Restrictive Red Blood Cell Transfusion Research Articles

The restrictive red blood cell transfusion strategy for critically injured patients: RESTRIC trial

The restrictive red blood cell transfusion strategy for critically injured patients: RESTRIC trial

Review article: Upper gastrointestinal bleeding - review of current evidence and implications for management.

Acute upper gastrointestinal bleeding (UGIB) is a common emergency requiring hospital-based care. Advances in care across pre-endoscopic, endoscopic and post-endoscopic phases have led to improvements in clinical outcomes. To provide a detailed, evidence-based update on major aspects of care across pre-endoscopic, endoscopic and post-endoscopic phases. We performed a structured bibliographic database search for each topic. If a recent high-quality meta-analysis was not available, we performed a meta-analysis with random effects methods and odds ratios with 95% confidence intervals. Pre-endoscopic management of UGIB includes risk stratification, a restrictive red blood cell transfusion policy unless the patient has cardiovascular disease, and pharmacologic therapy with erythromycin and a proton pump inhibitor. Patients with cirrhosis should be treated with prophylactic antibiotics and vasoactive medications. Tranexamic acid should not be used. Endoscopic management of UGIB depends on the aetiology. For peptic ulcer disease (PUD) with high-risk stigmata, endoscopic therapy, including over-the-scope clips (OTSCs) and TC-325 powder spray, should be performed. For variceal bleeding, treatment should be customised by severity and anatomic location. Post-endoscopic management includes early enteral feeding for all UGIB patients. For high-risk PUD, PPI should be continued for 72 h, and rebleeding should initially be evaluated with a repeat endoscopy. For variceal bleeding, high-risk patients or those with further bleeding, a transjugular intrahepatic portosystemic shunt can be considered. Management of acute UGIB should include treatment plans for pre-endoscopic, endoscopic and post-endoscopic phases of care, and customise treatment decisions based on aetiology and severity of bleeding.

Red blood cell transfusion in neurocritical patients: a systematic review and meta-analysis

BackgroundAnemia can lead to secondary brain damage by reducing arterial oxygen content and brain oxygen supply. Patients with acute brain injury have impaired self-regulation. Brain hypoxia may also occur even in mild anemia. Red blood cell (RBC) transfusion is associated with increased postoperative complications, poor neurological recovery, and mortality in critically ill neurologic patients. Balancing the risks of anemia and red blood cell transfusion-associated adverse effects is challenging in neurocritical settings.MethodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and MEDLINE (PubMed) from inception to January 31, 2024. We included all randomized controlled trials (RCTs) assessing liberal versus restrictive RBC transfusion strategies in neurocritical patients. We included all relevant studies published in English. The primary outcome was mortality at intensive care unit (ICU), discharge, and six months.ResultsOf 5195 records retrieved, 84 full-text articles were reviewed, and five eligible studies were included. There was no significant difference between the restrictive and liberal transfusion groups in ICU mortality (RR: 2.53, 95% CI: 0.53 to 12.13), in-hospital mortality (RR: 2.34, 95% CI: 0.50 to 11.00), mortality at six months (RR: 1.42, 95% CI: 0.42 to 4.78) and long-term mortality (RR: 1.22, 95% CI: 0.64 to 2.33). The occurrence of neurological adverse events and most major non-neurological complications was similar in the two groups. The incidence of deep venous thrombosis was lower in the restrictive strategy group (RR: 0.41, 95% CI: 0.18 to 0.91).ConclusionsDue to the small sample size of current studies, the evidence is insufficiently robust to confirm definitive conclusions for neurocritical patients. Therefore, further investigation is encouraged to define appropriate RBC transfusion thresholds in the neurocritical setting.

Adherence to a restrictive red blood cell transfusion strategy in critically ill patients: An observational study.

Randomized controlled trials relatively consistently show that restrictive red blood cell (RBC) transfusion strategies are safe and associated with similar outcomes compared to liberal transfusion strategies in critically ill patients. Based on these data, the general threshold for RBC transfusion was changed to 70 g/L at a 9-bed tertiary level intensive care unit in September 2020. Implementation measures included lectures, webinars and feedback during clinical practice. The aim of this study was to investigate how implementation of a restrictive transfusion strategy influenced RBC usage, haemoglobin trigger levels and adherence to prescribed trigger levels. In this registry-based, observational study, critically ill adult patients without massive bleeding were included and divided into a pre-cohort, with admissions prior to the change of transfusion strategy, and a post-cohort, with admissions following the change of transfusion strategy. These cohorts were compared regarding key RBC transfusion-related variables. In total 5626 admissions were included in the analyses (pre-cohort n = 4373, post-cohort n = 1253). The median volume (interquartile range, IQR) of RBC transfusions per 100 admission days, in the pre-cohort was 6120 (4110-8110) mL versus 3010 (2890-4970) mL in the post-cohort (p < .001). This corresponds to an estimated median saving of 1128 € per 100 admission days after a restrictive RBC transfusion strategy was implemented. In total, 26% of the admissions in the pre-cohort and 19% in the post-cohort (p < .001) received RBC transfusion(s) during days 0-10. Both median (IQR) prescribed trigger levels (determined by intensivist) and actual haemoglobin trigger levels (i.e., levels prior to actual administration of transfusion) were higher in the pre- versus post-cohort (90 [80-100] vs. 80 [72-90] g/L, p < .001 and 89 [82-96] g/L vs. 83 [79-94], p < .001, respectively). Percentage of days without compliance with the prescribed transfusion trigger was higher in the pre-cohort than in the post-cohort (23% vs. 14%, p < .001). Sensitivity analyses, excluding patients with traumatic brain injury, ischemic heart disease and COVID-19 demonstrated similar results. Implementation of a restrictive transfusion trigger in a critical care setting resulted in lasting decreased RBC transfusion use and costs, decreased prescribed and actual haemoglobin trigger levels and improved adherence to prescribed haemoglobin trigger levels.

Red Blood Cell Transfusion Practice Pattern Before and After Implementation of a Local Restrictive Transfusion Protocol in a Neonatal Intensive Care Unit

Background: A restrictive red blood cell (RBC) transfusion guideline was established in 2019 in a neonatal intensive care unit (NICU), suggesting a hemoglobin concentration threshold of 7 g/dL. Objectives: (a) To determine its impact on the number of RBC transfusions and donor exposure; (b) to characterize RBC-transfusion determinants and justifications. Study Design: Single-center retrospective historical control study comparing all neonates consecutively admitted to the NICU during two five-month periods: 401 patients in 2013 before and 402 patients in 2021 after restrictive guideline implementation. Possible determinants were assessed via logistic regressions and justifications via a questionnaire. Results: In 2021, 9.2% of neonates received at least one RBC transfusion compared to 13.5% in 2013 ( p = .075). Adherence to protocol thresholds was 50%. Implementation of a restrictive transfusion protocol had some impact on determinants related to neonatal morbidity and illness severity and some impact on justifications being mainly based on hemoglobin value. Conclusion: Our study demonstrates that the implementation of a restrictive RBC transfusion protocol tended to decrease transfusion rates and donor exposure in the NICU, but the trend was not statistically significant. Future work should focus on improving protocol adherence.

Restrictive Versus Liberal Red Blood Cell Transfusion Strategies for Patients with Hematologic Malignancies Receiving Intensive Chemotherapy

Background: It is estimated that one-quarter to one-half of people diagnosed with hematologic malignancies experience anemia and red blood cell (RBC) transfusion plays an essential supportive role in their management. There are different strategies for RBC transfusions to treat anemia. A restrictive transfusion strategy seeks to maintain a lower hemoglobin level (usually between 70 g/L to 90 g/L with a trigger for transfusion when the hemoglobin drops below 70 g/L), whereas a liberal transfusion strategy aims to maintain a higher hemoglobin (usually between 100 g/L to 120 g/L, with a threshold for transfusion when hemoglobin drops below 100 g/L). The most effective and safest strategy is unknown in people with hematological malignancies. Objectives: To determine the efficacy and safety of a restrictive versus liberal RBC transfusion strategies for people diagnosed with hematological malignancies treated with intensive chemotherapy, radiotherapy, or both, with or without a hematopoietic stem cell transplant (HSCT). Methods: Review was completed using Cochrane standard methodological procedures. We included randomized controlled trials RCTs and prospective non-randomized studies NRS that evaluated a liberal compared with a restrictive RBC transfusion strategy in children or adults with malignant hematological disorders receiving intensive chemotherapy/radiotherapy or undergoing HSCT. We searched for RCTs and NRS in MEDLINE, Embase, CINAHL, Cochrane Central Register of Controlled Trials, and eight other databases and three trial registries to 21 March 2023. For dichotomous outcomes such as mortality, results were presented as a risk ratio (RR) with 95% confidence interval (CI) to compare restrictive versus liberal transfusion strategies. For continuous outcomes using the same scale, we assessed the mean difference (MD) with 95% CI. Where outcome measures were heterogenous, a narrative synthesis was used. Review Manager Web was used to meta-analyze the data. GRADE rating methodology was used for the overall certainty of evidence from included studies. Main Results: Nine studies were included: eight RCTs and one NRS. 644 participants were included in analyses from six completed RCTs (n=560) and one completed NRS (n=84). Two ongoing RCTs consisting of 294 participants (260 adult and 34 pediatric) are pending inclusion. One completed RCT included children receiving HSCT (n=6) and five RCTs only included adults (n=239 with acute leukemia receiving chemotherapy and n=315 with a hematological malignancy receiving HSCT). The restrictive strategies varied from 70 g/L to 80 g/L and liberal strategies from 80 g/L to 120 g/L. A restrictive strategy was found to result in a reduction in the number of RBC units per participant compared to a liberal strategy (Four studies; 457 participants; MD: -2.39, 95%CI -3.38 to -1.39, P = &amp;lt;0.00001). No difference was seen in bleeding between strategies although there was high concern for bias in included trials. Effects were reported in the summary of findings tables for RCTs (Table 1) which included results from adults only to reduce indirectness as a result of limited information from the single published pediatric RCT which was terminated early. Overall, a restrictive RBC transfusion strategy may result in little to no difference in the risk of death at 31 to 100 days compared to a liberal transfusion strategy (three studies; 382 participants; RR 0.74, 95% CI 0.13 to 4.09, P= 0.73; I 2=28%; low-certainty evidence). Two outcomes (mortality at 31 to 100 days and clinically significant bleeding) were reported from the one NRS (Table 2). The evidence is very uncertain whether there is a difference in mortality and clinically significant bleeding between the transfusion strategies based on the very low-certainty evidence. Conclusions: A restrictive transfusion strategy demonstrated a reduction in RBC usage, while there may be no impact on mortality. Definite conclusions are challenging given the relatively few studies with low numbers of included participants, concern for bias, heterogeneity of intervention and outcome reporting and overall certainty of evidence. There is a need for larger and methodologically better designed and executed studies. There is insufficient evidence to answer this review's primary outcome. Further RCTs are required overall, particularly trials inclusive of pediatric participants.

The Restrictive Red Blood Cell Transfusion Strategy for Critically Injured Patients (RESTRIC) trial: a cluster-randomized, crossover, non-inferiority multicenter trial of restrictive transfusion in trauma.

The efficacies of fresh frozen plasma and coagulation factor transfusion have been widely evaluated in trauma-induced coagulopathy management during the acute post-injury phase. However, the efficacy of red blood cell transfusion has not been adequately investigated in patients with severe trauma, and the optimal hemoglobin target level during the acute post-injury and resuscitation phases remains unclear. Therefore, this study aimed to examine whether a restrictive transfusion strategy was clinically non-inferior to a liberal transfusion strategy during the acute post-injury phase. This cluster-randomized, crossover, non-inferiority multicenter trial was conducted at 22 tertiary emergency medical institutions in Japan and included adult patients with severe trauma at risk of major bleeding. The institutions were allocated a restrictive or liberal transfusion strategy (target hemoglobin levels: 7-9 or 10-12g/dL, respectively). The strategies were applied to patients immediately after arrival at the emergency department. The primary outcome was 28-day survival after arrival at the emergency department. Secondary outcomes included transfusion volume, complication rates, and event-free days. The non-inferiority margin was set at 3%. The 28-day survival rates of patients in the restrictive (n = 216) and liberal (n = 195) strategy groups were 92.1% and 91.3%, respectively. The adjusted odds ratio for 28-day survival in the restrictive versus liberal strategy group was 1.02 (95% confidence interval: 0.49-2.13). Significant non-inferiority was not observed. Transfusion volumes and hemoglobin levels were lower in the restrictive strategy group than in the liberal strategy group. No between-group differences were noted in complication rates or event-free days. Although non-inferiority of the restrictive versus liberal transfusion strategy for 28-day survival was not statistically significant, the mortality and complication rates were similar between the groups. The restrictive transfusion strategy results in a lower transfusion volume. umin.ac.jp/ctr: UMIN000034405, registration date: 8 October 2018.

A pilot randomized study for optimal red cell transfusion in acute myeloid leukemia patients with intensive chemotherapy.

Although blood transfusion is fundamental throughout the course of hematologic malignancies, acute myeloid leukemia (AML) patients requiring intensive chemotherapy are left at the edges of patient blood management programs because current guidelines do not have established recommendations for red blood cell (RBC) transfusion threshold in patients treated for hematological disorders with anemia and accompanied severe thrombocytopenia. To provide answers for the trigger and doses of ideal RBC transfusion in such situation, we conducted this prospective randomized trial. Newly diagnosed non-acute promyelocytic AML patients undergoing chemotherapy were considered eligible for enrollment. Patients were randomized into 4 groups using a 2 by 2 factorial design, according to the RBC transfusion trigger (hemoglobin [Hb], 7 vs 8 g/dL) and the number of units per transfusion episode (quantity, single vs double-unit). Initially 91 patients were randomized into 4 groups, but the protocol adherence rate was 90.1%. Hb trigger did not affect the amount of RBC transfusion required during treatment. Patients receiving RBC transfusion at Hb <7 g/dL used a median of 4 units of RBC (range 0-12), and those receiving transfusion at Hb <8 g/dL also used a median of 4 units of RBC (range 0-24) (p=0.305). The number of RBC units per transfusion did not affect the total amount of RBC transfusion required during treatment. AML treatment outcomes and bleeding events did not differ across the 4 groups. This study demonstrated the feasibility for restrictive RBC transfusion (Hb <7 g/dL, RBC 1 unit) in AML patients undergoing chemotherapy, regardless of chemotherapy intensity.

Trends of Blood Transfusion According to Diseases in Korea: A 10-Year Nationwide Cohort Study

Introduction: Recent guidelines recommend restrictive red blood cell transfusion; therefore, hospitals have started introducing and implementing patient blood management programs. This is the first study to analyze changes in the trends of blood transfusions in the whole population over the past 10 years according to sex, age group, blood component, disease, and hospital type. Methods: This cohort study analyzed blood transfusion records for 10 years, from January 2009 to December 2018, using nationwide population-based data from the Korean National Health Insurance Service-Health Screening Cohort database. Results: The proportion of transfusion procedures conducted in the total population has increased constantly for 10 years. Although its proportion in the age group of 10–79 years decreased, the total number of transfusions increased significantly due to the increase in the population and proportion of transfusions in those aged 80 years or older. Furthermore, the proportion of multicomponent transfusion procedures increased in this age group, which was greater than that of transfusions. The most common disease among transfusion patients in 2009 was cancer, of which gastrointestinal (GI) cancer accounted for more than half, followed by trauma and hematologic diseases (GI cancers > trauma > other cancers > hematologic diseases). The proportion of patients with GI cancer decreased, whereas that of trauma and hematologic diseases increased over the 10 years, with trauma becoming the most common disease type in 2018 (trauma > GI cancers > hematologic diseases > other cancers). Although transfusion rates per hospitalization decreased, the total number of inpatients increased, thus increasing the number of blood transfusions in all types of hospitals. Discussion/Conclusions: The proportion of transfusion procedures in the total population increased owing to the increase in the total number of transfusions in patients aged 80 years or older. The proportion of patients with trauma and hematologic diseases has also increased. Moreover, the total number of inpatients has been increasing, which subsequently increases the number of blood transfusions performed. Specific management strategies targeting these groups may improve blood management.

Endoscopic diagnosis and management of esophagogastric variceal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

1: ESGE recommends that patients with compensated advanced chronic liver disease (ACLD; due to viruses, alcohol, and/or nonobese [BMI < 30 kg/m2] nonalcoholic steatohepatitis) and clinically significant portal hypertension (hepatic venous pressure gradient [HVPG] > 10 mmHg and/or liver stiffness by transient elastography > 25 kPa) should receive, if no contraindications, nonselective beta blocker (NSBB) therapy (preferably carvedilol) to prevent the development of variceal bleeding.Strong recommendation, moderate quality evidence. 2: ESGE recommends that in those patients unable to receive NSBB therapy with a screening upper gastrointestinal (GI) endoscopy that demonstrates high risk esophageal varices, endoscopic band ligation (EBL) is the endoscopic prophylactic treatment of choice. EBL should be repeated every 2-4 weeks until variceal eradication is achieved. Thereafter, surveillance EGD should be performed every 3-6 months in the first year following eradication.Strong recommendation, moderate quality evidence. 3: ESGE recommends, in hemodynamically stable patients with acute upper GI hemorrhage (UGIH) and no history of cardiovascular disease, a restrictive red blood cell (RBC) transfusion strategy, with a hemoglobin threshold of ≤70 g/L prompting RBC transfusion. A post-transfusion target hemoglobin of 70-90 g/L is desired.Strong recommendation, moderate quality evidence. 4 : ESGE recommends that patients with ACLD presenting with suspected acute variceal bleeding be risk stratified according to the Child-Pugh score and MELD score, and by documentation of active/inactive bleeding at the time of upper GI endoscopy.Strong recommendation, high quality of evidence. 5 : ESGE recommends the vasoactive agents terlipressin, octreotide, or somatostatin be initiated at the time of presentation in patients with suspected acute variceal bleeding and be continued for a duration of up to 5 days.Strong recommendation, high quality evidence. 6 : ESGE recommends antibiotic prophylaxis using ceftriaxone 1 g/day for up to 7 days for all patients with ACLD presenting with acute variceal hemorrhage, or in accordance with local antibiotic resistance and patient allergies.Strong recommendation, high quality evidence. 7 : ESGE recommends, in the absence of contraindications, intravenous erythromycin 250 mg be given 30-120 minutes prior to upper GI endoscopy in patients with suspected acute variceal hemorrhage.Strong recommendation, high quality evidence. 8 : ESGE recommends that, in patients with suspected variceal hemorrhage, endoscopic evaluation should take place within 12 hours from the time of patient presentation provided the patient has been hemodynamically resuscitated.Strong recommendation, moderate quality evidence. 9 : ESGE recommends EBL for the treatment of acute esophageal variceal hemorrhage (EVH).Strong recommendation, high quality evidence. 10 : ESGE recommends that, in patients at high risk for recurrent esophageal variceal bleeding following successful endoscopic hemostasis (Child-Pugh C ≤ 13 or Child-Pugh B > 7 with active EVH at the time of endoscopy despite vasoactive agents, or HVPG > 20 mmHg), pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) within 72 hours (preferably within 24 hours) must be considered.Strong recommendation, high quality evidence. 11 : ESGE recommends that, for persistent esophageal variceal bleeding despite vasoactive pharmacological and endoscopic hemostasis therapy, urgent rescue TIPS should be considered (where available).Strong recommendation, moderate quality evidence. 12 : ESGE recommends endoscopic cyanoacrylate injection for acute gastric (cardiofundal) variceal (GOV2, IGV1) hemorrhage.Strong recommendation, high quality evidence. 13: ESGE recommends endoscopic cyanoacrylate injection or EBL in patients with GOV1-specific bleeding.Strong recommendations, moderate quality evidence. 14: ESGE suggests urgent rescue TIPS or balloon-occluded retrograde transvenous obliteration (BRTO) for gastric variceal bleeding when there is a failure of endoscopic hemostasis or early recurrent bleeding.Weak recommendation, low quality evidence. 15: ESGE recommends that patients who have undergone EBL for acute EVH should be scheduled for follow-up EBLs at 1- to 4-weekly intervals to eradicate esophageal varices (secondary prophylaxis).Strong recommendation, moderate quality evidence. 16: ESGE recommends the use of NSBBs (propranolol or carvedilol) in combination with endoscopic therapy for secondary prophylaxis in EVH in patients with ACLD.Strong recommendation, high quality evidence.

Indications and hemoglobin thresholds for red blood cell transfusion and iron replacement in adults with gastrointestinal bleeding: An algorithm proposed by gastroenterologists and patient blood management experts.

Gastrointestinal (GI) bleeding is associated with considerable morbidity and mortality. Red blood cell (RBC) transfusion has long been the cornerstone of treatment for anemia due to GI bleeding. However, blood is not devoid of potential adverse effects, and it is also a precious resource, with limited supplies in blood banks. Nowadays, all patients should benefit from a patient blood management (PBM) program that aims to minimize blood loss, optimize hematopoiesis (mainly by using iron replacement therapy), maximize tolerance of anemia, and avoid unnecessary transfusions. Integration of PBM into healthcare management reduces patient mortality and morbidity and supports a restrictive RBC transfusion approach by reducing transfusion rates. The European Commission has outlined strategies to support hospitals with the implementation of PBM, but it is vital that these initiatives are translated into clinical practice. To help optimize management of anemia and iron deficiency in adults with acute or chronic GI bleeding, we developed a protocol under the auspices of the Spanish Association of Gastroenterology, in collaboration with healthcare professionals from 16 hospitals across Spain, including expert advice from different specialties involved in PBM strategies, such as internal medicine physicians, intensive care specialists, and hematologists. Recommendations include how to identify patients who have anemia (or iron deficiency) requiring oral/intravenous iron replacement therapy and/or RBC transfusion (using a restrictive approach to transfusion), and transfusing RBC units 1 unit at a time, with assessment of patients after each given unit (i.e., “don’t give two without review”). The advantages and limitations of oral versus intravenous iron and guidance on the safe and effective use of intravenous iron are also described. Implementation of a PBM strategy and clinical decision-making support, including early treatment of anemia with iron supplementation in patients with GI bleeding, may improve patient outcomes and lower hospital costs.

ONTraC: A 20-Year History of a Successfully Coordinated Provincewide Patient Blood Management Program: Lessons Learned and Goals Achieved

Our understanding of the risks associated with perioperative anemia and transfusion, in terms of increased morbidity and mortality, has evolved over the past 2 decades. By contrast, our understanding of the potential mechanisms of injury and optimal treatment strategies remains incomplete. As such, the important role of effective patient blood management (PBM) programs, which address both the effective treatment of anemia and minimizes the need for red blood cell (RBC) transfusion, is of central importance to optimizing patient care and improving patient outcomes. We report on important clinical outcomes of the Ontario Transfusion Coordinator (ONTraC Program), a network of 25 hospital sites, working in coordination over the past 20 years. Transfusion nurse coordinators were assigned to apply multimodal best practice in PBM (including recommended changes in surgical approach; diagnosis, assessment, and treatment of anemia; and adherence to more restrictive RBC transfusion thresholds). Data were collected on various clinical parameters. We further described lessons learned and difficulties encountered in this multisite PBM initiative. A significant reduction in RBC transfusions was observed for numerous indexed surgeries. For example, RBC transfusion rates for knee arthroplasty decreased from 25% in 2002 to 0.4% in 2020. For coronary artery bypass graft (CABG) surgery, transfusion rates decreased from 60% in 2002 to 27% in 2020. We also observed a decrease in RBC units utilized per transfused patient for knee (2.1 ± 0.5 [2002] vs 1.0 ± 0.6 [2020] units per patient) and CABG surgery (3.3 ± 0.6 [2002] vs 2.3 ± 1.9 [2020] units per patient). These reductions were associated with favorable clinical outcomes, including reduced length of hospital stay (P = .00003) and a reduced rate of perioperative infections (P < .001) for nontransfused versus transfused patients. These advances have been achieved with estimated savings in the tens of millions of dollars annually. Our experience and data support the hypothesis that instituting an integrated network of transfusion nurse coordinators can provide an effective provincewide PBM program, reduce RBC transfusions, improve some patient outcomes, and reduce health care costs, as an example of a "win-win-win" medical program.

PERIOPERATIVE PATIENT BLOOD MANAGEMENT

Anemia and its treatment using red blood cell (RBC) transfusions are known to be the risk factors for posto­perative morbidity and mortality. These disadvantages led to the need for an approach that supports the proper and timely evaluation and management of anemia as well as a rational utilization of blood products. In recent de­cades, the World Health Organization (WHO) advoca­ted Patient Blood Management (PBM), which focuses on the patient’s own blood as a resource that should be conserved and managed appropriately, and the avoidance of irrational use of blood transfusions. The implemen­tation of PBM in the perioperative period is based on 3 pillars: 1. the optimization of the erythrocyte volume, through early detection of anemia before surgery, its pro­per management, and evaluation of applied treatment; 2. minimization of blood loss, by limiting blood drawn for blood testing, adhering to adequate anesthetic principles to maintain hemodynamics, using blood-sparing surgical techniques, implementing viscoelastic methods for the evaluation of blood, and prescribing antifibrinolytics; 3. optimization of the patient’s physiological tolerance toward anemia and rational usage of blood transfusion, which can be achieved by ensuring optimized cardiac output, minimized oxygen consumption, and maximi­zed oxygen delivery to tissues as well as following a restrictive RBC transfusion strategy.

Impact of restrictive red blood cell transfusion strategy on thrombosis-related events: A meta-analysis and systematic review.

There is an ongoing controversy regarding the risks of restrictive and liberal red blood cell (RBC) transfusion strategies. This meta-analysis assessed whether transfusion at a lower threshold was superior to transfusion at a higher threshold, with regard to thrombosis-related events, that is, whether these outcomes can benefit from a restrictive transfusion strategy is debated. We searched PubMed, Cochrane Central Register of Controlled Trials and Scopus from inception up to 31 July 2021. We included randomized controlled trials (RCTs) in any clinical setting that evaluated the effects of restrictive versus liberal RBC transfusion in adults. We used random-effects models to calculate the risk ratios (RRs) and 95% confidence intervals (CIs) based on pooled data. Thirty RCTs involving 17,334 participants were included. The pooled RR for thromboembolic events was 0.65 (95% CI 0.44-0.94; p= 0.020; I2 = 0.0%, very low-quality evidence), favouring the restrictive strategy. There were no significant differences in cerebrovascular accidents (RR=0.83; 95% CI 0.64-1.09; p= 0.180; I2 = 0.0%, very low-quality evidence) or myocardial infarction (RR=1.05; 95% CI 0.87-1.26; p= 0.620; I2 = 0.0%, low-quality evidence). Subgroup analyses showed that a restrictive (relative to liberal) strategy reduced (1) thromboembolic events in RCTs conducted in North America and (2) myocardial infarctions in the subgroup of RCTs where the restrictive transfusion threshold was 7g/dl but not in the 8g/dl subgroup (with a liberal transfusion threshold of 10g/dl in both subgroups). A restrictive (relative to liberal) transfusion strategy may be effective in reducing venous thrombosis but not arterial thrombosis.

Individualised or liberal red blood cell transfusion after cardiac surgery: a randomised controlled trial

BackgroundCurrent practice guidelines for red blood cell (RBC) transfusion in ICUs are based on haemoglobin threshold, without consideration of oxygen delivery or consumption. We aimed to evaluate an individual physiological threshold-guided by central venous oxygen saturation ScvO2. MethodsIn a randomised study in two French academic hospitals, 164 patients who were admitted to ICU after cardiac surgery with postoperative haemoglobin <9 g dl−1 were randomised to receive a transfusion with one unit of RBCs (haemoglobin group) or transfusion only if the ScvO2 was <70% (individualised group). The primary outcome was the number of subjects receiving at least one unit of RBCs. The secondary composite outcome was acute kidney injury, stroke, myocardial infarction, acute heart failure, mesenteric ischaemia, or in-hospital mortality. One- and 6-month mortality were evaluated during follow-up. ResultsThe primary outcome was observed for 80 of 80 subjects (100%) in the haemoglobin group and in 61 of 77 patients (79%) in the individualised group (absolute risk –21% [–32.0; –14.0]; P<0.001). There was no significant difference in the secondary outcome between the two groups. Follow-up showed a non-significant difference in mortality at 1 and 6 months. ConclusionsAn individualised strategy based on an central venous oxygen saturation threshold of 70% allows for a more restrictive red blood cell transfusion strategy with no incidence on postoperative morbidity or 6-month mortality. Clinical trial registrationNCT02963883.

Restrictive vs. Liberal Red Blood Cell Transfusion Strategy in Patients With Acute Myocardial Infarction and Anemia: A Systematic Review and Meta-Analysis

Objective: Anemia is frequent in patients with acute myocardial infarction (AMI), and the optimal red blood cell transfusion strategy for AMI patients with anemia is still controversial. We aimed to compare the efficacy of restrictive and liberal red cell transfusion strategies in AMI patients with anemia.Methods: We systematically searched PubMed, EMBASE, Web of Science, Cochrane Library, and Clinicaltrials.gov, from their inception until March 2021. Studies designed to compare the efficacy between restrictive and liberal red blood cell transfusion strategies in patients with AMI were included. The primary outcome was all-cause mortality, including overall mortality, in-hospital or follow-up mortality. Risk ratios (RR) with 95% confidence intervals (CI) were presented and pooled by random-effects models.Results: The search yielded a total of 6,630 participants in six studies. A total of 2,008 patients received restrictive red blood cell transfusion while 4,622 patients were given liberal red blood cell transfusion. No difference was found in overall mortality and follow-up mortality between restrictive and liberal transfusion groups (RR = 1.07, 95% CI = 0.82–1.40, P = 0.62; RR = 0.89, 95% CI = 0.56–1.42, P = 0.62). However, restrictive transfusion tended to have a higher risk of in-hospital mortality compared with liberal transfusion (RR = 1.22, 95% CI = 1.00–1.50, P = 0.05). No secondary outcomes, including follow-up reinfarction, stroke, and acute heart failure, differed significantly between the two groups. In addition, subgroup analysis showed no differences in overall mortality between the two groups based on sample size and design.Conclusion: Restrictive and liberal red blood cell transfusion have a similar effect on overall mortality and follow-up mortality in AMI patients with anemia. However, restrictive transfusion tended to have a higher risk of in-hospital mortality compared with liberal transfusion. The findings suggest that transfusion strategy should be further evaluated in future studies.

Diagnosis and management of acute lower gastrointestinal bleeding: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

1: ESGE recommends that the initial assessment of patients presenting with acute lower gastrointestinal bleeding should include: a history of co-morbidities and medications that promote bleeding; hemodynamic parameters; physical examination (including digital rectal examination); and laboratory markers. A risk score can be used to aid, but should not replace, clinician judgment.Strong recommendation, low quality evidence. 2 : ESGE recommends that, in patients presenting with a self-limited bleed and no adverse clinical features, an Oakland score of ≤ 8 points can be used to guide the clinician decision to discharge the patient for outpatient investigation.Strong recommendation, moderate quality evidence. 3 : ESGE recommends, in hemodynamically stable patients with acute lower gastrointestinal bleeding and no history of cardiovascular disease, a restrictive red blood cell transfusion strategy, with a hemoglobin threshold of ≤ 7 g/dL prompting red blood cell transfusion. A post-transfusion target hemoglobin concentration of 7-9 g/dL is desirable.Strong recommendation, low quality evidence. 4 : ESGE recommends, in hemodynamically stable patients with acute lower gastrointestinal bleeding and a history of acute or chronic cardiovascular disease, a more liberal red blood cell transfusion strategy, with a hemoglobin threshold of ≤ 8 g/dL prompting red blood cell transfusion. A post-transfusion target hemoglobin concentration of ≥ 10 g/dL is desirable.Strong recommendation, low quality evidence. 5: ESGE recommends that, in patients with major acute lower gastrointestinal bleeding, colonoscopy should be performed sometime during their hospital stay because there is no high quality evidence that early colonoscopy influences patient outcomes.Strong recommendation, low quality of evidence. 6 : ESGE recommends that patients with hemodynamic instability and suspected ongoing bleeding undergo computed tomography angiography before endoscopic or radiologic treatment to locate the site of bleeding.Strong recommendation, low quality evidence. 7 : ESGE recommends withholding vitamin K antagonists in patients with major lower gastrointestinal bleeding and correcting their coagulopathy according to the severity of bleeding and their thrombotic risk. In patients with hemodynamic instability, we recommend administering intravenous vitamin K and four-factor prothrombin complex concentrate (PCC), or fresh frozen plasma if PCC is not available.Strong recommendation, low quality evidence. 8 : ESGE recommends temporarily withholding direct oral anticoagulants at presentation in patients with major lower gastrointestinal bleeding.Strong recommendation, low quality evidence. 9: ESGE does not recommend withholding aspirin in patients taking low dose aspirin for secondary cardiovascular prevention. If withheld, low dose aspirin should be resumed, preferably within 5 days or even earlier if hemostasis is achieved or there is no further evidence of bleeding.Strong recommendation, moderate quality evidence. 10: ESGE does not recommend routinely discontinuing dual antiplatelet therapy (low dose aspirin and a P2Y12 receptor antagonist) before cardiology consultation. Continuation of the aspirin is recommended, whereas the P2Y12 receptor antagonist can be continued or temporarily interrupted according to the severity of bleeding and the ischemic risk. If interrupted, the P2Y12 receptor antagonist should be restarted within 5 days, if still indicated.Strong recommendation, low quality evidence.

Liberal blood transfusion strategies and associated infection in orthopedic patients: A meta-analysis.

Objective:It remains unclear whether transfusion strategies during orthopedic surgery and infection are related. The purpose of this study is to evaluate whether liberal blood transfusion strategies contribute to infection risk in orthopedic patients by analyzing randomized controlled trials (RCTs).Methods:RCTs with liberal versus restrictive red blood cell (RBC) transfusion strategies were identified by searching PubMed, Embase, the Cochrane Central Register of Controlled Trials from their inception to July 2019. Ten studies with infections as outcomes were included in the final analysis. According to the Jadad scale, all studies were considered to be of high quality.Results:Ten trials involving 3938 participants were included in this study. The pooled risk ratio (RR) for the association between liberal transfusion strategy and infection was 1.34 (95% confidence intervals [CI], 0.94–1.90; P = .106). The sensitivity analysis indicated unstable results, and no significant publication bias was observed.Conclusion:This pooled analysis of RCTs demonstrates that liberal transfusion strategies in orthopedic patients result in a nonsignificant increase in infections compared with more restrictive strategies. The conclusions are mainly based on retrospective studies and should not be considered as recommendation before they are supported by larger scale and well-designed RCTs.

A Reaffirm on Interpretation of Postoperative Anemia. A Valid Strategy to Limit Blood Transfusions after Hepatectomy for Liver Tumors

Purpose: Hepatectomy is the most effective treatment for several malignant diseases but may be associated with blood loos and need for red blood cell transfusions (RBCT). However, the need for RBCT relies on the interpretation of postoperative anemia and on the transfusions policy locally adopted. The purpose of this study was to investigate the risk of RBCT, the associated trend of postoperative anemia, and the associations of RBCT with the range of complexity of hepatectomies. Methods: Data from all consecutive patients treated at our center were retrospectively reviewed. Both transfused and not transfused patients were considered. Blood loss and RBCT, hematocrit and hemoglobin levels in postoperative-day (POD) 1, 3, 5 and 7 were systematically analyzed. Complexity of operations was analyzed by using the CLISCO group classification. Results: Between 1998 and 2019, 1476 patients without missing data were considered. Of these, 174 (11.7%) patients were transfused. The hematocrit and hemoglobin levels were significantly lower in POD3 in comparison with POD1, POD5 and POD7 both in the transfused (P<0.001) and not transfused patients (P<0.001) (Figure 1) with a spontaneous increase from POD5. A statistically significant association was found between blood loss and RBCT with the complexity of hepatectomies (P<0.001). Conclusions: Drop in postoperative hemoglobin and hematocrit levels after hepatectomy is associated with increase from POD5 both in transfused and not transfused patients. Such phenomenon allows for restrictive RBCT, which should be limited to complex operations or symptomatic or multi-morbidity patients.

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.