Randomized, double-blind, placebo-controlled study of the effect of rectal paracetamol on morphine consumption after abdominal hysterectomy

Background: Paracetamol is widely used for postoperative analgesia. The effect is well documented in minor and moderate extensive surgery, but the effect of paracetamol as an adjunct to opioids in major abdominal surgery is less examined. Methods: Seventy-eight patients scheduled for elective, benign, and abdominal hysterectomy were included in a prospective, randomized, double-blind, parallel group, placebo-controlled study to evaluate the effect of rectal paracetamol in conjunction with intravenous patient-controlled analgesia (PCA) morphine. Paracetamol 1000 mg or placebo suppositories were given four times daily during the 60-h study period. I.V. morphine was administered via a PCA pump, limited to maximum of 12 mg h(-1) . Morphine consumption, pain and morphine-related adverse effects were recorded. A single-point analysis was comprised of serum concentrations of paracetamol and morphine. Results: Sixty patients were evaluated: 30 in each group. A 16.6% reduction in overall-accumulated morphine consumption in the treatment group (99.6 vs. 83.3 mg) was observed (NS, P=0.06). Mean paracetamol serum concentration was 0.03 mmol l(-1) (range: 0.01-0.06 mmol l(-1)). None of the patients had a paracetamol concentration within the therapeutic range for antipyretic efficacy. Patients with a higher paracetamol concentration had a lower concomitant morphine (P=0.025) and morphine-6-glucuronide (P=0.014) concentration 2 h after paracetamol administration. Conclusions: A dosage of rectal paracetamol 1000 mg four times daily is too low, as all displayed a suboptimal serum paracetamol concentration. To study the effect of rectal paracetamol after major surgery we have to increase the dose, as higher serum concentrations of paracetamol may cause lower serum concentrations of morphine.