Christian Auboyer

Do Antifibrinolytics Reduce Allogeneic Blood Transfusion in Orthopedic Surgery

Studies have shown that antifibrinolytic (aprotinin, tranexamic acid, or ϵ-aminocaproic acid) reduce blood loss in orthopedic surgery. However, most lacked sufficient power to evaluate the efficacy and safety on clinical outcomes. This meta-analysis aims to evaluate whether intravenous antifibrinolytics, when compared with placebo, reduce perioperative allogeneic erythrocyte transfusion requirement in adults undergoing orthopedic surgery and whether it might increase the risk of venous thromboembolism. From MEDLINE, EMBASE, and the Cochrane Controlled Trials Register, the authors identified 43 randomized controlled trials in total hip and knee arthroplasty, spine fusion, musculoskeletal sepsis, or tumor surgery performed to July 2005 (for aprotinin, 23 trials with 1,268 participants; tranexamic acid, 20 with 1,084; ϵ-aminocaproic acid, 4 with 171). Aprotinin and tranexamic acid reduced significantly the proportion of patients requiring allogeneic erythrocyte transfusion according to a transfusion protocol. The odds ratio was 0.43 (95% confidence interval, 0.28–0.64) for aprotinin and 0.17 (0.11–0.24) for tranexamic acid. Results suggest a dose–effect relation with tranexamic acid. ϵ-Aminocaproic acid was not efficacious. Unfortunately, data were too limited for any conclusions regarding safety. Although the results suggest that aprotinin and tranexamic acid significantly reduce allogeneic erythrocyte transfusion, further evaluation of safety is required before recommending the use of antifibrinolytics in orthopedic surgery.

De-escalation as part of a global strategy of empiric antibiotherapy management. A retrospective study in a medico-surgical intensive care unit

IntroductionMost data on de-escalation of empirical antimicrobial therapy has focused on ventilator-associated pneumonia. In this retrospective monocentric study, we evaluated de-escalation as part of a global strategy of empiric antibiotherapy management irrespective of the location and the severity of the infection. The goal of this trial was to assess the application of a de-escalation strategy and the impact in terms of re-escalation, recurrent infection and to identify variables associated with de-escalation.MethodsAll consecutive patients treated with empiric antibiotic therapy and hospitalized in the intensive care unit for at least 72 hours within a period of 16 months were included. We compared the characteristics and outcome of patients who have experienced de-escalation therapy with those who have not.ResultsA total of 116 patients were studied corresponding to 133 infections. Antibiotic therapy was de-escalated in 60 cases (45%). De-escalation, primarily accomplished by a reduction in the number of antibiotics used, was observed in 52% of severe sepsis or septic shock patients. Adequate empiric antibiotic and use of aminoglycoside were independently linked with de-escalation. De-escalation therapy was associated with a significant reduction of recurrent infection (19% vs 5% P = 0.01). Mortality was not changed by de-escalation.ConclusionsAs part of a global management of empiric antibiotherapy in an intensive care unit, de-escalation might be safe and feasible in a large proportion of patients.

Ventilator temperature sensors: an unusual source of Pseudomonas cepacia in nosocomial infection

A prospective study was undertaken to determine the source of Pseudomonas cepacia colonization and infection that had affected ventilated patients in an Intensive Care Unit (ICU) for three years. Thirty-eight patients undergoing mechanical ventilation were enrolled during a six-week period. Samples were taken from patients, ventilator circuits and the environment for culture. P. cepacia was isolated from the condensate formed in the ventilator circuit and the source of the contamination was shown to be the temperature sensor. Ribotyping of the representative strains of P. cepacia performed with two endonucleases, EcoRI and PvuII, confirmed the homogeneity of the isolates from patients and ventilator circuits. A modification of the procedure for disinfection of the temperature sensors resulted in the eradication of P. cepacia from the ICU.

A Comparison of Target- and Manually Controlled Infusion Propofol and Etomidate/Desflurane Anesthesia in Elderly Patients Undergoing Hip Fracture Surgery

Elderly patients have a higher risk of developing adverse drug reactions during anesthesia, especially anesthesia affecting cardiovascular performance. In this prospective randomized study we compared quality of induction, hemodynamics, and recovery in elderly patients scheduled for hip fracture surgery and receiving either etomidate/desflurane (ETO/DES) or target-controlled (TCI) or manually controlled (MAN) propofol infusion for anesthesia. Sixteen patients were anesthetized with ETO (0.4 mg/kg) followed by DES titrated from an initial end-tidal concentration of 2.5%. Eighteen patients received propofol TCI at an initial plasma concentration of 1 &mgr;g/mL and titrated upwards by 0.5-&mgr;g/mL steps. Fifteen patients received a bolus induction of propofol 1 mg/kg over 60 s followed by an infusion initially set at 5 mg · kg−1 · h−1. All received a bolus (20 &mgr;g/kg) followed by an infusion of 0.4 &mgr;g · kg−1 · min−1 alfentanil. According to hemodynamics, concentrations of DES or propofol (TCI group) and propofol infusion rate (MAN group) were respectively adjusted by a step of 20% and 50%. In the TCI and ETO/DES groups, the time spent at a mean arterial blood pressure within 15% and 30% of baseline values was more than 60% and 80% of anesthesia time, whereas in the MAN group it was <30% and 60%, respectively. In the MAN group more anesthetic drug adjustments were recorded (6.4 ± 2.8 versus 2.5 ± 1.2 [ETO/DES] and 2.6 ± 1 [TCI]). TCI improves the time course of propofols hemodynamic effects in elderly patients.

Optimal low-molecular-weight heparin regimen in major orthopaedic surgery A meta-analysis of randomised trials

Low-molecular-weight heparins (LMWH) are routinely used for thromboprophylaxis in major lower limb orthopaedic surgery. However the optimal LMWH regimen, offering the greatest efficacy with an acceptable risk of bleeding, has not been clearly established with regard to dose and timing of treatment initiation. We performed a meta-analysis of all available randomised trials comparing LMWH to placebo. Relative risks (RR) and corresponding 95% confidence intervals (CI) were calculated. By means of subgroup analysis, we evaluated the consistency of the results according to the timing of treatment initiation (preoperative versus postoperative) and dose of LMWH used (low doses, i.e. 4000 anti-Xa IU or below versus high doses). The possibility of a dose-effect relationship of LMWH was also evaluated by meta-regression. Thirteen studies were included (1925 patients). In four studies, LMWH treatment was started postoperatively. Daily LMWH doses ranged from 3000 anti-Xa IU to over 6000 anti-Xa IU. Compared to placebo, LMWH significantly reduced the risk of asymptomatic deep-vein thrombosis (DVT) (RR=0.51, 95% CI=[0.45-0.59], p<0.001) without significantly increasing the risk of major haemorrhage (RR=0.80 [0.36-1.79], p=0.58). We found no convincing evidence that starting prophylaxis preoperatively was associated with a significantly reduced risk of asymptomatic DVT relative to starting postoperatively. Our results showed a strong correlation between the risk of DVT and LMWH dose (meta-regression, test of slope p=0.03). These findings are tentative because the comparisons are across trials, but nevertheless suggest that the different LMWH regimens currently recommended are effective and safe.

Prospective Determination of Serum Ceftazidime Concentrations in Intensive Care Units

Introduction: The purpose of this study was to assess the value of a serum assay for ceftazidime (CAZ) in patients in the intensive care unit (ICU) of the Saint-Etienne University Teaching Hospital and in other ICUs in the region to optimize therapy. Material and Methods: Between November 1, 2005, and February 29, 2008, for patients hospitalized in ICUs not on dialysis and undergoing continuous CAZ infusion, serum assay of the antibiotic was performed 36 to 48 hours after the start of treatment using a single serum sample. The target serum CAZ concentration was 40 ± 10 mg/L with a concentration/minimum inhibitory concentration ratio of 5 or greater × minimum inhibitory concentration of CAZ when a strain was isolated. Results: Serum CAZ concentration was determined in 92 patients (28 females, 64 males) receiving CAZ by continuous infusion. The mean age was 66 years (range, 19-89 years) and the mean weight was 73 kg (range, 33-122 kg). The CAZ dose was between 1 g and 6 g/24 hours. The mean serum CAZ concentration was 46.9 mg/L (range, 7.4-162.3 mg/L). Serum CAZ concentrations were as follows: 30 to 50 mg/L in 35.9% of patients, less than 30 mg/L in 36.9%, and greater than 50 mg/L in 27.2%. Infection was documented in 51 patients, with 42 strains of Pseudomonas aeruginosa being detected. The serum concentration/minimum inhibitory concentration ratio was 5 or greater for 84.3%. Antibiotic dosage was adjusted based on the CAZ assay results. Conclusion: Our study suggests that CAZ measurement is needed in ICUs to achieve adequate CAZ concentrations to avoid treatment toxicity and to achieve efficacy as rapidly as possible, particularly in strains having limited susceptibility to antibiotics.

Conversion of Prevalence Survey Data on Nosocomial Infections to Incidence Estimates: A Simplified Tool for Surveillance?

We calculated the incidence of nosocomial infection in 2 intensive care units (ICUs) on the basis of prevalence data recorded from 1997 through 2002 and compared these estimates to cumulative incidences measured in the 2 ICUs during the same period to investigate the feasibility and the reliability of converting prevalence data to incidence estimates. Decreases in the calculated and measured incidences over time in the ICUs were found to be statistically significantly related.

Transcranial Color Duplex Ultrasound: A Reliable Tool for Cerebral Hemodynamic Assessment in Brain Injuries.

Background: Transcranial color duplex ultrasound (TCCD) is becoming an important tool for cerebral monitoring of brain-injured patients. To date, TCCD reproducibility has been studied in healthy volunteers or patients with subarachnoid hemorrhage and its efficiency in many brain injuries has not been proved. Our aim was to evaluate TCCD interobserver agreement in different brain injuries. Patients and Methods: We performed a prospective monocentric trial conducted from January 2014 to September 2014 in intensive care unit (ICU) of Saint-Etienne university teaching hospital, France. Brain-damaged patients admitted in ICU were included, excluding those with decompressive craniectomy. Two randomized operators among the ICU medical staff consecutively performed measurements of cerebral blood flow velocities with TCCD. Results: One hundred measurements were obtained from 42 patients. Hemodynamic and end-tidal CO2 pressure were similar between both measurement set. The results obtained with the Bland-Altman method showed bias at 0.52 (95% confidence interval [CI], −4.19 to 3.16), 0.53 (95% CI, −1.86 to 2.92), and 0.002 (95% CI, −0.06 to 0.06) for mean velocity, diastolic velocity, and pulsatility index, respectively. The limits of agreement were (−32.4; 31.4), (−20.4; 21.4), (−0.5; 0.5) for mean velocity, diastolic velocity, and pulsatility index, respectively. The Passing and Bablok regression have shown a quasilinear relationship between measurements. Conclusions: We reported the reliability of TCCD interobserver agreement in brain-damaged patients.

Feasibility and Interest of Continuous Diaphragmatic Fatigue Monitoring Using Wavelet Denoising in ICU and Anesthesia

Measures of diaphragmatic electromyography (Edi), and respiratory mechanics, have demonstrated early changes before clinical complications. However, automatic Edi data collection is not adequate today due mainly to severe artefacts as well as to loss of signal. We thus intended to develop a new device with embedded artificial intelligence to optimize automatic Edi recordings independantly of artefacts and of probe displacement. We first chose the best mathematical tool to denoise Edi, using an established database, giving multiresolution wavelets as the best, resulting in the permanent availability of the H/L spectral index, a recognized representative of diaphragmatic fatigue. Fatigue was simultaneously measured using the classical mechanical f/Vt index (Rapid Shallow Breathing Index, RSBI), as well as the transdiaphragmatic pressure. We then performed a comparison of real-time H/L and RSBI in a group of seven healthy volunteers, before and during midazolam sedation infusion 0.1 mg.kg -1 , with a parallel CPAP administration (2.5, 5.0, and 10 cm H2O) intended to compensate for airways resistance due to midazolam. Procedure was ended by delivering the antagonistic flumazenil 0.2 to 0.5 mg.kg -1 . Progressive fatigue due to midazolam, the relief due to CPAP, as well as the answer to the anatgonist flu-

Septic shock due to Legionella pneumophila serogroup 2: usefulness of molecular biology for diagnosis, treatment and epidemiological investigation

During the last 10 years, nucleic acid detection methods have been shown to offer a good alternative to the diagnosis of legionellosis (reviewed by Diederen in [1]), especially when non-L. pneumophila sg1 strains are involved [2]. The case presented herein is illustrative of the benefit of using molecular techniques to diagnose and manage such infections. A 48-year-old woman without previous history of morbidity except cigarette smoking experienced fever and cough for which she received beta-lactam therapy. Six days later, she was admitted to the hospital for severe hypoxemic pneumonia that became bilateral in 4 days and required mechanical ventilation. The diagnosis of legionellosis was documented 2 days after admission in respiratory samples by a 16S rDNA real-time PCR method using the primers described by Jonas et al. [3]. Further complications occurred including pleuritis and infusion of the peritoneal space because of a relapse of Legionella infection (Table 1), alithiasic cholecystitis treated by surgery and bacterial pansinusitis. Finally, after a 3-month stay in the intensive care unit, the patient recovered without any long-term sequelae. The microbiological data relative to the diagnosis and follow-up of legionellosis are depicted in Table 1, together with the anti-infective treatment. An extensive investigation was performed on environmental samples, including the hot water circuits in the patient’s home and in the building where she worked and took showers regularly, as well as the main water circuit of the Turkish bath that she had attended once during the week preceding the onset of symptoms. Using standardized culture methods