Intravenous versus intraperitoneal morphine before surgery to provide postoperative pain relief

Opioid receptors have been demonstrated on peripheral afferent nerves throughout the body. The aim of the present study was to compare the effects of intravenous and intraperitoneal administration of morphine with regard to pain, postoperative morphine requirement, and recovery after major abdominal surgery, and to describe the pharmacokinetics of intraperitoneal morphine in humans.

In a double-blind manner, 30 patients scheduled for major abdominal surgery were randomized to either 50 mg of morphine intravenously (i.v.) or 50 mg of morphine intraperitoneally (i.p.) before operation. Pain was measured on a visual analogue scale and morphine requirements were registered for 3 days. Recovery was measured as time to oral intake of food, time to flatulence and days in hospital. Plasma morphine, morphine-3-glucuronide, and morphine-6-glucuronide concentrations were determined during the first 4 h after morphine administration.

During the first postoperative hours there was less pain at rest (P = 0.02) and on coughing (P = 0.004) in the intravenous group. The requirement of additional morphine (P = 0.016) was lower in the intravenous group during the first postoperative day. No major differences in recovery were seen. The plasma concentrations of morphine measured as area under the curve (AUC) during the first 4 h were similar, but the intravenous group showed significantly higher concentrations of the active metabolite morphine-6-glucuronide, (P = 0.016), indicating a difference in pharmacokinetics after intraperitoneal compared to intravenous administration of morphine.

Intraperitoneal administration of 50 mg of morphine before major abdominal surgery is less efficient in reducing pain and postoperative morphine requirements than the same amount of morphine given intravenously.