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S Paulus

Publications and source records attributed to S Paulus.

13 recordsLinked to original sources

Evaluation of the estimation of midazolam concentrations and pharmacokinetic parameters in intensive care patients using a bayesian pharmacokinetic software (PKS) according to sparse sampling approach.

The aim of the study was to assess the performance of a bayesian program (PKS System, Abbott) for predicting midazolam concentrations and pharmacokinetic parameters in intensive care patients by comparing the pharmacokinetic parameters estimated by PKS to those calculated according to rich data. The study involved 42 patients receiving midazolam infusion for two hours or for several days. The program was used to predict plasma midazolam concentrations after feedback of 1, 2 or 3 concentrations. High correlation between observed and estimated concentrations was shown (r(2) > 0.992). Mean prediction error, mean absolute prediction error and root mean squared error were low for the patients of the reference and validation groups. From two or three feedback concentrations, midazolam pharmacokinetic parameters estimated by PKS were statistically comparable with those obtained using a rich pharmacokinetic analysis (P > 0.05 paired Wilcoxon test). Thus, PKS is useful for predicting midazolam concentrations and pharmacokinetic parameters when at least two feedback concentrations are known. This software seems to be appropriate for providing significant help to the clinician for midazolam dosage adjustment, according to midazolam concentrations and clinical sedation.

Area Under Curve↗

[Sedation induced by midazolam in intensive care: pharmacologic and pharmacokinetic aspects].

OBJECTIVE: Review on midazolam in order to optimize drug utilisation and therapeutic monitoring. DATA SOURCES: Research of English or French articles published until August 2001, using Medline database. The key words were: midazolam, pharmacokinetics, pharmacodynamic, sedation, drug interaction. STUDY SELECTION: Original articles, clinical cases and letters to the Editor were selected. Animal studies were excluded. DATA EXTRACTION: The articles were analysed according to their interest in midazolam clinical practice. DATA SYNTHESIS: Midazolam is a benzodiazepine widely used in intensive care unit, as a sedative, anxiety-relieving, and amnesic drug. Midazolam could be used in patients with cardiac, or respiratory failure, and in neurosurgery. A great interindividual variability on pharmacokinetic and pharmacodynamic response was observed. In intensive care patients, elimination half-life is known to be widely increased. Midazolam is metabolised by hepatic microsomes. The major metabolite is the 1-hydroxymidazolam, which is pharmacologically active. A prolonged sedation due to an accumulation of conjugated metabolite was observed in renal failure patients. Enzymatic inductors or inhibitors could influence pharmacokinetics and pharmacodynamic effects of midazolam. CONCLUSION: According to midazolam pharmacokinetic and pharmacodynamic variability, an individual dosage adjustment is essential for long-term sedation. Target controlled sedation could be a mean to limit the variability and to reach quickly the pharmacodynamic effect.

Critical Care↗

Midazolam disposition in patients undergoing continuous venovenous hemodialysis.

The aim of the study was to investigate the pharmacokinetics and removal of midazolam and unconjugated and glucuronidated 1-hydroxy-midazolam in 4 intensive care patients on continuous venovenous hemodialysis. Plasma midazolam and its metabolites were assessed by HPLC from blood samples collected during continuous infusion and after the end of infusion. Additional samples from the arterial and venous bloodlines and ultrafiltrate were drawn to calculate sieving coefficient and clearance of ultrafiltration. The elimination half-life of midazolam ranged from 7.6 to 22.8 hours. The clearance of ultrafiltration was between 0.13 and 4.7 ml/min and reached approximately 11% of the total clearance. The range of sieving coefficient was from 0.006 to 0.26, with an average fraction removal of 0.2%. 1-Hydroxy-midazolam glucuronide was removed by continuous hemodialysis (sieving 0.36 to 0.63), with a clearance of ultrafiltration ranging from 7.8 to 12.0 ml/min. These preliminary results showed that midazolam is not removed efficiently, and approximately half of the 1-hydroxy-midazolam glucuronide was removed by dialysis.

Aged↗

[Intensive care in lung and heart-lung transplantation].

Intensive care after lung, and heart-lung transplantation may have simple post operative course specially after preventive procedures of reperfusion injury, nosocomial infections during mechanical ventilation and immunosuppression risks. Nevertheless a severe mediastinal shift may occurred after single lung transplantation in emphysema. Rapid changes in ventilation/perfusion ratio during lung infection or rejection specially in pulmonary hypertension are responsible of dramatic respiratory failure. Knowledge of multiorgan dysfunction and multidisciplinary experience encourage to future development.

Critical Care↗

Disseminated Scedosporium prolificans (S. inflatum) infection after single-lung transplantation.

This report concerns the first case of disseminated infection with Scedosporium prolificans (S. inflatum) that occurred in a patient who had received an organ transplant and was verified at autopsy. The patient underwent single (right)-lung transplantation and subsequently died on the 33rd postoperative day in a context of septic shock. S. prolificans was isolated from various specimens, including two cultured blood samples. The organism was associated with Candida albicans in some of these specimens. Autopsy revealed the presence of numerous nodular abscesses in the lungs, myocardium, kidneys, spleen, and gall bladder. These abscesses contained mycelial filaments and numerous oval conidia suggestive of Scedosporium species but no yeasts. MIC studies demonstrated the resistance of the S. prolificans isolate to amphotericin B, fluctyosine, miconazole, ketoconazole, and itraconazole, whereas the isolate of C. albicans was susceptible to amphotericin B, flucytosine, miconazole, and ketoconazole. From the data from our case and six published reports of cases of disseminated S. prolificans infection, it can be concluded that this filamentous fungus is a new agent responsible for the most serious mycoses in both neutropenic patients and patients who have undergone organ transplantation.

Candidiasis↗

Enoximone and acute left ventricular failure during weaning from mechanical ventilation after cardiac surgery.

OBJECTIVE: To evaluate enoximone, a phosphodiesterase III inhibitor, in the treatment of left ventricular failure during the weaning of patients from mechanical ventilation after heart surgery. DESIGN: Open label, prospective, weaning trial. SETTING: Cardiothoracic surgical intensive care unit (ICU) in a university hospital. PATIENTS: Nine patients were studied after one or more unsuccessful attempts at weaning from mechanical ventilation due to left ventricular dysfunction. INTERVENTION: For each patient, two respiratory weaning attempts were studied: the first one as a control and the second one with enoximone infused at a rate of 30 micrograms/kg/min for 30 mins, then at a rate of 10 micrograms/kg/min. MEASUREMENTS AND MAIN RESULTS: Hemodynamic measurements were performed at the following interval times: baseline during mechanical ventilation; during spontaneous ventilation with a T-piece for a minimum of 10 mins; during mechanical ventilation after the enoximone infusion for 30 mins; during spontaneous ventilation for a minimum of 10 mins with an enoximone infusion running. During spontaneous ventilation, enoximone increased cardiac index by 34% but mean artery, right atrial, and pulmonary artery occlusion pressures did not change. Despite an increase in venous admixture due to augmented cardiac index and inhibition of hypoxic vasoconstriction, no oxygen debt occurred because oxygen delivery increased. Seven of nine patients were weaned successfully from mechanical ventilation. CONCLUSION: Because of its positive inotropic and vasodilatory properties, enoximone is helpful for respiratory weaning of patients with left ventricular failure after cardiac surgery.

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[Current role of intra-aortic diastolic balloon counterpulsation in heart surgery].

Intra-aortic balloon counterpulsation (IABP) is a relatively non-invasive method of circulating assistance, easy to use and which has benefitted from a number of technological improvements in recent years. This retrospective study over 4 years was undertaken to analyse the results of IABP and to determine its role in therapeutic arsenal against cardiac failure. Sixty five patients, 57 coronary and 8 valvular cases, with an average age of 61 +/- 10 years were included. The indications of IABP were: a bridge to transplantation (3 cases), complications of coronary angioplasty (4 cases), and low cardiac output after cardiopulmonary bypass (58 cases), where IABP was curative in 85% of cases and prophylactic in 15% of cases (patients with risk factors of low output state after CPB). Beforehand, 65% of patients had poor left ventricular function (LVEF < 40% and/or CI < 2.2 l/mn/m2). An Aries Medical M700 console was used. The percutaneous femoral approach was feasible in 87% of cases. The results were: improvement with discharge from intensive care unit in 60% of cases, transient improvement in 7% of cases, no improvement in 15% of cases and cardiac transplantation in 8% of cases. The outcome was worse when the preoperative LV function was poor and when high dose inotropic agents had to be used. Survival was 100% in those patients in whom IABP was a prophylactic measure. The average duration of IABP was 72 hours, survival being significantly lower in those in whom IABP was continued for over 3 days. The complications (12.7%) were thromboembolic.(ABSTRACT TRUNCATED AT 250 WORDS)

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