Microdialysis and Intensive Care. Clinical and experimental studies

Detta är en avhandling från Dept of Anaesthesiology and Intensive Care. University Hospital, SE-221 85 LUND, Sweden

Sammanfattning: Microdialysis was used to monitor local concentrations of energy metabolites in different organs, and to study the pharmacokinetics of morphine over the blood-brain barrier in intact and injured brain tissue in conditions treated in the Intensive Care Unit. After major abdominal or thoracoabdominal surgery, postoperative thoracic epidural analgesia resulted in higher glycerol concentrations in the deltoid subcutaneous adipose tissue, implying increased lipolysis, on the third postoperative day as compared to intravenous infusion of morphine, possibly due to a locally increased sympathetic tone. In patients with severe traumatic brain lesions, the correlation between the glucose concentrations in blood and abdominal subcutaneous adipose tissue was poor during the first 6 hours of intensive care, with lower levels in the tissue than in blood. Experimental pancreatitis in the rat immediately increased the interstitial concentrations of glucose and lactate in the pancreas. In the small intestine, a remote organ, a significant increase of lactate and the lactate/pyruvate ratio started already one hour after induction of pancreatitis. Experimental meningitis in the piglet increases the exposure of the brain to unbound morphine. The terminal half-life for unbound morphine in the brain was similar during meningitis and the control period. Significant decreases in relative recovery for nalorphine during meningitis and for morphine in traumatized brain tissue in humans as compared to relatively intact brain tissue was demonstrated. In the human brain, pharmacokinetic evidence of active efflux of unbound morphine over the blood-brain barrier was found. The terminal half-life for unbound morphine was longer than in plasma and unaffected by brain tissue trauma. The time to maximum concentration for unbound morphine was longer in the uninjured brain tissue as compared to the subcutaneous adipose tissue. In some patients there was an increased morphine exposure in the extracellular fluid in the human brain. This was not seen in uninjured brain tissue in patients with surgically evacuated focal mass lesions.

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