transfusion strategy in patients who develop postoperative MI.

Indications for red blood cell transfusion in cardiac surgery: a systematic review and meta-analysis

Good blood management is an important determinant of outcome in cardiac surgery. Guidelines recommend restrictive red blood cell transfusion. Our objective was to systematically review the evidence from randomised controlled trials and observational studies that are used to inform transfusion decisions in adult cardiac surgery. We did a systematic review by searching PubMed, Embase, Cochrane Library, and DARE, from inception to May 1, 2015, databases from specialist societies, and bibliographies of included studies and recent relevant review articles. We included randomised controlled trials that assessed the effect of liberal versus restrictive red blood cell transfusion in patients undergoing cardiac and non-cardiac surgery, and observational studies that assessed the effect of red blood cell transfusion compared with no transfusion on outcomes in adult cardiac patients after surgery. We pooled adjusted odds ratios using fixed-effects and random-effects meta-analyses. The primary outcome was 30-day mortality. We included data from six cardiac surgical randomised controlled trials (3352 patients), 19 non-cardiac surgical trials (8361 patients), and 39 observational studies (232,806 patients). The pooled fixed effects mortality odds ratios comparing liberal versus restrictive transfusion thresholds was 0.70 (95% CI 0.49-1.02; p=0.060) for cardiac surgical trials and 1.10 (95% CI 0.96-1.27; p=0.16) for trials in settings other than cardiac surgery. By contrast, observational cohort studies in cardiac surgery showed that red blood cell transfusion compared with no transfusion was associated with substantially higher mortality (random effects odds ratio 2.72, 95% CI 2.11-3.49; p<0.0001) and other morbidity, although with substantial heterogeneity and small study effects. Evidence from randomised controlled trials in cardiac surgery refutes findings from observational studies that liberal thresholds for red blood cell transfusion are associated with a substantially increased risk of mortality and morbidity. Observational studies and trials in non-cardiac surgery should not be used to inform treatment decisions or guidelines for patients having cardiac surgery. None.