title: Is the clinical efficacy of epidural diamorphine concentration-dependent when used as analgesia for labour?
abstract: BACKGROUND
  The physicochemical properties of diamorphine (3,6-diacetylmorphine) enhance its bioavailability compared with more lipid-soluble opioids when administered into the epidural space. However, the influence of concentration, volume or mass on the clinical efficacy of diamorphine is not known.
  
  
  METHODS
  In this double-blind, randomized, prospective study, 62 women in active labour and </=5 cm cervical dilatation were recruited to determine whether the mode of action of diamorphine in the epidural space is concentration-dependent. After insertion of a lumbar epidural catheter, patients received epidural diamorphine 3 mg either as a high-volume, low-concentration solution (group A) or a low-volume, high-concentration solution (group B). The concentration of diamorphine was determined by the response of the previous patient in the same group using up-down sequential allocation. Pain corresponding to the previous contraction was assessed using a 100-mm visual analogue score and effective analgesia was defined as </=10 mm within 30 min of epidural injection.
  
  
  RESULTS
  There was no significant difference in EC50 for diamorphine between the groups: the difference was 15.0 microg ml(-1) (95% CI -40.3 to 10.3). The EC50 for group A was 237.5 microg ml(-1) (95% CI 221.2 to 253.8) and the EC50 for group B was 252.5 microg ml(-1) (95% CI 232.2 to 272.8). The EC50 ratio was 0.95 (95% CI 0.87 to 1.06). The groups exhibited parallelism (P=0.98). The overall EC50 for all data was 244.2 microg ml(-1) (95% CI 230.8 to 257.2).
  
  
  CONCLUSIONS
  We conclude that diamorphine provides analgesia in labour by a concentration-dependent effect.
authors.affiliation: Department of Anaesthetics, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. g.a.mcleod@dundee.ac.uk
authors.forename: G A
authors.initials: GA
authors.lastname: McLeod
authors.forename: B
authors.initials: B
authors.lastname: Munishankar
authors.forename: M O
authors.initials: MO
authors.lastname: Columb
mesh_terms: D000328:Adult; D015360:Analgesia, Epidural / Q000379:methods*; D016362:Analgesia, Obstetrical / Q000379:methods*; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D036861:Delivery, Obstetric / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D003932:Heroin / Q000008:administration & dosage*; D006801:Humans; D010147:Pain Measurement / Q000379:methods; D011247:Pregnancy; D011256:Pregnancy Outcome; D011446:Prospective Studies
chemical_list: D000701:Analgesics, Opioid; D003932:Heroin