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The aim of this study was to develop a population-pharmacokinetic model of ceftazidime in intensive care unit patients to include the influence of patients' characteristics on the pharmacokinetics. Forty-nine patients for model building and 23 patients for validation were included in a randomized study. They received ceftazidime at 2 g three times a day or as 6 g per day continuously. A NONMEM pharmacokinetic model was constructed, and the influences of covariates were studied. The model was validated by a comparison of the predicted and observed concentrations. A final model was elaborated from the whole population. Total clearance (CL) was significantly correlated with the glomerular filtration rate (GFR) calculated by modification of the diet in renal disease (MDRD), the central volume of distribution (V1) with intubation, and the peripheral volume of distribution (V2) with the reason for admission. The mean pharmacokinetic parameters were as follows: CL, 5.48 liters/h, 40%; V1, 10.48 liters, 34%; V2, 32.12 liters, 59%; total volume, 42.60 liters, 45%; and intercompartmental clearance, 16.19 liters/h, 42%. In the polytrauma population (mechanically ventilated), the time above the MIC at steady state never corresponds to 100% for discontinuous administration, and the target concentration of five times the MIC was reached with a 6-g/day dose only for patients with an MDRD of

International audience; BACKGROUND: Using the intubation difficulty scale (IDS), we sought to confirm that obese patients are more difficult to intubate than lean patients. We assessed classical bedside tests and included neck circumference. METHODS: We prospectively compared the incidence of difficult tracheal intubation in 70 obese [body mass index (BMI) > or = 30 kg/m(2)] and 61 lean patients (BMI < 30 kg/m(2)). The IDS scores, categorized as difficult intubation (IDS > 5) or not (IDS < or = 5), and the patient data, were compared between lean and obese patients. Preoperative measurements [BMI, neck circumference (at the level of the thyroid cartilage), width of mouth opening, sternomental distance, and thyromental distance], medical history of obstructive sleep apnea syndrome, and several scores (Mallampati, Wilson, El Ganzouri) were recorded. The view during direct laryngoscopy was graded, and the IDS was recorded. We then compared patients with IDS < or = 5 and > 5, concerning each item. RESULTS: The results indicate that difficult tracheal intubation is more frequent in obese than in lean patients (14.3% vs 3%; P = 0.03). In the patients with IDS > 5, thyromental distance, BMI, large neck circumference, and higher Mallampati score were the only predictors of potential intubation problems. CONCLUSION: We found that problematic intubation was associated with thyromental distance, increasing neck circumference, BMI, and a Mallampati score of > or = 3. Neck circumference should be assessed preoperatively to predict difficult intubation.

Antigen presentation to inflammatory cells via pattern recognition receptors leads to the synthesis of NF-kappaB and other cytokine transcriptional factors. Leukocytes in the blood bind to endothelial receptors, the expression of which is mediated by proinflammatory cytokines via leukocyte integrins; the leukocytes then migrate to the site of inflammation. Endothelial procoagulant activity during sepsis is partly responsible for the disseminated intravascular coagulation (DIVC) and tissue hypoperfusion that follow. The endothelium synthesizes numerous proinflammatory factors, including nitric oxide, which is responsible for the resistance acquired to endogenous catecholamines and for vasomotor paralysis. During sepsis, the autonomic nervous system activity decreases in favor of proinflammatory parasympathetic activity. Secretion of counterregulatory rather than proinflammatory hormones increases during sepsis. Organ dysfunctions may alter cell functions, essentially mitochondrial, as well as intertissue communication.

Critically ill patients at some stage may develop adrenal insufficiency (AI). This article reviews the mechanisms, diagnosis criteria, consequences, and treatment of AI in various ICU conditions. Glucocorticoid insufficiency may be related to a decrease in glucocorticoid synthesis (ie, adrenal insufficiency) or to a reduced delivery of glucocorticoid to target tissues and cells. Diagnosis relies on clinical suspicion and ACTH test results. The length of cortisol replacement therapy should be at least 7 days and the adjunction of fludrocortisone is recommended.

This monocentric prospective study was conducted to determine if tissue oxygen saturation measured non invasively over masseter muscle site (Masseter-StO2) can predict the central venous oxygen saturation (ScvO2) level in severe sepsis and septic shock.Sixteen consecutive patients with severe sepsis (n = 10) or septic shock (n = 6) were included in this study. ScvO2 was measured on blood samples taken from the superior vena cava via the distal line of a central venous catheter. Masseter-StO2 was measured with a 25 mm depth infrared probe, applied and attached to the skin using transparent adhesive shields. Fifty-seven pairs of measures were obtained.Mean ScvO2 was 76.5% (median 81, standard deviation 15, range [14-94]). Twenty percent of the ScvO2 measures were lower than 70%. Seven out of 16 patients had at least one measure of 70% or less. Mean Masseter-StO2 was 81% (median 91, standard deviation 18, range [29-98]). We found a significant association between ScvO2 and Masseter-StO2 (correlation coefficient 0.65, P0.01), however agreement was moderate.In patients with severe sepsis or septic shock, non invasive recording of Masseter-StO2 was significantly associated with ScvO2 Further studies are required to determine the usefulness of Masseter-StO2 guided management of severe sepsis or septic shock.

To explore whether sagittal abdominal diameter as a marker of abdominal obesity is a risk factor for death and morbidity in patients in the intensive care unit and a better outcome determinant for obese patients than body mass index.Prospective, observational study from April 2008 to January 2009.Two general intensive care units, both in Toulouse University Hospitals, France.All adult patients admitted in the two intensive care units except those routinely discharged within 48 hrs or those having conditions with possible effect on anthropometric indices.Measurement of the sagittal abdominal diameter at admission allowed us to divide the studied population into abdominally obese, underweight, and control groups.The primary outcome measure was mortality in the intensive care unit until day 60 after admission. Secondary outcomes were morbidity and length of stay in the intensive care unit. Among 503 patients admitted, 403 were included. At admission, age, diabetes, dyslipidemia, hypertension, Simplified Acute Physiology Score II, and McCabe scores were higher in the abdominally obese group (n = 109) than in the control group (n = 277). The rate of death was higher in the abdominally obese group compared to control (44% vs. 25.3%; p.01). After adjustment for age, simplified acute physiology score, II and McCabe score, a multivariate analysis showed an increased risk of death in the abdominally obese group (adjusted odds ratio, 2.12; 95% confidence interval, 1.25-3.60). A body mass index30 kg/m2 was not an independent risk factor for death. During the stay in the intensive care unit, incidence of acute renal failure and abdominal compartment syndrome were higher in the abdominally obese group.A high sagittal abdominal diameter, and not a high body mass index, is an independent risk factor of death in critically ill patients.

Antigen presentation to inflammatory cells via pattern recognition receptors leads to the synthesis of NF-kappaB and other cytokine transcriptional factors. Leukocytes in the blood bind to endothelial receptors, the expression of which is mediated by proinflammatory cytokines via leukocyte integrins; the leukocytes then migrate to the site of inflammation. Endothelial procoagulant activity during sepsis is partly responsible for the disseminated intravascular coagulation (DIVC) and tissue hypoperfusion that follow. The endothelium synthesizes numerous proinflammatory factors, including nitric oxide, which is responsible for the resistance acquired to endogenous catecholamines and for vasomotor paralysis. During sepsis, the autonomic nervous system activity decreases in favor of proinflammatory parasympathetic activity. Secretion of counterregulatory rather than proinflammatory hormones increases during sepsis. Organ dysfunctions may alter cell functions, essentially mitochondrial, as well as intertissue communication.