Abstract

BACKGROUND Preoperative anaemia is associated with increased use of blood transfusions, a greater risk of postoperative complications, and patient morbidity. The IRON NOF trial aimed to investigate whether the administration of i.v. iron in anaemic patients during hip fracture surgery reduced the need for blood transfusion and improved patient outcomes. METHODS This phase III double-blind, randomised, placebo-controlled trial included patients >60 yr old with preoperative anaemia undergoing surgery for femoral neck or subtrochanteric fracture across seven Australian Hospitals. Patients were randomly allocated on a 1:1 basis to receive either i.v. iron carboxymaltose 1000 mg or placebo (saline) at operation. The primary endpoint was blood transfusion use, with secondary endpoints of haemoglobin concentration at 6 weeks, length of hospital stay, rehabilitation duration to discharge, and 6-month mortality. Subgroup analysis compared outcomes in patients <80 yr old and patients >80 yr old. All analyses were performed by intention-to-treat. This trial was terminated early because of jurisdictional changes of more restrictive transfusion practices and changes in consent requirements. RESULTS Participants (n=143) were recruited between February 2013 and May 2017. There was no difference observed in the incidence of blood transfusion between the treatment group (18/70) (26%) compared with the placebo group (27/73) (37%) (odds ratio for transfusion if receiving placebo: 1.70; 95% confidence interval [CI] 0.83-3.47; P=0.15) and there was no overall difference in the median number of blood units transfused between groups (odds ratio 1.52; 95% CI 0.77-3.00; P=0.22). Patients receiving i.v. iron had a higher haemoglobin 6 weeks after intervention compared with the placebo group (Hb 116 g L(-1)vs 108 g L(-1); P=0.01). No difference was observed in length of hospital stay, rehabilitation duration to discharge, or 6-month mortality. However, in younger patients without major bleeding, the use of placebo compared with i.v. iron was associated with an increased number of units of blood transfused (placebo transfusion incidence rate ratio 3.88; 95% CI 1.16-13.0; P=0.03). CONCLUSIONS In anaemic patients undergoing surgery for hip fracture, i.v. iron did not reduce the overall proportion of patients receiving blood transfusion. The use of i.v. iron may reduce the amount of blood transfused in younger patients. The use of i.v. iron is associated with increased haemoglobin concentrations 6 weeks after the operation. CLINICAL TRIAL REGISTRATION ACTRN12612000448842.

Abstract

BACKGROUND Postoperative anemia is a risk factor for adverse surgical outcomes. Our study aimed to assess the role of intravenous iron and erythropoietin therapy for the rapid correction of anemia following orthopedic surgery. METHODS Patients undergoing elective orthopedic surgery were prospectively enrolled and randomly divided into three groups: Control (placebo), Group 1 (IV iron monotherapy), and Group 2 [combined IV iron and recombinant human erythropoietin (rHuEPO) therapy]. Blood tests were performed preoperative (baseline) and on postoperative days (PODs) 1, 3, and 7. RESULTS All groups demonstrated significantly lower hemoglobin (Hb) concentrations compared to baseline, with no significant inter-group differences in postoperative Hb concentrations (p > 0.05). Serum erythropoietin, ferritin, and vitamin B(12) levels, and reticulocyte count increased beyond normal ranges in all groups. Significantly lower serum iron levels were observed postoperatively in all groups (p < 0.05). No significant inter-group differences in hepcidin level were observed (p > 0.05). CONCLUSION Postoperative treatment with combined intravenous iron and rHuEPO was ineffective in correcting postoperative anemia among orthopedic surgery patients, besides achieving higher reticulocyte counts in the first week of surgery. No improvement in mobilization of storage iron was achieved with rHuEPO. We further suggest against vitamin B(12) administration during the early postoperative period.

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.

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.

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.

Abstract

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.

Abstract

PURPOSE To find the best short-term daily recombinant human erythropoietin (rhEPO)-based treatment protocols for blood-saving purpose in THA. METHOD The patients were randomized to 1 of 3 interventions: Patients in group A received 10,000 IU (150 IU/kg) of subcutaneous rhEPO (1 ml) daily from 5 days preoperatively to 3 days postoperatively (9 doses in total); Patients in group B received 1 ml of subcutaneous normal saline daily from 5 days preoperatively to 3 days preoperatively and then 10,000 IU (150 IU/kg) of subcutaneous rhEPO daily until 3 days postoperatively (6 doses in total). Patients in group C received 1 ml of subcutaneous normal saline daily from 5 days preoperatively to one day preoperatively and then 10,000 IU (150 IU/kg) of subcutaneous rhEPO daily from the day of surgery to 3 days postoperatively (4 doses in total). RESULTS One hundred eighty patients were included. On postoperative day one, patients in the group A showed significantly higher Hb level (108.4 ± 11.4 g/L) than group C (103.9 ± 8.8 g/L). Group B (107.8 ± 8.4 g/L) also showed significantly higher Hb level than group C (103.9 ± 8.8 g/L) (p < 0.05). On postoperative day 3, no significant difference was found between group B and group C in Hb level (98.7 ± 10.5 and 94.9 ± 8.7 g/L, respectively) (p = 0.094), but the Hb level in group A (103.6 ± 11.0 g/L) was still markedly higher than in group B and the Hb level in group A was also markedly higher than in group C. In terms of blood loss, no markedly difference was found in intraoperative blood loss among group A, B and C (78.3 ± 22.4, 84.6 ± 29.1, and 80.3 ± 23.9 ml, respectively) (p = 0.381), but on postoperative day one, the mean blood loss in group C (522.4 ± 189.4 ml) was significantly more than group B (371.2 ± 124.6 ml), and group B was also significantly more than group A (284.8 ± 112.9 ml) with 95% confidence interval, and group B had significantly less blood loss than group C (p < 0.001). With respect to the total blood loss, the total blood loss in group C (881.6 ± 314.9 ml) was significantly more than group B (642.6 ± 232.9 ml), and group B was also significantly more than group A (514.5 ± 204.6 ml) with 95% confidence interval (Table 2). Only 2 patients in each group received allogeneic blood transfusion and each patient received 2 units of red blood cells, so, the transfusion requirements among the three groups were comparable. CONCLUSIONS Daily small-dose of subcutaneous rhEPO administered from 5 days before THA could significantly decrease perioperative blood loss and improve postoperative Hb levels, without increasing risks of complications, when compared with the application of rhEPO from 3 days before THA or from the day of surgery. However, surgeons should choose the regimen individually according to different patients' personal circumstances.

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.

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.

Abstract

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.