Lack of analgesic effect of paracetamol for palliative patients requiring high-dose opioids: A randomised controlled trial

The usefulness of the addition of paracetamol for pain relief in palliative patients already requiring high-dose opioids is questionable. This study investigated potential analgesic benefits from 4g paracetamol tablets daily for patients using at least 200mg of oral morphine equivalent daily. Thirty-one patients were recruited to the prospective, double-blinded, randomised crossover trial. They received usual medications plus 4g paracetamol or placebo for five days each in random order. Primary outcome, effect on pain, was assessed using daily diaries including numeric rating scales [NRS] from 0 [no pain] to 10 [unbearable] and recording numbers of breakthrough analgesics. Secondary outcomes - nausea, vomiting, cognitive impairment, constipation and overall well-being were assessed similarly, Data from the last four days of each treatment were analysed. Patients indicated in which part of the study their pain was better controlled. Twenty-two patients completed the trial. There were no significant order or treatment by order interaction effects for any variable; paired t-tests were conducted to investigate change in mean levels on outcome variables with placebo vs paracetamol. For none of the variables was there a statistically significant difference when assessed with placebo compared to paracetamol. No change approached clinically significant levels, with a mean difference in rated pain of 0.16, and mean difference of 0.42 for number of breakthrough medications. Fifteen patients were undecided whether paracetamol improved pain. These data do not support the common practice of adding regular paracetamol daily as an adjunct to high-dose strong opioids for pain control in palliative cancer patients.

This has been published since as:
Fiona J. Israel, Greg Parker, Margaret Charles, and Liz Reymond. Lack of Benefit From Paracetamol (Acetaminophen) for Palliative Cancer Patients Requiring High-Dose Strong Opioids: A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial. Journal of Pain and Symptom Management, Vol. 39 No. 3 March 2010