Effect of surgery under general anaesthesia on antipyrine clearance.

1 The effect of surgery under general anaesthesia on drug metabolism was investigated in man. The activity of hepatic drug-metabolizing enzymes was evaluated by measurement of antipyrine clearance, before surgery and 3 days after surgery, in eighteen patients. 2 In those patients in whom the operation lasted 2 h or less, the postoperative clearance of antipyrine was significantly (P less than 0.05) increased by 48%; in those patients in whom the operation lasted 2--4 h, it was non-significantly decreased by 36%; in those patients in whom the operation lasted more than 4 h, it was significantly decreased by 47% (P less than 0.01). 3 It is concluded (a) that short operations are followed by increased activity of hepatic drug-metabolizing enzymes, whereas (b) protracted operations are followed by decreased activity. It is suggested (a) that the former effect may be a consequence of enzyme induction by drugs used for premedication and anaesthesia, whereas (b) the latter effect may be the result of major surgical trauma.