Effectiveness of Iron Supplementation With or Without Erythropoiesis-Stimulating Agents on Red Blood Cell Utilization in Patients With Preoperative Anaemia Undergoing Elective Surgery: A Systematic Review and Meta-Analysis
Transfusion medicine reviews. 2021
Patient Blood Management (PBM) is an evidence-based, multidisciplinary, patient-centred approach to optimizing the care of patients who might need a blood transfusion. This systematic review aimed to collect the best available evidence on the effectiveness of preoperative iron supplementation with or without erythropoiesis-stimulating agents (ESAs) on red blood cell (RBC) utilization in all-cause anaemic patients scheduled for elective surgery. Five databases and two trial registries were screened. Primary outcomes were the number of patients and the number of RBC units transfused. Effect estimates were synthesized by conducting meta-analyses. GRADE (Grades of Recommendation, Assessment, Development and Evaluation) was used to assess the certainty of evidence. We identified 29 randomized controlled trials (RCTs) and 2 non-RCTs comparing the effectiveness of preoperative iron monotherapy, or iron + ESAs, to control (no treatment, usual care, placebo). We found that: (1) IV and/or oral iron monotherapy may not result in a reduced number of units transfused and IV iron may not reduce the number of patients transfused (low-certainty evidence); (2) uncertainty exists whether the administration route of iron therapy (IV vs oral) differentially affects RBC utilization (very low-certainty evidence); (3) IV ferric carboxymaltose monotherapy may not result in a different number of patients transfused compared to IV iron sucrose monotherapy (low-certainty evidence); (4) oral iron + ESAs probably results in a reduced number of patients transfused and number of units transfused (moderate-certainty evidence); (5) IV iron + ESAs may result in a reduced number of patients transfused (low-certainty evidence); (6) oral and/or IV iron + ESAs probably results in a reduced number of RBC units transfused in transfused patients (moderate-certainty evidence); (7) uncertainty exists about the effect of oral and/or IV iron + ESAs on the number of patients requiring transfusion of multiple units (very low-certainty evidence). Effect estimates of different haematological parameters and length of stay were synthesized as secondary outcomes. In conclusion, in patients with anaemia of any cause scheduled for elective surgery, the preoperative administration of iron monotherapy may not result in a reduced number of patients or units transfused (low-certainty evidence). Iron supplementation in addition to ESAs probably results in a reduced RBC utilization (moderate-certainty evidence).
Lack of Cost-Effectiveness of Preoperative Erythropoiesis-Stimulating Agents and/or Iron Therapy in Anaemic, Elective Surgery Patients: A Systematic Review and Updated Analysis
OBJECTIVES For anaemic elective surgery patients, current clinical practice guidelines weakly recommend the routine use of iron, but not erythrocyte-stimulating agents (ESAs), except for short-acting ESAs in major orthopaedic surgery. This recommendation is, however, not based on any cost-effectiveness studies. The aim of this research was to (1) systematically review the literature regarding cost effectiveness of preoperative iron and/or ESAs in anaemic, elective surgery patients and (2) update existing economic evaluations (EEs) with recent data. METHODS Eight databases and registries were searched for EEs and randomized controlled trials (RCTs) reporting cost-effectiveness data on November 11, 2020. Data were extracted, narratively synthesized and critically appraised using the Philips reporting checklist. Pre-existing full EEs were updated with effectiveness data from a recent systematic review and current cost data. Incremental cost-effectiveness ratios were expressed as cost per (quality-adjusted) life-year [(QA)LY] gained. RESULTS Only five studies (4 EEs and 1 RCT) were included, one on intravenous iron and four on ESAs + oral iron. The EE on intravenous iron only had an in-hospital time horizon. Therefore, cost effectiveness of preoperative iron remains uncertain. The three EEs on ESAs had a lifetime time horizon, but reported cost per (QA)LY gained of 20-65 million (GBP or CAD). Updating these analyses with current data confirmed ESAs to have a cost per (QA)LY gained of 3.5-120 million (GBP or CAD). CONCLUSIONS Cost effectiveness of preoperative iron is unproven, whereas routine preoperative ESA therapy cannot be considered cost effective in elective surgery, based on the limited available data. Future guidelines should reflect these findings.
Elective surgery patients with anaemia (5 studies).
Erythrocyte-stimulating agents (ESAs) and oral iron.
The economic evaluation on intravenous iron only had an in-hospital time horizon. Cost effectiveness of preoperative iron remained uncertain. The three economic evaluations on ESAs had a lifetime time horizon, but reported cost per (QA)LY gained of 20-65 million (GBP or CAD). Updating these analyses with current data confirmed ESAs to have a cost per (QA)LY gained of 3.5-120 million (GBP or CAD).
Patient Blood Management: Recommendations From the 2018 Frankfurt Consensus Conference
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.
Is there a risk of transfusion-transmissible infections after percutaneous needle treatments in blood donors? A systematic review and meta-analysis
Vox sanguinis. 2019
BACKGROUND AND OBJECTIVES The donor medical questionnaire identifies a blood donor's history of known blood safety risks. Current Australian, Canadian, European and USA legislation temporarily defers blood donors who received different percutaneous needle treatments (i.e. tattooing, acupuncture and piercing) from blood donation. This systematic review aimed to scientifically underpin these deferrals by identifying the best available evidence on the association between percutaneous needle treatments and the risk of transfusion-transmissible infections (TTIs). MATERIALS AND METHODS Studies from three databases investigating the link between percutaneous needle treatments and TTIs (HBV, HCV and HIV infection) in blood donors were retained and assessed on eligibility by two reviewers independently. The association between percutaneous needle treatments and TTIs was expressed by conducting meta-analyses and calculating pooled effect measures (odds ratios (ORs) and 95% CIs). The GRADE methodology (Grades of Recommendation, Assessment, Development and Evaluation) was used to assess the quality of evidence. RESULTS We identified 1242 references and finally included 21 observational studies. Twenty studies assessed the link between percutaneous needle treatments and HCV infection and found that blood donors receiving these treatments had an increased risk of HCV infection (tattooing: pooled OR 5.28, 95% CI [4.33, 6.44], P < 0.00001 (low-quality evidence); acupuncture: pooled OR 1.56, 95% CI [1.17, 2.08], P = 0.03 (very low-quality evidence); and piercing: pooled OR 3.25, 95% CI [1.68, 6.30], P = 0.0005 (low-quality evidence)). CONCLUSION Percutaneous needle treatments may be associated with an increased HCV infection risk. Further high-quality studies are required to formulate stronger evidence-based recommendations on percutaneous needle treatments as a blood donor deferral criterion.
The systematic use of evidence-based methodologies and technologies enhances shared decision-making in the 2018 International Consensus Conference on Patient Blood Management
Vox sanguinis. 2019
BACKGROUND AND OBJECTIVES Patient Blood Management (PBM) aims to optimize the care of patients who might need a blood transfusion. The International Consensus Conference on PBM (ICC-PBM) aimed to develop evidence-based recommendations on three topics: preoperative anaemia, red blood cell transfusion thresholds and implementation of PBM programmes. This paper reports how evidence-based methodologies and technologies were used to enhance shared decision-making in formulating recommendations during the ICC-PBM. MATERIALS & METHODS Systematic reviews on 17 PICO (Population, Intervention, Comparison, Outcomes) questions were conducted by a Scientific Committee (22 international topic experts and one methodologist) according to GRADE (Grades of Recommendation, Assessment, Development and Evaluation) methodology. Evidence-based recommendations were formulated using Consensus Development Conference methodology. RESULTS We screened 17 607 references and included 145 studies. The overall certainty in the evidence of effect estimates was generally low or very low. During the ICC, plenary sessions (100-200 stakeholders from a range of clinical disciplines and community representatives) were followed by closed sessions where multidisciplinary decision-making panels (>50 experts and patient organizations) formulated recommendations. Two chairs (content-expert and methodologist) moderated each session and two rapporteurs documented the discussions. The Evidence-to-Decision template (GRADEpro software) was used as the central basis in the process of formulating recommendations. CONCLUSION This ICC-PBM resulted in 10 clinical and 12 research recommendations supported by an international stakeholder group of experts in blood transfusion. Systematic, rigorous and transparent evidence-based methodology in a formal consensus format should be the new standard to evaluate (cost-) effectiveness of medical treatments, such as blood transfusion.
Is sexual risk behaviour associated with an increased risk of transfusion-transmissible infections in blood donors from Western and Pacific countries? A systematic review and meta-analysis
Vox sanguinis. 2019
BACKGROUND AND OBJECTIVES The donor medical questionnaire is designed to aid blood establishments in supporting a safe blood supply. According to blood donor deferral policies, sexual risk behaviour (SRB) leads to a (temporary) deferral from blood donation. This systematic review aimed to scientifically underpin these policies by identifying the best available evidence on the association between SRB and the risk of transfusion transmissible infections (TTIs). MATERIALS & METHODS Studies from three databases investigating the link between SRB (excluding men who have sex with men (MSM)) and TTIs (HBV, HCV, HIV, Treponema pallidum) in donors from Western and Pacific countries were obtained and assessed on eligibility by two reviewers independently. The association between SRB and TTIs was expressed by calculating pooled effect measures via meta-analyses. The GRADE methodology (Grades of Recommendation, Assessment, Development and Evaluation) was used to assess the quality of evidence. RESULTS We identified 3750 references and finally included 15 observational studies. Meta-analyses showed that there is a significant (P < 0.05) positive association between the following SRB and HBV and/or HCV infection: having sex with an intravenous drug user (high-certainty evidence), receiving money or goods for sex (moderate-high certainty evidence), having a sex partner with hepatitis/HIV (moderate-certainty evidence) and paid for sex or anal sex (low-certainty evidence). CONCLUSION Sexual risk behaviour (including having sex with an intravenous drug user, receiving money or goods for sex or having a sex partner with hepatitis/HIV) is probably associated with an increased risk of HBV/HCV infection in blood donors from Western and Pacific countries.
The effect of a standard whole blood donation on oxygen uptake and exercise capacity: a systematic review and meta-analysis
BACKGROUND Blood is a life-saving product for many people worldwide. Voluntary blood donation serves the demand for blood but there are concerns among potential donors about the impact of blood loss on exercise performance. This systematic review aimed to collect the best available evidence of the effect of a standard whole blood donation on aerobic exercise performance. STUDY DESIGN AND METHODS Studies from six databases dealing with a standard whole blood donation (400-500 mL) followed by (sub)maximal exercise were retained. The outcomes included exercise-related blood variables (hemoglobin [Hb] concentration, hematocrit, and red blood cell count) and endurance exercise variables ((sub)maximal oxygen uptake, peak work rate, and time to exhaustion). Overall effects at different time points postdonation were investigated by performing meta-analyses and calculating mean differences (and 95% confidence intervals). The GRADE methodology (Grades of Recommendation, Assessment, Development, and Evaluation) was used to assess the quality of evidence. RESULTS We identified 6237 references and finally included 18 before-after studies of low quality. Twenty-four to 48 hours after a blood donation, 1) Hb concentration was reduced (7% decrease) until 14 days after the blood donation (4% decrease), 2) maximal oxygen uptake (VO2max ) was lower (7% decrease), and 3) a reduction in maximal exercise capacity (10% decrease) was present. CONCLUSION The best available evidence indicates that a standard whole blood donation (400-500 mL) leads to small but potentially physiologically important reductions in Hb levels, VO2max , and maximal exercise capacity in the first 2 days after the blood donation.
Methodologic quality assessment of red blood cell transfusion guidelines and the evidence base of more restrictive transfusion thresholds
BACKGROUND Recent literature suggests that more restrictive red blood cell (RBC) transfusion practices are equivalent or better than more liberal transfusion practices. The methodologic quality of guidelines recommending more restrictive transfusion thresholds and their underlying scientific evidence is unclear. Therefore, we aimed to evaluate the quality of the development process of RBC transfusion guidelines and to investigate the underlying evidence of guidelines recommending a more restrictive hemoglobin (Hb) threshold. STUDY DESIGN AND METHODS Via systematic literature screening of relevant databases (NGC, GIN, Medline, and Embase), RBC transfusion guidelines recommending a more restrictive Hb level (<6, <7, or <8 g/dL) were included. Four assessors independently evaluated the methodologic quality by scoring the rigor of development domain (AGREE II checklist). The level of evidence served as a reference for the quality of the underlying evidence. RESULTS The methodologic quality of 13 RBC transfusion guidelines was variable (18%-72%) but highest for those developed by Advancing Transfusion and Cellular Therapies Worldwide (72%), the Task Force of Advanced Bleeding Care in Trauma (70%), and the Dutch Institute for Healthcare Improvement (61%). A Hb level of less than 7 g/dL (intensive care unit patients) or less than 8 g/dL (postoperative patients) were the only thresholds based on high-quality evidence. Only four of 32 recommendations had a high-quality evidence base. CONCLUSION Methodologic quality should be guaranteed in future RBC transfusion guideline development to ensure that the best available evidence is captured when recommending restrictive transfusion strategies. More high-quality trials are needed to provide a stronger scientific basis for RBC transfusion guidelines that recommend more restrictive transfusion thresholds.