Ferric derisomaltose and tranexamic acid, combined or alone, for reducing blood transfusion in patients with hip fracture (the HiFIT trial): a multicentre, 2 × 2 factorial, randomised, double-blind, controlled trial.

BACKGROUND: Anaemia and blood transfusion are associated with poor outcomes after hip fracture. We evaluated the efficacy of intravenous iron and tranexamic acid in reducing blood transfusions after hip fracture surgery. METHODS: In this double-blind, randomised, 2 × 2 factorial trial, we recruited adults hospitalised for hip fractures in 12 medical centres in France who had preoperative haemoglobin concentrations between 9·5 and 13·0 g/dL. We randomly allocated participants (1:1:1:1), via a secure web-based service, to ferric derisomaltose (20 mg/kg intravenously) and tranexamic acid (1 g bolus followed by 1 g over 8 h intravenously at inclusion and 3 g topically during surgery), iron plus placebo (normal saline), tranexamic acid plus placebo, or double placebo. Unmasked nurses administered study drugs; participants and other clinical and research staff remained masked to treatment allocation. The primary outcome was the percentage of patients transfused during hospitalisation (or by day 30). The primary analysis included all randomised patients. This study is registered on ClinicalTrials.gov (NCT02972294) and is closed to new participants. FINDINGS: Of 413 patients (51-104 years old, median [IQR] 86 [78-91], 312 [76%] women, 101 [24%] men), 104 received iron plus tranexamic acid, 103 iron plus placebo, 103 tranexamic acid plus placebo, and 103 double placebo between March 31, 2017 and June 18, 2021 (study stopped early for efficacy after the planned interim analysis done on the first 390 patients included on May 25, 2021). Data for the primary outcome were available for all participants. Among patients on double placebo, 31 (30%) were transfused versus 16 (15%) on both drugs (relative risk 0·51 [98·3% CI 0·27-0·97]; p=0·012). 27 (26%) participants on iron (0·81 [0·50-1·29]; p=0·28) and 28 (27%) on tranexamic acid (0·85 [0·54-1·33]; p=0·39) were transfused. 487 adverse events were reported with similar event rates among the groups; among prespecified safety endpoints, severe postoperative anaemia (haemoglobin <8 g/dL) was more frequent in the double placebo group. Main common adverse event were sepsis, pneumonia, and urinary infection, with similar rates among all groups. INTERPRETATION: In patients hospitalised for hip fracture surgery with a haemoglobin concentration 9·5-13·0 g/dL, preoperative infusion of ferric derisomaltose plus tranexamic acid reduced the risk of blood transfusion by 50%. Our results suggest that combining treatments from two different pillars improves patient blood-management programmes. Either treatment alone did not reduce transfusion rates, but we might not have had the power to detect it. FUNDING: French Ministry of Health, HiFIT trial.

Perioperative Iron Deficiency in Patients Scheduled for Major Elective Surgeries: A French Prospective Multicenter Cross-Sectional Study.

BACKGROUND: The management of perioperative iron deficiency is a component of the concept of patient blood management. The objective of this study was to update French data on the prevalence of iron deficiency in patients scheduled for major surgery. METHODS: The CARENFER PBM study was a prospective cross-sectional study in 46 centers specialized in orthopedic, cardiac, urologic/abdominal, or gynecological surgery. The primary end point was the prevalence of iron deficiency at the time of surgery (D-1/D0) defined as serum ferritin <100 µg/L and/or transferrin saturation (TSAT) <20%. RESULTS: A total of 1494 patients (mean age, 65.7 years; women, 49.3%) were included from July 20, 2021 to January 3, 2022. The prevalence of iron deficiency in the 1494 patients at D-1/D0 was 47.0% (95% confidence interval [CI], 44.5-49.5). At 30 days after surgery, the prevalence of iron deficiency was 45.0% (95% CI, 42.0-48.0) in the 1085 patients with available data. The percentage of patients with anemia and/or iron deficiency increased from 53.6% at D-1/D0 to 71.3% at D30 ( P < .0001), mainly due to the increase of patients with both anemia and iron deficiency (from 12.2% at D-1/D0 to 32.4% at D30; P < .0001). However, a treatment of anemia and/or iron deficiency was administered preoperatively to only 7.7% of patients and postoperatively to 21.7% (intravenous iron, 14.2%). CONCLUSIONS: Iron deficiency was present in half of patients scheduled for major surgery. However, few treatments to correct iron deficiency were implemented preoperatively or postoperatively. There is an urgent need for action to improve these outcomes, including better patient blood management.

Femoral nerve inguinal approach versus proximal femoral triangle ap proach for continuous regional analgesia in active rehabilitation after total knee arthroplasty: A prospective, randomised study.

BACKGROUND: A catheter in femoral nerve block (F-Cath) is an effective regional analgesia technique in total knee arthroplasty (TKA) but results in significant quadriceps weakness. The femoral triangle catheter (FTB-Cath) seems to be an interesting alternative. In this study, we aim to demonstrate that the nerve block administration for analgesic purposes via an FTB-Cath results in less quadriceps weakness than via an F-Cath. METHODS: This study included patients scheduled for TKA performed under general anaesthesia. The patients were randomised to receive either an F-Cath or an FTB-Cath. A unique regimen of 0.2% ropivacaine was administrated for 72 h. The primary endpoint was quadriceps strength assessed clinically on postoperative day (POD) 2 by the Manual Muscle Test (MMT) using a motor grading scores (0-5). The secondary endpoints were quadriceps strength measured by a dynamometer, the Timed Up and Go (TUG) test, the 30-m walk test (30MWT) and pain scores. RESULTS: Forty-four patients were analysed (22 in each group). On POD 2, 77.3% of the patients in the FTB-Cath group had MMT scores ≥ 4 and 13.6% in the F-Cath group (p < 0.001). During the first four POD assessments, quadriceps strength evaluated with a dynamometer was less diminished in the FTB-Cath group (p < 0,001). There was no difference between groups regarding pain scores, TUG test results and 30MWT assessment. CONCLUSION: The FTB-Cath provided a better preservation of quadriceps strength than the F-Cath in TKA, with a similar pain relief.

Risk Factors for Carbetocin Failure after a Cesarean Section: Is Obesity One of Them?

Obese pregnant women have increased rates of fetal macrosomia, long labor, and cesarean sections, which lead to an increased risk of postpartum hemorrhage (PPH). Carbetocin is useful for the prevention of PPH after a cesarean section. Our study aimed to investigate predictors of carbetocin failure after a cesarean section, and specifically whether obesity is associated with carbetocin failure. We retrospectively analyzed all women who received carbetocin after a cesarean section. Carbetocin failure was defined as changes in hematocrit and hemoglobin, blood loss ≥ 1000 mL, and the need for an additional uterotonic agent or second-line therapies for persistent PPH. Univariate and multivariate analyses were performed to investigate predictors of carbetocin failure. The study included 600 women, with 131 (21.8%) obese women. Overall, 44 (7.3%) carbetocin failures were reported, and rates of obese women were similar between groups (carbetocin failure, 11.4% vs. 22.9%; p = 0.08). Previous PPH (p < 0.001), a cesarean section during labor (p = 0.01), cervical ripening (p = 0.02), and birthweight (p = 0.01) were significantly different between groups. In the multivariable logistic regression analysis adjusted for potential confounders, cervical ripening (adjusted odds ratio (OR) 2.23, 95% confidence interval (CI) 1.01-4.80), compared with spontaneous labor, was significantly associated with carbetocin failure. Obesity was not associated with carbetocin failure after cesarean sections.

Study protocol for a multicentre, 2×2 factorial, randomised, controlled trial evaluating the interest of intravenous iron and tranexamic acid to reduce blood transfusion in hip fracture patients (the HiFIT study).

INTRODUCTION: Blood transfusion and anaemia are frequent and are associated with poor outcomes in patients with hip fracture (HF). We hypothesised that preoperative intravenous iron and tranexamic acid (TXA) may reduce the transfusion rate in these patients. METHODS AND ANALYSIS: The HiFIT study is a multicentre, 2×2 factorial, randomised, double-blinded, controlled trial evaluating the effect of iron isomaltoside (IIM) (20 mg/kg) vs placebo and of TXA (intravenously at inclusion and topically during surgery) versus placebo on transfusion rate during hospitalisation, in patients undergoing emergency surgery for HF and having a preoperative haemoglobin between 95 and 130 g/L. 780 patients are expected. The primary endpoint is the proportion of patients receiving an allogenic blood transfusion of packed red blood cells from the day of surgery until hospital discharge (or until D30 if patient is still hospitalised). Enrolment started on March 2017 in 11 French hospitals. The study was stopped between July 2017 and August 2018 (because of investigation of serious AEs with IIM in Spain) and slowed down since March 2020 (COVID-19 crisis). The expected date of final follow-up is May 2022. Analyses of the intent-to-treat and per-protocol populations are planned. ETHICS AND DISSEMINATION: The HiFIT trial protocol has been approved by the Ethics Committee of Comité de Protection des Personnes Ouest II and the French authorities (ANSM). It will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals. The HiFIT trial will be the largest study evaluating iron and TXA in patients with HF. TRIAL REGISTRATION NUMBER: clinicalTrials.gov identifier: NCT02972294; EudraCT Number 2016-003087-40.