[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.

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.

[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.

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.

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.

Pharmacodynamics and atracurium and laudanosine concentrations during a fixed continuous infusion of atracurium in mechanically ventilated patients with acute respiratory distress syndrome.

The present study was designed to assess the pharmacodynamics and the plasma levels of atracurium and laudanosine found during a 72-hour fixed rate infusion of atracurium in acute respiratory distress syndrome patients without renal or liver failure. Nine sedated and mechanically ventilated acute respiratory distress syndrome patients without renal or liver failure were paralysed with a bolus of atracurium (1 mg x kg(-1)) followed by a 72-hour continuous infusion (1 mg x kg(-1) x h(-1)). The count of train-of-four (TOF) and TOF ratio were monitored by an accelerograph until full neuromuscular recovery (T4/T1 > or = 0.7). Atracurium and laudanosine concentrations were measured from the onset to four days after cessation of the infusion. An electroencephalogram was recorded daily. Analysis showed that TOF count was always < or = 3 until cessation of the infusion. Following cessation, neuromuscular recovery occurred between 31 and 96 minutes (median value = 45 min). The highest atracurium and laudanosine concentrations ranged from 3.3 to 5.8 microg x ml(-1) and from 3 to 20 microg x ml(-1) respectively. In four patients with renal impairment, the highest laudanosine concentration was > 10 microg x ml(-1). No seizure was recorded. A fixed infusion rate of atracurium in acute respiratory distress syndrome patients provided an effective muscle paralysis with a rapid neuromuscular recovery but can lead to accumulation of laudanosine in patients with renal impairment.

[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).

Insertion time of the pulmonary artery catheter in critically ill patients.

OBJECTIVES: Measurement of the time elapsed from the decision to use a pulmonary artery catheter to the onset of the adapted treatment. DESIGN: Prospective study. SETTING: Critical care unit of a university hospital. PATIENTS: A total of 104 critically ill patients. INTERVENTIONS: The time elapsed from the decision to use a pulmonary artery catheter to the onset of the adapted treatment. Five time intervals (availability, preparation, catheterization, data collection, and therapeutic intervals) were individualized according to the times of decision of pulmonary artery catheter insertion, operator's hand washing, venipuncture, postoperative dressing, data collection, and the effective onset of subsequent therapy. MEASUREMENTS AND MAIN RESULTS: Among 120 used pulmonary artery catheters, seven could not be inserted. The time to use the pulmonary artery catheter was never shorter than 45 mins (median value = 120 mins). For availability, preparation, catheterization, data collection, and therapeutic intervals, the median values were 30, 20, 20, 20, and 10 mins, respectively. The availability and data collection intervals were shortened during the night period and the fourth quarter of the study, respectively. CONCLUSIONS: The pulmonary artery catheter use is time consuming. However, the availability and data collection intervals could be shortened.

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.

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.

Pulsed Doppler ultrasonography guidance for catheterization of the subclavian vein: a randomized study.

BACKGROUND: Catheterization of the subclavian vein may lead to severe complications. The current randomized study compared a technique of pulsed Doppler ultrasonography guidance and the standard method for subclavian vein catheterization. METHODS: Standard and Doppler ultrasonography guidance methods were performed by the same physician in 286 patients, 143 in each group. Primary end points were immediate complications (arterial puncture, pneumothorax, wrong position of catheter tip), failures, the number of subclavian vein catheterizations with immediate complication or failure, the number of skin punctures per catheterization, and the time to placement of the guide wire. The secondary end points were the determination of predicting factors of successful cannulation in each group. RESULTS: Both groups were similar according to morphologic parameters of the patients. A greater number of subclavian vein catheterizations were performed on the right side using Doppler guidance (105 vs. 73, P < 0.01). Doppler guidance decreased complications (5.6% vs. 16.8%, P < 0.01), largely because of a smaller number of catheters for which the tip was defined to be in incorrect position (0.7% vs. 7.7%, P < 0.01). The time to catheterization was longer with Doppler guidance (300 vs. 27 s, P < 0.001). Failures, catheterizations of the subclavian vein with immediate complications or failure, and the total number of skin punctures per catheterization were similar in both groups. Using Doppler guidance, the presence of a good Doppler signal (124 of 143) was predictive of successful catheterization (123 successful cannulations, P < 0.001). CONCLUSIONS: Doppler guidance reduces the incidence of inappropriately positioned subclavian catheters.

Population pharmacokinetics of amikacin in critically ill patients.

The pharmacokinetic parameters of amikacin were determined in a population of 20 adults and 36 pediatric patients admitted into an intensive care unit. Amikacin was administered by repeated intravenous infusion over 0.5 h (600 to 1,350 mg for adults; 70 to 1,500 mg for children). The number of administrations ranged from 2 to 17, and the number of samples collected from each patient ranged from 2 to 70. The population enrolled in the study had large variabilities in age (0.5 to 85 years), weight (6 to 95 kg), height (72 to 187 cm), creatinine clearance rate (18 to 110 ml/min), blood urea nitrogen concentration (1.5 to 15 mmol/liter), and total protein concentration (30 to 91 g/liter). The mean population parameters and their interindividual variabilities were obtained for an initial group of 44 patients (16 adults and 28 children). A two-compartment model was fitted to the population data by using the computer program P-PHARM. Model selection was guided by evaluation of the minimum objective function and the weighted residuals. The population analysis has been performed with the complete set of the collected data, including the individual serum amikacin concentration together with the individual estimate of the creatinine clearance values. The potential sources of variability in the population parameters were investigated by using patients' age, height, weight, creatinine clearance, blood urea nitrogen concentration, and total protein concentration as covariables. A test group of 12 additional patients (4 adults and 8 children) was used to evaluate the predictive performances of the population parameters. The individual pharmacokinetic parameters were computed by a Bayesian fitting procedure. From the resulting individualized values of the parameters, the concentrations of amikacin in the serum of the patients were calculated. To evaluate the performance of the Bayesian estimation, the experimental concentrations were compared with the predicted ones. The Bayesian approached developed in the study accurately predicts amikacin concentrations in serum and allows for the estimation of amikacin pharmacokinetics parameters, minimizing the risk of bias in the prediction. This was demonstrated in patients with both stable and unstable renal functions.

[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.

Cardiac output measurement in critically ill patients: comparison of continuous and conventional thermodilution techniques.

The purpose of the study was to compare cardiac output (CO) measurement by continuous (CTD) with that by conventional thermodilution (TD) in critically ill patients. In 19 of 20 critically ill patients requiring a pulmonary artery catheterism, 105 paired CO measurements were performed by both CTD and TD. Regression analysis showed that: CTD CO = 1.18 TD CO - 0.47. Correlation coefficient was 0.96. Bias and limit of agreement were -0.8 and 2.4 L.min-1, respectively. When a Bland and Altman diagram was constructed according to cardiac index ranges, biases were -0.2 and -0.3 and -0.8 L.min-1.m-2 and limits of agreement were 0.3, 0.7 and 1.6 L.min-1.m-2 for low (< 2.5 L.min-1.m-2), normal (between 2.5 and 4.5 L.min-1.m-2) and high (> 4.5 L.min-1.m-2) cardiac indexes, respectively. It is concluded that CTD, compared with TD, is a reliable method of measuring CO, especially when cardiac index is < or = 4.5 L.min-1.m-2.