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Six domestic shorthair cats, aged three to four years and weighing 5.1 to 7.4 kg, were used to assess the thermal antinociceptive effect of a transdermal buprenorphine patch, designed to supply 35 mug buprenorphine/hour, which was applied to the shaved thorax. The cats' thermal thresholds were tested before the patch was applied and two, four, six, eight, 10, 12, 14 and 16 hours after it had been applied, and then every six hours until it was removed after 72 hours, and for a further 24 hours afterwards. Blood was collected at each time to measure the plasma concentration of buprenorphine. The patches did not produce a significant change in the thermal thresholds of the cats throughout the testing period. The mean (sd) peak plasma buprenorphine concentration was 10 (0.81) ng/ml.

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The disposition of buprenorphine has been studied in two patient groups to assess the influence of impaired renal function on the metabolism of buprenorphine and two of its metabolites, buprenorphine-3-glucuronide (B3G) and norbuprenorphine (NorB). A single i.v. dose of 0.3 mg was given to 15 patients (nine with dialysis-dependent renal failure) undergoing lower abdominal or peripheral body surface surgery. Blood was sampled up to 24 h. Concentrations of buprenorphine, B3G and NorB were assayed by a differential radioimmunoassay technique. There were no differences in buprenorphine kinetics between anaesthetized healthy patients and those with renal impairment: mean elimination half-lives 398 and 239 min; clearance 651 and 988 ml min-1; apparent volume of distribution at steady state 313 and 201 litre, respectively. Both metabolites were undetectable following the single i.v. dose. In a second group of 20 patients (eight with renal impairment), buprenorphine was administered by continuous infusion for provision of analgesia and control of ventilation in the ITU (median infusion rate 161 micrograms h-1 (range 36-230 micrograms h-1) for a median duration of 30 h (2-565 h). Buprenorphine clearance in patients with normal and impaired renal function was similar (934 and 1102 ml min-1, respectively), as were dose-corrected plasma concentrations of buprenorphine. In patients with renal failure, plasma concentrations of NorB were increased by a median of four times, and B3G concentrations by a median of 15 times.

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SummaryOne hundred and eighty-three patients were studied to examine the role of a number of risk factors in the development of silent ischaemia after general anaesthesia for general and vascular surgery. We collected evidence of cardiovascular risk factors using a binary questionnaire. The patients were monitored pre-and postoperatively using a Holter ECG monitor. Usable data were collected on 140 patients. Pre-operative silent myocardial ischaemia was found to be strongly associated with postoperative silent myocardial ischaemia (odds ratio: 10.8, 95% confidence intervals: 3.8-30.7). A history of hypertension, indicated by treatment with antihypertensive drugs, was associated with increased risk (odds ratio: 2.58, 95% confidence intervals: 1.12-5.96). A linear trend was found for risk associated with increasing admission systolic blood pressure (odds ratio: 1.20 for each 10-mmHg increase in systolic pressure, 95% confidence intervals: 1.01-1.42). An association between vascular surgery and postoperative silent myocardial ischaemia was also confirmed (odds ratio: 2.36, 95% confidence intervals: 1.1-5.1).

SummaryWe analysed the pharmaco-economics of the prospective peri-operative studies of statin administration for major elective vascular surgery, using the NHS reference costs for 2004. This analysis suggests that peri-operative statin therapy for patients undergoing vascular surgery may present the most cost-effective use of statin therapy yet described. With a number-needed-to-treat of 15, the reduction in peri-operative cardiovascular complications offsets the total additional cost of atorvastatin therapy (that is the cost of the drugs, the laboratory screening for adverse effects and the cost of treating the rare adverse event). Statin therapy decreases long-term cardiovascular events in patients with or at risk of coronary heart disease [1-10]. Statins also improve both short-and long-term cardiovascular outcomes following acute coronary syndromes [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]. There is increased evidence that statins may improve peri-operative cardiovascular outcome in the high-risk cardiac patient for non-cardiac surgery [26][27][28][29][30][31][32][33]. The cardiovascular protection of statins is multifactorial and includes increasing the stability of atherosclerotic plaques, improving endothelial function and decreasing the thrombogenic response to plaque rupture [34].In high-risk cardiac patients presenting for non-cardiac surgery, a number of strategies have been used to prevent or reduce adverse cardiac complications. These include high dose opioid anaesthesia and regional anaesthesia (to minimise the stress response), pre-operative coronary artery revascularisation and peri-operative cardioprotective drugs. When considering the utility of peri-operative statin therapy, there are two prospective, randomised controlled trials showing a significant reduction in postoperative morbidity and mortality when statin therapy is started before surgery and continued into the postoperative period [29,33]. In the study by Durazzo et al. [29], adverse cardiac events within 6 months of vascular surgery were reduced more than threefold in the statin group. In the second study by Schouten et al. [33], the combined end-point of in-hospital death or myocardial infarction was nearly halved in the statin group.From both of these studies, it is possible to calculate the absolute risk reduction (ARR) for all-cause peri-operative events at 6 months [29] and in-hospital death and myocardial infarction [33]. One way of assessing the efficacy of such treatment is to calculate the numberneeded-to-treat (NNT; equal to 1 ⁄ ARR). However, against this there is the need to consider the risks or complications of such therapies. In the present analysis, we have conducted a cost-effectiveness analysis for the use of statin therapy in high-risk non-cardiac surgical patients. MethodsThis pharmaco-economic analysis compared the total expected cost of patients receiving atorvastatin vs placebo for 45 days peri-operatively for major vascular surgery [29]. We selected the two prospective peri-operative studies...

SummaryIn order to avoid Cremophor-related reactions and reduce the incidence of pain on injection, diisopropylphenol (ICI 35,868; propof) Key wordsAnaesthetics, intravenous; propofol.2,6-di-isopropylphenol (ICI 35,868; propofol; 'Diprivan,' formerly disoprofol) is one of a series of alkylphenols which were found to have anaesthetic properties in animals.' Initial investigations of the pharmacological properties of propofol were conducted using a formulation containing the surfactant Cremophor EL.2 Anaesthetic properties were demonstrated in who received 1-3 mg/kg intravenously although in unpremedicated patients 2 mg/kg was generally successful. s * 7 There was pain on when the drug was given into veins on the dorsum of the hand. To reduce the frequency of this side-effect, and because of circumstantial evidence of a n association of Cremophor-containing agents with anaphylactoid reactions,10-12 an emulsion formulation of propofol has been developed. We have determined the effective dose of propofol* in the new emulsion formulation for induction of anaesthesia in 95% (AD 95) of healthy, unpremedicated patients. MethodsFive hospitals in the United Kingdom participated in an open study for which individual hospital ethics committee approval had been G