Pharmacokinetics And Pharmacodynamics Of Dexmedetomidine Applied To Patients Undergoing General Anesthesia With End-stage Renal Failure And Insecondary Hyperparathyroidism

Objective Rencently, people are increasingly concerned about the issue of clinical medicine in patients with chronic renal failure due to the number of this kind of patients has been increasing every year. And the prevalence of insecondary hyperparathyroidism which caused by chronic renal failure has also shown an increasing trend. The internal main therapy of insecondary hyperparathyroidism is parathyroid autologous transplantation which would be in progress under general anesthesia. Dexmedetomidine was a new highly selective and specific a 2-adrenoreceptor agonist as a sedative and anesthesia adjuvant which was widely used in clinical. It has a good sedative, analgesic and anxiolytic effects which can compensate to some extent brought by lack of routine anesthesia and make it perfect. However, the pharmacokinetics and pharmacodynamics of dexmedetomidine applied to patients undergoing general anesthesia with end-stage chronic renal failure and insecondary hyperparathyroidism was unknown. Therefore, the purpose of this trial was to explore the properties of the pharmacokinetics and pharmacodynamics of dexmedetomidine applied to this kind of patients due to guide the clinical medicine.Method Fifteen ASA physical status Ⅱ-Ⅲ patients with end-stage renal failure, which scheduled for parathyroidectomy and autotransplantation and insecondary hyperparathyroidism (Renal Failure Group, Group R) and five ASA physical status Ⅰ～Ⅱ patients with normal renal function, which scheduled for excision of adenoma of thyroid (Control Group, Group C), aged 18～65yr, with body mass index of 18～30 kg/m2, received 3.6 μg/kg/h dexmedetomidine for 10 min before anesthesia induction. Arterial blood samples for demedetomidine plasma concentration analysis were drawn at lmin, 5min and 7min during the infusion, and at lmin,3min,7min,20min,45min,75min, 1.5h,2h,4h and 8h after the infusion stopped. The pharmacokinetics and pharmacodynamics were analysed using a nonlinear mixed-effect model.Nonlinear mixed-effects model with NONMEM software was used to analyze the pharmacokinetics. The statistical significance of a covariate was examined using the objective function (-2 log likelihood). In the forward inclusion and backward deletion, the covariates such as age, weight, gender, height, lean body mess (LBM), body surface area (BSA), body mass index (BMI) and grouping factor (renal failure or not) were tested for significant effects on pharmacokinetic parameters. The validity of our population model was also evaluated using the bootstrap simulations.Result The dexmedetomidine concentration-time curves were found to be fitted best with two-compartmental pharmacokinetic models in principles. There was no covariate of systemic clearance that could further improve the model. The final pharmacokinetic parameter values were as follows:Vi=60.6 L, V2=222 L, Cl1=0.825 L/min, and Cl2=4.48 L/min. Although the dosage of propofol was significantly less in Group R (81.68±18.08 vs.63.07±13.45 μg/kg/min, respectively, P<0.05), the context-sensitive half-life and the revival time of anesthesia had no differences between two groups.Conclusion This study validated that there was no influence of age, weight, gender, height, LBM, BSA, BMI and grouping factor (renal failure or not) on pharmacokinetic parameters, and the context-sensitive half-life had no difference between two groups. But for its reduced dosage of propofol, which might be due to the reduced plasma albumin concentration, the increased drug sensitivity, or the secondary hyperparathyroidism, the dosage of dexmedetomidine should be lessen accordingly, and the time of administration should be prolonged properly.