Disease severity is a major determinant for the pharmacodynamics of propofol in critically ill patients.

As oversedation is still common and significant variability between and within critically ill patients makes empiric dosing difficult, the population pharmacokinetics and pharmacodynamics of propofol upon long-term use are characterized, particularly focused on the varying disease state as determinant of the effect. Twenty-six critically ill patients were evaluated during 0.7-9.5 days (median 1.9 days) using the Ramsay scale and the bispectral index as pharmacodynamic end points. NONMEM V was applied for population pharmacokinetic and pharmacodynamic modeling. Propofol pharmacokinetics was described by a two-compartment model, in which cardiac patients had a 38% lower clearance. Severity of illness, expressed as a Sequential Organ Failure Assessment (SOFA) score, particularly influenced the pharmacodynamics and to a minor degree the pharmacokinetics. Deeper levels of sedation were found with an increasing SOFA score. With severe illness, critically ill patients will need downward titration of propofol. In patients with cardiac failure, the propofol dosages should be reduced by 38%.

Early transection of a central venous catheter in a sedated ICU patient.

We report transection and embolization to the heart of a subclavian venous catheter in an immobilized and mechanical ventilated patient. The catheter tip was retrieved using a percutaneous method via the left femoral vein. Mechanical compression of the subclavian venous catheter at the costoclavicular area is termed pinch-off syndrome. It can be recognized by intermittent difficulties with drug injection, and chest wall swelling at the insertion site. The diagnosis can be confirmed by chest radiography with or without contrast administration. A more lateral approach of the subclavian vein is advocated to prevent compression.

Pharmacokinetics and pharmacodynamics of propofol 6% SAZN versus propofol 1% SAZN and Diprivan-10 for short-term sedation following coronary artery bypass surgery.

OBJECTIVE: A new formulation of propofol 6% in Lipofundin MCT/LCT 10% (propofol 6% SAZN) has been developed in order to reduce the fat, emulsifier and volume load that is given during prolonged infusions of propofol. The pharmacokinetics, pharmacodynamics and safety characteristics of propofol 6% SAZN were investigated during a short-term infusion and compared with the commercially available product propofol 1% in Intralipid 10% (Diprivan-10) and propofol 1% in Lipofundin MCT/LCT 10% (propofol 1% SAZN). METHODS: In a randomised double-blind study, 24 male patients received a 5-h infusion of propofol at the rate of 1 mg/kg/h for sedation in the immediate postoperative period following coronary artery bypass surgery. RESULTS: The average pharmacokinetic parameter estimates of clearance (Cl), volume of distribution at steady state (Vd,ss), elimination half-life (t1/2,beta) and distribution half-life (t1/2,alpha) observed in the three groups were 28 +/- 1.1 ml/kg/min, 1.8 +/- 0.12 l/kg, 94 +/- 4.1 min and 3.1 +/- 0.26 min, respectively (mean +/- SEM, n = 24) and no significant differences were noted between the three formulations (P > 0.05). In one patient receiving propofol 6% SAZN, in two patients receiving propofol 1% SAZN and in three patients receiving Diprivan-10, the level of sedation was inadequate and additional sedative medication had to be given. In all other 18 patients, the level of sedation was adequate. The mean propofol concentration in these six inadequately sedated patients was lower than the adequately sedated patients (P = 0.015). The serum triglyceride concentrations were not significantly different between the groups studied. No adverse events occurred in any of the patients. CONCLUSIONS: The pharmacokinetics, pharmacodynamics and safety characteristics of propofol 6% SAZN are in good agreement with those of the 1% formulations. Propofol 6% SAZN therefore provides a useful alternative to the commercially available 1% formulation for short-term sedation in the intensive care unit. Expected advantages in long-term sedation of the 6% over 1% formulation are the subject of an ongoing study.

High pressure liquid chromatographic analysis of the serum concentration of cefuroxime after an intravenous bolus injection of cefuroxime in patients with a coronary artery bypass grafting.

A simple reversed-phase high pressure liquid chromatographic method was developed for the determination of cefuroxime in the serum of patients undergoing coronary artery bypass grafting. The serum was cleaned up with a 3.3% solution of perchloric acid in water. Cefalexine was used as an internal standard. Detection was made by a UV multi-wavelength detector. The optimum wavelength for cefuroxime is 275 nm. The absolute recovery of this method was 90.9%; the limit of quantification was 0.7 mg/l. This analytical method was used in a study to investigate the cefuroxime serum concentration--time curves in 26 patients undergoing coronary artery bypass grafting. It was found that one single dose is sufficient to obtain effective serum concentrations.