The effect of cocaine and morphine on hepatic injury from subanesthetic halothane and isoflurane in the guinea pig

Hepatic injury may occur with cocaine, morphine or halothane administration. Theoretical considerations suggest that the combined administration of these agents might provoke enhanced hepatic injury. To investigate this we studied the time course (4-96 hours) of plasma isocitrate dehydrogenase activity (ICDH) in eight groups of guinea pigs (total 96) given either intra-peritoneal saline, cocaine (30 mg/Kg), morphine (100 mg/Kg) or a combination there of and then exposed to either 40% oxygen alone or with halothane 0.3% or isoflurane 0.4% for a period of 4 hours. Cocaine plus morphine (at 4, 24 and 48 hr), halothane (at 24 and 48 hr), or isoflurane (at 4hr) administration resulted in significant ICDH elevations. Cocaine sped the onset (at 4 hr) but did not enhance the hepatic injury from halothane (at 24 and 48 hr). Cocaine prolonged (at 48 hr) the hepatic injury from isoflurane. Morphine resulted in less hepatic injury than cocaine when administered with isoflurane (at 4hr). The a priori hypothesis could not be demonstrated. This study suggests that cocaine may provoke earlier hepatic injury from halothane and prolong hepatic injury from isoflurane in guinea pigs.