Effective Analgesia at What Cost? A study of narcotic induced delay of gallbladder emptying I To identify the ideal analgesic for treating biliary tract pain, a double-blind crossover trial was conducted to determine the effects of 4 narcotic agents on cholecystokinin octapeptide (CCK-OP) ptimulated gallbladder emptying in 8 healthy volunteers. Subjects received boluses of saline (2ml), morphine 7.5mg, pethidine 70mg, pentazocine 40mg or butorphanol 1.5mg added to a continuous intravenous saline infusion . 30 minutes later cholecystokinin octapeptide ('kinevac') infusion was started, with infusion rates increasing every 15 min to deliver 10, 20, 40, 70 and 110 ng/kg/hour. Five investigations at ~ 3-day intervals were conducted in each subject, one treatment being studied on each occasion, in random order.

Morphine caused the most marked delay in CCK-OP induced gallbladder emptying with a 90 minute delay. Pentazocine, pethidine and butorphanol all exhibited similar delays except at 60 minutes (40 ng/ kg/hour CCK-OP infusion rate) postdose when butorphanol produced a significantly shorter delay. There was no significant change in common bile duct diameter or biochemical parameters with any agent. Only morphine produced a significant change in gallbladder volume; a 13-15% increase was seen after the morphine injection and before the CCK-OP infusion, and a significant increase, compared with saline, was maintained throughout the study.

Narcotic-induced delays in gallbladder emptying may be mediated directly through opiate receptors in the sphincter of Oddi or through anticholinergic effects in the gallbladder wall, and most probably through a combination of these effects.

The results of the study confirm that morphine should be avoided in biliary disorders. The other analgesics studied were shown to affect the gallbladder to a lesser extent than morphine and can thus be recommended for use in biliary analgesia until a more acceptable analgesic is developed. Hahn M, Baker R , Sullivan S. Alimentary Pharmacology and Therapeutics 2: 129·134, Apr 1988 7123

0156-2703/ 88/ 0702-0015/0$01.00/0 © ADIS Press INPHARMA" 2 July 1988 15