The morphine-sparing effect of propacetamol in orthopedic postoperative pain

The analgesic efficacy and safety of propacetamol (Pro-Dafalgan), an injectable prodrug of acetaminophen, in combination with morphine administered by patient-controlled analgesia (PCA) were studied in 60 patients (56 men, 4 women; age 18–40 years; mean age, 26 years) after knee ligamentoplasty. Using a double-blind, randomized, parallel-group design, the effects of four (every 6 hr) intravenous injections of 2 g propacetamol (= 1 g acetaminophen) were compared with four injections of placebo (PL) in the recovery room immediately after surgery. Efficacy was assessed over 24 hr by automatic recording on the PCA device of the cumulative dose of morphine and the number of boluses requested. It was also assessed on pain scores rated on a five-point verbal scale and a visual analogue scale before administration, at 1, 2, 3, and 4 hr, and then every 2 hr until the 24th hr after administration. A five-point global efficacy scale was also administered. Any side effects were recorded throughout the duration of the study, and the ability to tolerate the drug was assessed by recording arterial pressure, cardiac and respiratory frequency, and sedation at the same assessment times as the pain scores. The 24-hr morphine consumption was significantly decreased in the propacetamol group (number of 1 mg boluses: 14.7 ± 11.3 versus 23.2 ± 13.8, P = 0.01; PCA usage: 26.4 ± 12.3 mg versus 34.6 ± 15.4 mg, P = 0.03; PCA usage + titration: 34.5 ± 12.7 mg versus 43.1 ± 15.9 mg, P = 0.02). Analysis of the hourly morphine doses showed a significant decrease from the fourth hr. There was no difference in pain scores between the two groups. Although there was also no significant difference in the global efficacy score, 75 % of patients in the propacetamol group versus 58% ( P = 0.21) found it “good” or “very good.” No difference was observed in safety criteria and four side effects were recorded: one in the propacetamol group and three in the placebo group. In conclusion, propacetamol has demonstrated a morphinesparing effect (⋍ 37%) in orthopedic postoperative pain, thus confirming that it is a useful and safe injectable non-NSAID, nonopioid analgesic in postoperative period.