Administration of propofol by target-controlled infusion in patients undergoing coronary artery surgery.

OBJECTIVES: To study the predictive performance of a target-controlled infusion (TCI) system of propofol in patients undergoing coronary bypass graft (CABG) surgery, using a referenced pharmacokinetic set derived from healthy patients. Also, to determine the propofol concentrations required for clinically acceptable induction and maintenance of anesthesia when combined with midazolam as premedication and a continuous alfentanil infusion and to study the hemodynamic stability of this technique. DESIGN: Prospective noncomparative study analysis. SETTING: Operating room at a university hospital. PARTICIPANTS: Twenty-on patients with good left ventricular function undergoing coronary artery surgery. INTERVENTIONS: Patients were anesthetized using a continuous infusion of alfentanil (mean infusion rate: 1 microgram/kg/min) and propofol administered by TCI. MEASUREMENTS AND MAIN RESULTS: The predictive performance of the TCI system (212 arterial samples) was measured at specified time points before, during, and after bypass. The TCI system underestimated the measured blood propofol concentrations with a bias of +21.2% and +9.6% during the prebypass and the bypass periods, respectively. The predictive inaccuracy, expressed by the median absolute prediction error, was 23% and 18.5%, respectively. Mean target propofol concentrations required to induce and maintain anesthesia before bypass were 0.92 microgram/mL and 3.64 micrograms/mL, respectively. In the period during and after bypass, the mean target concentrations required to maintain anesthesia was 2.22 micrograms/mL. The administration of propofol by TCI was still associated with some short episodes of hemodynamic instability that were easily controlled by adjusting the target concentration in the majority of the patients. Therefore, the overall quality and ease of control of anesthesia were considered as being good or adequate. CONCLUSIONS: In this group of patients undergoing CABG surgery, the TCI system used underestimated the measured propofol concentrations. However, the predictive performance of the selected mean pharmacokinetic parameters derived from healthy patients was acceptable during the whole surgical procedure.

Endocrine profiles during administration of the new non-steroidal anti-androgen Casodex in prostate cancer.

OBJECTIVE: Casodex (Zeneca) is a new potent, long-acting non-steroidal anti-androgen, which produces androgen deprivation by blocking the androgen receptor. We evaluated the endocrine effects of Casodex 150 mg daily given in monotherapy as primary treatment for patients with prostate cancer. DESIGN: As part of a large, multicentre study comparing the therapeutic effects of surgical castration with 150 mg/day Casodex in monotherapy for patients with prostate cancer, a subgroup of 23 patients on Casodex were studied in detail for changes in endocrine parameters. Serum levels of LH, FSH, testosterone, DHT, oestradiol, prolactin, sex hormone binding globulin and free testosterone were measured at the start of therapy and after 1, 4, 8, 12 and 24 weeks. Effects on libido, sexual activity and the appearance of hot flushes, breast pain and gynaecomastia were recorded. RESULTS: Administration of Casodex resulted in a rise in LH levels in all patients with a mean increase after 24 weeks of 102% (P < 0.001). Mean FSH levels showed a limited increase (7%) after 24 weeks, which was significant only after 1 week (P < 0.001). As a result of the high LH levels, total testosterone levels increased after 24 weeks by 66% (P < 0.001), free testosterone by 57% (P < 0.001) and dihydrotestosterone by 24% (P = 0.0112). Parallel to testosterone, oestradiol levels rose by a mean of 66% (P < 0.001). Mean sex hormone binding globulin and prolactin levels rose by respectively 8% (P = NS) and 65% (P < 0.01). Despite an increase in testosterone levels, excellent androgen blockade was obtained, as shown by a decrease in prostate specific antigen levels in 22/23 patients. Libido was maintained in 8/11 patients, and sexual activity in 5/6. No patient complained of hot flushes. However, mild gynaecomastia and/or breast tenderness were seen in 48 and 30% of cases respectively. CONCLUSION: Casodex 150 mg/day monotherapy resembles surgical castration in achieving androgen deprivation, despite an increase in LH and testosterone levels. In contrast to castration, libido and sexual activity are usually maintained and hot flushes are rare. However, mild gynaecomastia and/or breast tenderness were noted in 48 and 30% of patients.