Clinical and Laboratory Studies on Propofol

Abstract

Abstract: The aims of this study were to assess the suitability during major surgery of an intravenous anaesthetic technique based on propofol and to study the influence of this technique on early and late recovery, on postoperative bowel and lung function, and on the incidence of complications. Further, the effects of propofol were evaluated on the migration ability of human leucocytes, and on the cytoskeletal organization and the intracellular calcium ion concentration of cultured cells.Patients undergoing major abdominal surgery were randomly given either total intravenous anaesthesia based on propofol and fentanyl, or 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 1 (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 social orientation than patients anaesthetized with isoflurane.Clinically relevant concentrations of propofol decreased random and chemotactic locomotion of leucocytes in an agarose assay. Concentration dependent and reversible effects of propofol (concentrations between 0.3μg·ml‐1 and 50 μg·ml‐1(1.7 to 280μM) were found on the actin distribution of the cytoskeleton in cultured cells. The maximal effect was seen after 20 min. of incubation. 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, 60–75% 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 neurons.