Lack of Benefit From Paracetamol (Acetaminophen) for Palliative Cancer Patients Requiring High-Dose Strong Opioids: A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial

Abstract

Context The adjunctive use of paracetamol (acetaminophen) with strong opioids has become entrenched practice in palliative care pain management, despite little evidence to support its use. Objective The study aim was to investigate potential analgesic benefits of 4 g of paracetamol daily for palliative cancer patients requiring high-dose opioids. Methods Thirty-one patients, using at least 200 mg of oral morphine equivalent daily, were recruited to a prospective, double-blinded, randomized, crossover trial. Patients received usual medications plus 4 g of paracetamol or placebo for five days each in random order. Primary outcome, effect on pain, was assessed using daily diaries, including a numerical rating scale (NRS) from zero (no pain) to 10 (unbearable) and recording numbers of breakthrough analgesics. Secondary outcomes-nausea, vomiting, cognitive impairment, constipation, and overall well-being-were assessed using the NRS. Data from the last four days of each treatment were analyzed. Patients also indicated in which part of the study their pain was better controlled. Results Twenty-two patients, requiring a median dose of 255 mg of oral morphine equivalent daily, 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 with paracetamol. No change approached clinically significant levels, with a mean difference in rated pain of 0.16, and mean difference of 0.42 for a number of breakthrough medications. Fifteen patients were undecided whether paracetamol improved pain. Conclusions These data do not support the common practice of adding regular paracetamol daily as an adjunct to high-dose opioids for pain control in cancer patients receiving palliative care.