title: Platelet dysfunction after intravenous ketorolac or propacetamol.
abstract: BACKGROUND
  Paracetamol is a weak cyclo-oxygenase inhibitor in vitro. A recent study in children has shown that high doses of paracetamol are effective and safe. We studied the effect of propacetamol on haemostasis in adult volunteers.
  
  
  METHODS
  Ten volunteers were investigated in a double-blind, randomized, crossover study. They received propacetamol 60 mg kg(-1) or ketorolac 0.4 mg kg(-1) in saline i.v. (30 min) in two different sessions. Platelet function was evaluated before the test infusion (S-0), two (S-2) and 24 h (S-24) after the start of the infusion. Coagulation parameters (PT, APTT, factor V and VII activities) were measured at S-0, S-24 and 48 h (S-48).
  
  
  RESULTS
  One of the volunteers had no secondary platelet aggregation in S-0 and was excluded from the final analysis. Two hours (S-2) after propacetamol and ketorolac administration the adrenaline (0.9 microg ml(-1) and 9.0 microg ml(-1)) induced maximal platelet aggregation was decreased compared with S-0. At S-2 platelet aggregation was inhibited more after ketorolac than after propacetamol. At 24 h after ketorolac, but not after propacetamol, there was still a decrease in the adrenaline-induced maximal platelet aggregation. Propacetamol did not affect adenosine diphosphate (ADP)-induced maximal platelet aggregation, whereas ketorolac decreased 3 and 6 microM ADP-induced maximal platelet aggregation at S-2 and S-24. However, 2 h after both ketorolac and propacetamol, thromboxane B2 (TxB2) concentration decreased in platelet rich plasma after 5 min aggregation induced by 8 microM ADP. Coagulation was unaffected.
  
  
  CONCLUSIONS
  Propacetamol 60 mg kg(-1) i.v. causes reversible platelet dysfunction demonstrated by a decrease in maximal platelet aggregation and TxB2 concentration. After 0.4 mg kg(-1) ketorolac i.v. platelet aggregation and TxB2 formation are inhibited more in comparison with propacetamol, and platelet dysfunction is still seen after 24 h.
authors.affiliation: Department of Anaesthesiology, Helsinki University Central Hospital, Finland.
authors.forename: T T
authors.initials: TT
authors.lastname: Niemi
authors.forename: J T
authors.initials: JT
authors.lastname: Backman
authors.forename: M T
authors.initials: MT
authors.lastname: Syrjälä
authors.forename: L U
authors.initials: LU
authors.lastname: Viinikka
authors.forename: P H
authors.initials: PH
authors.lastname: Rosenberg
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects / Q000031:analogs & derivatives*; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001792:Blood Platelets / Q000187:drug effects*; D018592:Cross-Over Studies; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D004311:Double-Blind Method; D006801:Humans; D007262:Infusions, Intravenous; D020910:Ketorolac / Q000009:adverse effects*; D008297:Male
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D000082:Acetaminophen; C063776:propacetamol; D020910:Ketorolac