title: Methylnaltrexone to prevent intrathecal morphine-induced pruritus after Caesarean delivery: a multicentre, randomized clinical trial.
abstract: BACKGROUND
  Intrathecal morphine-induced pruritus is a very common side-effect that is difficult to prevent or treat. Central and peripheral mechanisms are believed to be involved. The aim of this study was to determine if a peripherally acting, μ-opioid antagonist would reduce morphine-induced pruritus.
  
  
  METHODS
  We conducted a multicentre, randomized, blinded, placebo-controlled trial of women having elective Caesarean section under spinal anaesthesia with intrathecal morphine 100 μg. After delivery, participants received either subcutaneous methylnatrexone bromide 12 mg (MNTX group, n=69) or saline (placebo group, n=68). Pruritus, nausea, pain, analgesic use, and side-effects were assessed at 2, 4, 8, and 24 h. The primary outcome was the severity of pruritus (0-10 score).
  
  
  RESULTS
  One hundred and thirty-seven women completed the study, with five major protocol violations. There was no statistically significant difference between the MNTX and placebo groups for the median (IQR) pruritus AUC scores [24 (9-47) vs 36 (11-68), median difference 8.5, 95% confidence interval (CI) 0-20, P=0.09] or the worst pruritus score [3 (2-7) vs 5 (2-6), median difference 1, 95% CI 0-2, P=0.24]. The incidence of pruritus was 84% in the MNTX group and 88% in the placebo group (P=0.48). Analgesic and gastrointestinal outcomes did not significantly differ between the groups.
  
  
  CONCLUSIONS
  A single dose of subcutaneous methylnaltrexone bromide 12 mg did not reduce the overall severity or incidence of pruritus. In this study, treatment with a peripherally acting μ-opioid antagonist was generally ineffective against intrathecal morphine-induced pruritus, but a small clinical effect cannot be excluded.
  
  
  BACKGROUND
  Australian New Zealand Clinical Trials Registry (ACTRN12611000345987).
authors.affiliation: Pharmacology, Pharmacy and Anaesthesiology Unit, School of Medicine and Pharmacology, The University of Western Australia, Crawley, WA 6009, Australia Department of Anaesthesia and Pain Medicine, King Edward Memorial Hospital for Women, 374 Bagot Rd, Subiaco, WA 6008, Australia michael.paech@health.wa.gov.au.
authors.forename: M
authors.initials: M
authors.lastname: Paech
authors.affiliation: Department of Women's Anaesthesia, KK Women's and Children's Hospital, Singapore.
authors.forename: B
authors.initials: B
authors.lastname: Sng
authors.affiliation: Department of Anaesthesia and Pain Medicine, King Edward Memorial Hospital for Women, 374 Bagot Rd, Subiaco, WA 6008, Australia.
authors.forename: L
authors.initials: L
authors.lastname: Ng
authors.affiliation: Women and Infants Research Foundation, Perth, WA, Australia.
authors.forename: E
authors.initials: E
authors.lastname: Nathan
authors.affiliation: Department of Women's Anaesthesia, KK Women's and Children's Hospital, Singapore.
authors.forename: A
authors.initials: A
authors.lastname: Sia
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Carvalho
mesh_terms: D000328:Adult; D016362:Analgesia, Obstetrical / Q000379:methods; D000701:Analgesics, Opioid / Q000009:adverse effects; D000775:Anesthesia, Spinal / Q000379:methods; D001315:Australia; D002585:Cesarean Section; D005260:Female; D006801:Humans; D008875:Middle Aged; D009020:Morphine / Q000009:adverse effects*; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000627:therapeutic use; D011183:Postoperative Complications / Q000139:chemically induced / Q000517:prevention & control*; D011247:Pregnancy; D011537:Pruritus / Q000139:chemically induced* / Q000517:prevention & control*; D000644:Quaternary Ammonium Compounds / Q000627:therapeutic use; D012846:Singapore; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds; C032257:methylnaltrexone; D009271:Naltrexone; D009020:Morphine
keywords: analgesics, opioid, morphine; antipruritics; quaternary ammonium compounds, methylnaltrexone