Morphine elimination and hepatic blood flow--a study in patients with portal hypertension

To investigate the influence of changes in portal venous blood flow on the clearance of morphine, the elimination of a single intravenous dose of morphine sulphate was studied in twelve patients with periportal fibrosis undergoing distal splenorenal shunt for portal hypertension. All patients had almost normal preoperative liver function. Six patients (Group A) received morphine after induction of anesthesia but before surgery; a further six patients (Group B) received morphine after completion of the splenorenal shunt and removal of all vascular clamps. Blood was sampled for 24 hours after morphine administration and analysed for plasma morphine concentration using high performance liquid chromatography. The maximum concentration of morphine was significantly greater in those patients in Group B who received morphine after the shunt (P < .002). Clearance of morphine during the operation was also significantly reduced in these patients compared with the initial clearance (before release of the clamps) in Group A (P < .004). As a consequence of these changes the AUC was greater in this group (P < 0.004). However, there were no differences with the elimination rates after surgery had finished. The results suggest that in individuals with normal liver function, the clearance of morphine is dependent on hepatic blood flow.