The antinociceptive effects of dexmedetomidine, a highly selective new alpha 2-adrenoceptor agonist, were evaluated in rats after intrathecal, intraperitoneal and subcutaneous administration. Antinociception was tested using the tail-flick method. Both 3 and 6 micrograms of intrathecal dexmedetomidine produced maximal antinociception within 10 min. The effect lasted for up to 6 hr. The smaller dose of 1.5 micrograms produced a mean antinociception of 50% (of the maximum possible effect, MPE%) which lasted for about 2 hr. Subcutaneous atipamezole, a specific alpha 2-adrenergic antagonist completely abolished the antinociception produced by intrathecal dexmedetomidine. When given intraperitoneally, dexmedetomidine produced on average a 50% antinociceptive effect with the highest dose of 60 micrograms/kg. The lower doses of 10 and 30 micrograms/kg were ineffective. After subcutaneous administration a maximal effect was achieved with 120 micrograms/kg, a 70% effect, on average, with 60 micrograms/kg and a short lasting effect of 60% with 30 micrograms/kg. In conclusion, dexmedetomidine is a very potent antinociceptive agent when given intrathecally to rats.

Intravenous morphine and oxycodone were given double blind in doses of 0.05 mg/kg after major abdominal surgery to 39 patients. The dosing interval was 5 min, until the patient did not want any further analgesics. Less oxycodone was needed than morphine, both to achieve the "first state of pain relief" (13.2 mg vs. 24.9 mg) and during the whole 2-h study period (21.8 mg vs. 34.2 mg). The "first state of pain relief" was achieved faster (28 min vs. 46 min) and lasted longer (39 min vs. 27 min) with oxycodone than morphine. Morphine caused more sedation and a greater decrease in the mean arterial blood pressure than oxycodone. In other respects the two opioids were comparable.

1 The pharmacokinetics and metabolism of oxycodone were studied in nine healthy young volunteers in a cross-over study. Each subject received oxycodone chloride once intramuscularly (0.14 mg kg-') and twice orally (0.

Kidney injury occurs in most patients undergoing infrarenal aortic surgery, but only 22% develop acute renal dysfunction. Hypotension and low cardiac output are risk factors that could be avoided by optimizing perioperative management.

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