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1.
A restrictive versus liberal transfusion strategy to prevent myocardial injury in patients undergoing surgery for fractured neck of femur: a feasibility randomised trial (RESULT-NOF)
Gillies, M. A., Ghaffar, S., Moppett, I. K., Docherty, A. B., Clarke, S., Rea, N., Stephen, J., Keerie, C., Ray, D. C., White, T. O., et al
British Journal of Anaesthesia. 2021;126(1):77-86
Abstract
BACKGROUND The optimum transfusion strategy in patients with fractured neck of femur is uncertain, particularly if there is coexisting cardiovascular disease. METHODS We conducted a prospective, single-centre, randomised feasibility trial of two transfusion strategies. We randomly assigned patients undergoing surgery for fractured neck of femur to a restrictive (haemoglobin, 70-90 g L(-1)) or liberal (haemoglobin, 90-110 g L(-1)) transfusion strategy throughout their hospitalisation. Feasibility outcomes included: enrolment rate, protocol compliance, difference in haemoglobin, and blood exposure. The primary clinical outcome was myocardial injury using troponin estimations. Secondary outcomes included major adverse cardiac events, postoperative complications, duration of hospitalisation, mortality, and quality of life. RESULTS We enrolled 200 (22%) of 907 eligible patients, and 62 (31%) showed decreased haemoglobin (to 90 g L(-1) or less) and were thus exposed to the intervention. The overall protocol compliance was 81% in the liberal group and 64% in the restrictive group. Haemoglobin concentrations were similar preoperatively and at postoperative day 1 but lower in the restrictive group on day 2 (mean difference [MD], 7.0 g L(-1); 95% confidence interval [CI], 1.6-12.4). Lowest haemoglobin within 30 days/before discharge was lower in the restrictive group (MD, 5.3 g L(-1); 95% CI, 1.7-9.0). Overall, 58% of patients in the restrictive group received no transfusion compared with 4% in the liberal group (difference in proportion, 54.5%; 95% CI, 36.8-72.2). The proportion with the primary clinical outcome was 14/26 (54%, liberal) vs 24/34 (71%, restrictive), and the difference in proportion was -16.7% (95% CI, -41.3 to 7.8; P=0.18). CONCLUSION A clinical trial of two transfusion strategies in hip fracture with a clinically relevant cardiac outcome is feasible. CLINICAL TRIAL REGISTRATION NCT03407573.
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2.
Liberal blood transfusion strategies and associated infection in orthopedic patients: A meta-analysis
Wang Y, Chen J, Yang Z, Liu Y
Medicine. 2021;100(10):e24430
Abstract
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; Pā=ā.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.
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3.
Restrictive versus liberal strategy for red blood-cell transfusion in hip fracture patients: A systematic review and meta-analysis
Zhu C, Yin J, Wang B, Xue Q, Gao S, Xing L, Wang H, Liu W, Liu X
Medicine. 2019;98(32):e16795
Abstract
BACKGROUND Most clinical guidelines recommend a restrictive red-blood-cell (RBC) transfusion threshold. However, indications for transfusion in patients with a hip fracture have not been definitively evaluated or remain controversial. We compared the pros and cons of restrictive versus liberal transfusion strategies in patients undergoing hip fracture surgery. METHODS Electronic databases were searched to identify randomized controlled trials (RCTs) and retrospective cohort studies (RCSs) to investigate the effects of a restrictive strategy versus its liberal counterpart in patients undergoing hip fracture surgery. The main clinical outcomes included delirium, mortality, infections, cardiogenic complications, thromboembolic events, cerebrovascular accidents, and length of hospital stay. The meta-analysis program of the Cochrane Collaboration (RevMan version 5.3.0) was used for data analysis. Statistical heterogeneity was assessed by both Cochran chi-squared test (Q test) and I test. Both Begg and Egger tests were used to assess potential publication bias. RESULTS We identified 7 eligible RCTs and 2 eligible RCSs, involving 3,575 patients in total. In patients undergoing hip fracture surgery, we found no differences in frequency of delirium, mortality, the incidence rates of all infections, pneumonia, wound infection, all cardiovascular events, congestive heart failure, thromboembolic events or length of hospital stay between restrictive and liberal thresholds for RBC transfusion (P >.05). However, we found that the use of restrictive transfusion thresholds is associated with higher rates of acute coronary syndrome (P <.05) while liberal transfusion thresholds increase the risk of cerebrovascular accidents (P <.05). CONCLUSION In patients undergoing hip fracture surgery, clinicians should evaluate the patient's condition in detail and adopt different transfusion strategies according to the patient's specific situation rather than merely using a certain transfusion strategy.
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4.
Mortality, Morbidity and Related Outcomes Following Perioperative Blood Transfusion in Patients with Major Orthopaedic Surgery: A Systematic Review
Muller S, Oberle D, Drechsel-Bauerle U, Pavel J, Keller-Stanislawski B, Funk MB
Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie. 2018;45((5):):355-367.
Abstract
Background: Benefits and risks of liberal and restrictive transfusion regimens are under on-going controversial discussion. This systematic review aimed at assessing both regimens in terms of pre-defined outcomes with special focus on patients undergoing major orthopaedic surgery. Methods: We performed a literature search for mortality, morbidity and related outcomes following peri-operative blood transfusion in patients with major orthopaedic surgery in electronic databases. Combined outcome measure estimates were calculated within the scope of meta-analyses including randomised clinical trials comparing restrictive versus liberal blood transfusion regimens (e.g. MH risk ratio, Peto odds ratio). Results: A total of 880 publications were identified 15 of which were finally included (8 randomised clinical trials (RCTs) with 3,693 patients and 6 observational studies with 4,244,112 patients). Regarding RCTs, no significant differences were detected between the transfusion regimes for all primary outcomes (30-day mortality, thromboembolic events, stroke/transitory ischaemic attack, myocardial infarction, wound infection and pneumonia) and a secondary outcome (length of hospital stay), whereas there was a significantly reduced risk of receiving at least one red blood concentrate under a restrictive regimen. Conclusion: The results of this systematic review do not suggest an increased risk associated with either a restrictive or a liberal transfusion regimen in patients undergoing major orthopaedic surgery.
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5.
Blood transfusion and postoperative infection in spine surgery: A systematic review
Fisahn C, Schmidt C, Schroeder J E, Vialle E, Lieberman I H, Dettori J R, Schildhauer T A
Global Spine Journal. 2018;8((2)):198-207.
Abstract
Study Design: Systematic review. Objectives: Allogeneic blood transfusion-related immunomodulation may relatively suppress the immune system, heightening the risk of infection following spine surgery. This systematic review seeks to determine whether allogeneic blood transfusion increases the risk of postoperative infection and whether there are any factors that modify this association. Methods: PubMed, Cochrane Central Register of Controlled Trials, and reference lists from included studies were searched from inception to April 20, 2017 to identify studies examining the risk of infection following allogeneic blood transfusion in adult patients receiving surgery for degenerative spine disease. Results: Eleven retrospective cohort or case-control studies, involving 8428 transfusion patients and 43 242 nontransfusion patients, were identified as meeting the inclusion criteria. Regarding surgical site infection (SSI), the results were mixed with roughly half reporting a significant association. There was an association between allogeneic transfusion and urinary tract infection (UTI) and any infection, but not respiratory tract infection. There was no statistical modifying effect of lumbar versus thoracic surgery on the association of allogeneic transfusion and SSI, though subgroup analyses in 3 of 4 studies reported a statistical association between transfusion and postoperative infections, including SSI, UTI, and any infection within the lumbar spine. Conclusions: This systematic review failed to find a consistent association between allogeneic transfusion and postoperative infection in spine surgery patients. However, these studies were all retrospective with a high or moderately high risk of bias. To properly examine this association an observational prospective study of sufficient power, estimated as 2400 patients, is required.
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6.
Restrictive versus liberal transfusion strategies for red blood cell transfusion after hip or knee surgery: a systematic review and meta-analysis
Mao T, Gao F, Han J, Sun W, Guo W, Li Z, Wang W
Medicine. 2017;96((25)):e7326.
Abstract
BACKGROUND Red blood cell (RBC) transfusions are commonly used in surgical patients, but accompanied by many risks such as metabolic derangement, and allergic and febrile reactions. Indications for transfusion in patients after hip or knee surgery have not been definitively evaluated and remain controversial. We performed a meta-analysis to compare the benefits and harms of restrictive versus liberal transfusion strategies in patients after hip or knee surgery. METHODS The PubMed, EMBASE, and Cochrane Library databases were searched for relevant studies through September 2015. The main clinical outcomes reported in randomized controlled trials (RCTs) included 30-day mortality, infection rate, cardiogenic complications, and length of hospital stay. The meta-analysis program of the Cochrane Collaboration (RevMan version 5.3.0) was used for data analysis. Statistical heterogeneity was assessed by both Cochran chi-squared test (Q test) and I test. Begg and Egger test were used to assess potential publication bias. RESULTS We identified 10 eligible RCTs, involving 3788 patients in total. In patients undergoing hip or knee surgery, we found no differences in mortality, or the incidence rates of pneumonia, wound infection, myocardial infarction, or congestive heart failure, between restrictive and liberal thresholds for RBC transfusion (P > .05). CONCLUSION Restrictive transfusion has no advantage over the liberal strategy. However, considerably less patients received blood transfusion via the restrictive strategy than with the liberal counterpart. Due to variations in the included studies, additional larger scale and well-designed studies are required to validate these conclusions.
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7.
Postoperative red blood cell transfusion strategy in frail anemic elderly with hip fracture. A randomized controlled trial
Gregersen, M.
Danish Medical Journal. 2016;63((4))
Abstract
Hip fracture in the elderly is associated with poor recovery from physical disability and mortality. Perioperative blood loss is common, and anemia might be fatal in the frail elderly. Red blood cell transfusions might increase the risk of infection. In an observational study, a liberal transfusion strategy with hemoglobin (Hb) target of 7 mmol/l (11.3 g/dl) seemed to improve survival in nursing home residents with hip fracture compared to the recommended restrictive strategy with a Hb target of 6 mmol/l (9.7 g/dl) according to the Danish Health Authority. Our aim was to compare these two strategies in the frail elderly in a randomized controlled trial on the outcomes: recovery from physical disabilities, mortality, infection, infection biomarkers, and overall Quality of Life (OQoL). We included 284 elderly admitted to hospital for surgical hip fracture repair from nursing homes or sheltered housing facilities. The anemic patients were assigned postoperatively to the liberal or the restrictive transfusion strategy. Randomization divided each transfusion group into two equal blocks with regard to type of the residence. Hb was measured daily during the first three postoperative days, at least once during the following 4-6 days, then at least once a week during the subsequent three weeks. The transfusions were administered according to group assignments, but no later than 24 hours after the Hb determination, one unit at a time, and no more than two units per day. The intervention lasted for 30 days after surgery. Outcome measurements were performed on days 10, 30, 90, and 365. Blinded assessors evaluated physical performance and OQoL. The liberal transfusion strategy did not improve recovery from physical disabilities, mortality, infection rate, or OQoL compared to the restrictive strategy. However, in nursing home residents, 90-day mortality rate (20%) following the liberal strategy was statistically significantly lower than that (36%) after the restrictive strategy. Per protocol, the 30-day mortality rate was statistically significantly lower following the liberal strategy in all patients (7% versus 16%). No statistically significant difference was found in repeated leukocyte counts and C-reactive protein measurements, or in rate of all infections after ten days (66% versus 72%). Physical recovery from 30 days until one year after hip fracture surgery was improved by the liberal strategy. A liberal strategy did not improve 30-day OQoL. Physical performance was improved from 30 days to one year after fracture in patients treated according to the liberal strategy and was associated with better progress of OQoL in the same period. We conclude that according to our used Hb thresholds, the liberal Hb target of 7 mmol/l (11.3 g/dl) improves survival in the frailest elderly (the nursing home residents) without impairing recovery from physical disabilities and OQoL or increasing risk of infections compared to the restrictive Hb target of 6 mmol/l (9.7 g/dl). The liberal strategy seems to improve recovery of physical performance within one year after hip fracture surgery which was associated with better overall QoL.
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8.
Postoperative blood transfusion strategy in frail, anemic elderly patients with hip fracture
Gregersen M, Borris LC, Damsgaard EM
Acta Orthopaedica. 2015;86((3)):363-72.
Abstract
Background and purpose - Hip fracture (HF) in frail elderly patients is associated with poor physical recovery and death. There is often postoperative blood loss and the hemoglobin (Hb) threshold for red blood cell (RBC) transfusions in these patients is unknown. We investigated whether RBC transfusion strategies were associated with the degree of physical recovery or with reduced mortality after HF surgery. Patients and methods - We enrolled 284 consecutive post-surgical HF patients (aged > 65 years) with Hb levels < 11.3 g/dL (7 mmol/L) who had been admitted from nursing homes or sheltered housing. Allocation was stratified by residence. The patients were randomly assigned to either restrictive (Hb < 9.7 g/dL; < 6 mmol/L) or liberal (Hb < 11.3 g/dL; < 7 mmol/L) RBC transfusions given within the first 30 days postoperatively. Follow-up was at 90 days. Results - No statistically significant differences were found in repeated measures of daily living activities or in 90-day mortality rate between the restrictive group (where 27% died) and the liberal group (where 21% died). Per-protocol 30-day mortality was higher with the restrictive strategy (hazard ratio (HR) = 2.4, 95% CI: 1.1-5.2; p = 0.03). The 90-day mortality rate was higher for nursing home residents in the restrictive transfusion group (36%) than for those in the liberal group (20%) (HR = 2.0, 95% CI: 1.1-3.6; p = 0.01). Interpretation - According to our Hb thresholds, recovery from physical disabilities in frail elderly hip fracture patients was similar after a restrictive RBC transfusion strategy and after a liberal strategy. Implementation of a liberal RBC transfusion strategy in nursing home residents has the potential to increase survival.
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9.
Restrictive blood transfusion strategies and associated infection in orthopedic patients: a meta-analysis of 8 randomized controlled trials
Teng Z, Zhu Y, Liu Y, Wei G, Wang S, Du S, Zhang X
Scientific Reports.. 2015;5:13421.
Abstract
This study sought to evaluate whether restrictive blood transfusion strategies are associated with a risk of infection in orthopedic patients by conducting a meta-analysis of randomized controlled trials (RCTs). RCTs with restrictive versus liberal red blood cell (RBC) transfusion strategies were identified by searching Medline, Embase, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews from their inception to December 2014. Eight RCTs with infections as outcomes were included in the final analysis. According to the Jadad scale, all studies were considered to be of high quality. The pooled risk ratio [RR] for the association between transfusion strategy and infection was 0.65 (95% CI, 0.47-0.91; p=0.012), and the number of patients needed to treat to avoid an infection using a restrictive transfusion strategy was 62. No heterogeneity was observed. The sensitivity analysis indicated unstable results, and no significant publication bias was observed. This meta-analysis of RCTs demonstrates that restrictive transfusion strategies in orthopedic patients result in a significant reduction in infections compared with more liberal strategies.
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10.
Liberal versus restrictive blood transfusion strategy: 3-year survival and cause of death results from the FOCUS randomised controlled trial
Carson JL, Sieber F, Cook DR, Hoover DR, Noveck H, ChaitmanBR, Fleisher L, Beaupre L, Macaulay W, Rhoads GG, et al
Lancet. 2015;385((9974):):1183-9
Abstract
BACKGROUND Blood transfusion might affect long-term mortality by changing immune function and thus potentially increasing the risk of subsequent infections and cancer recurrence. Compared with a restrictive transfusion strategy, a more liberal strategy could reduce cardiac complications by lowering myocardial damage, thereby reducing future deaths from cardiovascular disease. We aimed to establish the effect of a liberal transfusion strategy on long-term survival compared with a restrictive transfusion strategy. METHODS In the randomised controlled FOCUS trial, adult patients aged 50 years and older, with a history of or risk factors for cardiovascular disease, and with postoperative haemoglobin concentrations lower than 100 g/L within 3 days of surgery to repair a hip fracture, were eligible for enrolment. Patients were recruited from 47 participating hospitals in the USA and Canada, and eligible participants were randomly allocated in a 1:1 ratio by a central telephone system to either liberal transfusion in which they received blood transfusion to maintain haemoglobin level at 100 g/L or higher, or restrictive transfusion in which they received blood transfusion when haemoglobin level was lower than 80 g/L or if they had symptoms of anaemia. In this study, we analysed the long-term mortality of patients assigned to the two transfusion strategies, which was a secondary outcome of the FOCUS trial. Long-term mortality was established by linking the study participants to national death registries in the USA and Canada. Treatment assignment was not masked, but investigators who ascertained mortality and cause of death were masked to group assignment. Analyses were by intention to treat. The FOCUS trial is registered with ClinicalTrials.gov, number NCT00071032. FINDINGS Between July 19, 2004, and Feb 28, 2009, 2016 patients were enrolled and randomly assigned to the two treatment groups: 1007 to the liberal transfusion strategy and 1009 to the restrictive transfusion strategy. The median duration of follow-up was 31 years (IQR 24-41 years), during which 841 (42%) patients died. Long-term mortality did not differ significantly between the liberal transfusion strategy (432 deaths) and the restrictive transfusion strategy (409 deaths) (hazard ratio 109 [95% CI 095-125]; p=021). INTERPRETATION Liberal blood transfusion did not affect mortality compared with a restrictive transfusion strategy in a high-risk group of elderly patients with underlying cardiovascular disease or risk factors. The underlying causes of death did not differ between the trial groups. These findings do not support hypotheses that blood transfusion leads to long-term immunosuppression that is severe enough to affect long-term mortality rate by more than 20-25% or cause of death. FUNDING National Heart, Lung, and Blood Institute.Copyright © 2015 Elsevier Ltd. All rights reserved.