The Longitudinal Pattern of Response When Morphine Is Used To Treat Chronic Refractory Dyspnea
Publication: Journal of Palliative Medicine
Volume 16, Issue Number 8
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.
Conclusion: 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.
Get full access to this article
View all available purchase options and get full access to this article.
References
1.
Abernethy APCurrow DCFrith PFazekas BSMcHugh ABui C. Randomised double-blind placebo-controlled crossover trial of sustained-release morphine for the management of refractory dyspnoeaBr Med J20037414327523-525. 1. Abernethy AP, Currow DC, Frith P, Fazekas BS, McHugh A, Bui C: Randomised double-blind placebo-controlled crossover trial of sustained-release morphine for the management of refractory dyspnoea. Br Med J 2003;7414(327):523–525.
2.
Currow DCPlummer JCrockett AAbernethy AP. A community population survey of prevalence and severity of dyspnoea in adultsJ Pain Symptom Manage200938533-545. 2. Currow DC, Plummer J, Crockett A, Abernethy AP: A community population survey of prevalence and severity of dyspnoea in adults. J Pain Symptom Manage 2009;38:533–545.
3.
Hammond E. Some preliminary findings on physical complaints from a prospective study of 1,064,004 men and womenAm J Pub Health19645411-23. 3. Hammond E: Some preliminary findings on physical complaints from a prospective study of 1,064,004 men and women. Am J Pub Health 1964;54:11–23.
4.
Currow DCSmith JDavidson PMNewton PJAgar MRAbernethy AP. Do the trajectories of dyspnoea differ in prevalence and intensity by diagnosis at the end of life? A consecutive cohort studyJ Pain Symptom Manage201039680-690. 4. Currow DC, Smith J, Davidson PM, Newton PJ, Agar MR, Abernethy AP: Do the trajectories of dyspnoea differ in prevalence and intensity by diagnosis at the end of life? A consecutive cohort study. J Pain Symptom Manage 2010;39:680–690.
5.
Seow HBarbera LSutradhar RHowell DDudgeon DAtzema CLiu YHusain ASussman JEarle C. Trajectory of performance status and symptom scores for patients with cancer during the last six months of lifeJ Clin Oncol2011291151-1158. 5. Seow H, Barbera L, Sutradhar R, Howell D, Dudgeon D, Atzema C, Liu Y, Husain A, Sussman J, Earle C: Trajectory of performance status and symptom scores for patients with cancer during the last six months of life. J Clin Oncol 2011; 29:1151–1158.
6.
Jennings ALDavies ANHiggins JPGibbs JRBroadley KE. A systematic review of the use of opioids in the management of dyspneaThorax200257939-944. 6. Jennings AL, Davies AN, Higgins JP, Gibbs JR, Broadley KE: A systematic review of the use of opioids in the management of dyspnea. Thorax 2002;57:939–944.
7.
Currow DCMcDonald COaten SKenny BAllcroft PFrith PBriffa MJohnson MJAbernethy AP. Once-daily opioids for chronic dyspnoea: A dose increment and pharmacovigilance studyJ Pain Symptom Manage201142388-399. 7. Currow DC, McDonald C, Oaten S, Kenny B, Allcroft P, Frith P, Briffa M, Johnson MJ, Abernethy AP: Once-daily opioids for chronic dyspnoea: A dose increment and pharmacovigilance study. J Pain Symptom Manage 2011;42:388–399.
8.
Johnson MJBland MJOxberry SGAbernethy APCurrow DC. Opioids for chronic refractory breathlessness: Patient predictors of beneficial responseEur Respir J2012Epub ahead of printDec.202012 8. Johnson MJ, Bland MJ, Oxberry SG, Abernethy AP, Currow DC: Opioids for chronic refractory breathlessness: Patient predictors of beneficial response. Eur Respir J 2012. (Epub ahead of print, Dec. 20, 2012)
9.
Mahler DAMurray JAWaterman LA et al. Endogenous opioids modify dyspnoea during treadmill exercise in patients with COPDEur Respir J200933771-777. 9. Mahler DA, Murray JA, Waterman LA, et al.: Endogenous opioids modify dyspnoea during treadmill exercise in patients with COPD. Eur Respir J 2009;33:771–777.
10.
Gifford AHMahler DAWaterman LAWard JKraemer WJKupchak BRBaird JC. Neuromodulatory effect of endogenous opioids on the intensity and unpleasantness of breathlessness during resistive load breathing in COPDCOPD20118160-166. 10. Gifford AH, Mahler DA, Waterman LA, Ward J, Kraemer WJ, Kupchak BR, Baird JC: Neuromodulatory effect of endogenous opioids on the intensity and unpleasantness of breathlessness during resistive load breathing in COPD. COPD 2011;8:160–166.
11.
Mahler DASelecky PAHarrod CGBenditt JOCarrieri-Kohlman VCurtis JRManning HLm Mularski RAVarkey BCampbell MCarter ERChiong JREly EWHansen-Flaschen JO'Donnell DEWaller A. American College of Chest Physicians consensus statement on the management of dyspnea in patients with advanced lung or heart diseaseChest2010137674-691. 11. Mahler DA, Selecky PA, Harrod CG, Benditt JO, Carrieri-Kohlman V, Curtis JR, Manning HLm Mularski RA, Varkey B, Campbell M, Carter ER, Chiong JR, Ely EW, Hansen-Flaschen J, O'Donnell DE, Waller A: American College of Chest Physicians consensus statement on the management of dyspnea in patients with advanced lung or heart disease. Chest 2010;137:674–691.
12.
Parshall MBSchwartzstein RMAdams LBanzett RBManning HLBourbeau JCalverley PMGift AGHarver ALareau SCMahler DAMeek PMO'Donnell DEAmerican Thoracic Society Committee on Dyspnea. An official American Thoracic Society statement: Update on the mechanisms, assessment, and management of dyspneaAm J Respir Crit Care Med2012185435-452. 12. Parshall MB, Schwartzstein RM, Adams L, Banzett RB, Manning HL, Bourbeau J, Calverley PM, Gift AG, Harver A, Lareau SC, Mahler DA, Meek PM, O'Donnell DE; American Thoracic Society Committee on Dyspnea: An official American Thoracic Society statement: Update on the mechanisms, assessment, and management of dyspnea. Am J Respir Crit Care Med 2012;185:435–452.
13.
Fletcher CMElmes PCFairbairn MB et al. The significance of respiratory symptoms and the diagnosis of chronic bronchitis in a working populationBr Med J19592257-266. 13. Fletcher CM, Elmes PC, Fairbairn MB et al.: The significance of respiratory symptoms and the diagnosis of chronic bronchitis in a working population. Br Med J 1959;2:257–266.
14.
Medical Research Council Committee on Aetiology of Chronic Bronchitis: Standardized questionnaires on respiratory symptomsBr Med J1960II1665. 14. Medical Research Council Committee on Aetiology of Chronic Bronchitis: Standardized questionnaires on respiratory symptoms. Br Med J 1960;II:1665.
15.
Bestall JCPaul EAGarrod RGarnham RJones PWWedzicha JA. Usefulness of the Medical Research Council (MRC) dyspnoea scale as a measure of disability in patients with chronic obstructive pulmonary diseaseThorax199954581-586. 15. Bestall JC, Paul EA, Garrod R, Garnham R, Jones PW, Wedzicha JA: Usefulness of the Medical Research Council (MRC) dyspnoea scale as a measure of disability in patients with chronic obstructive pulmonary disease. Thorax 1999;54:581–586.
16.
Abernethy APShelby-James TMFazekas BSWoods DCurrow DC. The Australian-modified Karnofsky Performance Status (AKPS) scale: A revised scale for contemporary palliative care clinical practiceBMC Pall Care200547. 16. Abernethy AP, Shelby-James TM, Fazekas BS, Woods D, Currow DC: The Australian-modified Karnofsky Performance Status (AKPS) scale: A revised scale for contemporary palliative care clinical practice. BMC Pall Care 2005;4:7.
17.
Levey ASBosch JPLewis JBGreene TRogers NRoth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: A new prediction equation. Modification of Diet in Renal Disease Study GroupAnn Intern Med1999130461-470. 17. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D: A more accurate method to estimate glomerular filtration rate from serum creatinine: A new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999;130:461–470.
18.
Rossi SAustralian Medicines HandbookAdelaideAustralian Medicines Handbook2012. 18. Rossi S (ed): Australian Medicines Handbook. Adelaide: Australian Medicines Handbook, 2012.
19.
Folstein MFFolstein SEMcHugh PR. “Mini-mental state:” A practical method for grading the cognitive state of patients for the clinicianJ Psychiatr Res197512189-198. 19. Folstein MF, Folstein SE, McHugh PR: “Mini-mental state:” A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–198.
20.
Cohen SRMount BMStrobel MGBui F. The McGill Quality of Life Questionnaire, a measure of quality of life appropriate for people with advanced disease: A preliminary study of validity and acceptabilityPalliat Med19959207-219. 20. Cohen SR, Mount BM, Strobel MG, Bui F: The McGill Quality of Life Questionnaire, a measure of quality of life appropriate for people with advanced disease: A preliminary study of validity and acceptability. Palliat Med 1995;9:207–219.
21.
Ries AL. Minimally clinically important difference for the UCSD Shortness of Breath Questionnaine, Borg Scale, and Visual Analogue ScaleCOPD20052105-110. 21. Ries AL: Minimally clinically important difference for the UCSD Shortness of Breath Questionnaine, Borg Scale, and Visual Analogue Scale. COPD 2005;2:105–110.
22.
Mahler DA. Mechanisms and measurement of dyspnea in chronic obstructive pulmonary diseaseProc Am Thorac Soc20063234-238. 22. Mahler DA: Mechanisms and measurement of dyspnea in chronic obstructive pulmonary disease. Proc Am Thorac Soc 2006;3:234–238.
23.
Oxberry SGBland JMClark ALCleland JGFJohnson MJ. Minimally Clinically Important Difference (MCID) in chronic breathlessness: Every little helpsJ Am Heart Assoc2012164229-235. 23. Oxberry SG, Bland JM, Clark AL, Cleland JGF, Johnson MJ: Minimally Clinically Important Difference (MCID) in chronic breathlessness: Every little helps. J Am Heart Assoc 2012;164:229–235.
24.
Sloan JA. Assessing the minimally clinically significant difference: Scientific considerations, challenges and solutionsCOPD2005257-62. 24. Sloan JA: Assessing the minimally clinically significant difference: Scientific considerations, challenges and solutions. COPD 2005;2:57–62.
25.
Wyrwich KWTierney WMWolinsky FD. Further evidence supporting an SEM-based criterion for identifying meaningful intra-individual changes in health-related quality of lifeJ Clin Epidemiol199952861-873. 25. Wyrwich KW, Tierney WM, Wolinsky FD: Further evidence supporting an SEM-based criterion for identifying meaningful intra-individual changes in health-related quality of life. J Clin Epidemiol 1999;52:861–873.
26.
Mahler DAWitek TJ Jr. The MCID of the transition dyspnea index is a total score of one unitCOPD2005299-103. 26. Mahler DA, Witek TJ, Jr.: The MCID of the transition dyspnea index is a total score of one unit. COPD 2005;2:99–103.
27.
Norman GRSloan JAWyrwich KW. Interpretation of changes in health-related quality of life: The remarkable universality of half a standard deviationMed Care200341582-592. 27. Norman GR, Sloan JA, Wyrwich KW: Interpretation of changes in health-related quality of life: The remarkable universality of half a standard deviation. Med Care 2003;41:582–592.
28.
Johnson MJBland JMOxberry SGAbernethy APCurrow DC. Clinically important differences in the intensity of chronic fractory breathlessnessJ Pain Symptom ManageEpub a head of print2013Apr19. 28. Johnson MJ, Bland JM, Oxberry SG, Abernethy AP, Currow DC: Clinically important differences in the intensity of chronic fractory breathlessness. J Pain Symptom Manage doi:ppi: S0885–3924(13)00186-3.10.1016/j.jpainsymman.2013.01.011. [Epub a head of print 2013 Apr 19.]
29.
Klepstad PKaasa SJystad A et al. Immediate- or sustained-release morphine for dose finding during start of morphine to cancer patients: A randomized, double-blind trialPain20031011193-198. 29. Klepstad P, Kaasa S, Jystad A, et al.: Immediate- or sustained-release morphine for dose finding during start of morphine to cancer patients: A randomized, double-blind trial. Pain 2003;101(1):193–198.
30.
Jensen DAlsuhail AViola RDudgeon DJWebb KAO'Donnell DE. Inhaled fentanyl citrate improves exercise endurance during high-intensity constant work rate cycle exercise in chronic obstructive pulmonary diseaseJ Pain Symptom Manage201243706-719. 30. Jensen D, Alsuhail A, Viola R, Dudgeon DJ, Webb KA, O'Donnell DE: Inhaled fentanyl citrate improves exercise endurance during high-intensity constant work rate cycle exercise in chronic obstructive pulmonary disease. J Pain Symptom Manage 2012;43:706–719.
31.
Baker PSBodner EVAllman RM. Measuring life-space mobility in community-dwelling older adultsJ Am Geriatr Soc2003511610-1614. 31. Baker PS, Bodner EV, Allman RM: Measuring life-space mobility in community-dwelling older adults. J Am Geriatr Soc 2003;51:1610–1614.
32.
Maddocks MWilcock A. Exploring physical activity level in patients with thoracic cancer: Implications for use as an outcome measureSupport Care Cancer2012201113-1116. 32. Maddocks M, Wilcock A: Exploring physical activity level in patients with thoracic cancer: Implications for use as an outcome measure. Support Care Cancer 2012;20:1113–1116.
33.
Currow DCAbernethy APJohnson MJ. Activity as a measure of symptom controlJ Pain Symptom Manage201244e1-e2. 33. Currow DC, Abernethy AP, Johnson MJ. Activity as a measure of symptom control. J Pain Symptom Manage 2012;44:e1–e2.
34.
Currow DCAbernethy APJohnson MJ. Activity as a measure of symptom controlJ Pain Symptom ManageEpub ahead of print2012Sep24 34. Currow DC, Abernethy AP, Johnson MJ: Activity as a measure of symptom control. J Pain Symptom Manage doi: 10.1016/j.jpainsymman.2012.07.005. [Epub ahead of print 2012 Sep 24]
35.
Abernethy APMcDonald CFFrith PAClark KHerndon JEMarcello JYoung IHBull JWilcock ABooth SWheeler JLTulsky JACrockett AJCurrow DC. Effect of palliative oxygen versus room air in relieving breathlessness in patients with refractory dyspnea: A double-blind randomized controlled trial (NCT00327873)Lancet2010376784-793. 35. Abernethy AP, McDonald CF, Frith PA, Clark K, Herndon JE, Marcello J, Young IH, Bull J, Wilcock A, Booth S, Wheeler JL, Tulsky JA, Crockett AJ, Currow DC: Effect of palliative oxygen versus room air in relieving breathlessness in patients with refractory dyspnea: A double-blind randomized controlled trial (NCT00327873). Lancet 2010;376:784–793.
36.
von Leupoldt AAmbruzsova RNordmeyer SJeske NDahme B. Sensory and affective aspects of dyspnea contribute differentially to the Borg scale's measurement of dyspneaRespiration200673762-768 36. von Leupoldt A, Ambruzsova R, Nordmeyer S, Jeske N, Dahme B: Sensory and affective aspects of dyspnea contribute differentially to the Borg scale's measurement of dyspnea. Respiration 2006;73:762–768
Information & Authors
Information
Published In
Journal of Palliative Medicine
Volume 16 • Issue Number 8 • August 2013
Pages: 881 - 886
PubMed: 23746231
Copyright
Copyright 2013, Mary Ann Liebert, Inc.
History
Published in print: August 2013
Published online: 22 July 2013
Published ahead of print: 8 June 2013
Accepted: 12 March 2013
Topics
Authors
Author Disclosure Statement
The authors declare they have no competing interests.
Metrics & Citations
Metrics
Citations
Export Citation
Export citation
Select the format you want to export the citations of this publication.
View Options
Get Access
Access content
To read the fulltext, please use one of the options below to sign in or purchase access.⚠ Society Access
If you are a member of a society that has access to this content please log in via your society website and then return to this publication.