Anesthesia and anesthetics have the potential to influence drug pharmacokinetics through changes in body perfusion, hepatic and metabolic function, protein binding, and renal function. A chronically catheterized sheep preparation has been developed whereby blood flow through, and drug and oxygen extraction by, the heart and lungs, kidneys, gut, and liver can be measured. Thiopentone/halothane general anesthesia consistently decreased regional blood flow and extraction of test drugs by each of the organ groups. High subarachnoid anesthesia with tetracaine scarcely perturbed flow or function. Test drugs chosen were cefoxitin for kidney extraction, mepiridine for liver and kidney extraction, and chlormethiazole for liver, lung, and kidney extraction. It is suggested that the lack of effects of subarachnoid block on regional blood flow drug pharmacokinetics commend its use over general anesthesia for patients with limited cardiovascular or organ reserve. Further investigation of drug pharmacokinetics in surgical patients is still required so that deleterious effects are not experienced from drugs in use during the peroperative period.
- Blood flow
- Drug clearance
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