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1.
Patient Blood Management: Recommendations From the 2018 Frankfurt Consensus Conference
Mueller MM, Van Remoortel H, Meybohm P, Aranko K, Aubron C, Burger R, Carson JL, Cichutek K, De Buck E, Devine D, et al
Jama. 2019;321(10):983-997
Abstract
Importance: Blood transfusion is one of the most frequently used therapies worldwide and is associated with benefits, risks, and costs. Objective: To develop a set of evidence-based recommendations for patient blood management (PBM) and for research. Evidence Review: The scientific committee developed 17 Population/Intervention/Comparison/Outcome (PICO) questions for red blood cell (RBC) transfusion in adult patients in 3 areas: preoperative anemia (3 questions), RBC transfusion thresholds (11 questions), and implementation of PBM programs (3 questions). These questions guided the literature search in 4 biomedical databases (MEDLINE, EMBASE, Cochrane Library, Transfusion Evidence Library), searched from inception to January 2018. Meta-analyses were conducted with the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology and the Evidence-to-Decision framework by 3 panels including clinical and scientific experts, nurses, patient representatives, and methodologists, to develop clinical recommendations during a consensus conference in Frankfurt/Main, Germany, in April 2018. Findings: From 17607 literature citations associated with the 17 PICO questions, 145 studies, including 63 randomized clinical trials with 23143 patients and 82 observational studies with more than 4 million patients, were analyzed. For preoperative anemia, 4 clinical and 3 research recommendations were developed, including the strong recommendation to detect and manage anemia sufficiently early before major elective surgery. For RBC transfusion thresholds, 4 clinical and 6 research recommendations were developed, including 2 strong clinical recommendations for critically ill but clinically stable intensive care patients with or without septic shock (recommended threshold for RBC transfusion, hemoglobin concentration <7 g/dL) as well as for patients undergoing cardiac surgery (recommended threshold for RBC transfusion, hemoglobin concentration <7.5 g/dL). For implementation of PBM programs, 2 clinical and 3 research recommendations were developed, including recommendations to implement comprehensive PBM programs and to use electronic decision support systems (both conditional recommendations) to improve appropriate RBC utilization. Conclusions and Relevance: The 2018 PBM International Consensus Conference defined the current status of the PBM evidence base for practice and research purposes and established 10 clinical recommendations and 12 research recommendations for preoperative anemia, RBC transfusion thresholds for adults, and implementation of PBM programs. The relative paucity of strong evidence to answer many of the PICO questions supports the need for additional research and an international consensus for accepted definitions and hemoglobin thresholds, as well as clinically meaningful end points for multicenter trials.
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2.
The effectiveness of a de-implementation strategy to reduce low-value blood management techniques in primary hip and knee arthroplasty: a pragmatic cluster-randomized controlled trial
Voorn VMA, Marang-van de Mheen PJ, van der Hout A, Hofstede SN, So-Osman C, van den Akker-van Marle ME, Kaptein AA, Stijnen T, Koopman-van Gemert AWMM, Dahan A, et al
Implementation Science : Is. 2017;12((1)):72.
Abstract
BACKGROUND Perioperative autologous blood salvage and preoperative erythropoietin are not (cost) effective to reduce allogeneic transfusion in primary hip and knee arthroplasty, but are still used. This study aimed to evaluate the effectiveness of a theoretically informed multifaceted strategy to de-implement these low-value blood management techniques. METHODS Twenty-one Dutch hospitals participated in this pragmatic cluster-randomized trial. At baseline, data were gathered for 924 patients from 10 intervention and 1040 patients from 11 control hospitals undergoing hip or knee arthroplasty. The intervention included a multifaceted de-implementation strategy which consisted of interactive education, feedback on blood management performance, and a comparison with benchmark hospitals, aimed at orthopedic surgeons and anesthesiologists. After the intervention, data were gathered for 997 patients from the intervention and 1096 patients from the control hospitals. The randomization outcome was revealed after the baseline measurement. Primary outcomes were use of blood salvage and erythropoietin. Secondary outcomes included postoperative hemoglobin, length of stay, allogeneic transfusions, and use of local infiltration analgesia (LIA) and tranexamic acid (TXA). RESULTS The use of blood salvage (OR 0.08, 95% CI 0.02 to 0.30) and erythropoietin (OR 0.30, 95% CI 0.09 to 0.97) reduced significantly over time, but did not differ between intervention and control hospitals (blood salvage OR 1.74 95% CI 0.27 to 11.39, erythropoietin OR 1.33, 95% CI 0.26 to 6.84). Postoperative hemoglobin levels were significantly higher (beta 0.21, 95% CI 0.08 to 0.34) and length of stay shorter (beta -0.36, 95% CI -0.64 to -0.09) in hospitals receiving the multifaceted strategy, compared with control hospitals and after adjustment for baseline. Transfusions did not differ between the intervention and control hospitals (OR 1.06, 95% CI 0.63 to 1.78). Both LIA (OR 0.0, 95% CI 0.0 to 0.0) and TXA (OR 0.3, 95% CI 0.2 to 0.5) were significantly associated with the reduction in blood salvage over time. CONCLUSIONS Blood salvage and erythropoietin use reduced over time, but not differently between intervention and control hospitals. The reduction in blood salvage was associated with increased use of local infiltration analgesia and tranexamic acid, suggesting that de-implementation is assisted by the substitution of techniques. The reduction in blood salvage and erythropoietin did not lead to a deterioration in patient-related secondary outcomes. TRIAL REGISTRATION www.trialregister.nl, NTR4044.
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3.
Erythropoietin to reduce allogeneic red blood cell transfusion in patients undergoing total hip or knee arthroplasty
Voorn VM, van der Hout A, So-Osman C, Vliet Vlieland TP, Nelissen RG, van den Akker-van Marle ME, Dahan A, Marang-van de Mheen PJ, van Bodegom-Vos L
Vox Sanguinis. 2016;111((3):):219-225
Abstract
BACKGROUND AND OBJECTIVES To determine the value of erythropoietin in reducing allogeneic transfusions, it is important to assess the effects, safety and costs for individual indications. Previous studies neither compared the effects of erythropoietin between total hip and total knee arthroplasty, nor evaluated the safety or costs. We performed a meta-analysis to assess the effects of erythropoietin in total hip and knee arthroplasty separately. Safety and costs were evaluated as secondary outcomes. MATERIALS AND METHODS A systematic literature search was performed to identify randomized controlled trials evaluating the effect of erythropoietin in total hip and knee arthroplasty until April 2014. Study data were extracted using standardized forms and pooled using a random-effects model. Strength of the evidence was evaluated using Cochrane's Collaboration's tool for risk of bias assessment. RESULTS Seven studies were included (2439 patients). Erythropoietin significantly reduced exposure to allogeneic transfusion in both hip (RR 0.45; 95%CI 0.33-0.61) and knee (RR 0.38; 95%CI 0.27-0.53) arthroplasty, without differences between indications (P = 0.44). Mean number of transfused red blood cell units was significantly decreased in erythropoietin-treated patients (mean difference -0.57; 95%CI -0.86 to -0.29)(unable to split). No differences in thromboembolic or adverse events were found. Only one study evaluated costs, so that no pooled cost-effectiveness estimates could be given. CONCLUSION Erythropoietin is effective in both hip and knee arthroplasty and can be considered as safe. However, the decision to use erythropoietin on a routine base should be balanced against its costs, which may be relatively high.
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4.
Patient blood management in elective orthopaedic hip-and knee replacement surgery: a report on clinical outcome
So-Osman C, Balradj J, Koopman-van Gemert AWMM, Onstenk R, van den Hout WB, Brand R, van Hilten JA, Brand A, Nelissen RGHH
Vox Sanguinis. 2016;111((S1)):282.. p-540.
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5.
Patient blood management in elective total hip- and knee-replacement surgery (part 2): a randomized controlled trial on blood salvage as transfusion alternative using a restrictive transfusion policy in patients with a preoperative hemoglobin above 13 g/dl
So-Osman C, Nelissen RG, Koopman-van Gemert AW, Kluyver E, Poll RG, Onstenk R, Van Hilten JA, Jansen-Werkhoven TM, van denHout WB, Brand R, et al
Anesthesiology. 2014;120((4):):852-60.
Abstract
BACKGROUND Patient blood management is introduced as a new concept that involves the combined use of transfusion alternatives. In elective adult total hip- or knee-replacement surgery patients, the authors conducted a large randomized study on the integrated use of erythropoietin, cell saver, and/or postoperative drain reinfusion devices (DRAIN) to evaluate allogeneic erythrocyte use, while applying a restrictive transfusion threshold. Patients with a preoperative hemoglobin level greater than 13 g/dl were ineligible for erythropoietin and evaluated for the effect of autologous blood reinfusion. METHODS Patients were randomized between autologous reinfusion by cell saver or DRAIN or no blood salvage device. Primary outcomes were mean intra- and postoperative erythrocyte use and proportion of transfused patients (transfusion rate). Secondary outcome was cost-effectiveness. RESULTS In 1,759 evaluated total hip- and knee-replacement surgery patients, the mean erythrocyte use was 0.19 (SD, 0.9) erythrocyte units/patient in the autologous group (n = 1,061) and 0.22 (0.9) erythrocyte units/patient in the control group (n = 698) (P = 0.64). The transfusion rate was 7.7% in the autologous group compared with 8.3% in the control group (P = 0.19). No difference in erythrocyte use was found between cell saver and DRAIN groups. Costs were increased by &OV0556;298 per patient (95% CI, 76 to 520). CONCLUSION In patients with preoperative hemoglobin levels greater than 13 g/dl, autologous intra- and postoperative blood salvage devices were not effective as transfusion alternatives: use of these devices did not reduce erythrocyte use and increased costs.
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6.
Patient blood management in elective total hip- and knee-replacement surgery (part 1): a randomized controlled trial on erythropoietin and blood salvage as transfusion alternatives using a restrictive transfusion policy in erythropoietin-eligible patients
So-Osman C, Nelissen RG, Koopman-van Gemert AW, Kluyver E, Poll RG, Onstenk R, Van Hilten JA, Jansen-Werkhoven TM, van denHout WB, Brand R, et al
Anesthesiology. 2014;120((4):):839-51.
Abstract
BACKGROUND Patient blood management combines the use of several transfusion alternatives. Integrated use of erythropoietin, cell saver, and/or postoperative drain reinfusion devices on allogeneic erythrocyte use was evaluated using a restrictive transfusion threshold. METHODS In a factorial design, adult elective hip- and knee-surgery patients with hemoglobin levels 10 to 13 g/dl (n = 683) were randomized for erythropoietin or not, and subsequently for autologous reinfusion by cell saver or postoperative drain reinfusion devices or for no blood salvage device. Primary outcomes were mean allogeneic intra- and postoperative erythrocyte use and proportion of transfused patients (transfusion rate). Secondary outcome was cost-effectiveness. RESULTS With erythropoietin (n = 339), mean erythrocyte use was 0.50 units (U)/patient and transfusion rate 16% while without (n = 344), these were 0.71 U/patient and 26%, respectively. Consequently, erythropoietin resulted in a nonsignificant 29% mean erythrocyte reduction (ratio, 0.71; 95% CI, 0.42 to 1.13) and 50% reduction of transfused patients (odds ratio, 0.5; 95% CI, 0.35 to 0.75). Erythropoietin increased costs by &OV0556;785 per patient (95% CI, 262 to 1,309), that is, &OV0556;7,300 per avoided transfusion (95% CI, 1,900 to 24,000). With autologous reinfusion, mean erythrocyte use was 0.65 U/patient and transfusion rate was 19% with erythropoietin (n = 214) and 0.76 U/patient and 29% without (n = 206). Compared with controls, autologous blood reinfusion did not result in erythrocyte reduction and increased costs by &OV0556;537 per patient (95% CI, 45 to 1,030). CONCLUSIONS In hip- and knee-replacement patients (hemoglobin level, 10 to 13 g/dl), even with a restrictive transfusion trigger, erythropoietin significantly avoids transfusion, however, at unacceptably high costs. Autologous blood salvage devices were not effective.
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7.
Cost effectiveness of patient blood management methods
So-Osman C
Vox Sanguinis. 2014;107((S1):):11.. 2c-s06-02.
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8.
The impact of a restrictive transfusion trigger on post-operative complication rate and well-being following elective orthopaedic surgery: a post-hoc analysis of a randomised study
So-Osman C, Nelissen R, Brand R, Faber F, Slaa RT, Stiggelbout A, Brand A
Blood Transfusion. 2013;11((2):):289-95.
Abstract
BACKGROUND Peri-operative red blood cell transfusions have been associated with post-operative complications in patients undergoing elective orthopaedic hip or knee replacement surgery. MATERIALS AND METHODS We performed a post-hoc analysis of data extracted from a randomised study on transfusion triggers using pre-storage leucocyte-depleted red blood cells. Patients who were assigned to the most restrictive transfusion policy (restrictive group) were compared with patients who were assigned to the most liberal policy (liberal group). End-points were red blood cell use, hospital stay, haemoglobin levels, post-operative complications and quality of life scores. RESULTS Of 603 patients, 26.4% patients in the restrictive group and 39.1% in the liberal group were transfused (P =0.001). The rate of post-operative infections was lower, although not statistically significantly so, in the restrictive group than in the liberal group (5.4% vs. 10.2%, respectively) as was the rate of respiratory complications (1.7% vs. 4.9%, respectively), whereas hospital stay, cardiovascular complications and mortality rate were not different in the two groups. Quality of life scores were not associated with type of transfusion policy, the number of red blood cell transfusions or the transfusion status. DISCUSSION A restrictive transfusion protocol was not associated with worse outcome and resulted in a lower transfusion rate compared to the liberal policy. Well-being (quality of life) was not associated with transfusion policy or with red blood cell transfusions.
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9.
'Pre-operative iron' use as blood sparing technique in orthopaedic surgery (the POP-I study)
van Nordennen J, Koopman-van Gemert AWMM, So-Osman C, Zwaginga JJ, Nelissen RGHH
Vox Sanguinis. 2013;105((S1):):267.. Abstract No. P-604.
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10.
A randomised controlled trial on erythropoietin and blood salvage as transfusion alternatives in orthopaedic surgery using a restrictive transfusion policy
So-Osman C, Nelissen RGHH, Koopman-van Gemert A, Kluyver E, Poll R, Onstenk R, Van Hilten JA, Jansen-Werkhoven TM, Brand R, Brand A
Transfusion Alternatives in Transfusion Medicine. 2011;12((1, Poster Abstracts):):25-26.