Cefepime in critically ill patients: continuous infusion vs. an intermittent dosing regimen.

The aim of this study was to compare the pharmacokinetic and pharmacodynamic parameters of a continuous infusion of cefepime vs. an intermittent regimen in critically ill adult patients with Gram-negative bacilli infection. The prospective randomized parallel study was carried out in 50 patients with severe pneumonia (n = 41) or bacteremia (n = 9). They received cefepime 4 g/d either as a continuous infusion or intermittent administration 2 x 2 g in combination with amikacin. Patient characteristics and the minimal inhibitory concentration (MIC) of the isolated bacteria were comparable. Clinical outcomes were assessed along with pharmacodynamic indices and compared in both groups (chi2 and Mann-Whitney U-tests). Mechanical ventilation, clinical outcome and bacteriological eradication did not significantly differ between the two groups. Also, the area under the plasma cefepime concentration curve at steady state (AUCss: 612 +/- 369 vs. 623 +/- 319 mg x 1(-1) x h), AUCss > MIC (595 +/- 364 vs. 606 +/- 316 mg x 1(-1) x h) and the area under the inhibitory concentration curve (AUICss: 4258 +/- 5819 vs. 5194 +/- 7465 mg x 1(-1) x h) were similar. If the time above MIC (t > MIC) was not significantly higher in Group 1 (100 +/- 0%) than in Group 2 (90 +/- 11%), t > five-fold MIC in Group 1 (100 +/- 0%) was significantly higher (p < 0.01) than in Group 2 (82 +/- 25%). The mean time over the French breakpoint (4 mg/l) was 100 +/- 0% and 72 +/- 27% in Group 1 and 2 (p < 0.001), respectively. In contrast to intermittent cefepime administration, continuous infusion of cefepime consistently maintained a serum concentration > 5 x the MIC of typical Gram-negative nosocomial pathogens. This results in greater bactericidal activity against organisms with a higher (2 mg/l) cefepime breakpoint even if the clinical outcome is not significantly modified.

[Indication of endovascular stent grafts for traumatic rupture of the thoracic aorta]. / Place des endoprothèses dans le traitement des ruptures traumatiques de l'aorte thoracique.

OBJECTIVE: The usual treatment of traumatic aortic rupture (TAR) is surgical. This invasive technique necessitating thoracotomy and ECC is associated with a mortality rate of more than 20% and a paraplegia risk of about 10%. New minimally-invasive techniques (aortic stent-grafting) are emerging as less risky alternatives to surgery. We report our experience in the percutaneous treatment of TAR with stent-graft via a surgical femoral cut-down. PATIENTS AND METHODS: Between 1996 and 2002, 23 patients (16-65-year-old, mean 36 years) were treated by thoracic stent-grafting. An informed consent was obtained for every patients. Thirteen patients had an acute or sub-acute TAR (1-8 months, mean 5 months) and five patients had chronic TAR (13-24 years, mean 17 years). The technique was done under general anaesthesia and each patient received a preoperative blood-pressure reduction treatment. During the procedure, anticoagulation (heparin) was given and hypotension was induced when the stent-graft was deployed. Direct positioning control was obtained by means of TEE. RESULTS: Eighty percent of patients were extubed immediately after the procedure. Bleeding was <150 ml. The primary success rate was 100% with one minor type 2 endoleak that was spontaneously resolved after 2 months. There was no case of mortality or paraplegia. There were three minor complications (17%), two haematomas at the arteriotomy site and one inflammatory syndrome characterised by slight fever, raised biological markers but with negative blood culture. CONCLUSION: Percutaneous aortic stent-grafting for TAR is a minimally-invasive technique, which constitute an interesting alternative to surgery. It only necessitates a femoral surgical cut-down compared to the thoracotomy and ECC associated with surgery. The complication rate is low and no mortality or major complication was encountered in our patients. Eventually, the long-term follow-up will allow a widening of indications.

[Importance of a cefpirome-vancomycin combination on bactericidal kinetics in severe MRSA infections in intensive care]. / Intérêt de l'association cefpirome-vancomycine sur la cinétique de bactéricidie dans les infections sévères à SAMR en réanimation.

UNLABELLED: Vancomycin is always the drug of choice for treatment of infections caused by methicillin-resistant Staphylococcus aureus (MRSA) in spite of his bactericidal kinetic. BACKGROUND: The aim of this study was to evaluate in vivo the improvement of bactericidal kinetic of vancomycin associated with cefpirome against MRSA infection in critically ill patients. METHODS: The prospective cross-over study was carried out in 20 patients with severe pneumonia or bacteremia. There were randomized to receive vancomycin 2 g per day (Group 1, n = 10) or vancomycin with cefpirome 2 g x 2 (Group 2, n = 10). Clinical recovery, bacteriologic parameters (bactericidal kinetic and bactericidal power in vivo at the peak and the valley), duration of ventilation and stay in ICU were comparatively explored in both groups. RESULTS: Clinical outcome did not significantly differ between Group 1 and 2. Bactericidal kinetics were better in the Group 2 (40% vs 60% after 6 hours to the dilution for 1/8e) but the difference was not significant. However, bactericidal power in sera was also better in the Group 2 with more bactericidal dilution at 1/16e (68% vs 88.8%: NS) and overall at 1/32e (10.5% vs 50%: p < 0.05) and CRP, an inflammatory marker, was significantly lower in the Group 2 than in the Group 1 (119.5 +/- 24 mg/l vs 198.6 +/- 78 mg/l: p < 0.05) on the third day.

[Metabolic problems and nutrition in burns]. / Troubles métaboliques et nutrition du brûlé.

Metabolic changes with burns patients are enormous. The loss of skin substance and the necessity of its reconstruction are at the origin of this exceptional situation. In this context of major aggression with important metabolic alteration the nutritional needs are considerable. To assure a tissue reconstruction, nutrition is as important as the fight against infection. The authors make the point on the quantity needs and the quality needs. They raise up the perspectives concerning immunonutriments and note the importance of enteral administration. As a conclusion, they insist on the fundamental role of the clinical aspect, in the survey of nutritional state.

[Evaluation of regional anesthesia procedure in an emergency department]. / Evaluation de l'utilisation de l'anesthésie locorégionale dans un service d'urgence.

OBJECTIVES: Evaluation of regional anaesthesia procedures for limb traumatic surgery performed in an emergency department. METHOD: Anaesthetic procedures concerning traumatic emergencies have been studied from 1995 to 2000. RESULTS: A 32% increase in anaesthesia practice was observed from 1995 (221) to 2000 (292) with a 52% increase in regional anaesthesia. Since 1996, regional anaesthesia represents more than 80% of the anaesthetic procedures and 90% for the upper limb surgery (66% of the surgical procedures). Axillary block (50%), interscalene brachial plexus block (15%) and combined sciatic and femoral nerve block (17%) were the main regional anaesthesia procedures. Spinal anaesthesia (9 cases) and intravenous locoregional anaesthesia (12 cases) were rarely used. CONCLUSION: In our study, regional anaesthesia is the most used technique when compared to general anaesthesia for emergency procedure. The anaesthetic staff has to be motivated and trained.

Haemodynamic changes during retroperitoneoscopic adrenalectomy for phaeochromocytoma.

Surgical removal of phaeochromocytoma may be accompanied by acute cardiovascular changes. We report the haemodynamic changes in seven patients with retroperitoneal laparoscopic adrenalectomy for phaeochromocytoma. Transient hypertension (systolic pressure (SBP) > 160 mm Hg) was observed in all patients during manipulation of the tumour, in two patients during pneumoretroperitoneum insufflation, and in one patient during intubation. Small doses of nicardipine were sufficient to control these episodes of hypertension. Transient hypotension (SBP < 100 mm Hg) was observed in two patients during exsufflation and in one patient during repositioning to the lateral position. Our observations suggest that this approach provides relative haemodynamic stability, especially during pneumoretroperitoneum insufflation.

[Management of acute respiratory distress syndrome in Midi-Pyrnees]. / Prise en charge du syndrome de détresse respiratoire aiguë en Midi-Pyrénées.

OBJECTIVE: To assess management of acute respiratory distress syndrome (ARDS) in Midi-Pyrénées, France. METHODS: A prospective study using a questionnaire divided into 10 parts, definition, etiology, radiography, computed tomography, management, was conducted in 26 intensive care units in the Midi-Pyrénées. Management of ARDS in Midi-Pyrénées was comparted with management elsewhere as described in the literature. RESULTS: Overall participation rate was 73%. Disparities were found concerning the definition. Four etiologies accounted for 75% of all ARDS cases. Chest x-rays were used for positive diagnosis and thoracic scans for complications. Ventilatory and hemodynamic optimizations were the first line therapy used. Twenty-nine percent and 41% of the intensive care unites used nitric oxide and prone position respectively. CONCLUSIONS: There are differences between ARDS management in Midi-Pyrénées and that described in the current literature. Epidemiologic studies such as this one are necessary before publishing guidelines for the management of ARDS.

[Duration of antibiotic treatment in intensive care: current data]. / Durée du traitement antibiotique en réanimation: données actuelles.

OBJECTIVE: To review the current data on the duration of an antibiotic treatment. METHODS: Analysis of recent and older articles on criteria of discontinuation of an antibiotic treatment in intensive care patients. SYNTHESIS: In intensive care patients the initiation of an antibiotic therapy is more or less codified, in spite of numerous existing problems. The duration of its maintenance, although based on scientific data depends mainly on a multitude of variables. The first step is to assess the therapeutic efficiency in considering the regression of clinical manifestations, the normalization of the acute phase reactants, the sterility of bacteriological samples and the absence of relapse at therapy discontinuation. An assessment after 48 hours is essential, in order to decide the maintenance or the modification of therapy. Finally the indication of bitherapy is considered. The theoretical duration of antibiotic therapy is determined in taking into account the involved microbial agent(s), the centre of infection, the bacterial inoculum, the patient, the presence of foreign material, and the administered antibiotic.

[Continuous versus intermittent cefepime infusion in critical care. Preliminary results]. / Perfusion continue versus administration discontinue de céfépime en réanimation. Résultats préliminaires.

The bactericidal activity of beta-lactams is time-dependent, and the time spent above the MIC (T > MIC) is the best predictor of efficacy. A prospective, randomized, open-label study was conducted in intensive care unit (ICU) patients with gram-negative rod infections to compare the efficacy of cefepime given as a continuous versus an intermittent infusion. Of the 18 patients included to date, 14 had severe pneumonia and four bacteremia. All patients received amikacin, 15 mg/kg/d, and cefepime, 4 g/d. Patients were randomized to cefepime administration as a continuous infusion (Group 1, n = 9) or as an intermittent infusion (Group 2, n = 9, 2 g every 12 h). No significant differences were found between the two groups for age, sex, initial infection, IGS II score (46 vs 48, NS) or the MIC of the gram-negative organism. Mechanical ventilation and hospital stay durations, recovery rates, and pharmacokinetic parameters (24-h AUIC, 12-h AUIC, T > MIC, and T > 5 x MIC) were compared in the two groups using the chi-square and Mann-Whitney tests. P values < 0.05 were considered statistically significant. There were no significant differences for mechanical ventilation duration, recovery rate, hospital stay duration (34 vs 36 days, NS), 24-h AUIC (624 vs 473, NS), or the 12-h AUIC (235 vs 238, NS). There were two interesting findings: T > MIC was significantly (P < 0.05) higher in Group 1 (23.84 +/- 0.2) than in Group 2 (20.7 +/- 3), and T > 5 x MIC was also significantly (P < 0.01) higher in Group 1 (23.61 +/- 0.6) than in Group 2 (16.6 +/- 6). Although clinical outcomes were similar in the two groups, it is reasonable to assume that the longer time spent with a cefepime level above the MIC in the continuous infusion group was associated with a more stable bactericidal effect.

[Severe methicillin-resistant Staphylococcus aureus infections. Emergence of resistance to fusidic acid or fosfomycin during treatment with continuous infusion of vancomycin]. / Infections sévères à Staphylococcus aureus mticillino-résistants. Emergence de résistance à l'acide fusidique ou à la fostomycine lors du traitement par vancomycine en perfusion continue.

OBJECTIVES: To evaluate the development of resistance to fosfomycin or fucidic acid in severe infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and to assess the relationship with serum levels of vancomycin METHODS: A retrospective study was performed in patients hospitalized in our intensive care unit during a 3-year period (1993-1995) who were treated for severe MRSA infection with continuous infusion vacomycin and fosfomycin or fucidic acid. We analyzed the development of resistance and serum levels of vancomycin. RESULTS: During this period, only 20 patients received continuous infusion vancomycin plus fucidic acid or fosfomycin. MSRA resistant to fucidic or fosfomycin developed in 9. Vancomycin serum levels were significantly lower in patients who developed resistance to focidic acid or fosfomycin, both during the first 5 days of treatment (16.68 +/- 1.07 micrograms/ml vs. 22.64 +/- 1.05 mg/ml, p < 0.01) and throughout treatment duration (17.29 +/- 1.07 micrograms/ml vs. 21.85 +/- 0.78 microgram/ml, p < 0.01). CONCLUSIONS: Our findings confirm that in spite of continuous vancomycin infusion at an initial rate of 2 g/24 h, Staphylococcus aureus resistance to fosfomycin or fucidic acid an develop during ongoing treatment. Vancomycin levels of at least 20 micrograms/ml should be obtained as rapidly as possible.

Effects of pentobarbital and etomidate on plasma catecholamine levels and spectral analysis of blood pressure and heart rate in dogs.

The present paper investigates the effects of two anaesthetic drugs (pentobarbital and etomidate) on both short-term variabilities of systolic blood pressure (SBP) and heart rate (HR) using fast Fourier transformation and catecholamine plasma levels. HR and BP were continuously recorded through an arterial catheter and blood samples were taken from the jugular vein. Spectral analysis was performed first in the conscious state and six minutes after induction of anaesthesia on a series of 256 consecutive BP and HR values (delta t: 2 Hz). The area under the curve (AUC) was determined in the low-frequency component of the SBP (LF: 40-150 mHz), in the high-frequency band of HR (HF: respiratory frequency +/- 50 mHz) and in the total frequency spectra. Results were normalized by calculation of the ratio between AUC of LF and HF and the total AUC of the corresponding spectrum (TS). Etomidate (2 mg/kg i.v.) induced a significant increase in TS and LF without changing the LF/TS ratio or the HR variability when compared with the awake period. Catecholamine plasma levels did not change. In contrast, pentobarbital (30 mg/kg i.v.) decreased the values of LF, HF, LF/TS and HF/TS and catecholamine plasma levels. These results suggest that pentobarbital decreases the activity of the two components of the autonomic nervous system whereas etomidate induces only minimal changes.

[Continuous administration of vancomycin in patients with severe burns]. / Vancomycine en administration continue chez le grand brûlé.

OBJECTIVES: In the severely burned patient, a marked, rapid fall in serum concentrations is often observed after intermittent infusion of vancomycin at the usual dose of 30 mg/kg. This specific "jagged" pharmokinetic course with inadequate residual concentrations raises the problem of the efficacy of this time-dependent antibiotic. Studies in patients in general resuscitation units have shown the interest of vancomycin administration in continuous infusion. METHODS: We analyzed variations in serum concentrations of vancomycin during continuous infusion in 18 patients with burns involving a mean of 40% total body surface and reported the doses necessary to maintain serum vancomycin at therapeutic levels; the possible correlations between serum vancomycin concentrations, burn parameters, age and renal function; and clinical and biological tolerance. RESULTS: Higher initial doses were required in burn patients (40 mg/kg in patients aged under 60) than in other patients. Impairment of renal function is a contra-indication of continuous infusion. CONCLUSION: This mode of administration has the advantage of ensuring greater efficacy by preventing fluctuations in serum concentrations.

[Peribulbar anesthesia in surgery of the vitreous body and retina]. / L'anesthésie péribulbaire dans la chirurgie vitréorétinienne.

Peribulbar anaesthesia was used in 40 patients undergoing vitreoretinal surgery; two injections of a mixture of bupivacaine 0.5% and hyaluronidase were performed in the lower and the upper eyelid. Results were judged very satisfactory in 38 of these 40 cases, for anaesthesia as well as for akinesia; no local or systemic complications were observed. Peribulbar anaesthesia is one of the methods of choice, because of its safety; it seems well appropriate for vitreoretinal surgery, provided that its indications are judicious.