Clinical and laboratory studies on propofol

University dissertation from Linköping : Linköpings universitet

Abstract: Patients undergoing major abdominal surgery were randomly given total intravenous anaesthesia based on propofol and fentanyl, anaesthesia based on propofol, fentanyl and nitrous oxide or anaesthesia based on isoflurane and fentanyl. Postoperative atelectasis demonstrated by computed tomography of the chest was found to a similar extent and a similar decrease in arterial oxygen pressure was seen in the groups. No correlation was seen between the size of atelectasis and postoperative oxygen pressure. Cardiovascular stability was equally well maintained during surgery, but the patients anaesthetized with propofol needed more ephedrine and glycopyrrolate to achieve stability. In all groups the Acute Physiology Score was normal by day I (range 1-7). A similar impairment of bowel function after operation was found, with passage of gas day 3 ( 1-6) and tolerance of enteral intake day 5 (1-10). Hospital stay 11 (6-45) days and incidence of complications were unaffected by anaesthetic technique. Early recovery was similar in the three groups, but patients anaesthetized with propofol reported fewer symptoms, better subjective control and a higher degree of socially orientation than patients anaesthetized with isoflurane. On the whole, the advantages with propofol compared to isoflurane were small, and the addition of nitrous oxide to propofol had no influence on. the results.Laboratory tests on human leucocytes, cultured human glial cells and rat glial cells and neurons were performed with propofol in concentrations between 0.3 ~g·ml" and 50 ~g·ml" (1.7 to 280 ~M). Clinically relevant concentrations of propofol decreased random and chemotactic locomotion of leucocytes in an agarose assay. Concentration dependent and reversible effects of propofol were found on the actin distribution of the cytoskeleton in cultured cells. The maximal effect was seen after 20 min of incubation. Using a single cell microfluorometric method with Fura2 an increase in cytosolic free calcium in rat neurons was seen immediately after the addition of propofol, lasting 128±39 seconds and thereafter returning to normal. This effect was dual, 60-7 5% of the increase came from the extracellular buffer and the remaining part from intracellular stores. A rise in intracellular calcium can lead to changes in the cytoskeleton and to hyperpolarization of a neuron.

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