Nadia Rosencher

Orthopedic Surgery Transfusion Hemoglobin European Overview (OSTHEO) study: blood management in elective knee and hip arthroplasty in Europe*

BACKGROUND: The purpose of this study was to assess current practices in blood management in elective orthopedic surgery in Europe.

The safety and efficacy of extended thromboprophylaxis with fondaparinux after major orthopedic surgery of the lower limb with or without a neuraxial or deep peripheral nerve catheter: The EXPERT study

BACKGROUND:The benefit-risk ratio of extended fondaparinux therapy has not been assessed in patients undergoing major lower limb joint arthroplasty. Few data on the concomitant use of fondaparinux and continuous neuraxial or deep peripheral nerve blockade are available. We performed a prospective intervention study in patients undergoing major orthopedic surgery primarily designed to assess the efficacy of fondaparinux when drug administration was withheld for 48 h to permit removal of a neuraxial or deep peripheral nerve catheter. The safety and efficacy of extended fondaparinux therapy for the prevention of venous thromboembolism were also evaluated. METHODS:Patients received a daily subcutaneous injection of 2.5 mg fondaparinux for 3 to 5 wk postoperatively. In patients with a neuraxial or deep peripheral nerve catheter, the catheter was removed 36 h after the last fondaparinux dose. The next fondaparinux dose was administered 12 h after catheter removal. The primary end points were symptomatic venous thromboembolism and major bleeding up to 4–6 wk after surgery. RESULTS:We recruited 5704 patients. A neuraxial or deep peripheral nerve catheter was inserted in 1553 (27%) patients and 78 (1.4%) patients, respectively. The rate of venous thromboembolism was 1.0% (54 of 5387). There was no difference between patients without (1.1%) or with (0.8%) a catheter (the upper limit of the 95% confidence interval of the odds ratio, 1.49, being below the predetermined noninferiority margin of 1.75). The incidence of major bleeding was 0.8% (42 of 5382). No neuraxial or perineural hematoma was reported. CONCLUSIONS:Once-daily subcutaneous injection of 2.5 mg fondaparinux given for 3 to 5 wk was effective and safe for prevention of venous thromboembolism after major orthopedic surgery. Temporary discontinuation of fondaparinux for 48 h permitted safe removal of a neuraxial or deep peripheral nerve catheter without decreasing thromboprophylatic efficacy.

Nifedipine and intraoperative core body temperature in humans

BackgroundInitial anesthetic-induced hypothermia results largely from core-to-peripheral redistribution of heat. Nifedipine administration may minimize hypothermia by inducing vasodilation well before induction of anesthesia. Although vasodilation would redistribute heat to peripheral tissues, thermoregulatory responses would maintain core temperature. After equilibration, the patient would be left vasodilated, with a small core-to-peripheral temperature gradient. Minimal redistribution hypothermia may accompany subsequent induction of anesthesia, because heat flow requires a temperature gradient. In contrast, similar vasodilation concurrent with anesthetic-induced vasodilation may augment redistribution hypothermia. Accordingly, the authors tested the hypothesis that nifedipine treatment for 12 h before surgery would minimize intraoperative redistribution hypothermia, whereas nifedipine treatment immediately before induction of anesthesia would aggravate hypothermia. MethodsPatients undergoing hip arthroplasty were randomly assigned to: (1) 20 mg long-acting nifedipine orally 12 h before surgery, and 10 mg sublingually 1.5 h before surgery (n = 10); (2) nifedipine 10 mg sublingually just before induction of anesthesia (n = 10); and (3) no nifedipine (control, n = 10). Anesthesia was maintained with isoflurane and 60% nitrous oxide. Administered intravenous fluids were heated, but the patients were not otherwise actively warmed. ResultsCore temperature decreased 0.8° C in the first hour of surgery in the patients given nifedipine the night before and the morning of surgery, which was significantly less than in the control group (1.7° C in the first hour). In contrast, core temperature decreased 2.0° C in the first hour of surgery in the patients given nifedipine immediately before induction of anesthesia. During the subsequent 70–130 min of anesthesia, core temperature decreased at roughly comparable rates in each group. After 130 min of anesthesia, core temperature in the two nifedipine-treated groups differed by 1.6° C, and the temperatures in all three groups differed significantly. ConclusionsVasodilation induced by nifedipine well before induction of anesthesia minimized redistribution hypothermia, presumably by decreasing the core-to-peripheral tissue temperature gradient. In contrast, redistribution hypothermia was aggravated by administration of the same drug immediately before induction of anesthesia. Drug-induced modulation of vascular tone thus produces clinically important alterations in intraoperative core temperature.

Background and methodology of MONITOR-GCSF, a pharmaco-epidemiological study of the multi-level determinants, predictors, and clinical outcomes of febrile neutropenia prophylaxis with biosimilar granulocyte-colony stimulating factor filgrastim

The MONITOR-GCSF study is an international, prospective, observational, pharmaco-epidemiological study to evaluate the multi-level factors and outcomes associated with the use of Zarzio(®) in the prophylaxis of febrile neutropenia in chemotherapy-treated cancer patients. Driven by a novel, integrated, multi-focal framework for post-approval observational studies, it examines determinants of response at both the patient and the physician level; integrates statistical methodologies from the social and behavioral sciences; assesses factors predictive of poor treatment response; and evaluates the congruence of treatment with EORTC guidelines and the approved label. This pan-European study will recruit at least 1000 patients from a minimum of 75 centers and follow them for maximum 6 cycles of chemotherapy. Apart from descriptive and associative procedures, statistical analysis will include variance attribution methods; hierarchical linear, logistic, and Poisson modeling; Kaplan-Meier time-to-event analysis, Mantel-Cox log-rank or generalized Wilcoxon-Breslow tests, and Cox proportional hazards modeling; and clustering and related data mining techniques.

The “Critical Thrombosis Period” in Major Orthopedic Surgery: When to Start and When to Stop Prophylaxis

Patients undergoing major orthopedic surgery are at high venous thromboembolism (VTE) risk, with morbid and potentially fatal consequences. Anticoagulant VTE prophylaxis reduces rates of postoperative deep vein thrombosis by up to 60% to 70% in these patients. Therefore, pharmacological prophylaxis with low-molecular-weight heparins (LMWHs), vitamin K antagonists, or fondaparinux is recommended by current guidelines. However, there remains an ongoing debate regarding when to initiate and the optimal duration for prophylaxis. Here, we discuss the mechanisms underlying thrombus formation in patients undergoing major orthopedic surgery, and we review the current literature on the benefit-to-risk ratio associated with preoperative and postoperative initiation of thromboprophylaxis and also the benefit-to-risk ratio in cases of neuraxial anesthesia. We also discuss the duration of postoperative VTE risk following major orthopedic surgery and assess the ‘‘critical thrombosis period’’ when prophylaxis should be provided. Current literature reflects the need to balance the improved efficacy of initiating prophylaxis close to the surgery with increased risk of perioperative bleeding. Evidence from pathology, epidemiology, and clinical studies suggests the risk period for VTE begins at surgery and extends well beyond hospitalization—a crucial issue when considering how long to give prophylaxis—and, in the case of total hip arthroplasty, for at least 3 months after surgery. Literature supports the greater use of ‘‘just-in-time’’ thromboprophylaxis initiation and after-discharge continuation of optimal prophylaxis in orthopedic surgery patients. Providing optimal thromboprophylaxis throughout the critical thrombosis period where a patient is at VTE risk will ensure the best reductions in VTE-related morbidity and mortality.

Update on the MONITOR-GCSF study of biosimilar filgrastim to reduce the incidence of chemotherapy-induced febrile neutropenia in cancer patients: Protocol amendments

The MONITOR-GCSF study is an international, prospective, observational, pharmaco-epidemiological study to evaluate the multi-level factors and outcomes associated with the use of biosimilar filgrastim in the prophylaxis of febrile neutropenia in chemotherapy-treated cancer patients. The background and methodology of this study are described in an article published concurrently in this journal. As important amendments have been made to the protocol, and the purpose of the prior article was to serve as a resource for future referencing, we detail these amendments in this present article: explicit statement about the use of biosimilar filgrastim for both primary and secondary prophylaxis of chemotherapy-induced febrile neutropenia in the objectives and methodology of the study; length of observation; the addition of stage III and stage IV ovarian cancer and multiple myeloma to the tumor types studied; and the deletion of dose dense chemotherapy regimens as an exclusion criterion.

Fat embolism in orthopedic surgery: role of bone marrow fatty acid.

Fat marrow was systematically collected from 212 patients (l-year study) admitted for unilateral total knee arthroplasty (PFES incidence = 1.8%). Bone marrow was collected by aspiration in the tibia1 medulary canal. Lipid bone marrow composition of 50 patients were studied by thin-layer chromatography (TLC). Retrospectively, samples from eight patients were selected. Fat bone marrow from four patients meeting the criteria of PFES and four matched controls (patients hospitalized during the same week) were studied for their fatty acid composition by gas-liquid chromatography-mass spectrometry. Four patients ASA physical status I or II (aged 58 -74 years) undergoing unilateral total knee replacement developed a clinical picture that suggested moderate PFES within 24-48 h postoperatively. All four had moderate or severe confusion, hypoxemia when breathing room air, and diffuse pulmonary infiltrates without evidence of left ventricular failure. Two showed petechial rash. We used the semiquantitative PFES index score developed by Schonfeld et al. (4) (Table 1) because there is no consensus about PFES clinical and laboratory signs. This score is arbitrarily considered to be diagnostic of PFES if it is 5 or more.