Effect of Donor Sex on Recipient Mortality in Transfusion.

BACKGROUND: Conflicting observational evidence exists regarding the association between the sex of red-cell donors and mortality among transfusion recipients. Evidence to inform transfusion practice and policy is limited. METHODS: In this multicenter, double-blind trial, we randomly assigned patients undergoing red-cell transfusion to receive units of red cells from either male donors or female donors. Patients maintained their trial-group assignment throughout the trial period, including during subsequent inpatient and outpatient encounters. Randomization was conducted in a 60:40 ratio (male donor group to female donor group) to match the historical allocation of red-cell units from the blood supplier. The primary outcome was survival, with the male donor group as the reference group. RESULTS: A total of 8719 patients underwent randomization before undergoing transfusion; 5190 patients were assigned to the male donor group, and 3529 to the female donor group. At baseline, the mean (±SD) age of the enrolled patients was 66.8±16.4 years. The setting of the first transfusion was as an inpatient in 6969 patients (79.9%), of whom 2942 (42.2%) had been admitted under a surgical service. The baseline hemoglobin level before transfusion was 79.5±19.7 g per liter, and patients received a mean of 5.4±10.5 units of red cells in the female donor group and 5.1±8.9 units in the male donor group (difference, 0.3 units; 95% confidence interval [CI], -0.1 to 0.7). Over the duration of the trial, 1141 patients in the female donor group and 1712 patients in the male donor group died. In the primary analysis of overall survival, the adjusted hazard ratio for death was 0.98 (95% CI, 0.91 to 1.06). CONCLUSIONS: This trial showed no significant difference in survival between a transfusion strategy involving red-cell units from female donors and a strategy involving red-cell units from male donors. (Funded by the Canadian Institutes of Health Research; iTADS ClinicalTrials.gov number, NCT03344887.).

Impact of Perioperative Blood Transfusion in Anemic Patients Undergoing Infra Inguinal Bypass.

OBJECTIVE: Patients who present with lower extremity ischemia are frequently anemic and the optimal transfusion threshold for this cohort remains controversial. We sought to evaluate the impact of blood transfusion on postoperative major adverse cardiac events (MACE), including myocardial infarction, dysrhythmia, stroke, congestive heart failure, and 30-day mortality for these patients. METHODS: All consecutive patients who underwent infra-inguinal bypass at our institution from 2011 to 2020 were included. Perioperative red blood cell transfusion was the primary exposure, and the primary outcome was MACE. Univariate and multivariable analyses were performed to assess the impact of patient and procedural variables, including red blood cell transfusion, stratified by hemoglobin (Hgb) nadir: <7, 7-8, and >8 g/dL. RESULTS: Of the 287 patients reviewed for analysis, 146 (50.9%) had a perioperative transfusion (mean: 1.6 ± 3 units). Patients who received a transfusion had a mean nadir Hgb of 8.3 ± 1.0 g/dL, compared to 10.1 ± 1.7 g/dL without a transfusion. The overall incidence of MACE was 15.7% (45 of 287 patients). Univariate analysis demonstrated that MACE was associated with blood transfusion (P = 0.009), lower Hgb nadir (P = 0.02), and higher blood loss (P = 0.003). On multivariate analysis, transfusion was independently associated with MACE for patients with a Hgb nadir >8 g/dL (OR: 3.09; P = 0.006), but not for patients with Hgb nadir 7-8 g/dL (OR: 0.818; P = 0.77). Additionally, patients with MACE had significantly longer length of hospital stay than for patients without (13 vs. 7.7 days, P = 0.001). CONCLUSIONS: For patients undergoing infra-inguinal bypass, receiving a red blood cell transfusion with a Hgb nadir >8 g/dL was associated with a 3-fold increase in MACE, with nearly twice the length of stay. For patients with a Hgb 7-8 g/dL, transfusion did not increase or reduce the incidence of MACE. These findings suggest no benefit of blood transfusion for patients with Hgb nadir >7 g/dL and harm for Hgb >8 g/dL, however causation cannot be proven due to the retrospective nature of the study and randomized studies are needed to confirm or refute these findings.

Red blood cell transfusion-induced non-transferrin-bound iron promotes Pseudomonas aeruginosa biofilms in human sera and mortality in catheterized mice.

Transfusion of storage-damaged red blood cells (RBCs) increases non-transferrin-bound iron (NTBI) levels in humans. This can potentially enhance virulence of microorganisms. In this study, Pseudomonas aeruginosa replication and biofilm production in vitro correlated with NTBI levels of transfused subjects (R2 = 0·80; P < 0·0001). Transfusion of stored RBCs into catheterized mice enhanced P. aeruginosa virulence and mortality in vivo, while pre-administration of apotransferrin reduced NTBI levels improving survival (69% vs 27% mortality; P < 0·05). These results suggest that longer RBC storage, by modulating the bioavailability of iron, may increase the risk of P. aeruginosa biofilm-related infections in transfused patients.

Restrictive versus liberal transfusion thresholds in very low birth weight infants: A systematic review with meta-analysis.

BACKGROUND: To assess the efficacy and safety of restrictive versus liberal red blood cell transfusion thresholds in very low birth weight infants. METHODS: We searched MEDLINE, EMBASE, and Cochrane database without any language restrictions. The last search was conducted in August 15, 2020. All randomized controlled trials comparing the use of restrictive versus liberal red blood cell transfusion thresholds in very low birth weight (VLBW) infants were selected. Pooled risk ratio (RR) for dichotomous variable with 95% confidence intervals were assessed by a random-effects model. The primary outcome was all-cause mortality. RESULTS: Overall, this meta-analysis included 6 randomized controlled trials comprising 3,483 participants. Restrictive transfusion does not increase the risk of all-cause mortality (RR, 0.99; 95% CI, 0.84 to 1.17; I2 = 0%; high-quality evidence), and does not increase the composite outcome of death or neurodevelopmental impairment (RR, 1.01, 95% CI, 0.93-1.09; I2 = 7%; high-quality evidence) or other serious adverse events. Results were similar in subgroup analyses of all-cause mortality by weight of infants, gestational age, male infants, and transfusion volume. CONCLUSIONS: In very low birth weight infants, a restrictive threshold for red blood cell transfusion was not associated with increased risk of all-cause mortality, in either short term or long term.

Association between perioperative allogeneic red blood cell transfusion and infection after clean-contaminated surgery: a retrospective cohort study.

BACKGROUND: Allogeneic red blood cell (RBC) transfusion can induce immunosuppression, which can then increase the susceptibility to postoperative infection. However, studies in different types of surgery show conflicting results regarding this effect. METHODS: In this retrospective cohort study conducted in a tertiary referral centre, we included adult patients undergoing clean-contaminated surgery from 2014 to 2018. Patients who received allogeneic RBC transfusion from preoperative Day 30 to postoperative Day 30 were included into the transfusion group. The control group was matched for the type of surgery in a 1:1 ratio. The primary outcome was infection within 30 days after surgery, which was defined by healthcare-associated infection, and identified mainly based on antibiotic regimens, microbiology tests, and medical notes. RESULTS: Among the 8098 included patients, 1525 (18.8%) developed 1904 episodes of postoperative infection. Perioperative RBC transfusion was associated with an increased risk of postoperative infection after controlling for 27 confounders by multivariable regression analysis (odds ratio [OR]: 1.60; 95% confidence interval [CI]: 1.39-1.84; P<0.001) and propensity score weighing (OR: 1.64; 95% CI: 1.45-1.85; P<0.001) and matching (OR: 1.70; 95% CI: 1.43-2.01; P<0.001), and a dose-response relationship was observed. The transfusion group also showed higher risks of surgical site infection, pneumonia, bloodstream infection, multiple infections, intensive care admission, unplanned reoperation, prolonged postoperative length of hospital stay, and all-cause death. CONCLUSIONS: Perioperative allogeneic RBC transfusion is associated with an increased risk of infection after clean-contaminated surgery in a dose-response manner. Close monitoring of infections and enhanced prophylactic strategies should be considered after transfusion.

The Effect of Perioperative Blood Transfusion on Long-Term Survival Outcomes After Surgery for Pancreatic Ductal Adenocarcinoma: A Systematic Review.

OBJECTIVE: To evaluate survival outcomes associated with perioperative allogeneic red blood cell transfusion (RBCT) in patients with pancreatic ductal adenocarcinoma undergoing surgery. METHODS: PubMed, Embase, Cochrane, and Web of Science Core Collection were queried for English-language articles until May 28, 2020. Studies evaluating long-term outcomes of RBCT compared with no transfusion in adults with pancreatic ductal adenocarcinoma undergoing pancreatectomy were included. E-value sensitivity analysis assessed the potential for unmeasured confounders to overcome these findings. RESULTS: Of 4379 citations, 5 retrospective cohort studies were included. Three studies reported shorter recurrence-free survival by 1 to 5 months with RBCT. Two studies found shorter disease-specific survival by 5 to 13 months with RBCT. Overall survival was reduced by 5 to 7 months with RBCT in 3 studies. All multivariable findings associated with RBCT could be readily overcome unmeasured confounding on sensitivity analysis. Confounding in baseline characteristics resulted in high risk of bias. CONCLUSIONS: Imprecision, unmeasured confounding, small effect sizes, and overall low quality of the available literature result in uncertainty regarding the effect of transfusion on recurrence-free survival, disease-specific survival, and overall survival in patients undergoing surgery for pancreatic cancer. Randomized trials are needed to determine if there is a causal relationship between transfusion and survival after pancreatic resection.

Hematological Biomarkers, Mortality, Transfusion and Acute Heart Disease.

BACKGROUND: Patients hospitalized with acute heart disease [acute myocardial infarction (MI); heart disease exacerbation] may require red blood cell (RBC) transfusion. These patients are at increased risk for morbidity and mortality. Hematological biomarkers may help to identify increased mortality risk. The aim of the study was to evaluate the association between hematological biomarkers and survival in these patients. METHODS: A historical cohort study of all patients admitted to an internal medicine department, who were diagnosed with acute heart disease and requiring RBC transfusion, was carried out in a tertiary medical center between 2009-2014. The association between hematological biomarkers and 30-, 90-day and 5-year mortality was studied. RESULTS: A total of 254 patients (median age 80 years, IQR 74-86.25; 40.9% females; acute MI 24.8%), were included. During the 5-year follow-up 212(83.5%) patients died. In a multivariate analysis the lower platelet to neutrophil ratio (PNR) was significantly associated with increased 30-, 90-day and 5-year mortality (p<0.001, 0.041, 0.003 respectively). A higher red cell distribution width (RDW) was significantly associated with 30- and 90-day mortality (p=0.003, 0.023 respectively), while higher neutrophil to lymphocyte ratio (NLR) was associated with increased 30-day and 5-year mortality (p= 0.036, 0.033 respectively). CONCLUSIONS: Hematological biomarkers may help to identify increased mortality risk of acute heart disease patients, receiving RBC transfusions in an internal medicine department.

Association of perioperative red blood cell transfusions with all-cause and cancer-specific death in patients undergoing surgery for gastrointestinal cancer: Long-term outcomes from a population-based cohort.

BACKGROUND: Red blood cell transfusions are common in patients undergoing gastrointestinal cancer surgery. Yet, to adequately balance their risks and benefits, clinicians must understand how transfusions may affect long-term outcomes. We aimed to determine if perioperative red blood cell transfusions are associated with a higher risk of all-cause and cancer-specific death among patients who underwent gastrointestinal cancer resection. METHOD: We identified a population-based cohort of patients who underwent gastrointestinal cancer resection in Ontario, Canada (2007-2019). All-cause death was compared between transfused and nontransfused patients using Cox proportional hazards regression, while cancer-specific death was compared with competing risk regression. RESULT: A total of 74,962 patients (mean age, 67.7 years; 55.4% male; 79.7% colorectal cancer) had gastrointestinal cancer surgery during the study period; 20.8% received perioperative red blood cell transfusions. Patients who received red blood cell transfusions had increased hazards of all-cause and cancer-specific death relative to patients who did not (hazard ratio: 1.39, 95% confidence interval 1.34-1.44; cause-specific hazard ratio: 1.36, 1.30-1.43). The adjusted risk of all-cause death was higher in early follow-up intervals (3-6 months postoperatively) but remained elevated in each interval over 5 years. The association persisted after restricting to patients without postoperative complications or bleeding and was robust to unmeasured confounding. CONCLUSION: Red blood cell transfusion among patients with gastrointestinal cancer is associated with increased all-cause death. This was observed long beyond the immediate postoperative period and independent of short-term postoperative morbidity and mortality. These findings should help clinicians balance the risks and benefits of transfusion before well-designed trials are conducted in this patient population.

Red blood cell transfusions and the survival in patients with cancer undergoing curative surgery: a systematic review and meta-analysis.

Allogenic red blood cell transfusions exert a potential detrimental effect on the survival when delivered to cancer patients undergoing surgery with curative intent. We performed a systematic review and meta-analysis to assess the association between perioperative allogenic red blood cell transfusions and risk of death as well as relapse after surgery for localized solid tumors. PubMed, the Cochrane Library, and EMBASE were searched from inception to March 2019 for studies reporting the outcome of patients receiving transfusions during radical surgery for non-metastatic cancer. Risk of death and relapse were pooled to provide an adjusted hazard ratio with a 95% confidence interval [hazard ratio (HR) (95% confidence interval {CI})]. Mortality and relapse associated with perioperative transfusion due to cancer surgery were evaluated among participants (n = 123 studies). Overall, RBC transfusions were associated with an increased risk of death [HR = 1.50 (95% CI 1.42-1.57), p < 0.01] and relapse [HR = 1.36 (95% CI 1.26-1.46), p < 0.01]. The survival was reduced even in cancer at early stages [HR = 1.45 (1.36-1.55), p < 0.01]. In cancer patients undergoing surgery, red blood cell transfusions reduced the survival and increased the risk of relapse. Transfusions based on patients' blood management policy should be performed by applying a more restrictive policy, and the planned preoperative administration of iron, if necessary, should be pursued.

Evaluation of a novel Cardiac Peri-Operative Transfusion Trigger Scoring system in patients with coronary artery disease.

BACKGROUND: A simple and accurate scoring system to guide perioperative blood transfusion in patients with coronary artery disease (CAD) undergoing cardiac surgery is lacking. The trigger point for blood transfusions for these patients may be different from existing transfusion guidelines. This study aimed to evaluate the safety and efficacy of a new scoring strategy for use in guiding transfusion decisions in patients with CAD. METHODS: A multicenter randomized controlled trial was conducted at three third-level grade-A hospitals from January 2015 to May 2018. Data of 254 patients in a Cardiac Peri-Operative Transfusion Trigger Score (cPOTTS) group and 246 patients in a group receiving conventional evaluation of the need for transfusion (conventional group) were analysed. The requirements for transfusion and the per capita consumption of red blood cells (RBCs) were compared between groups. RESULTS: Baseline characteristics of the two groups were comparable. Logistic regression analyses revealed no significant differences between the two groups in primary outcomes (1-year mortality and perioperative ischemic cardiac events), secondary outcomes (shock, infections, and renal impairment), ICU admission, and ICU stay duration. However, patients in the cPOTTS group had significantly shorter hospital stays, lower hospital costs, lower utilization rate and lower per capita consumption of transfused RBCs than controls. Stratified analyses revealed no significant differences between groups in associations between baseline characteristics and perioperative ischemic cardiac events, except for hemofiltration or dialysis and NYHA class in I. CONCLUSIONS: This novel scoring system offered a practical and straightforward guideline of perioperative blood transfusion in patients with CAD. Trial registration chiCTR1800016561(2017/7/19).

The incidence and effect of resternotomy following cardiac surgery on morbidity and mortality: a 1-year national audit on behalf of the Association of Cardiothoracic Anaesthesia and Critical Care.

Over 30,000 adult cardiac operations are carried out in the UK annually. A small number of these patients need to return to theatre in the first few days after the initial surgery, but the exact proportion is unknown. The majority of these resternotomies are for bleeding or cardiac tamponade. The Association of Cardiothoracic Anaesthesia and Critical Care carried out a 1-year national audit of resternotomy in 2018. Twenty-three of the 35 centres that were eligible participated. The overall resternotomy rate (95%CI) within the period of admission for the initial operation in these centres was 3.6% (3.37-3.85). The rate varied between centres from 0.69% to 7.6%. Of the 849 patients who required resternotomy, 127 subsequently died, giving a mortality rate (95%CI) of 15.0% (12.7-17.5). In patients who underwent resternotomy, the median (IQR [range]) length of stay on ICU was 5 (2-10 [0-335]) days, and time to tracheal extubation was 20 (12-48 [0-2880]) hours. A total of 89.3% of patients who underwent resternotomy were transfused red cells, with a median (IQR [range]) of 4 (2-7 [1-1144]) units of red blood cells. The rate (95%CI) of needing renal replacement therapy was 23.4% (20.6-26.5). This UK-wide audit has demonstrated that resternotomy after cardiac surgery is associated with prolonged intensive care stay, high rates of blood transfusion, renal replacement therapy and very high mortality. Further research into this area is required to try to improve patient care and outcomes in patients who require resternotomy in the first 24 h after cardiac surgery.

Systematic review of plasma/packed red blood cell ratio on survival in ruptured abdominal aortic aneurysms.

BACKGROUND: The ideal perioperative fluid resuscitation for patients with ruptured abdominal aortic aneurysms (rAAAs) is unknown. It has been shown in trauma studies that a higher ratio of plasma and platelets to packed red blood cells confers a mortality benefit. Controversy remains whether this is true also in the rAAA population. The objective of the present study was to investigate the benefit of a greater ratio of plasma/packed red blood cells in patients with rAAAs. METHODS: A health sciences librarian searched four electronic databases, including PubMed, Embase, Cochrane, and ClinicalTrials.gov, using concepts for the terms "fluid resuscitation," "survival," and "ruptured abdominal aortic aneurysm." Two reviewers independently screened the studies that were identified through the search strategy and read in full any study that was potentially relevant. Studies were included if they had compared the mortality of patients with rAAAs who had received a greater ratio of plasma to other component therapy with that of patients who had received a lower ratio. The risk of bias was assessed using the ROBINS-I (risk of bias in nonrandomized studies of interventions) validated tool, and evidence quality was rated using the GRADE (grades of recommendation assessment, development, and evaluation) profile. No data synthesis or meta-analysis was planned or performed, given the anticipated paucity of research on this topic and the high degree of heterogeneity of available studies. RESULTS: Our search identified seven observational studies for inclusion in the present review. Of these seven studies, three found an associated decrease in mortality with a greater ratio of plasma to packed red blood cells. The remaining four found no significant differences. The overall risk of bias was serious, and the evidence quality was very low. CONCLUSIONS: Overall, the findings from the available studies would suggest that for patients who have undergone open surgery for a rAAA, mortality tends to be decreased when the amount of plasma transfused perioperatively is similar to the amount of packed red blood cells. However, the included studies reported very low-quality evidence based solely on highly heterogeneous observational studies, and further research is warranted.

Preoperative Blood Transfusions and Morbidity in Neonates Undergoing Surgery.

BACKGROUND: Blood transfusions in the neonatal patient population are common, but there are no established guidelines regarding transfusion thresholds. Little is known about postoperative outcomes in neonates who receive preoperative blood transfusions (PBTs). METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program-Pediatric Participant Use Data Files from 2012 to 2015, we identified all neonates who underwent surgery. Mortality and composite morbidity (defined as any postoperative complication) in neonates who received a PBT within 48 hours of surgery were compared with that in neonates who did not receive a transfusion. RESULTS: A total of 12 184 neonates were identified, of whom 1209 (9.9%) received a PBT. Neonates who received a PBT had higher rates of preoperative comorbidities and worse postoperative outcomes when compared with those who did not receive a transfusion (composite morbidity: 46.2% vs 16.2%; P < .01). On multivariable regression analysis, PBTs were independently associated with increased 30-day morbidity (odds ratio [OR] = 1.90; 95% confidence interval [CI]: 1.63-2.22; P < .01) and mortality (OR = 1.98; 95% CI: 1.55-2.55; P < .01). In a propensity score-matched analysis, PBTs continued to be associated with increased 30-day morbidity (OR = 1.53; 95% CI: 1.29-1.81; P < .01) and mortality (OR = 1.58; 95% CI: 1.24-2.01; P = .01). CONCLUSIONS: In a propensity score-matched model, PBTs are independently associated with increased morbidity and mortality in neonates who undergo surgery. Prospective data are needed to better understand the potential effects of a red blood cell transfusion in this patient population.

Red Blood Cell Transfusions and Outcomes After Intracerebral Hemorrhage.

BACKGROUND: Low red blood cell (RBC) levels are associated with worse intracerebral hemorrhage (ICH) outcomes. However, relationships of RBC transfusions on ICH outcomes are unclear given the overlap of RBC transfusion, comorbidities, and disease severity. We investigated RBC transfusion relationships on ICH outcomes while accounting for comorbidities and disease severity. METHODS: ICH hospitalizations between 2002 and 2011 and RBC transfusion exposure were identified from the Nationwide Inpatient Sample using ICD-9-CM codes. Logistic regression was used to study the relationship between RBC transfusion on outcomes after adjusting for demographics, baseline comorbidities, and markers of disease severity. Additional sensitivity analyses stratified by comorbidity burden and disease severity were performed. RESULTS: Of 597,046 ICH hospitalizations, RBC transfusions were administered in 22,904 (4%). RBC transfusion was associated with higher odds of in-hospital mortality (adjusted OR: 1.22 [95%CI: 1.10-1.35]). In sensitivity analyses, RBC transfusions resulted in poor outcomes regardless of the comorbidity burden, but attenuation in this relationship was notable with lower comorbidities (adjusted OR 1.43 [95%CI: 1.34-1.51] vs 1.18 [95%CI: 1.10-1.29]). There were no associations of RBC transfusions with poor outcomes in hospitalizations without mechanical ventilation (adjusted OR 0.88 [95%CI: 0.83-1.13]) and in cases requiring ventriculostomy drains (adjusted OR 1.05 [95%CI: 0.97-1.10]). CONCLUSIONS: In a large, nationally representative sample, RBC transfusion was associated with poor ICH outcomes. However, there were variations in this relationship based on comorbidities and disease severity. Additional prospective studies are required to assess direct risks and benefits from RBC transfusions in ICH.

No clear survival benefit of azacitidine for lower-risk myelodysplastic syndromes: A retrospective study of Nagasaki.

The efficacy of azacitidine (AZA) on survival of lower risk (LR) - myelodysplastic syndromes (MDS) is controversial. To address this issue, we retrospectively evaluated the long-term survival benefit of AZA for patients with LR-MDS defined by International Prognostic Scoring System (IPSS). Using data from 489 patients with LR-MDS in Nagasaki, hematologic responses according to International Working Group 2006 and overall survival (OS) were compared among patients that received best supportive care (BSC), immunosuppressive therapy (IST), erythropoiesis-stimulating agents (ESA), and AZA. Patients treated with AZA showed complete remission (CR) rate at 11.3%, marrow CR at 1.9%, and any hematologic improvement at 34.0%, with transfusion independence (TI) of red blood cells in 27.3% of patients. and platelet in 20% of patients, respectively. Median OS for patients received IST, ESA, BSC, and AZA (not reached, 91 months, 58 months, and 29 months, respectively) differed significantly (P < .001). Infection-related severe adverse events were observed in more than 20% of patients treated with AZA. Multivariate analysis showed age, sex, IPSS score at diagnosis, and transfusion dependence were significant for OS, but AZA treatment was not, which maintained even response to AZA, and IPSS risk status at AZA administration was added as factors. We could not find significant survival benefit of AZA treatment for LR-MDS patients.

Effects of Liberal vs Restrictive Transfusion Thresholds on Survival and Neurocognitive Outcomes in Extremely Low-Birth-Weight Infants: The ETTNO Randomized Clinical Trial.

Importance: 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. Objective: To compare the effect of liberal vs restrictive red blood cell transfusion strategies on death or disability. Design, Setting, and Participants: 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. Interventions: 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. Main Outcome and Measures: 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. Results: 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. Conclusions and Relevance: 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. Trial Registration: ClinicalTrials.gov Identifier: NCT01393496.

Systematic reviews and meta-analyses comparing mortality in restrictive and liberal haemoglobin thresholds for red cell transfusion: an overview of systematic reviews.

BACKGROUND: There are no overviews of systematic reviews investigating haemoglobin thresholds for transfusion. This is important as the literature on transfusion thresholds has grown considerably in recent years. Our aim was to synthesise evidence from systematic reviews and meta-analyses of the effects of restrictive and liberal transfusion strategies on mortality. METHODS: This was a systematic review of systematic reviews (overview). We searched MEDLINE, Embase, Web of Science Core Collection, PubMed, Google Scholar, and the Joanna Briggs Institute EBP Database, from 2008 to 2018. We included systematic reviews and meta-analyses of randomised controlled trials comparing mortality in patients assigned to red cell transfusion strategies based on haemoglobin thresholds. Two independent reviewers extracted data and assessed methodological quality. We assessed the methodological quality of included reviews using AMSTAR 2 and the quality of evidence pooled using an algorithm to assign GRADE levels. RESULTS: We included 19 systematic reviews reporting 33 meta-analyses of mortality outcomes from 53 unique randomised controlled trials. Of the 33 meta-analyses, one was graded as high quality, 15 were moderate, and 17 were low. Of the meta-analyses presenting high- to moderate-quality evidence, 12 (75.0%) reported no statistically significant difference in mortality between restrictive and liberal transfusion groups and four (25.0%) reported significantly lower mortality for patients assigned to a restrictive transfusion strategy. We found few systematic reviews addressed clinical differences between included studies: variation was observed in haemoglobin threshold concentrations, the absolute between group difference in haemoglobin threshold concentration, time to randomisation (resulting in transfusions administered prior to randomisation), and transfusion dosing regimens. CONCLUSIONS: Meta-analyses graded as high to moderate quality indicate that in most patient populations no difference in mortality exists between patients assigned to a restrictive or liberal transfusion strategy. TRIAL REGISTRATION: PROSPERO CRD42019120503.

Red Blood Cell Transfusion After Stage I Palliation Is Associated With Worse Clinical Outcomes.

Background Packed red blood cell transfusion may improve oxygen content in single-ventricle neonates, but its effect on clinical outcomes after Stage 1 palliation is unknown. Methods and Results Retrospective multicenter analysis of packed red blood cell transfusion exposures in neonates after Stage 1 palliation, excluding those with intraoperative mortality or need for extracorporeal membrane oxygenation. Transfusion practice variability was assessed, and multivariable regression used to identify transfusion risk factors. After propensity score adjustment for severity of illness, clinical outcomes were compared between transfused and nontransfused subjects. Of 396 subjects, 323 (82%) received 930 postoperative red blood cell transfusions. Packed red blood cell volume (median 9-42 mL/kg [P<0.0001]), donor exposures (1-2 [P<0.0001]), transfusion number (1-3 [P<0.0001]), and pretransfusion hemoglobin (12.1-13 g/dL, P=0.0049) varied between sites. Cyanosis (P=0.02), chest tube output (P=0.0003), and delayed sternal closure (P=0.0033) increased transfusion risk. Transfusion was associated with prolonged mechanical ventilation (6 [interquartile range 4, 12] versus 3 [1, 5] days, P=0.02) and intensive care unit stay (19 [12, 33] versus 9 [6, 19] days, P=0.016). When stratified by number of transfusions (0, 1, or >1), duration of mechanical ventilation (3 [1, 5] versus 4 [3, 6] versus 9 [5, 16] days [P<0.0001]) and intensive care unit stay (9 [6, 19] versus 13 [8, 25] versus 21 [13, 38] days [P<0.0001]) increased for those transfused more than once. Most subjects who died were transfused, though the association with mortality was not significant. Conclusions Packed red blood cell transfusion after Stage 1 palliation is common, and transfusion practice is variable. Transfusion is a significant predictor of longer intensive care unit stay and mechanical ventilation. Further studies to define evidence-based transfusion thresholds are warranted.

Cost-effectiveness evaluation of the PROPPR trial transfusion protocols.

BACKGROUND: There have been no prior investigations of the cost effectiveness of transfusion strategies for trauma resuscitation. The Pragmatic, Randomized, Optimal Platelet and Plasma Ratios (PROPPR) study was a Phase III multisite, randomized trial in 680 subjects comparing the efficacy of 1:1:1 transfusion ratios of plasma and platelets to red blood cells with the 1:1:2 ratio. We hypothesized that 1:1:1 transfusion results in an acceptable incremental cost-effectiveness ratio, when estimated using patients' age-specific life expectancy and cost of care during the 30-day PROPPR trial period. STUDY DESIGN AND METHODS: International Classification of Diseases, Ninth Revision codes were prospectively collected, and subjects were matched 1:2 to subjects in the Healthcare Utilization Program State Inpatient Data to estimate cost weights. We used a decision tree analysis, combined with standard costs and estimated years of expected survival to determine the cost effectiveness of the two treatments. RESULTS: The 1:1:1 group had higher overall costs for the blood products but were more likely to achieve hemostasis and decreased hemorrhagic death by 24 hours (p = 0.006). For every 100 patients treated in the 1:1:1 group, eight more achieved hemostasis than in the 1:1:2 group. At 30 days, the total hospital cost per 100 patients was $5.6 million in the 1:1:1 group compared with $5.0 million in the 1:1:2 group. For each 100 patients, the 1:1:1 group had 218.5 more years of life expectancy. This was at a cost of $2994 per year gained. CONCLUSION: The 1:1:1 transfusion ratio in severely injured hemorrhaging trauma patients is a very cost-effective strategy for increasing hemostasis and decreasing trauma deaths.

Red Blood Cell Product Transfusion Thresholds and Clinical Outcomes.

OBJECTIVE: To determine whether patients transfused red blood cell (RBC) products according to guideline-specified pretransfusion hemoglobin (Hb) concentrations or for other reasons were more likely to survive their intensive care unit (ICU) stay. DESIGN: An observational study of 375 478 episodes of ICU care, over 5 years, was performed with ICU survival as the primary outcome. Outcomes were analyzed as a function of pretransfusion Hb concentration for groups with distinct transfusion indications while adjusting for potential confounders. SETTING AND PATIENTS: This study included all adult patients discharged from 1 of 203 adult ICUs from 32 US health-care systems. The patients were from community hospitals, tertiary, and academic medical centers. INTERVENTION: Transfusion of allogenic packed RBCs or whole blood was prescribed at the discretion of the treating clinicians. MEASUREMENTS AND MAIN RESULTS: We found that 15% of adult ICU patients are transfused RBC products, and most transfusions for hemodynamically stable patients are administered above the guideline-specified pretransfusion Hb threshold of 7 g/dL. Hemodynamically stable patients transfused below this threshold were significantly more likely to survive their ICU stay than those not transfused (odds ratio [OR] 0.59, 95% confidence interval [CI], 0.43-0.81; P = .001), and patients transfused at thresholds above 9 g/dL were less likely to survive their ICU stay than those not transfused. Patients of the acute blood loss group who were transfused appeared to benefit or were not harmed by transfusion. CONCLUSION: Conservative RBC product transfusion practices for groups that are targeted by guidelines are justified by outcomes observed in clinical practice. This study provides evidence for the liberal administration of RBC products to critically ill adults with acute blood loss based on association with lower risk of mortality.