The clinical effects and pharmacokinetics of ketamine, administered as an i.v. infusion, were studied in 31 patients. Anaesthesia was induced with ketamine 2 mg kg-1 i.v. and maintained using an i.v. infusion of ketamine, supplemented by nitrous oxide. The plasma concentrations of ketamine, nor-ketamine and dehydro-nor-ketamine were analysed using gas-liquid chromatography. The average maintenance dose of ketamine was 41 +/- 21 microgram kg-1 min-1, but there was an obvious decrease in the dose required as anaesthesia progressed. This dose gave a stable plasma concentration of ketamine of 9.3 +/- 0.8 mumol litre-1. Patients recovered at 2.7 +/- 0.9 mumol litre-1. Plasma half-life of ketamine was 79 +/- 8 min. Maximum concentration of nor-ketamine was 4.7 +/- 2.4 mumol litre-1 and of dehydro-nor-ketamine 3.2 +/- 1.9 mumol litre-1. There were transient increases (15-30% of pre anaesthetic values) in arterial pressure, heart rate and cardiac output during operation. No post-operative respiratory depression was seen.

The radioactive microsphere technique was applied to determine simultaneous cardiac output and flow distribution in the rat. Left ventricular injections of large numbers of microspheres were given, without significant adverse effects, allowing determination of flow to organs and tissues with low perfusion rates. In order to determine coronary blood flow it was necessary to excise the inner lining of the left ventricle, thus eliminating activity from deposits of microspheres. Cardiac output determination showed less variation with the sampling catheter in the abdominal aorta than in the femoral artery. It is concluded that the microsphere method can be conveniently used for nemo-dynamic studies in the rat, and that the abdominal aorta is the preferred site for the placement of the reference catheter in the rat.

A transient arrest of arterial blood flow can be accomplished by intra-arterial injection of a new type of degradable microspheres. The effects of single and multiple injections of these microspheres into rat hepatic arteries were studied by measurement of fractional cardiac output distribution and ¹³³Xe washout from the liver before and after embolization. Injection of these microspheres into the hepatic artery caused a significant but transient reduction of the arterial blood flow to the liver. Repetition of the injection several times over several days produced identical effects on each embolization. No signs of hepatic cell damage were detected after repeated embolization, as suggested by assay of the serum enzymes or the Brom-sulphalein retention test.

A new method for intermittent hepatic arterial flow arrest has been used in combination with intraarterial 5-fluorouracil (5-Fu) for the treatment of secondary liver neoplasms in 12 patients. Polysaccharide microspheres with a half-life of 1 h were infused together with 5-Fu via a percutaneously introduced catheter into the hepatic artery. There were no significant side effects to the treatment. Clinical effects and overall survival were comparable to those of hepatic artery ligation.

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