title: Median effective dose (ED₅₀) of paracetamol and morphine for postoperative pain: a study of interaction.
abstract: BACKGROUND
  Paracetamol 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.
  
  
  METHODS
  Ninety 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  Our study showed that the combination of the paracetamol and morphine produces an additive analgesic effect. Clinical trial registration NCT01366313.
authors.affiliation: Department of Anaesthesiology, Procare Riaya Hospital, Lebanese University, Sport City Road, PO Box 20425, Al-Khobar 31952, Kingdom of Saudi Arabia.
authors.forename: A
authors.initials: A
authors.lastname: Zeidan
authors.forename: J X
authors.initials: JX
authors.lastname: Mazoit
authors.forename: M
authors.initials: M
authors.lastname: Ali Abdullah
authors.forename: H
authors.initials: H
authors.lastname: Maaliki
authors.forename: Th
authors.initials: T
authors.lastname: Ghattas
authors.forename: A
authors.initials: A
authors.lastname: Saifan
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage*; D000293:Adolescent; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage*; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage*; D010149:Postoperative Pain / Q000188:drug therapy*
chemical_list: D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D000082:Acetaminophen; D009020:Morphine
keywords: median effective dose; morphine; pain; paracetamol; postoperative