Intraoperative and Postoperative Iron Supplementation in Elective Total Joint Arthroplasty: A Systematic Review
The Journal of the American Academy of Orthopaedic Surgeons. 2021
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.
Association of iron supplementation with risk of transfusion, hospital length of stay, and mortality in geriatric patients undergoing hip fracture surgeries: a meta-analysis
European geriatric medicine. 2021;12(1):5-15
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.
Use of preoperative erythropoietin therapy to facilitate autologous blood donation in orthopedic surgery: A meta-analysis
BACKGROUND Autologous blood transfusion helps to avoid or reduce the need for allogenic blood transfusion in patients undergoing major surgery. We examined the value of erythropoietin therapy to support preoperative autologous blood donation (PABD) in patients undergoing orthopedic surgery. METHODS For this systematic review and meta-analysis, Medline, Cochrane, EMBASE, and Google Scholar databases were searched from October 26th, 1989 until September 30th, 2017. Primary outcomes were percentages of patients able to donate ≥4 units of blood for autologous transfusion, amount of allogeneic blood transfused, changes in hematocrit and hemoglobin levels from before PABD to immediately before surgery, and adverse events. RESULTS Of 256 studies identified, 18 studies met the inclusion criteria with a total of 1914 patients (mean age 51-69 years), of whom 1153 were treated with erythropoietin. Erythropoietin was associated with a greater percentage of patients able to donate ≥4 units of blood for autologous use compared to controls (OR = 6.00, 95% CI = 3.97 to 9.09, P < .001). Patients receiving preoperative erythropoietin had significantly less of a reduction in hematocrit and hemoglobin levels from before PABD to immediately before surgery compared with controls (hematocrit: mean differences = -1.438, 95% CI = -2.14 to -0.73, P < .001; hemoglobin: mean differences = -1.426, 95% CI = -1.78 to -1.07, P < .001). No significant differences were observed in the amount of allogenic blood transfused between patients receiving erythropoietin and controls (difference in means = -0.220, 95% CI = -0.536 to 0.097, P = .174). Patients who received erythropoietin were less likely to experience dizziness than controls, but the incidence of nausea or fatigue were similar between groups. CONCLUSION Erythropoietin therapy during the PABD period results in less of a reduction in hematocrit and hemoglobin levels and an increase in the percentage of patients able to donate blood preoperatively.
Does subcutaneous administration of recombinant human erythropoietin increase thrombotic events in total hip arthroplasty? A prospective thrombelastography analysis
Journal of orthopaedic surgery and research. 2020;15(1):546
BACKGROUND Anemia is one of severe complications in the perioperative period of total hip arthroplasty (THA). Erythropoietin (EPO) has been considered to improve patients' anemia state, but its efficiency and safety remains controversial. METHODS A total of 152 patients who underwent total hip arthroplasty from January 2017 to March 2019 were randomized to 2 groups. Recombinant human erythropoietin (rHu-EPO) group was treated with rHu-EPO subcutaneous injection 10000 IU after operation and once daily in the next week, while control group was treated with none extra treatment. Routine hematologic examination and thrombelastography (TEG) performed at different time point respectively. Doppler ultrasound for bilateral lower limbs was performed 1 day before surgery and 7 days after surgery. Auxiliary examination outcomes, blood transfusions outcomes, and postoperative complications were recorded as assessment indicators. RESULTS The difference in the relevant indexes of traditional coagulation and TEG values between two groups were not significantly. No significant difference was observed in the incidence of thromboembolism events and other complications between two groups during postoperative period. The amount of intraoperative blood loss was similar between the two groups. However, the postoperative use and dosage of allogeneic blood in the rHu-EPO group were lower than those in the control group. The hemoglobin and hematocrit level in the rHu-EPO group were higher than that in the control group after surgery. CONCLUSION Postoperative subcutaneous injection of rHu-EPO can improve hematological anemia-related parameters, reduce the use and dosage of allogeneic blood transfusions (ABTs), and has no significant influence on the formation of thrombosis and other complications in patients undergoing total hip arthroplasty in short term.
Effectiveness of iron supplementation in the perioperative management of total knee arthroplasty: a systematic review
Knee surgery & related research. 2020;32(1):44
INTRODUCTION/PURPOSE The purpose of this systematic review was to evaluate the effect of iron supplementation during total knee arthroplasty (TKA): (1) Is the iron supplementation necessary during TKA? (2) When is the optimal timing of iron supplementation? (3) Which is better, between orally and intravenously administered iron supplementation? And (4) What is the optimal dose of iron supplementation? MATERIALS AND METHODS A rigorous and systematic approach was used and each of the selected studies was evaluated for methodological quality. Data about study design, total number of cases enrolled, iron administration method, timing, and dose were extracted. Change in hemoglobin and transfusion rates were extracted to evaluate the effectiveness of iron supplementation. RESULTS Eleven studies were included in the final analysis. Most of studies reported that hemoglobin change between iron and control group did not show any difference. Only one study reported that iron supplementation could reduce the decrease in hemoglobin. However, transfusion rate showed a decrease in the iron supplementation group compared with the control group. There was no clear consensus on the optimum timing and dose of iron supplementation and intravenously administered iron was more effective than orally administered iron, especially in anemic patients. CONCLUSION Iron supplementation is not clear as a way to raise hemoglobin levels after TKA, but an effective treatment for lowering transfusion rate, especially in patients with anemia. We could not determine the optimal timing and dose of the iron. Intravenously administered iron was similar to, or better than, orally administered iron for improving hemoglobin levels and transfusion rate.
Preoperative Anemia Treatment With Intravenous Iron in Patients Undergoing Major Orthopedic Surgery: A Systematic Review
Geriatr Orthop Surg Rehabil. 2020;11:2151459320935094
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.
Efficacy of intra-operative administration of iron isomaltoside for preventing postoperative anaemia after total knee arthroplasty: A randomised controlled trial
European journal of anaesthesiology. 2020
BACKGROUND Postoperative anaemia is common after total knee arthroplasty (TKA). Emerging evidence shows the beneficial effects of peri-operative iron supplementation in patients at risk of postoperative anaemia. OBJECTIVE To evaluate the efficacy of intra-operative administration of iron isomaltoside for the prevention of postoperative anaemia in patients undergoing TKA. DESIGN Randomised, controlled, double-blind, parallel-group study. SETTING A tertiary care teaching hospital; between 29 March 2018 and 16 April 2019. PATIENTS Eighty-nine patients scheduled for unilateral TKA were included. INTERVENTION Iron isomaltoside or placebo were administered intravenously over 30 min during surgical wound closure. MAIN OUTCOME MEASURES The primary outcome measure was the incidence of anaemia at 30 days after TKA: anaemia was defined as haemoglobin less than 12 g dl for female and less than 13 g dl for male. RESULTS In total, 89 patients were included in the final analysis (44 in the treatment group; 45 in the control group). The administered dose of iron isomaltoside in the treatment group was 1136 ± 225 mg. The incidence of anaemia at 30 days after TKA was significantly lower in the treatment group (34.1%, 15/44) than that in the control group (62.2%, 28/45): relative risk 0.55 (95% confidence interval, 0.34 to 0.88), P = 0.008. Haemoglobin concentration, serum ferritin concentrations, and transferrin saturation were also significantly higher in the treatment group at 30 days after TKA. CONCLUSION The intra-operative administration of iron isomaltoside effectively prevents postoperative anaemia in patients undergoing TKA, and thus it can be included in patient blood management protocols for reducing postoperative anaemia in these population. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT03470649.
Clinical Effectiveness of 3 days Preoperative Treatment with Recombinant Human Erythropoietin in Total Knee Arthroplasty Surgery - A Clinical Trial
QJM : monthly journal of the Association of Physicians. 2019
AIMS: The purpose of study is to evaluate the effect and complication of preoperative short-term daily recombinant human erythropoietin (rhEPO) treatment for blood-saving in patients undergoing unilateral primary total knee arthroplasty (TKA). METHODS This three-arm randomized clinical trial compared three different rhEPO-based treatment protocols for unilateral primary total knee arthroplasty. Group A: application of daily doses of rhEPO combined with iron supplement starting 3 days before surgery; Group B: application of daily doses of rhEPO combined with iron supplement starting the day of surgery; Group C: iron supplement alone. Perioperative hemoglobin (Hb) level gaps, total perioperative blood loss, reticulocyte levels and treatment-related complications were studied. RESULTS 102 patients were included (35, 35, and 32 patients in group A, B, and C, respectively). Total blood loss in group A, B, and C was 490.84ml, 806.76ml, and 924.21ml respectively. Patients in group A had a significant lower total blood loss than group B and C (A vs B: P = 0.010; A vs C: P < 0.001). There was no difference as for total blood loss between group B and C (P = 0.377). Group A patients had significant smaller Hb decline than group C on the 3rd and 5th postoperative day (P = 0.049, P = 0.037), as well as than group B on the 5th postoperative day (P = 0.048). There was no difference as for Hb decline between group B and C. No difference was shown in levels of inflammatory biomarkers or blood-saving protocol-related complications among three groups. CONCLUSIONS Daily dose of rhEPO combined with iron supplement administered 3 days before TKA procedures could significantly decrease perioperative blood loss and improve postoperative Hb levels, without significantly elevating risks of complication, when compared with admission of rhEPO on the day of surgery and iron supplement alone. Preoperative daily rhEPO treatment could be a more effective blood-saving protocol in TKA procedures.
The Effect of Intraoperative Ferric Carboxymaltose in Joint Arthroplasty Patients: A Randomized Trial
Journal of clinical medicine. 2019;8(10)
This study assessed the efficacy of intraoperative high-dose intravenous iron therapy in facilitating recovery from postoperative anemia and reducing the transfusion rate in patients with total knee and total hip arthroplasty. This prospective randomized controlled study involved 58 subjects. Group F received 1000 mg intravenous ferric carboxymaltose and Group C received normal saline. The changes in hemoglobin (Hb), hematocrit, iron metabolism variables, transfusion rates, and the arterial partial pressure of oxygen and the fraction of oxygen (PaO2/FiO2) ratio were recorded. There were 29 patients of each group. The change in Hb levels from baseline to 1 month post-surgery was higher in Group F than in Group C (0.3 +/- 1.0 g/dl vs. -0.8 +/- 0.8 g/dl, p < 0.001). Functional iron deficiency occurred more frequently in Group C (0% vs. 48.3%, p < 0.001) after the operation. The incidence of postoperative anemia, transfusion rate and P/F ratio did not significantly differ between the two groups. This study suggests that intraoperative high-dose ferric carboxymaltose during lower limb total arthroplasty can facilitate the recovery from postoperative anemia. Although it could not prevent the occurrence of postoperative anemia or the administration of transfusion, this treatment seemed to overcome surgery-related decrease of iron availability.
Efficacy of perioperative intravenous iron therapy for transfusion in orthopedic surgery: A systematic review and meta-analysis
PloS one. 2019;14(5):e0215427
Perioperative anemia frequently occurs in patients undergoing orthopedic surgery. We aimed to evaluate the efficacy of perioperative intravenous iron therapy (IVIT) on transfusion and recovery profiles during orthopedic surgery. We searched PubMed, Embase, Cochrane, and Google Scholar for eligible clinical trials (randomized controlled trials, RCTs; case-control studies, CCSs) in comparing IVIT and no iron therapy, up to September 2018. Primary outcomes were the effects of IVIT on the proportion of patients transfused and units of red blood cells (RBCs) transfused perioperatively. Secondary outcomes were the effects of IVIT on recovery profiles, such as length of hospital stay (LOS), post-operative infection, and mortality. Subgroup analysis was performed based on iron dose (low: ≤ 300 mg, high: > 400 mg), IVIT period (pre-operative, post-operative, perioperative), and study design. We identified 12 clinical trials (4 RCTs with 616 patients and 8 CCSs with 1,253 patients). IVIT significantly reduced the proportion of patients transfused by 31% (RR, 0.69; P = 0.0002), and units of RBCs transfused by 0.34 units/person (MD, -0.34; P = 0.0007). For subgroup analysis by iron dose, low- or high-dose IVIT significantly reduced the proportion of patients transfused (RR, 0.73, P = 0.005; RR, 0.68, P = 0.008), and RBC units transfused (MD, -0.47, P < 0.0001; MD, -0.28, P = 0.04). For subgroup analysis by period, IVIT administered post-operatively significantly reduced the proportion of patients transfused (post-operative: RR, 0.60, P = 0.002; pre-operative: RR, 0.74, P = 0.06) and RBC units transfused (post-operative: MD, -0.44, P <0.00001; pre-operative: MD, -0.29, P = 0.06). For subgroup analysis by study design, IVIT decreased the proportion of patients transfused and RBC units transfused in the group of CCSs, but IVIT in the group of RCTs did not. IVIT significantly shortened LOS by 1.6 days (P = 0.0006) and reduced post-operative infections by 33% (P = 0.01). IVIT did not change mortality. Perioperative IVIT during orthopedic surgery, especially post-operatively, appears to reduce the proportion of patients transfused and units of RBCs transfused, with shorter LOS and decreased infection rate, but no change in mortality rate. These were only found in CCSs and not in RCTs due to the relatively small number of RCTs with low to high risk of bias.