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.

Avaliação da bioatividade dos extratos de cúrcuma (Curcuma longa L., Zingiberaceae) em Artemia salina e Biomphalaria glabrata / Bioactivity evaluation of the turmeric (Curcuma longa L., Zingiberaceae) extracts in Artemia salina and Biomphalaria glabrata

A cúrcuma é o rizoma limpo, em boas condições, seco e moído da Curcuma longa L., uma planta herbácea da família Zingiberaceae. Visando novas alternativas para o controle da esquistossomose, os extratos de Curcuma longa L. foram testados para a avaliação da atividade moluscicida contra caramujos adultos da espécie Biomphalaria glabrata, e toxicidade (ensaio de letalidade com Artemia salina). A oleoresina e o óleo essencial de cúrcuma foram ativos contra Artemia salina (CL50 = 80,43 e CL50 = 319,82 μg/mL, respectivamente) e também ativos contra os indivíduos adultos de Biomphalaria glabrata (CL50 = 58,3 e CL50 = 46,73 μg/mL, respectivamente). A partir dos resultados obtidos pôde ser concluído que ambos os extratos podem constituir uma alternativa no controle da população desses caramujos e na redução da esquistossomose.

The turmeric is the clean rhizome at good conditions, dried and powdered of Curcuma longa L., an herbaceous plant of Zingiberaceae family. Aiming new alternatives for Schistosomiasis control, the Curcuma longa L. extracts were tested for molluscicidal activity evaluation against adult snails of Biomphalaria glabrata specie, and the toxicity (Brine Shrimp Lethality-BSL-bioassay). The oleoresin and the essential oil of turmeric were active against Artemia salina (CL50 = 80.43 and CL50 = 319.82 μg.mL-1, respectively) and also active against the adult snails of Biomphalaria glabrata (CL50 = 58.3 and CL50 = 46.73 μg.mL-1, respectively). From the obtained results it was concluded that both extracts can constitute an alternative to population control of these snails and in the reduction of Schistosomiasis.

Effects of cardiopulmonary bypass on propofol pharmacokinetics and bispectral index during coronary surgery

PURPOSE: Cardiopulmonary bypass is known to alter propofol pharmacokinetics in patients undergoing cardiac surgery. However, few studies have evaluated the impact of these alterations on postoperative pharmacodynamics. This study was designed to test the hypothesis that changes in propofol pharmacokinetics increase hypnotic effects after cardiopulmonary bypass. METHODS: Twenty patients scheduled for on-pump coronary artery bypass graft (group, n=10) or off-pump coronary artery bypass graft (group, n=10) coronary artery bypass grafts were anesthetized with sufentanil and a propofol target controlled infusion (2.0 µg/mL). Depth of hypnosis was monitored using the bispectral index. Blood samples were collected from the induction of anesthesia up to 12 hours after the end of propofol infusion, at predetermined intervals. Plasma propofol concentrations were measured using high-performance liquid chromatography, followed by a non-compartmental propofol pharmacokinetic analysis. Data were analyzed using ANOVA, considering p<0.05 as significant. RESULTS: After cardiopulmonary bypass, despite similar plasma propofol concentrations in both groups, bispectral index values were lower in the on-pump coronary artery bypass graft group. Time to extubation after the end of propofol infusion was greater in the on-pump coronary artery bypass graft group (334 ± 117 vs. 216 ± 85 min, p = 0.04). Patients undergoing cardiopulmonary bypass had shorter biological (1.82 ± 0.5 vs. 3.67 ± 1.15h, p < 0.01) and terminal elimination (6.27 ± 1.29 vs. 10.5h ± 2.18, p < 0.01) half-life values, as well as higher total plasma clearance (28.36 ± 11.40 vs.18.29 ± 7.67 mL/kg/min, p = 0.03), compared to patients in the off-pump coronary artery bypass graft group. CONCLUSION: Aside from the increased sensitivity of the brain to anesthetics after cardiopulmonary bypass, changes in propofol pharmacokinetics may contribute to its central nervous system effects.