title: Opioid Pharmacokinetics-Pharmacodynamics: Clinical Implications in Acute Pain Management in Trauma.
abstract: OBJECTIVE
  To evaluate acute traumatic pain protocols and to suggest optimization by characterizing opioid pharmacokinetics and pharmacodynamics (PK-PD).
  
  
  METHODS
  MEDLINE (1946 to November 2015), EMBASE (1974 to November 2015), International Pharmaceutical Abstracts (1970 to December 2014), and Cochrane Database of Systematic Reviews (2005 to November 2015).
  
  
  BACKGROUND
  morphine, hydromorphone, fentanyl, trauma, acute pain, intravenous, opioid, pharmacokinetics, and pharmacodynamics.
  
  
  METHODS
  Literature characterizing opioid PK-PD was included. Additionally, studies evaluatingoutcomes of opioids for acute severe pain in adult trauma patients were selected.
  
  
  RESULTS
  PK-PD literature suggests that morphine exhibits an effect delay of 1.6 to 4.8 hours; however, clinical significance is doubtful. The relative onset of morphine is approximately 6 minutes, and duration, 96 minutes. Morphine 0.1 mg/kg IV then 0.05 mg/kg every 5 minutes achieved pain control in 40% of patients at 10 minutes and 76% at 60 minutes. The effect delay of hydromorphone (orally) is 18 to 38 minutes; its relative onset (IV), 5 minutes; and duration, 120 minutes. Hydromorphone every 15 minutes achieved variable success in clinical trials. The effect delay of fentanyl IV is 16.4 minutes; relative onset, 2 minutes; and duration, 7 minutes. One randomized controlled trial used fentanyl 0.1 µg/kg IV every 5 minutes.
  
  
  CONCLUSIONS
  Further integration of opioid PK-PD into acutepain protocols is possible. One opioid should not be deemed more effective but rather titrated to effect. Morphine and hydromorphone can be titrated IV every 5 minutes until adequate pain control. Fentanyl can be titrated every 3 minutes.
authors.affiliation: Dalhousie University College of Pharmacy, Nova Scotia Health Authority, Central Zone,Pharmacy Department, Halifax, NS, Canada Meghan.MacKenzie@nshealth.ca.
authors.forename: Meghan
authors.initials: M
authors.lastname: MacKenzie
authors.affiliation: The University of British Columbia, Vancouver, BC, Canada.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Zed
authors.affiliation: The University of British Columbia, Vancouver, BC, Canada Children's and Women's Health Centre of British Columbia, Vancouver, BC, Canada.
authors.forename: Mary H H
authors.initials: MH
authors.lastname: Ensom
mesh_terms: D000701:Analgesics, Opioid / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D005283:Fentanyl / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D004091:Hydromorphone / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D009020:Morphine / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D059408:Pain Management; D010147:Pain Measurement; D014947:Wounds and Injuries / Q000503:physiopathology*
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine; D004091:Hydromorphone; D005283:Fentanyl
keywords: acute pain; opioids; pharmacodynamics; pharmacokinetics; trauma