Population pharmacokinetics of linezolid in critically ill patients on renal replacement therapy: comparison of equal doses in continuous venovenous haemofiltration and continuous venovenous haemodiafiltration.

OBJECTIVES: Few data are available to guide linezolid dosing during renal replacement therapy. The objective of this study was to compare the population pharmacokinetics of linezolid during continuous venovenous haemofiltration (CVVHF, 30 mL/kg/h) and continuous venovenous haemodiafiltration (CVVHDF, 15 mL/kg/h + 15 mL/kg/h). METHODS: Patients requiring linezolid 600 mg iv every 12 h and CVVHF or CVVHDF were eligible for this prospective study. Seven blood samples were collected over one dosing interval and analysed by a validated chromatographic method. Population pharmacokinetic analysis was undertaken using Pmetrics. Monte Carlo simulations evaluated achievement of a pharmacodynamics target of an AUC from 0-24 h to MIC (AUC0-24/MIC) of 80. RESULTS: Nine CVVHDF and eight CVVHF treatments were performed in 13 patients. Regimens of CVVHDF and CVVHF were similar. A two-compartment linear model best described the data. CVVHDF was associated with a 20.5% higher mean linezolid clearance than CVVHF, without statistical significance (P = 0.39). Increasing patient weight and decreasing SOFA score were associated with increasing linezolid clearance. The mean (SD) parameter estimates were: clearance (CL), 3.8 (2.2) L/h; volume of the central compartment, 26.5 (10.3) L; intercompartmental clearance constants from central to peripheral, 8.1 (12.1) L/h; and peripheral to central compartments, 3.6 (4.0) L/h. Achievement of pharmacodynamic targets was poor for an MIC of 2 mg/L with the studied dose. CONCLUSIONS: During CVVHF and CVVHDF, there is profound pharmacokinetic variability of linezolid. Suboptimal achievement of therapeutic targets occurs at the EUCAST breakpoint MIC of 2 mg/L using 600 mg iv every 12 h.

[Assessment of BCG vaccine practices]. / Évaluation de la pratique du vaccin par le bacille de Calmette et Guérin (BCG).

Tuberculosis is a major public health problem. In France, the vaccine against tuberculosis (Bacillus Calmette-Guerin, BCG) is in decline. This decline is firstly due to changes in BGG administration that were implemented in 2006 and secondly because of new recommandations in 2007 that ended compulsory vaccination. To determine their position on this vaccine, in 2013-2014 we asked general practitioners, pediatricians, and Maternal and Infantile Protection Center physicians in the Gard and Herault departments (in Southern France) why this vaccine was not administered and their suggestions for improvement. Most of these doctors (73.9%) stated that they did not oppose this vaccination for children. They expressed concern about potential side effects, technical problems (intradermic injection, multi-dose bottles) and parents' refusal. One quarter of these physicians would have preferred that this vaccine remains compulsory and one third that this vaccine be administered in the maternity hospital. They also requested simplified criteria for patient eligibility, technical improvements (training for intradermal injection, single-dose vaccine) and more information for the public concerning this vaccination.

Multiple-dose pharmacokinetics of pefloxacin in patients with hepatocellular deficiency.

Multiple-dose pharmacokinetics of pefloxacin were evaluated in 25 patients with hepatocellular insufficiency. The severity of liver disease was graded A, B or C according to the Child-Pugh classification. Pharmacokinetic parameters evaluated in patients on day 1 of treatment were compared with those computed in 11 healthy volunteers (the control group) after a single dose. Blood samples were taken at frequent intervals after drug administration and assayed by high performance liquid chromatography. The mean age of patients with liver impairment was slightly greater (59.5 years, range 33 to 81 years) than that of the control group (46.7 years, range 42 to 51 years). In the patients with liver disease, the mean (+/- SD) half-life of elimination, although highly variable, was significantly longer (46.3 +/- 42.5 hours) than in the control group (11.3 +/- 3.5 hours, p < 0.001). The total clearance was significantly decreased (1.76 +/- 1.31 L/h vs 6.03 +/- 2.99 L/h in the control group). In groups B and C of the Child-Pugh classification, total body clearance was about 30% of normal values. Elimination half-life increased by 200% in group B and 373% in group C compared with values in healthy volunteers. Intergroup differences (group B vs group C of the Child-Pugh classification) were not statistically significant. The minimum concentrations inhibiting 90% of Gram-negative strains (MIC90) were exceeded by plasma pefloxacin concentrations throughout treatment. For most patients, trough plasma concentrations were above 2 mg/L and peak plasma concentrations averaged 8.5 mg/L. Large inter- and intraindividual variations in the elimination half-life, total clearance and volume of distribution were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Risk factors of failure and immediate complication of subclavian vein catheterization in critically ill patients.

OBJECTIVE: To identify the risk factors of failure and immediate complication of subclavian vein catheterization (SVC). DESIGN: Prospective observational study. SETTING: Surgical critical care unit of a tertiary university hospital. PATIENTS: Critically ill patients requiring a first SVC. INTERVENTION: Subclavian vein catheterization was attempted in 707 patients without histories of surgery or radiotherapy in the subclavian area. Failed catheterizations, arterial punctures, pneumothoraces and misplacements of the catheter tip were recorded. Risk factors of failure and immediate complication were isolated among patients' characteristics, procedure parameters (side and number of venipunctures) and the operator's experience using a univariate +/- multivariate analysis. MEASUREMENTS AND MAIN RESULTS: Five hundred sixty-two SVCs (79.5%) were achieved without adverse events. Among the remaining 145 catheterizations, 67 (9.5%) failures, 55 (7.8%) arterial punctures, 22 (3.1%) pneumothoraces and 30 (4.2%) misplacements of the catheter tip occurred. More than one venipuncture was the only risk factor of failed catheterization [2 venipunctures, odds ratio =7.4 (2.1-26); >2 venipunctures, odds ratio =49.1 (16.8-144.1)]. More than one venipuncture and age 77 years or more were predictive of the occurrence of immediate complications [2 venipunctures, odds ratio =3.6 (1.8-7.0); >2 venipunctures, odds ratio =14 (7.7-25.3); age >or=77, odds ratio =1.8 (1.0-3.1)]. The operator's training was not predictive of failed catheterization or immediate complication. CONCLUSION: For SVC, more than one venipuncture is predictive of failed catheterization and immediate complication. Age 77 years or more was predictive of immediate complications.

Temperature measurement in intensive care patients: comparison of urinary bladder, oesophageal, rectal, axillary, and inguinal methods versus pulmonary artery core method.

OBJECTIVE: Comparisons of urinary bladder, oesophageal, rectal, axillary, and inguinal temperatures versus pulmonary artery temperature. DESIGN: Prospective cohort study. SETTING: Intensive Care Unit of a University-Hospital. PATIENTS: Forty-two intensive care patients requiring a pulmonary artery catheter (PAC). INTERVENTION: Patients requiring PAC and without oesophageal, urinary bladder, and/or rectal disease or recent surgery were included in the study. Temperature was simultaneously monitored with PAC, urinary, oesophageal, and rectal electronic thermometers and with axillary and inguinal gallium-in-glass thermometers. Comparisons used a Bland and Altman method. MEASUREMENTS AND MAIN RESULTS: The pulmonary arterial temperature ranged from 33.7 degrees C to 40.2 degrees C. Urinary bladder temperature was assessed in the last 22 patients. A total of 529 temperature measurement comparisons were carried out (252 comparisons of esophageal, rectal, inguinal, axillary, and pulmonary artery temperature measurements in the first 20 patients, and 277 comparisons with overall methods in the last patients). Nine to 18 temperature measurement comparisons were carried out per patient (median = 13). The mean differences between pulmonary artery temperatures and those of the different methods studied were: oesophageal (0.11+/-0.30 degrees C), rectal (-0.07+/-0.40 degrees C), axillary (0.27+/-0.45 degrees C), inguinal (0.17+/-0.48 degrees C), urinary bladder (-0.21+/-0.20 degrees C). CONCLUSION: In critically ill patients, urinary bladder and oesophageal electronic thermometers are more reliable than the electronic rectal thermometer which is better than inguinal and axillary gallium-in-glass thermometers to measure core temperature.

Training is required to improve the reliability of esophageal Doppler to measure cardiac output in critically ill patients.

OBJECTIVES: Assessment of and effect of training on reliability of esophageal Doppler (ED) versus thermodilution (TD) for cardiac output (CO) measurement. DESIGN: Prospective study. SETTING: Intensive care unit of a university hospital. PATIENTS: 64 consecutive critically ill patients requiring a pulmonary artery catheter, sedation, and mechanical ventilation. INTERVENTIONS: Esophageal Doppler CO measurements were performed by the same operator, whereas TD CO measurements were carried out by other independent operators. A training period involving the first 12 patients made the operator self-confident. In the remaining patients, the reliability of ED was assessed (evaluation period), using correlation coefficients and the Bland and Altman diagram. Between training and evaluation periods, correlation coefficients, biases, and limits of agreement were compared. MEASUREMENTS AND RESULTS: During training and evaluation periods, 107 and 320 CO measurements were performed in 11 out of 12 patients and in 49 out of 52 patients, respectively. Continuous CO monitoring was achieved in 6 out of 11 patients and in 38 out of 49 patients during training and evaluation periods, respectively. Between the two periods, correlation coefficients increased from 0.53 to 0.89 (p < 0.001), bias decreased from 1.2 to 0.1 l x min(-1) (p < 0.001), and limits of agreement decreased from 3.2 to 2.2 l x min(-1) (p < 0.001). CONCLUSION: A period of training involving no more than 12 patients is probably required to ensure reliability of CO measurement by ED.

A population approach to the forecasting of amikacin plasma and urinary levels using a prescribed dosage regimen.

We retrospectively analyzed amikacin pharmacokinetics in 19 critically ill patients who received amikacin intravenously. Fourteen subjects (577 serum amikacin concentrations, 167 urine measurements) were studied to obtain data for population modeling, while 5 patients (267 serum amikacin concentrations, 68 urine measurements) were studied for the assessment of predictive performance. The population analysis was performed using serum and urine amikacin measurements; the renal clearance of amikacin was expressed as a function of creatinine clearance. A two-compartment model was fitted to the population data by using NONMEM. The population characteristics of the pharmacokinetic parameters (fixed and random effects) were estimated using the FOCE method. The population pharmacokinetic parameters with the interindividual variability (CV%) were as follows: slope (0.254, 126%) and intercept (3 l/h, 59.6%) of the linear model which relate the amikacin renal clearance to the creatinine clearance, initial volume of distribution (17.1 l, 22.2%), intercompartment clearance (5.22 l/h, 104%), steady state volume of distribution (55.2 l, 64.1%) and urinary elimination (67.5%, 36.3%). The Bayesian approach developed in this study accurately predicts amikacin concentrations in serum and urine and allows for the estimation of amikacin pharmacokinetic parameters, minimizing the risk of bias in the prediction.

[Severe preeclampsia. Analysis of a case with fatal outcome]. / Pré-éclampsie sévère. Analyse d'un cas d'évolution fatale.

We report a case of preeclampsia presenting initially as a moderate hypertension, and complicated over a ten-day period by eclampsia, retinal hemorrhage, cerebral and hepatic subcapsular hematomas, HELLP syndrome, disseminated intravascular coagulation and renal failure. Fatal outcome was related to cerebral death and rupture of the liver hematoma. The case analysis points out inaccurate initial management: probable misdiagnosis of epigastric pain related to subcapsular hematoma, ineffective antihypertensive therapy, aspiration of the gastric content after benzodiazepine treatment of eclampsia, transfer of the patient without stabilisation of her clinical status.

[Treatment of acute hepatic encephalopathy with flumazenil]. / Traitement de l'encéphalopathie hépatique aiguë par le flumazénil.

In animal studies as well as in a few cases in humans, the benzodiazepine antagonist flumazenil has been shown to reverse hepatic encephalopathy. The authors treated 3 patients with acute hepatic encephalopathy stage III or IV complicating cirrhosis. Two patients had an immediate recovery, maintained with a continuous infusion of flumazenil. In the third patient the clinical status dit not improve but the hepatic encephalopathy coexisted with major abnormalities in blood gases and electrolytes abnormalities, which could participate to the neurologic failure.

[Role of acute normovolemic hemodilution in treating retinal venous occlusions]. / Place de l'hémodilution aiguë normovolémique dans le traitement des occlusions veineuses rétiniennes.

The supposed state of retinal venous occlusions by a thrombus has led to the use of diverse antithrombotic treatments (heparin, fibrinolytic agents). This theory being considered at the moment as controversial, haemorheological theories being more particularly favoured, other treatments are proposed in an attempt to better retinal microcirculation, and this by changing the blood viscosity parameters. The study reported here compared the effects on recovery of visual acuity of retinal venous occlusion patients of anticoagulant treatment alone, haemodilution alone, or both together. After initial ophthalmic assessment, twenty-five patients were randomly assigned to one of three groups: group I (n = 5; mean age 62 +/- 14 yr) received heparin for 21 days, followed by antivitamin K drugs for a further 30 days; group II (n = 10; mean age 54 +/- 16 yr) were acutely hemodiluted with 40,000 daltons molecular weight dextran, bringing the haematocrit to between 0.25 and 0.30; on day 2, the same anticoagulant treatment as in group I was associated; group III (n = 10; mean age 58 +/- 18 yr) were only hemodiluted. The hemodiluted state was maintained for 21 days. A biological assessment was carried out for the three groups on days 1, 2, 7, 14, 21 and 30 (haematocrit, fibrinogen level, platelet count, kaolin-cephalin time, heparin level). The evolution of visual acuity was assessed on days 7, 14, 21, 30, 60 and 90. Mean visual acuity was assessed on days 7, 14, 21, 30, 60 and 90. Mean visual acuity was virtually the same for the three groups on day 0.(ABSTRACT TRUNCATED AT 250 WORDS)

[An aid in the diagnosis of cardiac rhythm disorders in anesthesia and intensive care]. / Aide au diagnostic des troubles du rythme cardlaque en anesthésie-réanimation.

Exact diagnosis of tachycardia was sometimes difficult to do as P waves were not easy to see on ECG. A simple device is described, with which ample P waves were recorded in patients with a central venous catheter. This catheter was used as conductor of cardiac electrical activity. It proved simpler and less aggressive for the patient in comparison with other techniques (intracardiac and oesophageal recording).

[Pulmonary artery catheterization in the intensive care unit: at what time?]. / Cathétérisme artériel pulmonaire en réanimation: à quelle heure?

OBJECTIVES: Recording the time at which the insertion of a pulmonary artery catheter was decided. STUDY DESIGN: Prospective and descriptive study. PATIENTS: Critically ill patients in an university hospital. METHODS: The times at which the insertion of a PAC was decided were recorded. For each pulmonary artery catheterization, immediate complications were recorded (arterial puncture, pneumothorax, ventricular arrhythmia, hard and failed pulmonary artery catheterization). RESULTS: One hundred and forty-nine patients were included (99 males, age = 63 +/- 15 year, body mass index = 25 +/- 6 kg.m-2, median Apache II score = 16). One hundred and sixty-five PAC insertions were decided (16 patients requiring two PACs). Nine arterial punctures, two pneumothoraces, 42 ventricular arrhythmias, 32 hard and eight failed pulmonary artery catheterizations occurred. Thirty-four PAC insertions were decided between 9 and 10 am whereas = 3 PAC insertions per hour were decided between 1 and 9 am. CONCLUSION: The rate of decision of PAC insertion are decreased during the second half of the night (1 to 9 AM).

[Prognostic factors of surgically-treated cancers of the right colon. Multifactorial analysis of a series of 50 curative excisions]. / Les facteurs pronostiques des cancers du côlon droit opérés. Analyse multifactorielle d'une série de 50 exérèses à visée curative.

Between 1970 and 1986, 502 colorectal cancers were operated in our department. In 82 cases, it was located on the right, including 50 patients who underwent curative right hemicolectomy. Overall, at 5 years, 23 patients are alive with no recurrence (46%), 17 died from their cancer (34%) and 10 patients died of intercurrent causes (20%). Among the 13 prognostic factors analyzed, only the pathologic stage of the tumor (extend of dissemination to the abdominal wall and lymph nodes) and preoperative fever had a statistically significant effect on 5 year survival (p = 0.001 for fever and p = 0.01 for Duke's stage). The multifactor analysis clearly delineates a group with a poor prognosis (group with lymph node involvement and fever) in which the median of survival was 30 months.

[Role of analgesia for sedation in intensive care medicine]. / Place de l'analgésie dans la sédation en réanimation.

Giving a definition of analgesia in ICU needs to answer several questions: Why sedation? Which drugs can we use? How can we deal with sedation? (monitoring, continuous administration, weaning...)? Two different types of sedation must be considered: treatment-sedation (status epilepticus, tetanus, intracranial hypertension...) and comfort-sedation in anxious and/or restless and/or painful patients and in those necessitating mechanical ventilation. Analgesic consumptions vary widely with diseases and their outcome, background diseases and ICU environment. Several studies have shown that pain and analgesia are frequently neglected in ICU. The authors review the different drugs in use, with their advantages and drawbacks. A particular place is reserved to regional techniques, often underused in ICU. Indications are then fully discussed, according to several specific pathological conditions. Monitoring and weaning of sedation are also discussed at the end of the review.

[ICU patients and days of intensive care: A mathematical model optimizing the consequences of ICU unit function, intensive care and continual monitoring on incurred supplementary costs]. / Patient de réanimation, journées de réanimation ? Modélisation d'un fonctionnement optimisé des unités de réanimation, de soins intensifs et de surveillance continue et conséquences sur les suppléments tarifaires induits.

INTRODUCTION: "Critical Care Units" are intended to admit patients with multiple organ failure. The severity of patients admitted is variable. The aim of the study was to estimate the number of days that an optimum care organization could release, and therefore the additional admissions that would have been allowed. Estimates of earnings related to the various supplements were carried out jointly. METHODS: Reporting days associated or not with a resuscitation care during the year 2011 in an ICU of a university hospital (16 beds), optimized patient flow simulation, and computation of medical act inducing financial supplements. RESULTS: Six hundred and fifty-seven patients (SAPS II from 0 to 110, 41% ventilated more than 48hours, mortality=26%) were admitted representing 5095days (occupancy rate=87%). Two hundred and twenty-two patients (34%) did not trigger supplement for resuscitation care for 415days in the unit. Four hundred and thirty-five patients have triggered this supplement representing 4680days, including 3035days with resuscitation care and 1645 (35% of days valued resuscitation, 32% of total days) without any. The entire year 2011 has generated earnings of 3,980,192€. Optimization of management would have allowed the admission of additional 235 to 295 patients and potential additional earnings from 524,735€ to 1,063,804€, depending on the occupancy rate chosen (80% or real 2011s) and the severity of discharged patients. CONCLUSION: Optimization of the patients flow between "Critical Care", Intensive Care and Continuous Monitoring Units would increase the number of patients admitted in "Critical Care" Units without any financial loss related to supplements.

[Patient's relatives wishes concerning the visiting hours in an intensive care unit]. / Elargissement des plages horaires de visites dans une unité de réanimation : l'avis des proches.

OBJECTIVE: The present study was aimed at assessing the opinion of the patient's relatives concerning the visiting hours in the ICU. METHOD: The visiting relatives were questioned about the information delivered in the Unit (assessed as 0 for minimal and 10 for maximal assessments, respectively) and the hypothesis to extend the Unit's visiting hours. The responses were given independently by the relatives. RESULTS: Eighty-seven out of 64 relatives responded (63% females). The delivered information was assessed by a median note=10 (interquartile: [8-10]). The current visiting times (2h per day during the week, 6h in weekend) were assessed as sufficient by 48 closest (58%). Fifty-four (67%, CI95%=[56-77]) requested more liberal visiting times and 38 (46%, CI95%=[36-57]) requested 24h visiting policy. Five relatives (6%, CI95%=[1-11]) would like to be present during patient's care. Most relatives do not wish to assist to patient's care to avoid interfering with caregiver's workload (81%), to respect the patient's intimacy (49%) and by fear of being impressed by the care (23%). Forty percent of the relatives would like to help feeding the patient. CONCLUSION: Most of the relatives wish for more liberal visiting times without interfering with patient's care.