Median effective dose (ED50) of paracetamol and morphine for postoperative pain: A study of interaction

BackgroundParacetamol is widely used to treat postoperative pain and is well known for its morphine-sparing effect. Therefore, the effect of morphine-paracetamol combination can be synergistic, additive, or infra-additive. The primary aim of our study is to define the median effective analgesic doses (ED50s) of paracetamol, morphine, and the combination of both. Also, the nature of the interaction for postoperative pain after moderately painful surgery using an up-and-down method and isobolographic analysis was determined.MethodsNinety patients, undergoing moderately painful surgery, were included in one of the three groups. Determination of the median ED50s was performed by the Dixon and Mood up-and-down method. Initial doses were 1.5 g and 5 mg, with dose adjustment intervals of 0.5 g and 1 mg, in the paracetamol and morphine groups, respectively. The initial doses of paracetamol and morphine were 1.5 g and 3 mg, in the paracetamol-morphine combination group with dose adjustment intervals of 0.25 g for paracetamol and 0.5 mg for morphine. Analgesic efficacy was defined as a reduction to or <3 on a 0-10 numeric rating scale, 45 min after the beginning of drug administration. Isobolographic analysis was used to define the nature of their interaction.ResultsThe median ED50s of paracetamol and morphine were 2.1 g and 5 mg, respectively. The median ED50 of the combination was 1.3 g for paracetamol and 2.7 mg for morphine.ConclusionsOur study showed that the combination of the paracetamol and morphine produces an additive analgesic effect.Clinical trial registrationNCT01366313. © 2014 The Author.