Evaluation of a Bayesian method of amikacin dosing in intensive care unit patients with normal or impaired renal function

Our study was designed to determine the population pharmacokinetic parameters of amikacin in intensive care unit patients and to develop a Bayesian method allowing individual estimation of pharmacokinetic parameters. A two-stage method was used for estimating the population characteristics of the pharmacokinetic parameters. Calculations of optimum doses and dosing intervals were based on individual parameters. Our results indicate that the Bayesian method is capable of estimating the individual pharmacokinetic parameters with no significant bias and good precision. Individualization of amikacin dosage was assessed 70 times in 52 patients. To determine the predictive performance of the method, observed peak and trough levels were compared with predicted values by computing precision, bias, and correlation. The amikacin dosing method was unbiased and showed a high correlation coefficient (r = 0.962) between measured and predicted drug serum concentrations. No significant differences were found between the predicted and observed peak (17.3 +/- 3.5 and 17.3 +/- 3.8 micrograms/ml, respectively) and trough (2.86 +/- 0.93 and 3.08 +/- 1.41 micrograms/ml, respectively) amikacin serum concentrations. Among the 52 patients, wide variations were observed in the pharmacokinetic parameters (Vd = 0.21-0.50 L/kg; t 1/2 = 1.1-22 h) and the daily doses (2.8-42 mg/kg/day).     

Non-invasive detection of coronary artery disease by dobutamine-stress echocardiography in children after heart transplantation.

BACKGROUND: Coronary vasculopathy is the main cause of cardiac graft failure. Because yearly coronary angiography is invasive in children, a non-invasive method for detecting graft vasculopathy is needed. The aim of this study was to test dobutamine-stress echocardiography in a pediatric population to determine its feasibility, safety and reliability in the detection of graft coronary artery disease. METHODS: Eighteen patients, aged 2 days to 16.8 years at transplantation (mean 8.4 years), underwent 44 dobutamine-stress echocardiography (DSE) exams, at a follow-up of 1.1 to 11.8 years (mean 5.1 years). Selective coronary angiography was performed for comparison. Echocardiographic recordings were obtained in 4 standard views of the left ventricle and measurements carried out within the frames of a 16-segment model. Segmental scores of contractility were obtained for each segment and a total segmental contractility index was calculated at each stage. RESULTS: All patients reached the maximum dose stage. Maximum heart rate was 57% to 90% of predicted maximum. Maximum systolic blood pressure reached 190 mmHg. Segmental scores were normal in 37 and abnormal in 7 cases. Echographic results were concordant with angiography in 82% and discordant in 18% of the cases (4 negative DSEs with minor angiographic lesions, 2 positive DSEs with normal angiography), but there was no significant angiographic lesion with normal DSE. CONCLUSIONS: DSE is a safe and highly feasible non-invasive technique in transplanted children. A normal DSE study successfully predicts the absence of significant coronary artery disease in the post-transplant population.