BACKGROUND
Patient blood management (PBM) programs are associated with improved patient outcomes, reduced transfusions and costs. In 2008, the Western Australia Department of Health initiated a ...comprehensive health‐system–wide PBM program. This study assesses program outcomes.
STUDY DESIGN AND METHODS
This was a retrospective study of 605,046 patients admitted to four major adult tertiary‐care hospitals between July 2008 and June 2014. Outcome measures were red blood cell (RBC), fresh‐frozen plasma (FFP), and platelet units transfused; single‐unit RBC transfusions; pretransfusion hemoglobin levels; elective surgery patients anemic at admission; product and activity‐based costs of transfusion; in‐hospital mortality; length of stay; 28‐day all‐cause emergency readmissions; and hospital‐acquired complications.
RESULTS
Comparing final year with baseline, units of RBCs, FFP, and platelets transfused per admission decreased 41% (p < 0.001), representing a saving of AU$18,507,092 (US$18,078,258) and between AU$80 million and AU$100 million (US$78 million and US$97 million) estimated activity‐based savings. Mean pretransfusion hemoglobin levels decreased 7.9 g/dL to 7.3 g/dL (p < 0.001), and anemic elective surgery admissions decreased 20.8% to 14.4% (p = 0.001). Single‐unit RBC transfusions increased from 33.3% to 63.7% (p < 0.001). There were risk‐adjusted reductions in hospital mortality (odds ratio OR, 0.72; 95% confidence interval CI, 0.67‐0.77; p < 0.001), length of stay (incidence rate ratio, 0.85; 95% CI, 0.84‐0.87; p < 0.001), hospital‐acquired infections (OR, 0.79; 95% CI, 0.73‐0.86; p < 0.001), and acute myocardial infarction‐stroke (OR, 0.69; 95% CI, 0.58‐0.82; p < 0.001). All‐cause emergency readmissions increased (OR, 1.06; 95% CI, 1.02‐1.10; p = 0.001).
CONCLUSION
Implementation of a unique, jurisdiction‐wide PBM program was associated with improved patient outcomes, reduced blood product utilization, and product‐related cost savings.
Objective To compare the benefit and harm of restrictive versus liberal transfusion strategies to guide red blood cell transfusions.Design Systematic review with meta-analyses and trial sequential ...analyses of randomised clinical trials.Data sources Cochrane central register of controlled trials, SilverPlatter Medline (1950 to date), SilverPlatter Embase (1980 to date), and Science Citation Index Expanded (1900 to present). Reference lists of identified trials and other systematic reviews were assessed, and authors and experts in transfusion were contacted to identify additional trials.Trial selection Published and unpublished randomised clinical trials that evaluated a restrictive compared with a liberal transfusion strategy in adults or children, irrespective of language, blinding procedure, publication status, or sample size.Data extraction Two authors independently screened titles and abstracts of trials identified, and relevant trials were evaluated in full text for eligibility. Two reviewers then independently extracted data on methods, interventions, outcomes, and risk of bias from included trials. random effects models were used to estimate risk ratios and mean differences with 95% confidence intervals.Results 31 trials totalling 9813 randomised patients were included. The proportion of patients receiving red blood cells (relative risk 0.54, 95% confidence interval 0.47 to 0.63, 8923 patients, 24 trials) and the number of red blood cell units transfused (mean difference −1.43, 95% confidence interval −2.01 to −0.86) were lower with the restrictive compared with liberal transfusion strategies. Restrictive compared with liberal transfusion strategies were not associated with risk of death (0.86, 0.74 to 1.01, 5707 patients, nine lower risk of bias trials), overall morbidity (0.98, 0.85 to 1.12, 4517 patients, six lower risk of bias trials), or fatal or non-fatal myocardial infarction (1.28, 0.66 to 2.49, 4730 patients, seven lower risk of bias trials). Results were not affected by the inclusion of trials with unclear or high risk of bias. Using trial sequential analyses on mortality and myocardial infarction, the required information size was not reached, but a 15% relative risk reduction or increase in overall morbidity with restrictive transfusion strategies could be excluded.Conclusions Compared with liberal strategies, restrictive transfusion strategies were associated with a reduction in the number of red blood cell units transfused and number of patients being transfused, but mortality, overall morbidity, and myocardial infarction seemed to be unaltered. Restrictive transfusion strategies are safe in most clinical settings. Liberal transfusion strategies have not been shown to convey any benefit to patients.Trial registration PROSPERO CRD42013004272.
Background
Severe bleeding and coagulopathy are serious clinical conditions that are associated with high mortality. Thromboelastography (TEG) and thromboelastometry (ROTEM) are increasingly used to ...guide transfusion strategy but their roles remain disputed. This review was first published in 2011 and updated in January 2016.
Objectives
We assessed the benefits and harms of thromboelastography (TEG)‐guided or thromboelastometry (ROTEM)‐guided transfusion in adults and children with bleeding. We looked at various outcomes, such as overall mortality and bleeding events, conducted subgroup and sensitivity analyses, examined the role of bias, and applied trial sequential analyses (TSAs) to examine the amount of evidence gathered so far.
Search methods
In this updated review we identified randomized controlled trials (RCTs) from the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 1); MEDLINE; Embase; Science Citation Index Expanded; International Web of Science; CINAHL; LILACS; and the Chinese Biomedical Literature Database (up to 5 January 2016). We contacted trial authors, authors of previous reviews, and manufacturers in the field. The original search was run in October 2010.
Selection criteria
We included all RCTs, irrespective of blinding or language, that compared transfusion guided by TEG or ROTEM to transfusion guided by clinical judgement, guided by standard laboratory tests, or a combination. We also included interventional algorithms including both TEG or ROTEM in combination with standard laboratory tests or other devices. The primary analysis included trials on TEG or ROTEM versus any comparator.
Data collection and analysis
Two review authors independently ed data; we resolved any disagreements by discussion. We presented pooled estimates of the intervention effects on dichotomous outcomes as risk ratio (RR) with 95% confidence intervals (CIs). Due to skewed data, meta‐analysis was not provided for continuous outcome data. Our primary outcome measure was all‐cause mortality. We performed subgroup and sensitivity analyses to assess the effect based on the presence of coagulopathy of a TEG‐ or ROTEM‐guided algorithm, and in adults and children on various clinical and physiological outcomes. We assessed the risk of bias through assessment of trial methodological components and the risk of random error through TSA.
Main results
We included eight new studies (617 participants) in this updated review. In total we included 17 studies (1493 participants). A total of 15 trials provided data for the meta‐analyses. We judged only two trials as low risk of bias. The majority of studies included participants undergoing cardiac surgery.
We found six ongoing trials but were unable to retrieve any data from them. Compared with transfusion guided by any method, TEG or ROTEM seemed to reduce overall mortality (7.4% versus 3.9%; risk ratio (RR) 0.52, 95% CI 0.28 to 0.95; I2 = 0%, 8 studies, 717 participants, low quality of evidence) but only eight trials provided data on mortality, and two were zero event trials. Our analyses demonstrated a statistically significant effect of TEG or ROTEM compared to any comparison on the proportion of participants transfused with pooled red blood cells (PRBCs) (RR 0.86, 95% CI 0.79 to 0.94; I2 = 0%, 10 studies, 832 participants, low quality of evidence), fresh frozen plasma (FFP) (RR 0.57, 95% CI 0.33 to 0.96; I2 = 86%, 8 studies, 761 participants, low quality of evidence), platelets (RR 0.73, 95% CI 0.60 to 0.88; I2 = 0%, 10 studies, 832 participants, low quality of evidence), and overall haemostatic transfusion with FFP or platelets (low quality of evidence). Meta‐analyses also showed fewer participants with dialysis‐dependent renal failure.
We found no difference in the proportion needing surgical reinterventions (RR 0.75, 95% CI 0.50 to 1.10; I2 = 0%, 9 studies, 887 participants, low quality of evidence) and excessive bleeding events or massive transfusion (RR 0.38, 95% CI 0.38 to 1.77; I2 = 34%, 2 studies, 280 participants, low quality of evidence). The planned subgroup analyses failed to show any significant differences.
We graded the quality of evidence as low based on the high risk of bias in the studies, large heterogeneity, low number of events, imprecision, and indirectness. TSA indicates that only 54% of required information size has been reached so far in regards to mortality, while there may be evidence of benefit for transfusion outcomes. Overall, evaluated outcomes were consistent with a benefit in favour of a TEG‐ or ROTEM‐guided transfusion in bleeding patients.
Authors' conclusions
There is growing evidence that application of TEG‐ or ROTEM‐guided transfusion strategies may reduce the need for blood products, and improve morbidity in patients with bleeding. However, these results are primarily based on trials of elective cardiac surgery involving cardiopulmonary bypass, and the level of evidence remains low. Further evaluation of TEG‐ or ROTEM‐guided transfusion in acute settings and other patient categories in low risk of bias studies is needed.
Advances in clinical research have led to reduced use of blood products. Judicious use has reduced the incidence of lung injury and circulatory overload. Testing of blood products for infectious ...agents has reduced their transmission.
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
Background
The incidence of hip fracture is increasing and it is more common with increasing age. Surgery is used for almost all hip fractures. Blood loss occurs as a consequence of both the fracture ...and the surgery and thus red blood cell transfusion is frequently used. However, red blood cell transfusion is not without risks. Therefore, it is important to identify the evidence for the effective and safe use of red blood cell transfusion in people with hip fracture.
Objectives
To assess the effects (benefits and harms) of red blood cell transfusion in people undergoing surgery for hip fracture.
Search methods
We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (31 October 2014), the Cochrane Central Register of Controlled Trials (The Cochrane Library, 2014, Issue 10), MEDLINE (January 1946 to 20 November 2014), EMBASE (January 1974 to 20 November 2014), CINAHL (January 1982 to 20 November 2014), British Nursing Index Database (January 1992 to 20 November 2014), the Systematic Review Initiative's Transfusion Evidence Library, PubMed for e‐publications, various other databases and ongoing trial registers.
Selection criteria
Randomised controlled trials comparing red blood cell transfusion versus no transfusion or an alternative to transfusion, different transfusion protocols or different transfusion thresholds in people undergoing surgery for hip fracture.
Data collection and analysis
Three review authors independently assessed each study's risk of bias and extracted data using a study‐specific form. We pooled data where there was homogeneity in the trial comparisons and the timing of outcome measurement. We used GRADE criteria to assess the quality (low, moderate or high) of the evidence for each outcome.
Main results
We included six trials (2722 participants): all compared two thresholds for red blood cell transfusion: a 'liberal' strategy to maintain a haemoglobin concentration of usually 10 g/dL versus a more 'restrictive' strategy based on symptoms of anaemia or a lower haemoglobin concentration, usually 8 g/dL. The exact nature of the transfusion interventions, types of surgery and participants varied between trials. The mean age of participants ranged from 81 to 87 years and approximately 24% of participants were men. The largest trial enrolled 2016 participants, over 60% of whom had a history of cardiovascular disease. The percentage of participants receiving a red blood cell transfusion ranged from 74% to 100% in the liberal transfusion threshold group and from 11% to 45% in the restrictive transfusion threshold group. There were no results available for the smallest trial (18 participants). All studies were at some risk of bias, in particular performance bias relating to the absence of blinding of personnel. We judged the evidence for all outcomes, except myocardial infarction, was low quality reflecting risk of bias primarily from imbalances in protocol violations in the largest trial and imprecision, often because of insufficient events. Thus, further research is likely to have an important impact on these results.
There was no evidence of a difference between a liberal versus restricted threshold transfusion in mortality, at 30 days post hip fracture surgery (risk ratio (RR) 0.92, 95% confidence interval (CI) 0.67 to 1.26; five trials; 2683 participants; low quality evidence) or at 60 days post surgery (RR 1.08, 95% CI 0.80 to 1.44; three trials; 2283 participants; low quality evidence). Assuming an illustrative baseline risk of 50 deaths per 1000 participants in the restricted threshold group at 30 days, these data equate to four fewer (95% CI 17 fewer to 14 more) deaths per 1000 in the liberal threshold group at 30 days.
There was no evidence of a difference between a liberal versus restricted threshold transfusion in functional recovery at 60 days, assessed in terms of the inability to walk 10 feet (3 m) without human assistance (RR 1.00, 95% CI 0.87 to 1.15; two trials; 2083 participants; low quality evidence).
There was low quality evidence of no difference between the transfusion thresholds in postoperative morbidity for the following complications: thromboembolism (RR 1.15 favouring a restrictive threshold, 95% CI 0.56 to 2.37; four trials; 2416 participants), stroke (RR 2.40 favouring a restrictive threshold, 95% CI 0.85 to 6.79; four trials; 2416 participants), wound infection (RR 1.61 favouring a restrictive threshold, 95% CI 0.77 to 3.35; three trials; 2332 participants), respiratory infection (pneumonia) (RR 1.35 favouring a restrictive threshold, 95% CI 0.95 to 1.92; four trials; 2416 participants) and new diagnosis of congestive heart failure (RR 0.77 favouring a liberal threshold, 95% CI 0.48 to 1.23; three trials; 2332 participants). There was very low quality evidence of a lower risk of myocardial infarction in the liberal compared with the restrictive transfusion threshold group (RR 0.59, 95% CI 0.36 to 0.96; three trials; 2217 participants). Assuming an illustrative baseline risk of myocardial infarction of 24 per 1000 participants in the restricted threshold group, this result was compatible with between one and 15 fewer myocardial infarctions in the liberal threshold group.
Authors' conclusions
We found low quality evidence of no difference in mortality, functional recovery or postoperative morbidity between 'liberal' versus 'restrictive' thresholds for red blood cell transfusion in people undergoing surgery for hip fracture. Although further research may change the estimates of effect, the currently available evidence does not support the use of liberal red blood cell transfusion thresholds based on a 10 g/dL haemoglobin trigger in preference to more restrictive transfusion thresholds based on lower haemoglobin levels or symptoms of anaemia in these people. Future research needs to address the effectiveness of red blood cell transfusions at different time points in the surgical pathway, whether pre‐operative, peri‐operative or postoperative. In particular, such research would need to consider people who are symptomatic or haemodynamically unstable who were excluded from most of these trials.
IMPORTANCE: More than 100 million units of blood are collected worldwide each year, yet the indication for red blood cell (RBC) transfusion and the optimal length of RBC storage prior to transfusion ...are uncertain. OBJECTIVE: To provide recommendations for the target hemoglobin level for RBC transfusion among hospitalized adult patients who are hemodynamically stable and the length of time RBCs should be stored prior to transfusion. EVIDENCE REVIEW: Reference librarians conducted a literature search for randomized clinical trials (RCTs) evaluating hemoglobin thresholds for RBC transfusion (1950-May 2016) and RBC storage duration (1948-May 2016) without language restrictions. The results were summarized using the Grading of Recommendations Assessment, Development and Evaluation method. For RBC transfusion thresholds, 31 RCTs included 12 587 participants and compared restrictive thresholds (transfusion not indicated until the hemoglobin level is 7-8 g/dL) with liberal thresholds (transfusion not indicated until the hemoglobin level is 9-10 g/dL). The summary estimates across trials demonstrated that restrictive RBC transfusion thresholds were not associated with higher rates of adverse clinical outcomes, including 30-day mortality, myocardial infarction, cerebrovascular accident, rebleeding, pneumonia, or thromboembolism. For RBC storage duration, 13 RCTs included 5515 participants randomly allocated to receive fresher blood or standard-issue blood. These RCTs demonstrated that fresher blood did not improve clinical outcomes. FINDINGS: It is good practice to consider the hemoglobin level, the overall clinical context, patient preferences, and alternative therapies when making transfusion decisions regarding an individual patient. Recommendation 1: a restrictive RBC transfusion threshold in which the transfusion is not indicated until the hemoglobin level is 7 g/dL is recommended for hospitalized adult patients who are hemodynamically stable, including critically ill patients, rather than when the hemoglobin level is 10 g/dL (strong recommendation, moderate quality evidence). A restrictive RBC transfusion threshold of 8 g/dL is recommended for patients undergoing orthopedic surgery, cardiac surgery, and those with preexisting cardiovascular disease (strong recommendation, moderate quality evidence). The restrictive transfusion threshold of 7 g/dL is likely comparable with 8 g/dL, but RCT evidence is not available for all patient categories. These recommendations do not apply to patients with acute coronary syndrome, severe thrombocytopenia (patients treated for hematological or oncological reasons who are at risk of bleeding), and chronic transfusion–dependent anemia (not recommended due to insufficient evidence). Recommendation 2: patients, including neonates, should receive RBC units selected at any point within their licensed dating period (standard issue) rather than limiting patients to transfusion of only fresh (storage length: <10 days) RBC units (strong recommendation, moderate quality evidence). CONCLUSIONS AND RELEVANCE: Research in RBC transfusion medicine has significantly advanced the science in recent years and provides high-quality evidence to inform guidelines. A restrictive transfusion threshold is safe in most clinical settings and the current blood banking practices of using standard-issue blood should be continued.
Purpose:
We describe an approach for anticoagulation and transfusions in veno-venous–extracorporeal membrane oxygenation (VV-ECMO), evaluating factors associated with higher transfusion requirements, ...and their impact on mortality.
Methods:
Observational study on consecutive adults supported with VV-ECMO for acute respiratory distress syndrome (ARDS). We targeted an activated partial thromboplastin time of 40 to 50 seconds and a hematocrit of 24% to 30%. Univariate and multiple analyses were done to evaluate factors associated with transfusion requirements and the influence of increasing transfusions on mortality during ECMO.
Results:
In a cohort of 82 VV-ECMO patients (PRedicting dEath for SEvere ARDS on VV-ECMO PRESERVE score: 4, Interquartile range IQR: 3-5, Respiratory Extracorporeal Membrane Oxygenation Survival Prediction RESP score: 2, IQR: 2-4), 76 (92.7%) patients received at least 1 unit of packed red blood cells (PRBCs) during the intensive care unit stay related to ECMO (median PRBC/d 156 mL, IQR: 93-218; median ECMO duration 14 days, IQR: 8-22). A higher requirement of PRBC transfusions was associated with pre-ECMO hematocrit, and with the following conditions during ECMO: platelet nadir, antithrombin III (ATIII), and stage 3 of acute kidney injury (all P < .05). Sixty-two (75.6%) patients survived ECMO. Pre-ECMO hospital stay, PRBC transfusion, and septic shock were associated with mortality (all P < .05). The adjusted odds ratio for each 100mL/d increase in PRBC transfusion was 1.9 (95% confidence interval CI: 1.1-3.2, P = .01); for the development of septic shock it was 15.4 (95% CI: 1.7-136.8, P = .01), and for each day of pre-ECMO stay it was 1.1 (95% CI: 1-1.2, P = .04).
Conclusion:
Implementation of a comprehensive protocol for anticoagulation and transfusions in VV-ECMO for ARDS resulted in a low PRBC requirement, and an ECMO survival comparable to data in the literature. Lower ATIII emerged as a factor associated with increased need for transfusions. Higher PRBC transfusions were associated with ECMO mortality. Further investigations are needed to better understand the right level of anticoagulation in ECMO, and the factors to take into account in order to manage personalized transfusion practice in this select setting.
CONTEXT Perioperative red blood cell transfusion is commonly used to address anemia, an independent risk factor for morbidity and mortality after cardiac operations; however, evidence regarding ...optimal blood transfusion practice in patients undergoing cardiac surgery is lacking. OBJECTIVE To define whether a restrictive perioperative red blood cell transfusion strategy is as safe as a liberal strategy in patients undergoing elective cardiac surgery. DESIGN, SETTING, AND PATIENTS The Transfusion Requirements After Cardiac Surgery (TRACS) study, a prospective, randomized, controlled clinical noninferiority trial conducted between February 2009 and February 2010 in an intensive care unit at a university hospital cardiac surgery referral center in Brazil. Consecutive adult patients (n = 502) who underwent cardiac surgery with cardiopulmonary bypass were eligible; analysis was by intention-to-treat. INTERVENTION Patients were randomly assigned to a liberal strategy of blood transfusion (to maintain a hematocrit ≥30%) or to a restrictive strategy (hematocrit ≥24%). MAIN OUTCOME MEASURE Composite end point of 30-day all-cause mortality and severe morbidity (cardiogenic shock, acute respiratory distress syndrome, or acute renal injury requiring dialysis or hemofiltration) occurring during the hospital stay. The noninferiority margin was predefined at −8% (ie, 8% minimal clinically important increase in occurrence of the composite end point). RESULTS Hemoglobin concentrations were maintained at a mean of 10.5 g/dL (95% confidence interval CI, 10.4-10.6) in the liberal-strategy group and 9.1 g/dL (95% CI, 9.0-9.2) in the restrictive-strategy group (P < .001). A total of 198 of 253 patients (78%) in the liberal-strategy group and 118 of 249 (47%) in the restrictive-strategy group received a blood transfusion (P < .001). Occurrence of the primary end point was similar between groups (10% liberal vs 11% restrictive; between-group difference, 1% 95% CI, −6% to 4%; P = .85). Independent of transfusion strategy, the number of transfused red blood cell units was an independent risk factor for clinical complications or death at 30 days (hazard ratio for each additional unit transfused, 1.2 95% CI, 1.1-1.4; P = .002). CONCLUSION Among patients undergoing cardiac surgery, the use of a restrictive perioperative transfusion strategy compared with a more liberal strategy resulted in noninferior rates of the combined outcome of 30-day all-cause mortality and severe morbidity. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01021631
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