title: Duloxetine reduces morphine requirements after knee replacement surgery.
abstract: BACKGROUND
  Multimodal analgesia is advocated for perioperative pain management to reduce opioid use and its associated adverse effects. Serotonin and norepinephrine are involved in the modulation of endogenous analgesic mechanisms via descending inhibitory pain pathways in the brain and spinal cord. An increase in serotonin and norepinephrine may increase inhibition of nociceptive input and improve pain relief. Duloxetine, a selective serotonin and norepinephrine reuptake inhibitor, has demonstrated efficacy in chronic pain conditions such as painful diabetic neuropathy and post-herpetic neuralgia. The objective of the study was to evaluate the efficacy of duloxetine in reducing morphine requirements in patients after knee replacement surgery.
  
  
  METHODS
  Fifty patients received either two doses of oral duloxetine 60 mg (2 h before surgery and on first postoperative day) or placebo. All patients received patient-controlled analgesia with morphine for 48 h after operation. Pain and adverse effects were assessed at 0.5, 1, 2, 6, 12, 24, and 48 h after surgery on an 11-point numeric rating scale.
  
  
  RESULTS
  Twenty-three patients in the duloxetine group and 24 patients in the placebo group completed the study. Morphine requirements during the 48 h after surgery were significantly lower in the duloxetine group [19.5 mg, standard deviation (sd) 14.5 mg] compared with the placebo group (30.3 mg, sd 18.1 mg) (P=0.017). There were no statistically significant differences between the groups in pain scores (at rest and on movement) or in adverse effects.
  
  
  CONCLUSIONS
  Perioperative administration of duloxetine reduced postoperative morphine requirements during the first 48 h after knee replacement surgery, without significant adverse effects.
authors.affiliation: Department of Anaesthesiology, Singapore General Hospital, Outram Road, Singapore. ho.kok.yuen@sgh.com.sg
authors.forename: K-Y
authors.initials: KY
authors.lastname: Ho
authors.forename: W
authors.initials: W
authors.lastname: Tay
authors.forename: M-C
authors.initials: MC
authors.lastname: Yeo
authors.forename: H
authors.initials: H
authors.lastname: Liu
authors.forename: S-J
authors.initials: SJ
authors.lastname: Yeo
authors.forename: S-L
authors.initials: SL
authors.lastname: Chia
authors.forename: N-N
authors.initials: NN
authors.lastname: Lo
mesh_terms: D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D000328:Adult; D000368:Aged; D016058:Analgesia, Patient-Controlled / Q000379:methods; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects; D019645:Arthroplasty, Replacement, Knee; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000068736:Duloxetine Hydrochloride; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage* / Q000009:adverse effects; D010147:Pain Measurement / Q000379:methods; D010149:Postoperative Pain / Q000517:prevention & control*; D011182:Postoperative Care / Q000379:methods; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D013876:Thiophenes / Q000008:administration & dosage* / Q000009:adverse effects; D055815:Young Adult
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000701:Analgesics, Opioid; D000068736:Duloxetine Hydrochloride; D009020:Morphine; D017367:Selective Serotonin Reuptake Inhibitors; D013876:Thiophenes