Morphine metabolism after major liver surgery

Impaired metabolism of morphine may lead to an increase in sedation and respiratory depression.

In the present study we investigated morphine pharmacokinetics in patients who had undergone liver resection (n = 15) compared to a control group undergoing colon resection (n = 15). Morphine was administered IV by patient-controlled analgesia. Plasma concentrations of morphine, morphine-6-glucuronide, and morphine-3-glucuronide were measured 2-3 times daily for the first two postoperative days. Pain intensity scores were assessed three times daily and respiratory rate and sedation scores every third hour.

There were no differences in morphine requirements 1.1 (0.8-2.5 [median, interquartile range]) mg/h (liver resection) and 1.5 (1.1-1.7) mg/h (colon resection) [P = 0.84]) or in pain intensity scores (P > 0.3) between the groups. Plasma morphine concentrations were higher in patients undergoing liver resection than in the control group (P < 0.01) reflecting a lower rate of morphine metabolism. Plasma morphine concentrations were correlated with the volume of liver resection (P < 0.02). However, plasma concentrations of morphine-6-glucuronide and morphine-3-glucuronide did not differ between the groups (P = 0.62 and P = 0.48, respectively). There was a higher incidence of sedation (P = 0.02), but not respiratory depression (P = 0.48), after liver resection.

The study demonstrates that plasma concentrations of morphine are higher in patients undergoing liver resection compared with patients undergoing colon resection. Sedation scores were higher in patients undergoing liver resection. Caution is therefore recommended when administering morphine to this patient group.