Propofol (mean dose 2.85 mg kg-1 h-1) was administered for 4 days by continuous i.v. infusion for sedation in 14 agitated and restless ICU patients. This provided rapid control of the level of sedation. When the infusion was discontinued, adequate recovery with response to commands was obtained in most patients by 10 min. Recovery times and the decrease in blood propofol concentration were similar after 24, 48, 72 and 96 h of infusion. Cumulative effects, tachyphylaxis, or other untoward effects were not observed.

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SERIOUS PROBLEMS arise frequently during anaesthesia for major vascular surgery associated with clamping of the aorta. Haemodynamic changes at the moment of recirculation are readily observed and have been the subject of numerous publications. 1-4 The hypotension, at times severe, that follows the unclamping of the aorta is not without danger for these arteriosclerotic and hypertensive patients. It is obvious that hypotension, even of short duration, can reduce cerebral, coronary or renal perfusion and jeopardize an otherwise successful operation.While the period of unclamping has been thoroughly examined, the events associated with clamping have not received much attention except for Perry's animal experiments, which showed decrease in cardiac output# The proximal occlusion of the aorta during operation for thoracic aneurysm can induce alarming increases in blood pressure and experienced anaesthetists will look for signs of left ventricular failure. The use of nitroprusside is often mandatory to relieve the acute afterload while the surgeon prepares a temporary bypass. It is not uncommon to see pulsus alternans, indicating ventricular failure probably due to discrepancy in regional perfusion of an already diseased myocardium.The clamping of the distal aorta also induces haemodynamic changes, the most obvious response again being the increase in systolic pressure due to an afterload which could be of clinical significance for these patients. With that in mind we decided to investigate the haemodynamic changes due to cross-clamping of the abdominal aorta. We also attempted to evaluate renal function during and following operation and to correlate changes, if any, to haemodynamic alterations. The latter will be the subject of a future publication. MATEBIAL AND METHODOLOGYEighteen patients requiring surgery of the abdominal aorta were included in this study. None presented clinical evidence of cardiac insufficiency or dysrythmia before operation. They were distributed at random in two groups involving nine Leriches and nine aneurysms of the infrarenal aorta. Anthropometrie data and type of surgery are summarized in Table I.After premedication with diazepam 5 mg intramuscularly, induction of anaesthesia was carried out with thiopentone 5 mg/kg, and pancuronium 0.15 mg/kg for tracheal intubation and muscular relaxation.

The pharmacokinetics of fusidic acid and 3-ketofusidic acid were investigated in cholestatic and noncholestatic patients after intravenous administration of single and multiple doses of 500 mg of sodium fusidate. The patients, all with low serum albumin levels, were divided into three groups. Group I consisted of six noncholestatic patients; group II consisted of nine mildly cholestatic patients with mild hepatic impairment (conjugated bilirubin, 47 pmol liter-l; alkaline phosphatase, 280 IU liter-'; y-tglutamyltranspeptidase, 190 IU liter-.); group m consisted of six benign intrahepatic cholestatic patients with high isolated conjugated hyperbilirubinemia (98.1 ,umol liter-'). Assays were performed by high-pressure liquid chromatography. At steady state, the mean peak concentrations in serum were 63.7, 44.9, and 92.2 tLg ml-l in groups I, II, and III, respectively; over a dosage interval, areas under the concentration-time curve were 411. 1, 238.7, and 603.4 t.g. h ml-' and the mean body clearances were 0.34, 0.53, and 0.25 ml min kg-' in groups I, II, and III, respectively. The accumulation ratio of fusidic acid increased from 2.8 and 2.4 in groups I and II to 4.2 in group II. At steady state, the ratios of the areas under the concentration-time curve from 0 to 8 h for 3-ketofusidic acid/fusidic acid were 0.11, 0.09, and 0.10 in the three groups, respectively. Only very small amounts of fusidic acid and 3-ketofusidic acid were found in urine. These results substantiate the following hypotheses. In group I and II patients the clearance is higher than that in healthy volunteers because of the increased free, unbound fraction of fusidic acid, a consequence of lower serum albumin concentrations, resulting in increased distribution in tissue and hepatic metabolism. In group MII patients, the higher bilirubinemia results in competition with fusidic acid for the limited glucuronidation mechanism, thus compensating for the increased elimination of fusidic acid because of the low serum albumin concentration. These results suggest that fusidic acid can be administered normally even to patients with high bilirubinemia because the postoperative serum albumin concentration is usually low.

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