Cardiovascular effects and intraoperative pharmacokinetics of tramadol in sheep undergoing spinal surgery

To evaluate the pharmacokinetics of two doses of tramadol during isoflurane anaesthesia in sheep and their ability to prevent the cardiovascular response induced by surgical stimulation.

Prospective randomized controlled study.

A total of 12 healthy sheep (mean weight, 47.5±7.9 kg) undergoing lumbar transpedicular intervertebral disk nucleotomy.

Sheep were sedated with medetomidine, anaesthesia was induced with propofol and maintained with isoflurane at 1.5 vol.%. Baseline heart rate and blood pressure were measured and sheep were randomly assigned an intravenous injection of tramadol (4 or 6 mg kg^-1). Fentanyl was injected as rescue analgesic if cardiovascular parameters were increased more than 20% compared to baseline. If those variables were below 20% of baseline, the concentration of isoflurane was gradually decreased until parameters returned to the original value. Blood collections were performed at pre-assigned times, and concentrations of tramadol and O-desmethyltramadol (M1) assessed by high-performance liquid chromatography.

Time from premedication to anaesthesia induction, anaesthesia time, propofol dose and intraoperative body temperature were similar between doses. Cardiovascular variables remained between ±20% of baseline value, and no statistical difference was observed between treatments. Regardless of the dose of tramadol administered, arterial blood pressure was statistically higher than baseline 10 minutes after tramadol administration, but it gradually returned to previous values. A two-compartment model and a non-compartment model described the pharmacokinetics of tramadol and M1, respectively. Plasma concentrations of tramadol rapidly decreased in the first 2 hours for both doses with an elimination half-life of more than 40 minutes. The M1 maximum concentration was similar for both doses, and it was detected in plasma after 35 minutes.

Both doses of tramadol provided adequate cardiovascular stability during spinal surgery in sheep. The pharmacokinetic variables may be used to plan the dosage regime during general anaesthesia.