title: Assessing analgesia in single and repeated administrations of propacetamol for postoperative pain: comparison with morphine after dental surgery.
abstract: We conducted this double-blinded, randomized study to assess the analgesic effect of repeated administrations of paracetamol, administered as propacetamol, an injectable prodrug formulation of paracetamol, and to compare this with the analgesic effects of morphine. Patients experiencing moderate to severe pain after elective surgical removal of bone-impacted third-molar teeth under general anesthesia were randomly assigned to receive IV propacetamol 2 g (n = 31), IM morphine 10 mg (n = 30), or placebo (n = 34). Five hours later, the treatments were readministered at half of the previous dosages. Standard measures of analgesia were collected repeatedly for 10 h. Propacetamol and morphine were significantly more effective than placebo in all primary measures of analgesia over 5 h after the first administration and globally over 10 h (first and second administrations). After the first dose, 21 of the 34 patients in the placebo group required rescue medication, compared with 6 of the 31 in the propacetamol group (P < 0.0009) and 4 of the 30 in the morphine group (P < 0.0001). No statistically or clinically significant differences were found between propacetamol and morphine for any sum or peak measures of analgesia. No serious adverse events were reported; adverse events were significantly less frequent in the propacetamol group than in the morphine group (P < 0.027). Propacetamol administered IV in repeated doses (2 g followed by 1 g) has a significant analgesic effect that is indistinguishable from that of morphine administered IM (10 mg followed by 5 mg) after dental surgery, with better tolerability.
  
  
  CONCLUSIONS
  After moderately painful surgical procedures, IV paracetamol, administered as propacetamol, may be an asset in the control of acute postoperative pain.
authors.affiliation: *Department of Anesthesiology and Intensive Care Medicine, University Hospital, University of Münster, Germany; †University Medical Center, Acadmish Ziekenhuis, Medical Intensive Care Unit, Amsterdam, the Netherlands; and ‡Department of Anesthesiology, University Hospital, Leuven, Belgium.
authors.forename: Hugo
authors.initials: H
authors.lastname: Van Aken
authors.forename: L
authors.initials: L
authors.lastname: Thys
authors.forename: Luc
authors.initials: L
authors.lastname: Veekman
authors.forename: Hartmut
authors.initials: H
authors.lastname: Buerkle
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D008964:Molar, Third / Q000601:surgery; D009020:Morphine / Q000008:administration & dosage / Q000627:therapeutic use*; D010147:Pain Measurement / Q000187:drug effects; D010149:Postoperative Pain / Q000188:drug therapy*; D015656:Respiratory Mechanics / Q000187:drug effects; D014081:Tooth Extraction
chemical_list: D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000082:Acetaminophen; C063776:propacetamol; D009020:Morphine