Perioperative intravenous iron to treat patients with fractured hip surgery: A systematic review and meta-analysis
Health science reports. 2022;5(3):e633
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.
Intravenous Ferric Carboxymaltose Improves Response to Postoperative Anemia Following Total Knee Arthroplasty: A Prospective Randomized Controlled Trial in Asian Cohort
Journal of clinical medicine. 2022;11(9)
BACKGROUND Ferric carboxymaltose (FCM) is an intravenous (IV) high-dose iron that is effective in the treatment of iron deficiency anemia. This study was performed to determine whether postoperative FCM infusion is effective at improving hemoglobin (Hb) responders, Hb and iron profiles, and the patient's quality of life (QOL). METHODS A total of 110 patients with postoperative anemia, defined by a Hb < 10 g/dL within 3 days of unilateral primary TKA, between June 2018 and February 2020 were randomized into either the FCM or Control group. On postoperative day 3, the FCM group (55 patients) received IV FCM while the Control group (55 patients) did not. The Hb responders (Hb increase ≥ 2 g/dL compared to baseline), Hb level, iron profiles (ferritin, total iron-binding capacity (TIBC), transferrin saturation (TSAT)), and EQ-5D scores were compared at weeks 2, 4, and 8. RESULTS The FCM group demonstrated a significantly greater number of Hb responders (p < 0.001) and a higher Hb level (p = 0.008) at 2 weeks postoperative than did the Control group. The FCM group recovered its preoperative Hb level between 4 and 8 weeks. In contrast, the Control group did not recover its preoperative level until 8 weeks. The FCM infusion group also had higher serum ferritin, iron and TSAT, and lower TIBC levels than those of the Control group between 2 and 8 weeks (all p < 0.001). However, there was no significant difference in the postoperative transfusion rate (p = 0.741) or EQ-5D score between the two groups (all p > 0.05). DISCUSSION In postoperative anemia following TKA, IV FCM increases the Hb response and improves Hb and iron metabolism variables, however, it does not affect the transfusion rate or QOL.
Postoperative Noninvasive Hemoglobin Monitoring Is Useful to Prevent Unnoticed Postoperative Anemia and Inappropriate Blood Transfusion in Patients Undergoing Total Hip or Knee Arthroplasty: A Randomized Controlled Trial
Geriatric orthopaedic surgery & rehabilitation. 2021;12:21514593211060575
INTRODUCTION Postoperative nadir hemoglobin (Hb) is related to a longer length of stay for geriatric patients undergoing orthopedic surgery. We investigated whether postoperative pulse Hb (SpHb) measurement is useful for avoiding anemia and inappropriate blood transfusion after total hip arthroplasty and total knee arthroplasty. MATERIAL AND METHODS This prospective randomized controlled study included 150 patients randomly assigned to receive blood transfusion, either guided by SpHb monitoring (SpHb group) or based on the surgeons' experience (control group). The target laboratory Hb value was set to >8 g/dL at postoperative day 1 (POD1). The primary endpoints were the product of total time and degree of SpHb <8 g/dL (area under SpHb 8 g/dL) during the period up to POD1 and the incidence of laboratory Hb <8 g/dL at POD1. The secondary endpoints were the amount of blood transfusion and inappropriate blood transfusion, which was defined as allogeneic blood transfusion unnecessary in a case of SpHb >12 g/dL or delayed transfusion in a case of SpHb <8 g/dL. RESULTS The area under SpHb 8 g/dL was 37.6 ± 44.1 g/dL-min (5 patients) in the control group and none in the SpHb group (P = .0281). There was 1 patient with Hb <8 g/dL at POD1 in the control group. There was no difference in laboratory Hb levels and the amount of blood transfusion. Forty-one patients (19 in the control group and 22 in the SpHb group) received an allogeneic blood transfusion. Among these patients, 7 in the control group and none in the SpHb group received inappropriate blood transfusion (P = .0022). DISCUSSION The SpHb monitoring could reduce unnoticed anemia, which may prevent complications and be useful in avoiding unnecessary and excessive blood transfusion. CONCLUSION Postoperative SpHb monitoring decreased the incidence of transient, unnoticed anemia during the period up to POD1 and inappropriate blood transfusion.
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.
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.
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.