title: The longitudinal pattern of response when morphine is used to treat chronic refractory dyspnea.
abstract: BACKGROUND
  While evidence supports using sustained release morphine for chronic refractory breathlessness, little is known about the longitudinal pattern of breathlessness intensity as people achieve symptomatic benefit. The aim of this study is to describe this pattern.
  
  
  METHODS
  This secondary analysis used breathlessness intensity scores (100 mm visual analogue scale (VAS)) from a prospective, dose increment study of once daily (morning) sustained release morphine for chronic refractory breathlessness. Participants who achieved <10% improvement over their own baseline at one week (10 mg) were titrated to 20 mg and if no response, another week later to 30 mg for one week. Time was standardized at the first day of the week in which participants responded generating twice daily data one week either side of symptomatic benefit. Analysis used random effect mixed modeling.
  
  
  RESULTS
  Of the 83 participants, 17/52 responders required >10 mg: 13 participants (20 mg) and 4 (30 mg), contributing 634 VAS observations. In the week leading to a response, average VAS scores worsened by 0.3 mm/day (p=0.16); the average improvement in the first 24 hours of response was 10.9 mm (7.0 to 14.7; p<0.0001), with continued improvement of 2.2 mm/day (p<0.001) for six more days.
  
  
  CONCLUSIONS
  When treating chronic refractory breathlessness with once daily sustained release morphine, titrate to effect, since inadequate dose may generate no response; and following an initial response, further dose increases should not occur for at least one week. Whether further benefit would be derived beyond day six on the dose to which people respond, and what net effect a further dose increase would have are questions yet to be answered.
authors.affiliation: Palliative and Supportive Services, Flinders University, Bedford Park, Australia. david.currow@health.sa.gov.au
authors.forename: David C
authors.initials: DC
authors.lastname: Currow
authors.forename: Stephen
authors.initials: S
authors.lastname: Quinn
authors.forename: Aine
authors.initials: A
authors.lastname: Greene
authors.forename: Janet
authors.initials: J
authors.lastname: Bull
authors.forename: Miriam J
authors.initials: MJ
authors.lastname: Johnson
authors.forename: Amy P
authors.initials: AP
authors.lastname: Abernethy
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use; D001315:Australia; D002908:Chronic Disease; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004417:Dyspnea / Q000188:drug therapy*; D006801:Humans; D009020:Morphine / Q000008:administration & dosage* / Q000627:therapeutic use; D011446:Prospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D009020:Morphine