Postoperative pain control by epidural analgesia after transabdominal surgery. Efficacy and problems encountered in daily routine.

BACKGROUND: The efficacy of postoperative epidural pain treatment has been well documented in controlled studies. However, the literature concerning results of daily routine use of this method often only emphasises certain aspects of it. METHODS: A prospective study of 168 patients scheduled for major surgery with transabdominal access was performed in order to evaluate efficacy, side effects, complications and rate of acceptance of postoperative epidural pain treatment. The epidural catheter was placed before surgery and the patients received epidural analgesia by a bupivacaine/morphine mixture for 3 days postoperatively, continued by another 3 days with bolus injections of morphine only. RESULTS: Only few complications followed the insertion of the epidural catheter, but in about 16% of the patients the epidural catheter or the drugs administered by it made reinsertion or change in the type of analgesia necessary during the first 3 post-operative days. Despite the possibility for individualising the treatment and p.r.n. analgesics, pain relief when coughing and moving during day 1-3 was insufficient in 30-50% of the patients. Serious side effects were rare, but pruritus was frequent, as were the symptoms of nausea and vomiting. The patients were generally satisfied with the treatment; however, a small group had unacceptable pain when the epidural catheter was inserted. CONCLUSION: Analgesia was insufficient when coughing and moving in an unacceptably large number of the patients. Also the number of epidural catheter related problems was high. In order to make early intervention possible, the patients and epidural catheters should be observed daily and systematically by members of the staff competent to detect possible problems.

Stereoselective pharmacokinetics of methadone in chronic pain patients.

Ten patients with chronic pain were randomized to an open, balanced, crossover study. Each patients received two different preparations of racemic methadone, i.e., tablets and intravenous infusion. The pharmacokinetic parameters of the R- and S-enantiomers of the racemate are reported. The analgesically active R-methadone has a significantly longer mean elimination half-life than the optical antipode S-methadone (t1/2 = 37.5 and 28.6 h, respectively). The mean total volume of distribution is 496.6 L for R-methadone and 289.1 L for S-methadone. Significant differences in the mean clearance between R- and S-methadone are seen (0.158 and 0.129 L/min, respectively). However, the lagtime after oral administration and the bioavailability did not show differences between the isomers. The data suggest that both enantiomers of methadone should be measured if correlations between pharmacodynamics and kinetics are made due to the stereoselective differences in half-life, total volume of distribution, and clearance.

Enantioselective high-performance liquid chromatographic method for the determination of methadone in serum using an AGP and a CN column as chiral and analytical column, respectively.

A simple and sensitive HPLC method with ultraviolet absorption detection at 200 nm is described for the determination of methadone enantiomers in human serum, using dextropropoxyphene as an internal standard and organic solvent extraction. Separation was performed on two serially coupled columns, CN and Chiral AGP, with a mobile phase consisting of acetonitrile, dimethylocytlamine and phosphate buffer. Using 1.0 ml of serum, 5 nmol/1 of each enantiomer could be determined with an acceptable precision. No interactions from several drugs were observed. The method has been successfully used in a pharmacokinetic study. More than 2500 serum samples have been separated on the same AGP column with acceptable selectivity and resolution.

Blood pressure and heart rate during orthostatic stress and walking with continuous postoperative thoracic epidural bupivacaine/morphine.

Thirty-one patients scheduled for elective cholecystectomy performed through a mini-laparotomy, were randomized to received either combined thoracic epidural anaesthesia/light general anaesthesia and postoperative balanced analgesia with continuous epidural bupivacaine 10 mg.h-1 and morphine 0.2 mg.h-1 for 38 h after surgery plus systemic ibuprofen 600 mg x 8 h-1 (N = 15) or general anaesthesia and postoperative analgesia with systemic morphine and ibuprofen 600 mg x 8 h-1 (N = 16). During postoperative epidural infusion sensory blockade to pinprick was Th4 to L1, and analgesia at rest and during mobilisation was superior compared to systemic morphine and NSAID. There were no significant differences between groups in haemodynamic responses (BP and heart rate) during rest, orthostatic stress and after walking assessed before, 24 and 48 h after operation except for a clinically unimportant lower heart rate (approximately 10 bpm) 48 h after surgery at rest and during orthostatic stress in the epidural group. There was no significant difference between groups in number of patients with a reduction > 20 mmHg (2.7 kPa) in systolic blood pressure during orthostatic stress (two in each group at 24 h) or in number of episodes of dizziness, nausea or vomiting during rest or mobilisation. These results do not support the common belief that low-dose thoracic epidural bupivacaine/morphine may prevent ambulation due to sympathetic blockade or to impaired cardiovascular adaptation to the upright position.