title: Morphine metabolism after major liver surgery.
abstract: BACKGROUND
  Impaired metabolism of morphine may lead to an increase in sedation and respiratory depression.
  
  
  METHODS
  In the present study we investigated morphine pharmacokinetics in patients who had undergone liver resection (n = 15) compared to a control group undergoing colon resection (n = 15). Morphine was administered IV by patient-controlled analgesia. Plasma concentrations of morphine, morphine-6-glucuronide, and morphine-3-glucuronide were measured 2-3 times daily for the first two postoperative days. Pain intensity scores were assessed three times daily and respiratory rate and sedation scores every third hour.
  
  
  RESULTS
  There were no differences in morphine requirements 1.1 (0.8-2.5 [median, interquartile range]) mg/h (liver resection) and 1.5 (1.1-1.7) mg/h (colon resection) [P = 0.84]) or in pain intensity scores (P > 0.3) between the groups. Plasma morphine concentrations were higher in patients undergoing liver resection than in the control group (P < 0.01) reflecting a lower rate of morphine metabolism. Plasma morphine concentrations were correlated with the volume of liver resection (P < 0.02). However, plasma concentrations of morphine-6-glucuronide and morphine-3-glucuronide did not differ between the groups (P = 0.62 and P = 0.48, respectively). There was a higher incidence of sedation (P = 0.02), but not respiratory depression (P = 0.48), after liver resection.
  
  
  CONCLUSIONS
  The study demonstrates that plasma concentrations of morphine are higher in patients undergoing liver resection compared with patients undergoing colon resection. Sedation scores were higher in patients undergoing liver resection. Caution is therefore recommended when administering morphine to this patient group.
authors.affiliation: Department of Anesthesiology and Intensive Care, Lund University Hospital, Lund, Sweden. asa.rudin@skane.se
authors.forename: Asa
authors.initials: A
authors.lastname: Rudin
authors.forename: Johan F
authors.initials: JF
authors.lastname: Lundberg
authors.forename: Margareta
authors.initials: M
authors.lastname: Hammarlund-Udenaes
authors.forename: Per
authors.initials: P
authors.lastname: Flisberg
authors.forename: Mads U
authors.initials: MU
authors.lastname: Werner
mesh_terms: D000368:Aged; D016058:Analgesia, Patient-Controlled; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000378:metabolism* / Q000627:therapeutic use; D010149:Postoperative Pain / Q000188:drug therapy / Q000378:metabolism*; D011446:Prospective Studies
chemical_list: D009020:Morphine