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Effect of erythropoietin on perioperative blood transfusions in primary total hip arthroplasty: A systematic review
Abram D, Tran MH
Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 2023;:103718
Abstract
BACKGROUND Primary total hip arthroplasty (THA) often requires blood transfusion. Transfusions are undesirable due to risks of infectious and noninfectious complications. This systematic review therefore studied the effectiveness of erythropoietin (EPO) in reducing allogeneic transfusion rate during THA. METHODS Using the MESH terms "Erythropoietin" AND "Total Hip" with restrictions to 'Randomized Controlled Trial', 'Clinical Trial', 'Humans', and 'English', a literature search was performed in PubMed and CINAHL. Articles were scanned by both authors and retained for further review if eligibility was met according to the inclusion criteria defined by the PICOS (population, intervention, comparator, outcomes, study design) configuration. Risk of bias was assessed using the Cochrane risk of bias criteria. Data extracted include patient demographics, intervention versus comparator arm, outcomes, laboratory data, and individual study characteristics. The primary outcome of focus was rate or amount of allogeneic blood transfusions intra- or postoperatively. In 6/8 studies, data permitted calculations of absolute risk reduction (ARR) in transfusion rate (%) and number needed to treat (NNT) to evade transfusions. RESULTS A total of 8 studies met all eligibility criteria and were retained for data extraction; risk of bias was low-moderate in 7/8 and high in 1/8. Allogeneic transfusion exposure was lowered by the intervention in 7/8 studies with ARR from 9.6% to 33.5% and NNT from 4 to 10. CONCLUSIONS In the blood conservation systems described, the addition of EPO was effective in reducing allogeneic transfusions. The studies included spanned a nearly 30-year period. Earlier studies incorporated preoperative autologous donation, a now outdated modality.
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Interventions for reducing red blood cell transfusion in adults undergoing hip fracture surgery: an overview of systematic reviews
Lewis, S. R., Pritchard, M. W., Estcourt, L. J., Stanworth, S. J., Griffin, X. L.
The Cochrane database of systematic reviews. 2023;6(6):Cd013737
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Editor's Choice
Abstract
BACKGROUND Following hip fracture, people sustain an acute blood loss caused by the injury and subsequent surgery. Because the majority of hip fractures occur in older adults, blood loss may be compounded by pre-existing anaemia. Allogenic blood transfusions (ABT) may be given before, during, and after surgery to correct chronic anaemia or acute blood loss. However, there is uncertainty about the benefit-risk ratio for ABT. This is a potentially scarce resource, with availability of blood products sometimes uncertain. Other strategies from Patient Blood Management may prevent or minimise blood loss and avoid administration of ABT. OBJECTIVES To summarise the evidence from Cochrane Reviews and other systematic reviews of randomised or quasi-randomised trials evaluating the effects of pharmacological and non-pharmacological interventions, administered perioperatively, on reducing blood loss, anaemia, and the need for ABT in adults undergoing hip fracture surgery. METHODS In January 2022, we searched the Cochrane Library, MEDLINE, Embase, and five other databases for systematic reviews of randomised controlled trials (RCTs) of interventions given to prevent or minimise blood loss, treat the effects of anaemia, and reduce the need for ABT, in adults undergoing hip fracture surgery. We searched for pharmacological interventions (fibrinogen, factor VIIa and factor XIII, desmopressin, antifibrinolytics, fibrin and non-fibrin sealants and glue, agents to reverse the effects of anticoagulants, erythropoiesis agents, iron, vitamin B12, and folate replacement therapy) and non-pharmacological interventions (surgical approaches to reduce or manage blood loss, intraoperative cell salvage and autologous blood transfusion, temperature management, and oxygen therapy). We used Cochrane methodology, and assessed the methodological quality of included reviews using AMSTAR 2. We assessed the degree of overlap of RCTs between reviews. Because overlap was very high, we used a hierarchical approach to select reviews from which to report data; we compared the findings of selected reviews with findings from the other reviews. Outcomes were: number of people requiring ABT, volume of transfused blood (measured as units of packed red blood cells (PRC)), postoperative delirium, adverse events, activities of daily living (ADL), health-related quality of life (HRQoL), and mortality. MAIN RESULTS We found 26 systematic reviews including 36 RCTs (3923 participants), which only evaluated tranexamic acid and iron. We found no reviews of other pharmacological interventions or any non-pharmacological interventions. Tranexamic acid (17 reviews, 29 eligible RCTs) We selected reviews with the most recent search date, and which included data for the most outcomes. The methodological quality of these reviews was low. However, the findings were largely consistent across reviews. One review included 24 RCTs, with participants who had internal fixation or arthroplasty for different types of hip fracture. Tranexamic acid was given intravenously or topically during the perioperative period. In this review, based on a control group risk of 451 people per 1000, 194 fewer people per 1000 probably require ABT after receiving tranexamic acid (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.46 to 0.68; 21 studies, 2148 participants; moderate-certainty evidence). We downgraded the certainty for possible publication bias. Review authors found that there was probably little or no difference in the risks of adverse events, reported as deep vein thrombosis (RR 1.16, 95% CI 0.74 to 1.81; 22 studies), pulmonary embolism (RR 1.01, 95% CI 0.36 to 2.86; 9 studies), myocardial infarction (RR 1.00, 95% CI 0.23 to 4.33; 8 studies), cerebrovascular accident (RR 1.45, 95% CI 0.56 to 3.70; 8 studies), or death (RR 1.01, 95% CI 0.70 to 1.46; 10 studies). We judged evidence from these outcomes to be moderate certainty, downgraded for imprecision. Another review, with a similarly broad inclusion criteria, included 10 studies, and found that tranexamic acid probably reduces the volume of transfused PRC (0.53 fewer units, 95% CI 0.27 to 0.80; 7 studies, 813 participants; moderate-certainty evidence). We downgraded the certainty because of unexplained high levels of statistical heterogeneity. No reviews reported outcomes of postoperative delirium, ADL, or HRQoL. Iron (9 reviews, 7 eligible RCTs) Whilst all reviews included studies in hip fracture populations, most also included other surgical populations. The most current, direct evidence was reported in two RCTs, with 403 participants with hip fracture; iron was given intravenously, starting preoperatively. This review did not include evidence for iron with erythropoietin. The methodological quality of this review was low. In this review, there was low-certainty evidence from two studies (403 participants) that there may be little or no difference according to whether intravenous iron was given in: the number of people who required ABT (RR 0.90, 95% CI 0.73 to 1.11), the volume of transfused blood (MD -0.07 units of PRC, 95% CI -0.31 to 0.17), infection (RR 0.99, 95% CI 0.55 to 1.80), or mortality within 30 days (RR 1.06, 95% CI 0.53 to 2.13). There may be little or no difference in delirium (25 events in the iron group compared to 26 events in control group; 1 study, 303 participants; low-certainty evidence). We are very unsure whether there was any difference in HRQoL, since it was reported without an effect estimate. The findings were largely consistent across reviews. We downgraded the evidence for imprecision, because studies included few participants, and the wide CIs indicated possible benefit and harm. No reviews reported outcomes of cognitive dysfunction, ADL, or HRQoL. AUTHORS' CONCLUSIONS Tranexamic acid probably reduces the need for ABT in adults undergoing hip fracture surgery, and there is probably little or no difference in adverse events. For iron, there may be little or no difference in overall clinical effects, but this finding is limited by evidence from only a few small studies. Reviews of these treatments did not adequately include patient-reported outcome measures (PROMS), and evidence for their effectiveness remains incomplete. We were unable to effectively explore the impact of timing and route of administration between reviews. A lack of systematic reviews for other types of pharmacological or any non-pharmacological interventions to reduce the need for ABT indicates a need for further evidence syntheses to explore this. Methodologically sound evidence syntheses should include PROMS within four months of surgery.
PICO Summary
Population
Adults undergoing hip fracture surgery (26 systematic reviews, n= 3,923).
Intervention
Pharmacological and non-pharmacological interventions to prevent or minimise blood loss, treat the effects of anaemia, and reduce the need for allogenic blood transfusions (ABT).
Comparison
Between and within categories of intervention, standard of care or placebo.
Outcome
17 reviews were found about tranexamic acid, 9 reviews about iron, and none for any other types of treatment. The three reviews providing the most relevant information were: A review about tranexamic acid including 24 studies with 2,148 people with a broken hip; a review about tranexamic acid including 10 studies with 1,123 people; and a review about iron including 2 studies with 403 people. The authors concluded that tranexamic acid probably reduces the need for ABT in adults undergoing hip fracture surgery, and there is probably little or no difference in adverse events. For iron, there may be little or no difference in overall clinical effects, but this finding is limited by evidence from only a few small studies. Reviews of these treatments did not adequately include patient-reported outcome measures, and evidence for their effectiveness remains incomplete.
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Effects of intraoperative or postoperative administration of intravenous iron supplements on hemoglobin recovery in patients with total knee arthroplasty: A systematic review and meta-analysis
Kwak, S. G., Kwon, J. B., Bae, J. W., Bae, D. J., Kim, D. K., Choi, W. K.
Medicine. 2023;102(43):e35744
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Abstract
BACKGROUND The objectives of the researchers are as follows: First, to investigate whether intraoperative or postoperative administration of Intravenous (IV) iron supplements in patients undergoing primary total knee arthroplasty (TKA) can contribute to the hemoglobin recovery during the postoperative period (between 4 and 8 weeks after surgery). Second, to examine whether the administration of IV iron supplements during or immediately after TKA in patients undergoing primary TKA can reduce the need for allogenic blood transfusion during hospitalization. METHODS Articles published between January 1, 1990, and June 30, 2023 were searched in PubMed, Cochrane, and Embase. The population, intervention, comparison, and outcome of this study are as follows; Population: Patients undergoing primary total knee arthroplasty; Intervention: Administration of IV iron supplements during or immediately after surgery; Comparison: Non-administration of IV iron supplements; Outcome: Degree of hemoglobin recovery (between 4 and 8 weeks after surgery) and the need for blood transfusion during hospitalization. RESULTS There was a statistically significant difference in the amount of change in hemoglobin between iron supplementation group and non-iron supplementation group. The effect size were -0.44 (95% confidence interval: -0.69 to -0.19, P value < .001) in all patients. This means that the amount of change in hemoglobin were significantly reduced in the iron supplementation group than in the non-iron supplementation group. There was a statistically significant difference for post-operative transfusion rate between 2 groups. The effect size were 0.28 (95% confidence interval: 0.10-0.81, P value = .02) in all patients. This means that the post-operative transfusion rate was significantly less in the iron supplementation group than in the non-iron supplementation group. CONCLUSION The administration of IV iron supplements during or after TKA surgery increases hemoglobin recovery between 4 and 8 weeks after surgery and reduces the need for allogeneic blood transfusion during hospitalization.
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Perioperative intravenous iron to treat patients with fractured hip surgery: A systematic review and meta-analysis
Sinclair RCF, Bowman MJA, Moppett IK, Gillies MA
Health science reports. 2022;5(3):e633
Abstract
BACKGROUND Treatment of preoperative anemia with intravenous iron is common within elective surgical care pathways. It is plausible that this treatment may improve care for people with hip fractures many of whom are anemic because of pre-existing conditions, fractures, and surgery. OBJECTIVE To review the evidence for intravenous iron administration on outcomes after hip fracture. DESIGN We followed a predefined protocol and conducted a systematic review and meta-analysis of the use of intravenous iron to treat anemia before and after emergency hip fracture surgery. The planned primary outcome was a difference in length of stay between those treated with intravenous iron and the control group. Other outcomes analyzed were 30-day mortality, requirement for blood transfusion, changes in quality of life, and hemoglobin concentration on discharge from the hospital. DATA SOURCES EMBASE, MEDLINE, The Cochrane Library (CENTRAL, DARE) databases, Clinicaltrials.gov, and ISRCTN trial registries. Date of final search March 2022. ELIGIBILITY CRITERIA Adult patients undergoing urgent surgery for hip fracture. Studies considered patients who received intravenous iron and were compared with a control group. RESULTS Four randomized controlled trials (RCT, 732 patients) and nine cohort studies (2986 patients) were included. The RCTs were at low risk of bias, and the nonrandomized studies were at moderate risk of bias. After metanalysis of the RCTs there was no significant difference in the primary outcome, length of hospital stay, between the control group and patients receiving intravenous iron (mean difference: -0.59, 95% confidence interval [CI]; -1.20 to 0.03; I (2) = 30%, p = 0.23). Intravenous iron was not associated with a difference in 30-day mortality (n = 732, OR: 1.14, 95% CI: 0.62-2.1; I (2) = 0%, p = 0.50), nor with the requirement for transfusion (n = 732, OR: 0.85, 95% CI: 0.63-1.14; I (2) = 0%, p < 0.01) in the analyzed RCTs. Functional outcomes and quality of life were variably reported in three studies. CONCLUSION The evidence on the use of intravenous iron in patients with hip fracture is low quality and shows no difference in length of acute hospital stay and transfusion requirements in this population. Improved large, multicentre, high-quality studies with patient-centered outcomes will be required to evaluate the clinical and cost-effectiveness of this treatment.
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The Efficacy and Safety of Intravenous Iron in Geriatric Hip Fracture Surgeries: A Systematic Review and Meta-Analysis
Cao MM, Chi JY, Zhang YW, Sheng RW, Gao W, Zhao YK, Rui YF
World journal of surgery. 2022
Abstract
BACKGROUND With the increasing evidence provided by recent high-quality studies, the intravenous iron appears to be a reliable therapy for blood administration in geriatric patients with hip fractures. Here, this systematic review and meta-analysis were aimed to assess the effectiveness and safety of intravenous iron in geriatric patients sustaining hip fractures. METHODS Potential pertinent literatures evaluating the effects of intravenous iron in the geriatric patients undergoing hip fractures were identified from Web of Science, PubMed, Embase, and Scopus. We performed a pairwise meta-analysis using fixed- and random-effects models, and the pooling of data was carried out by using RevMan 5.1. RESULTS Four randomized controlled trials and four observational studies conform to inclusion criteria. The results of meta-analysis showed that intravenous iron reduced transfusion rates compared to the control group, yet the result did not reach statistical significance. The intravenous iron was related to lower transfusion volumes, shorter length of stay, and a reduced risk of nosocomial infections. And there was no significant difference in terms of the mortality and other complications between the treatment group and the control group. CONCLUSION Current evidence suggests that intravenous iron reduces the transfusion volume, length of hospital stay, and risk of nosocomial infections. It takes about 7 days for intravenous iron to elevate hemoglobin by 1 g/dl and about 1 month for 2 g/dl. The safety profile of intravenous iron is also reassuring, and additional high-quality studies are needed.
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Preoperative anemia and complications after total joint arthroplasty: a systematic review and meta-analysis
Zhang, H. C., Zhang, Y., Dai, H. B., Wu, D., Xu, B.
European Review for Medical and Pharmacological Sciences. 2022;26(20):7420-7430
Abstract
OBJECTIVE The purpose of this review was to collect data from the literature to assess the impact of preoperative anemia on complications after total joint arthroplasty (TJA). MATERIALS AND METHODS We conducted a literature search on the websites of PubMed, Scopus, CENTRAL, Embase, and Google Scholar for comparative TJA studies reporting complication rates based on the presence of anemia. The last search was conducted on the 15th of May 2022. Studies only on hip and knee replacements were eligible for inclusion. RESULTS Twelve studies with 1,463,813 patients published between 2012-2022 were included. Meta-analysis indicated that anemic patients had increased risk of mortality (OR: 2.85 95% CI: 1.89, 2.48 I2=83% p<0.00001), wound complications (OR: 2.06 95% CI: 3.51, 2.48 I2=99% p=0.008), cardiac complications (OR: 2.40 95% CI: 1.56, 3.68 I2=98% p<0.0001), respiratory complications (OR: 2.46 95% CI: 1.10, 5.50 I2=100% p=0.03), renal complications (OR: 2.84 95% CI: 1.39, 5.80 I2=99% p=0.004), sepsis (OR: 3.93 95% CI: 1.15, 13.45 I2=99% p=0.03), urinary complications (OR: 2.42 95% CI: 1.27, 4.59 I2=100% p=0.007), and readmission rates (OR: 1.58 95% CI: 1.42, 1.76 I2=66% p<0.00001) as compared to non-anemic patients undergoing TJA. Most results did not change on sensitivity analysis. There were some non-significant results on subgroup analysis based on joint type and definition of anemia. CONCLUSIONS Our review suggests that preoperative anemia leads to increased morbidity and mortality after TJA. Specifically, anemia increases the risk of wound, cardiac, respiratory, renal, and urinary complications along with a higher incidence of sepsis and readmissions. Results should be interpreted with caution due to the high heterogeneity in the meta-analyses.
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Efficacy and safety of combined administration of erythropoietin and iron in comparison to iron therapy alone in orthopaedic surgery: systematic review and metanalysis
Kaur, M., Khatri, K., Kankaria, A., Dhir, T., Arora, H.
Acta Ortopedica Mexicana. 2021;35(6):547-556
Abstract
INTRODUCTION Iron deficiency anaemia in orthopaedic surgery is common and there is increased risk of blood transfusion and associated adverse reactions. The management involves administration of iron (oral or intravenous) and erythropoietin stimulating agents. MATERIAL AND METHODS We searched for PubMed, Embase, Google Scholar and Cochrane database to identify the studies from inception to April 2021. Randomized controlled trials with adult patients undergoing orthopedic surgery were included. The metanalysis compared patients who were administered combination of erythropoietin stimulating agents and iron in one group and iron alone. The primary outcome was the rate of blood transfusion and the secondary outcome studied were postoperative hemoglobin concentration, after treatment hemoglobin levels, and complications like mortality, stroke, myocardial infarction, deep vein thrombosis, pulmonary embolism and renal dysfunction. RESULTS Eleven studies were included. The combination of ESA and iron decreased number of patients who required blood transfusion in comparison to patients treated with iron therapy alone (RR, 0.73; 95% CI, 0.59 to 0.91, I. CONCLUSION [2] = 65%; p = 0.005). In subgroup analysis with oral and intravenous iron, the difference was not statistically significant (p = 0.24). Administration of erythropoietin either in high ( 80,000 IU) or low dose ( 80,000 IU) resulted in lower blood transfusion rates (p = 0.0007) with no significant difference between groups. The risk of mortality, myocardial infarction, stroke, deep vein thrombosis or pulmonary embolism did not significantly increase. Combined administration of ESA and iron versus iron only reduces the number of red blood cell transfusions in the postoperative period in orthopedic procedures with minimal risk of complications.
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Association of iron supplementation with risk of transfusion, hospital length of stay, and mortality in geriatric patients undergoing hip fracture surgeries: a meta-analysis
Chen R, Li L, Xiang Z, Li H, Hou XL
European geriatric medicine. 2021;12(1):5-15
Abstract
AIMS: To assess the efficacy and safety of iron supplementation for perioperative anemia in geriatric patients with hip fracture. METHODS A systematic search was conducted for studies published using PubMed, EMBASE and Cochrane Library Databases that compared iron supplementation with placebo in patients undergoing hip fracture surgery. The outcomes were blood transfusion rate and volume, length of stay, infection and mortality (last follow-up). Sub-group and sensitivity analyses were performed in cases of substantial heterogeneity. RESULTS The meta-analysis (6 studies: 1201 patients) indicated that iron supplements were not associated with reducing blood transfusion rate (OR 0.92, 95% CI 0.60-1.41; P = 0.69), but high heterogeneity (I(2) = 61%) was detected and a significant association was found in sensitivity analysis of four studies (n = 637; OR 0.68, 95% CI 0.49-0.95; P = 0.02). A significant reduction was detected in transfusion volume (two studies: n = 234; MD - 0.45 units/patient, 95% CI - 0.74 to - 0.16; P = 0.002), hospital stay (five studies: n = 998; MD - 1.42, 95% CI - 2.18 to - 0.67; P = 0.0002) and caused no increased risk of mortality (five studies: n = 937; OR 0.94, 95% CI 0.65-1.36; P = 0.76) and infection (four studies: n = 701; OR 0.58, 95% CI 0.38-0.90; P = 0.01). Sub-group analyses of four studies showed that the preoperative intravenous use of iron at 200-300 mg (two studies) may be the beneficial option for hip fractures patients. CONCLUSIONS Iron supplementation, especially preoperative intravenous use of 200-300 mg iron, is safe and associated with reducing transfusion requirement and hospital stay. Unfortunately, data were too limited to draw a definite conclusion. Further evaluation is required before recommending iron supplementation for older patients with hip fracture surgeries.
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Intraoperative and Postoperative Iron Supplementation in Elective Total Joint Arthroplasty: A Systematic Review
Chaudhry YP, MacMahon A, Hasan SA, Mekkawy K, Valaik D, Oni JK, Sterling RS, Khanuja HS
The Journal of the American Academy of Orthopaedic Surgeons. 2021
Abstract
INTRODUCTION Postoperative anemia is associated with substantial morbidity and mortality in total joint arthroplasty (TJA). Our primary objective was Postoperative anemia is associated with substantial morbidity and mortality in total joint arthroplasty (TJA). Our primary objective was to determine whether perioperative iron supplementation improves postoperative hemoglobin levels in TJA. Secondary objectives were to determine the effects of perioperative iron on adverse events, quality of life, and functional measures in TJA. METHODS We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using six databases. We included English-language, randomized controlled trials investigating intraoperative or postoperative iron supplementation in elective TJA that reported postoperative hemoglobin levels in patients aged 18 years or older. Seven eligible studies were identified, among which substantial heterogeneity was noted. Bias risk was low in four studies, unclear in two studies, and high in one study. Three studies assessed oral iron supplementation, three assessed intravenous iron supplementation, and one compared oral and intravenous iron supplementation. All intravenous iron was administered intraoperatively, except in the oral versus intravenous comparison. RESULTS Postoperative oral iron supplementation had no effect on postoperative hemoglobin levels. Intraoperative and postoperative intravenous iron supplementation was associated with higher postoperative hemoglobin levels and greater increases in hemoglobin levels. Two studies reported rates of anemia and found that intraoperative and postoperative intravenous iron supplementation reduced rates of postoperative anemia at postoperative day 30. No adverse events were associated with iron supplementation. One study found that intravenous iron improved quality of life in TJA patients with severe postoperative anemia compared with those treated with oral iron. Perioperative iron had no effects on functional outcomes. DISCUSSION We found no evidence that postoperative oral iron supplementation improves hemoglobin levels, quality of life, or functional outcomes in elective TJA patients. However, intraoperative and postoperative intravenous iron supplementation may accelerate recovery of hemoglobin levels in these patients. LEVEL OF EVIDENCE Level I, systematic review of randomized controlled trials.
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Preoperative Anemia Treatment With Intravenous Iron in Patients Undergoing Major Orthopedic Surgery: A Systematic Review
Smith A, Moon T, Pak T, Park B, Urman RD
Geriatr Orthop Surg Rehabil. 2020;11:2151459320935094
Abstract
Introduction: Based upon the Third National Health and Nutrition Examination Survey data, iron deficiency anemia is the cause of at least 20% of cases of anemia in adults over the age of 65. This is especially relevant in patients undergoing major orthopedic surgery as substantial perioperative blood loss is possible, leading to a high rate of allogeneic blood transfusion in total hip replacements, total knee replacements, and hip fracture repairs. Significance: The results of this systematic review may be of interest to clinicians and hospital administrators evaluating the clinical efficacy and cost effectiveness of intravenous (IV) iron administration prior to major orthopedic surgery. Materials and Methods: The original studies considered for this review included patients who were over 18 years of age, undergoing major orthopedic surgery, and who received an IV iron treatment in the preoperative setting. A total of 1083 articles were identified and reviewed. After removing duplicates, 1031 publications were screened, and 105 full-text studies were assessed for eligibility. A total of 98 were excluded and 7 articles remained which met the criteria for this review. The primary outcome examined in the included studies was the allogeneic blood transfusion rate. The secondary areas of interest were changes in serum hemoglobin, morbidity and mortality, length of stay, and cost effectiveness. Results: This systematic review found little evidence that IV iron therapy is effective at reducing transfusion in patients undergoing major orthopedic surgery. Conclusions: We do not recommend preoperative IV iron therapy for all patients scheduled for major orthopedic surgery.