Application of a pharmacokinetics-pharmacodynamics approach to the free propofol plasma levels during coronary artery bypass grafting surgery with hypothermic cardiopulmonary bypass.

OBJECTIVES: The objective of this study was to apply a pharmacokinetics-pharmacodynamics approach to investigate the free propofol plasma levels in patients undergoing coronary artery bypass grafting under hypothermic conditions compared with the off-pump procedure. METHODS: Nineteen patients scheduled for on-pump coronary artery bypass grafting under hypothermic conditions (n=10) or the equivalent off-pump surgery (n=9) were anesthetized with sufentanil and propofol target-controlled infusion (2 µg/mL) during surgery. The propofol concentration was then reduced to 1 µg/mL, and a pharmacokinetics-pharmacodynamics analysis using the maximum-effect-sigmoid model obtained by plotting the bispectral index values against the free propofol plasma levels was performed. RESULTS: Significant increases (two- to five-fold) in the free propofol plasma levels were observed in the patients subjected to coronary artery bypass grafting under hypothermic conditions. The pharmacokinetics of propofol varied according to the free drug levels in the hypothermic on-pump group versus the off-pump group. After hypothermic coronary artery bypass was initiated, the distribution volume increased, and the distribution half-life was prolonged. Propofol target-controlled infusion was discontinued when orotracheal extubation was indicated, and the time to patient extubation was significantly higher in the hypothermic on-pump group than in the off-pump group (459 versus 273 min, p=0.0048). CONCLUSIONS: The orotracheal intubation time was significantly longer in the hypothermic on-pump group than in the off-pump group. Additionally, residual hypnosis was identified through the pharmacokinetics-pharmacodynamics approach based on decreases in drug plasma protein binding in the hypothermic on-pump group, which could explain the increased hypnosis observed with this drug in this group of patients.

Application of a pharmacokinetics-pharmacodynamics approach to the free propofol plasma levels during coronary artery bypass grafting surgery with hypothermic cardiopulmonary bypass

OBJECTIVES: The objective of this study was to apply a pharmacokinetics-pharmacodynamics approach to investigate the free propofol plasma levels in patients undergoing coronary artery bypass grafting under hypothermic conditions compared with the off-pump procedure. METHODS: Nineteen patients scheduled for on-pump coronary artery bypass grafting under hypothermic conditions (n=10) or the equivalent off-pump surgery (n=9) were anesthetized with sufentanil and propofol target-controlled infusion (2 μg/mL) during surgery. The propofol concentration was then reduced to 1 μg/mL, and a pharmacokinetics-pharmacodynamics analysis using the maximum-effect-sigmoid model obtained by plotting the bispectral index values against the free propofol plasma levels was performed. RESULTS: Significant increases (two- to five-fold) in the free propofol plasma levels were observed in the patients subjected to coronary artery bypass grafting under hypothermic conditions. The pharmacokinetics of propofol varied according to the free drug levels in the hypothermic on-pump group versus the off-pump group. After hypothermic coronary artery bypass was initiated, the distribution volume increased, and the distribution half-life was prolonged. Propofol target-controlled infusion was discontinued when orotracheal extubation was indicated, and the time to patient extubation was significantly higher in the hypothermic on-pump group than in the off-pump group (459 versus 273 min, p=0.0048). CONCLUSIONS: The orotracheal intubation time was significantly longer in the hypothermic on-pump group than in the off-pump group. Additionally, residual hypnosis was identified through the pharmacokinetics-pharmacodynamics approach based on decreases in drug plasma protein binding in the hypothermic on-pump group, which could explain the increased hypnosis observed with this drug in this group of patients.

Confidence intervals for a ratio of binomial proportions based on paired data.

Four interval estimation methods for the ratio of marginal binomial proportions are compared in terms of expected interval width and exact coverage probability. Two new methods are proposed that are based on combining two Wilson score intervals. The new methods are easy to compute and perform as well or better than the method recently proposed by Nam and Blackwelder. Two sample size formulas are proposed to approximate the sample size required to achieve an interval estimate with desired confidence level and width.

[Evaluation of intraoperative standardized hypnosis with the State-Trait Anxiety Inventory]. / Evaluation des intraoperativen Einsatzes standardisierter Hypnose mit State-Trait-Angst-Inventar.

BACKGROUND: Surgical treatment under local anesthesia is commonly restricted by limited compliance of patients. Hypnosis may represent an alternative to sedation or general anesthesia. As the procedure demonstrated promising prospects during 1-year experience, the observed hypnosis-induced effects are now being evaluated in clinical studies. PATIENTS AND METHOD: The prospective study included 50 patients scheduled for dental surgery. All procedures were performed under standardized surgical conditions. The experimental group (n=25) received supplementary standardized tape hypnosis, whereas the control group received standard treatment (only local anesthesia). Individual and situative anxiety levels were determined by the State-Trait Anxiety Inventory (STAI). RESULTS: After simultaneous increase of preoperative state anxiety, anxiety levels in the hypnosis group showed a significant intraoperative reduction to baseline level, whereas intraoperative anxiety of the control group (n=25) remained unchanged. CONCLUSIONS: Hypnosis reduces intraoperative anxiety of oral and maxillofacial patients significantly. Further clinical studies on the use of hypnosis are considered useful.