Membrane Distillation for the Production of Pharmaceutical-Grade Water-Investigation into the Application of AGMD and VMD.

The production of pharmaceutical ingredients, intermediates and final products strongly depends on the utilization of water. Water is also required for the purification and preparation of reagents. Each specific application determines the respective water quality. In the European Union, the European Pharmacopeia (Ph. Eur.) contains the official standards that assure quality control of pharmaceutical products during their life cycle. According to this, the production of water for pharmaceutical use is mainly based on multi-stage distillation and membrane processes, especially, reverse osmosis. Membrane distillation (MD) could be an alternative process to these classical methods. It offers advantages in terms of energy demand and a compact apparatus design. In the following study, the preparation of pharmaceutical-grade water from tap water in a one-step process using MD is presented. Special emphasis is placed on the performance of two different module designs and on the selection of optimum process parameters.

Ultrasound-guided epidural catheter insertion in children.

UNLABELLED: Epidural catheters (EC) are often used in pediatric patients for intraoperative and postoperative pain relief. The small anatomical structures and catheter insertion under general anesthesia make it more difficult to perform EC and to prevent damage. In this study we investigated the use of ultrasound (US) in detecting neuraxial structures during insertion and placement of EC in children. ASA I-II children scheduled for elective surgery under combined general and epidural anesthesia were studied. Patients received balanced anesthesia using sevoflurane, opioids and rocuronium. Before EC insertion US examination in a lateral position was done to visualize and identify neuraxial structures. Quality of visualization and site and depth of structures were recorded. Using a sterile kit to hold the US probe in position and enable the visualization of the neuraxial structures, an epidural cannula was inserted, using the loss of resistance technique, as the EC passed under US control to the desired level. Of 25 children, 23 were evaluated. Epidural space, ligamentum flavum, and dural structures were clearly identified and the depth to skin level estimated in all patients. Loss of resistance was visualized in all patients with a lumbar epidural approach. Correlation of US measured depth and depth of loss of resistance was 0.88. In eight of 23 patients EC could be visualized during insertion and in 11 others it could be visualized with additional US planes. US is an excellent tool to identify neuraxial structures in both infants and children. The size and the incomplete ossification of the vertebra allow exact visualization and localization of the depth of the epidural space, the loss of resistance, and all relevant neuraxial structures. IMPLICATIONS: Epidural catheters in children are mostly inserted under sedation or general anesthesia. This study showed that the use of ultrasound could help visualize all relevant neuraxial structures and their site and depth from the skin.

Ropivacaine in neonates and infants: a population pharmacokinetic evaluation following single caudal block.

BACKGROUND: The aims of this study were to evaluate pharmacokinetics, efficacy and safety of ropivacaine in infants aged 0-12 months following a single caudal injection. METHODS: Term ASA I-III patients, scheduled for surgery, with a body weight of > or = 2500 g received a caudal block with ropivacaine 2 mg x ml(-1), 1.0 ml x kg(-1). Plasma samples were collected at different time intervals up to 30 h, for analysis of total and unbound ropivacaine and alpha-1-acid glycoprotein (AAG). Pharmacokinetic data were characterized by population analysis. Unbound and total concentrations from 35 patients, median (min-max) postnatal age of 66 (4-351) days, were included in the nonlinear mixed effects modeling to provide estimates of pharmacokinetic parameters and the exploration of covariate relationships. Simulations were made to test the predictive performance of the final model and to describe the effect of significant covariates on systemic exposure. RESULTS: The mean (min-max) peak plasma concentration of total ropivacaine was 0.83 (0.05-1.57) mg x l(-1) at 0.5-5.7 h (median: 1.0 h) and the plasma concentration of unbound ropivacaine was 0.042 (0.012-0.081) mg x l(-1) within 0.5-1 h. The observed unbound fraction in plasma was 6% (1%-14%). A one-compartment open model with first-order absorption and elimination, incorporating a linear-binding model of ropivacaine to AAG best described the data. The only significant covariate relationship was that of age on Clu/F according to the following relationship Clu/F = 3.01 x e0.00474 x Age. This predicts a Clu/F of 3.5 l x h(-1) x kg(-1) at 30 days and 10.8 l x h(-1) x kg(-1) at 270 days with corresponding terminal half-lives of 6.7 and 2.2 h. The interindividual variability (coefficient of variation, CV) in Clu/F was 39%. The population estimate (CV) of ka was 1.65 h(-1) (30%), Vu/F was 33.6 (l x kg(-1)) (45%) and Ka was 1.78 l x mg(-1) (14%). Thirty-five infants received supplementary analgesics (mostly paracetamol). The median time to first supplementary analgesic (based on all 37 patients) was 3.9 h. No safety concerns or signs of systemic toxicity were observed. CONCLUSIONS: Following a caudal block with ropivacaine 2 mg x kg(-1) plasma concentrations of unbound ropivacaine were well below threshold levels for toxicity in adults. Apparent volume of distribution is unchanged, apparent unbound clearance increases and the terminal half-life decreases with age in 0-12-month-old neonates and infants. The postoperative pain management provided adequate analgesia and was well tolerated.