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M L Buck

Publications and source records attributed to M L Buck.

22 records · Page 2Linked to original sources

Pharmacokinetics and pharmacodynamics of atenolol in children.

The pharmacokinetics and pharmacodynamics of intravenous atenolol were studied in 10 children during cardiac electrophysiologic studies. The intravenous pharmacokinetic data were best described by a two-compartment model and revealed the following (mean +/- SD): total body clearance, 0.15 +/- 0.06 L/hr/kg; volume of the central compartment 0.33 +/- 0.06 L/kg; volume of distribution at steady state, 0.83 +/- 0.15 L/kg; distributive elimination half-life, 0.29 +/- 0.08 hour; and terminal elimination half-life, 4.56 +/- 1.05 hours. The data suggest that children have a slightly shorter terminal elimination half-life than that of adults. Pharmacodynamic data showed a significantly (p less than 0.01) increased sinus cycle length and an increase in His to ventricle conduction time (p less than 0.05). Further studies are necessary to determine the optimal oral dose and dosing frequency of atenolol and to access the response of children to long-term treatment.

Adolescent↗

Effect of infusing fat emulsion into extracorporeal membrane oxygenation circuits.

Our objectives were to identify problems associated with the administration of fat emulsion by extracorporeal membrane oxygenation (ECMO) circuits, and gather information from other institutions on standards of practice and the complications associated with infusion of fat emulsion by ECMO to infants and children. In vitro analysis was performed using six circuits. Fat emulsion was infused into a prereservoir port at 3 ml/hour. Circuits and blood samples collected distal to the oxygenator were inspected visually for layering (separation of fat emulsion from blood), agglutination, and phase separation (formation of an oil layer) at 0.5, 1, 2, 4, 6, 12, and 24 hours. At 24 hours, samples were reevaluated and circuits dissected. All circuits showed layering and agglutination. Blood clots were present in five circuits during the simulation. There was no evidence of phase separation in the samples. Adhesion of emulsion to the equipment was present in all circuits. Five of the membrane oxygenators contained clots. One contained long strands of fat; separation of its mesh revealed an oily residue indicating disruption of the stability of the emulsion. Survey responses from 54 centers found that 78% used fat emulsion routinely in neonatal or pediatric patients receiving ECMO. Most used both ECMO and separate venous access for the infusion, depending on availability. Twenty-two (52%) of the 42 centers using fat emulsion had a policy in place regarding site selection. Of those, 73% preferred central venous access, another 18% used a prereservoir port of the ECMO circuit. The most frequently reported problems with administration through the circuit were cracking of stopcocks, clogging and malfunction of the membrane oxygenator, agglutination of the emulsion, and increase in blood clot formation. Our results suggest that fat emulsion should be infused through a separate intravenous site whenever possible. Based on these results and current practices of most ECMO centers, a clinical trial is currently being conducted to provide additional information.

Blood Coagulation↗

Vancomycin pharmacokinetics in neonates receiving extracorporeal membrane oxygenation.

Vancomycin is administered as both prophylaxis and treatment in neonates receiving extracorporeal membrane oxygenation (ECMO), typically after surgery. An open-label, retrospective study was conducted to determine dosing strategies in all neonates who received vancomycin during ECMO and compare pharmacokinetic values with those of matched controls not receiving ECMO. Fifteen neonates receiving ECMO were given vancomycin infused into the circuit, with dosages based on weight and gestational age. Blood for serum concentrations was drawn around the third dose, for trough concentrations immediately before the dose, and for peak concentrations 1 hour after infusion. Samples were analyzed by fluorescence polarization immunoassay. The most frequent regimen for both groups (8 ECMO, 13 controls) was 10 mg/kg every 8 hours. It produced peak and trough concentrations of 27.5 +/- 4.3 and 13.7 +/- 2.7 microg/ml, and 23.0 +/- 5.4 and 13.2 +/- 4.5 microg/ml, respectively. Pharmacokinetic analysis using a one-compartment model revealed volume of distribution of 0.45 +/- 0.18 L/kg, half-life of 8.29 +/- 2.23 hours, and total body clearance of 0.65 +/- 0.28 ml/min/kg in ECMO recipients. Volume of distribution and clearance were not significantly different in controls (0.39 +/- 0.12 L/kg, 0.79 +/- 0.41 ml/min/kg), but half-life was shorter (6.53 +/- 2.05 hrs, p = 0.02). Based on long volume of distribution in neonates receiving ECMO, we recommend that empiric vancomycin regimens incorporate a longer dosing interval than the 6-8 hours commonly recommended for term infants. The effects of severity of illness on drug elimination require additional study.

Anti-Bacterial Agents↗