The pharmacokinetics of epidural clonidine 150 micrograms was studied in 13 patients who had undergone abdominal hysterectomy. Plasma clonidine concentrations were measured up to 19 h in eight patients. In another five patients frequent blood sampling was performed only during the first 20 min to define early vascular uptake better. Peak plasma clonidine concentrations of 1.08 +/- 0.35 ng ml-1 (mean +/- s.d.) were reached between 5 and 10 min after injection. Plasma elimination half-life was 829 +/- 157 min and plasma clearance was 177 +/- 28 ml min-1. There was a significant decrease in arterial blood pressure within 10 min of the injection of clonidine. The maximum decrease in systolic blood pressure, from a pre-injection value of 135 +/- 24.7 to 99 +/- 14.4 mmHg (18.0 +/- 3.3 to 13.2 +/- 1.9 kPa), occurred at 60 min. Blood pressure remained significantly lower than the pre-injection value for 4 h. There was no change in heart rate. Verbal analogue pain scores, on a scale 0-10, decreased from a median of 7.6 before clonidine to 5.0 after 30 min (P less than 0.05). The median score at 60 min was 4.3. Thereafter, pain scores were not significantly different from the control score. We conclude that epidural clonidine 150 micrograms produces only moderate and short-lived postoperative analgesia. Absorption of clonidine from the epidural space into the blood is very rapid and may contribute to the hypotension that occurs.
We have studied the ability of clonidine to potentiate morphine analgesia in 28 patients (ASA I) after meniscectomy under general anaesthesia. One hour after surgery, morphine 3 mg (n = 10), clonidine 75 micrograms (n = 8) or morphine 3 mg plus clonidine 75 micrograms (n = 10) was injected extradurally. Morphine alone and in combination with clonidine produced similar and significant analgesia as assessed by verbal analogue pain scores. Pain scores did not decrease significantly in patients given clonidine alone. There were statistically, but not clinically significant decreases in systemic arterial pressure after morphine alone and clonidine alone. No patient developed sensory or motor block. One patient given morphine alone developed retention of urine. It is concluded that, in the dose used in this study, clonidine did not potentiate the analgesia produced by extradural morphine.
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