STUDY OBJECTIVE: To compare the frequency and duration of postoperative nausea and vomiting (PONV) following total intravenous anesthesia (TIVA) with propofol and either remifentanil or alfentanil in outpatients undergoing arthroscopic surgery of the extremities. DESIGN: Randomized, third-party blinded study. SETTING: University medical center. PATIENTS: 100 ASA physical status I and II patients scheduled for arthroscopic surgery of the knee or shoulder. INTERVENTIONS: The anesthesia regimen consisted of a bolus followed by continuous infusion of propofol (2 mg/kg followed by 120 microg/kg/min) and the opioid (remifentanil 0.5 microg/kg followed by 0.1 microg/kg/min or alfentanil 10 microg/kg followed by 0.25 microg/kg/min). Patients breathed 100% oxygen spontaneously through a Laryngeal Mask Airway (or an endotracheal tube when medically indicated). Opioids were titrated to maintain blood pressure and heart rate within 20% of baseline and a respiratory rate of 10 to 16 breaths/min. Propofol was titrated downward as low as possible without permitting patient movement. MEASUREMENTS: Nausea was determined by an 11-point categorical scale and was recorded before surgery and multiple time points thereafter. The times of emetic episodes were recorded. Treatment of PONV was at the discretion of the postanesthesia care unit (PACU) nurses who were blinded to the identity of the opioid used. MAIN RESULTS: Nausea scores were 0 at all time points in over 70% of the patients in each group. None of the 100 patients vomited while in the hospital, and only one patient required antiemetic therapy. CONCLUSION: When propofol-based TIVA is used for arthroscopic surgery, short-acting opioids do not significantly affect the risk of PONV.

BACKGROUND: A new pulmonary drug delivery system produces aerosols from disposable packets of medication. This study compared the pharmacokinetics and pharmacodynamics of morphine delivered by an AERx prototype with intravenous morphine. METHODS: Fifteen healthy volunteers were enrolled. Two subjects were administered four inhalations of 2.2 mg morphine each at 1-min intervals or 4.4 mg over 3 min by intravenous infusion. Thirteen subjects were given twice the above doses, i.e., eight inhalations or 8.8 mg intravenously over 7 min. Arterial blood sampling was performed every minute during administration and at 2, 5, 7, 10, 15, 20, 45, 60, 90, 120, 150, 180, and 240 min after administration. The effect of morphine was assessed by measuring pupil diameter and ventilatory response to a hypercapnic challenge. Pharmacokinetic and pharmacodynamic analyses were performed simultaneously using mixed-effect models. RESULTS: The pharmacokinetic data after intravenous administration were described by a three-exponent decay model preceded by a lag time. The pharmacokinetic model for administration by inhalation consisted of the three-exponent intravenous pharmacokinetic model preceded by a two-exponent absorption model. The authors found that, with administration by inhalation, the total bioavailability was 59%, of which 43% was absorbed almost instantaneously and 57% was absorbed with a half-life of 18 min. The median times to the half-maximal miotic effects of morphine were 10 and 5.5 min after inhalation and intravenous administration, respectively (P < 0.01). The pharmacodynamic parameter ke0 was approximately 0.003 min-1. CONCLUSIONS: The onset and duration of the effects of morphine are similar after intravenous administration or inhalation via this new pulmonary drug delivery system. Morphine bioavailability after such administration is 59% of the dose loaded into the dosage form.