Objectives To evaluate the long term effects of perioperative blockade on mortality and cardiac morbidity in patients with diabetes undergoing major non-cardiac surgery. Design Randomised placebo controlled and blinded multicentre trial. Analyses were by intention to treat. Setting University anaesthesia and surgical centres and one coordinating centre. Participants 921 patients aged > 39 scheduled for major non-cardiac surgery. Interventions 100 mg metoprolol controlled and extended release or placebo administered from the day before surgery to a maximum of eight perioperative days. Main outcome measures The composite primary outcome measure was time to all cause mortality, acute myocardial infarction, unstable angina, or congestive heart failure. Secondary outcome measures were time to all cause mortality, cardiac mortality, and non-fatal cardiac morbidity. Results Mean duration of intervention was 4.6 days in the metoprolol group and 4.9 days in the placebo group. Metoprolol significantly reduced the mean heart rate by 11% (95% confidence interval 9% to 13%) and mean blood pressure by 3% (1% to 5%). The primary outcome occurred in 99 of 462 patients in the metoprolol group (21%) and 93 of 459 patients in the placebo group (20%) (hazard ratio 1.06, 0.80 to 1.41) during a median follow-up of 18 months (range 6-30). All cause mortality was 16% (74/462) in the metoprolol group and 16% (72/459) in the placebo group (1.03, 0.74 to 1.42). The difference in risk for the proportion of patients with serious adverse events was 2.4% ( − 0.8% to 5.6%). Conclusions Perioperative metoprolol did not significantly affect mortality and cardiac morbidity in these patients with diabetes. Confidence intervals, however, were wide, and the issue needs reassessment. Trial registration Current Controlled Trials ISRCTN58485613.
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.
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.
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.
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