Pharmacological treatment of refractory breathlessness

Expert Review of Respiratory Medicine

Volumn 3, Issue 1, 2009, Pages 21-36

  Booth, Sara ^a,b   Bausewein, Claudia ^c   Higginson, Irene ^c   Moosavi, Shakeeb H ^d  

^a CAMBRIDGE UNIVERSITY HOSPITALS NHS FOUNDATION TRUST   (United Kingdom)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^c KING'S COLLEGE LONDON   (United Kingdom)

^d CHARING CROSS HOSPITAL   (United Kingdom)

Author keywords

Antidepressant; Anxiolytic; Breathlessness; Clinical trial; Inhaled Furosemide; Opioid; Palliation

Indexed keywords

ALFENTANIL; ANTIDEPRESSANT AGENT; ANXIOLYTIC AGENT; BENZODIAZEPINE; BUSPIRONE; CANNABINOID; FUROSEMIDE; HALOPERIDOL; HELIOX; LEVOMEPROMAZINE; LORAZEPAM; MIDAZOLAM; MIRTAZAPINE; MORPHINE; OPIATE; OXYGEN; PLACEBO; SEROTONIN UPTAKE INHIBITOR;

ANXIETY DISORDER; CANCER PATIENT; CHRONIC OBSTRUCTIVE LUNG DISEASE; CLINICAL TRIAL; COGNITIVE THERAPY; CONSTIPATION; CONTINUOUS INFUSION; DEPRESSION; DISEASE EXACERBATION; DIZZINESS; DROWSINESS; DRUG EFFICACY; DRUG EXCRETION; DRUG HALF LIFE; DRUG RESEARCH; DYSPHORIA; DYSPNEA; EVIDENCE BASED MEDICINE; EXPERIMENTAL MODEL; FUNCTIONAL MAGNETIC RESONANCE IMAGING; HEART DISEASE; HUMAN; HYPOTENSION; KINESIOTHERAPY; MEDICAL DECISION MAKING; MEDICAL RESEARCH; NAUSEA; PALLIATIVE THERAPY; PHYSICAL ACTIVITY; PRACTICE GUIDELINE; PRESCRIPTION; QUALITY OF LIFE; RESPIRATION DEPRESSION; RESPIRATORY TRACT DISEASE; REVIEW; SEDATION; SIDE EFFECT; SINGLE DRUG DOSE; SLEEP DISORDER; SYMPTOM; TERMINAL CARE; VISUAL ANALOG SCALE; VOMITING;

EID: 70049098554     PISSN: 17476348     EISSN: 17476356     Source Type: Journal    
DOI: 10.1586/17476348.3.1.21     Document Type: Review

References (111)

1. Edmonds P, Karlsen S, Khan S, Addington-Hall J. A comparison of the palliative care needs of patients dying from chronic respiratory diseases and lung cancer. Palliat. Med. 15, 287-295 (2001).
2. Muers MF, Round CE. Palliation of symptoms in non-small cell lung cancer: a study by the yorkshire regional cancer organisation thoracic group. Thorax 48(4), 339-343 (1993).
3. Mathers C, Locar D. Updated projections of global mortality and burden of disease 2002-2030. Data sources, methods and results. Evidence and information for policy WHO (2005).
4. American Thoracic Society. Dyspnea-mechanisms, assessment and management: a consensus statement. Am. J. Respir. Crit. Care Med. 159, 321-340 (1999).
5. Comroe JH. Some theories on the mechanism of dyspnea. In: Breathlessness: Proceedings of an International Symposium Held on 7 and 8 April 1965 Under the Auspices of the University of Manchester. (Volume 1-7). Blackwell Scientific, London, UK (1966).
6. Moosavi SH, Paydarfar D, Shea SA. Suprapontine control of breathing. In: Pharmacology and Pathophysiology of the Control of Breathing. Ward D, Dahan A, Teppema L (Eds). Taylor and Francis Group, NY, USA 71-102 (2005).
7. O'Donnell DE, Banzett RB, Carrieri-Kohlman et al. Pathophysiology of dyspnea in chronic obstructive pulmonary disease: a roundtable. Am. Thoracic Society 4, 145-168 (2007).
8. Schwartzstein RM, Lahive K, Pope A, Weinberger SE, Weiss JW. Cold facial stimulation reduces breathlessness induced in normal subjects. Am. Rev. Respir. Dis. 136, 58-61 (1987).
9. Simon PM, Basner RC, Weinberger SE, Fencl V, Weiss JW, Schwartzstein RM. Oral mucosal stimulation modulates intensity of breathlessness induced in normal subjects. Am. Rev. Respir. Dis. 144, 419-422 (1991).
10. 2. Respir. Physiol. 93, 203-219 (1993).
11. O'Donnell DE, Webb KA. Exertional breathlessness in patients with chronic airflow limitation. The role of lung hyperinflation. Am. Rev. Respir. Dis. 148, 1351-1357 (1993).
12. O'Donnell DE, Bertley JC, Chau LK, Webb KA. Qualitative aspects of exertional breathlessness in chronic airflow limitation: pathophysiologic mechanisms. Am. J. Respir. Crit. Care Med. 155, 109-115 (1997).
13. Fishman AP, Ledlie JF. Dyspnea. Bull. Eur. Physiopathol. Respir. 15, 789-804 (1979).
14. Campbell EJ, Howell JB. The sensation of breathlessness. Br. Med. Bull. 19, 36-40 (1963).
15. Manning HL, Schwartzstein RM. Pathophysiology of dyspnea. N. Engl. J. Med. 333, 1547-1553 (1995).
16. Booth S, Moosavi SH et al. The etiology and management of intractable breathlessness in patients with advanced cancer: with a systematic review of pharmacological and inhaled therapy. Nat. Clin. Pract. Oncol. 5(2), 90-100 (2008).
17. von Leupoldt A, Dahme B. The cortical substrate for dyspnoea perception. Chest 128, 345-354 (2005).
18. von Leupoldt A, Sommer T, Kegat S et al. The unpleasantness of perceived dyspnea is processed in the anterior insula and amygdala. Am. J. Respir. Crit. Care Med. 177(9), 1026-1032 (2008).
19. Augustine JR. Circuitry and functional aspects of the insular lobe in primates including humans. Brain Res. Rev. 22, 229-244 (1996).
20. Hanamori T, Kunitake T et al. Responses of neurons in the insular cortex to gustatory, visceral, and nociceptive stimuli in rats. J. Neurophysiol. 79, 2535-2545 (1998).
21. Murray SA, Kendall M, Boyd K. Illness trajectories and palliative care. BMJ 330, 1007-1011 (2005).
22. Booth S, Kelly M et al. Does oxygen help dyspnoea in cancer patients? Am. J. Resp. Crit. Care Med. 153, 1515-1518 (1996).
23. Jennings AL, Davies AN, Higgins JP, Gibbs JS, Broadley KE. A systematic review of the use of opioids in the management of dyspnoea. Thorax 57, 939-944 (2002).
24. Abernethy A, 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. BMJ 327, 523-528 (2003).
25. Johnson MA, Woodcock AA, Geddes DM. Dihydrocodeine for breathlessness in 'pink puffers'. BMJ 286, 675-677 (1983).
26. Rabe KF, Hurd S, Anzueto A et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD Executive Summary. Am. J. Respir. Crit. Care Med. 176, 532-555 (2007).
27. Johnson MJ, McDonagh TA, Harkness A, McKay SE, Dargie HJ. Morphine for the relief of breathlessness in patients with chronic heart failure - a pilot study. Eur. J. Heart Fail. 4, 753-756 (2002).
28. Dyspnoea in Advanced Disease. Booth S, Dudgeon D (Eds). Oxford University Press, Oxford, UK (2006).
29. Rocker G, Sinuff T, Horton R, Hernandez P. Advanced chronic obstructive pulmonary disease: innovative approaches to palliation. J. Palliat. Med. 10, 783-797 (2007).
30. Clemens KE, Klaschik E. Clinical experience with transdermal and orally administered opioids in palliative care patients - a retrospective study. Jpn. J. Clin. Oncol. 37(4), 302-309 (2007).
31. Coyne PJ, Viswanathan R, Smith TJ. Nebulized fentanyl citrate improves patients' perception of breathing, respiratory rate, and oxygen saturation in dyspnea. J. Pain Symptom Manage. 23, 157-160 (2002).
32. Benitez-Rosario MA, Martin AS, Feria M. Oral transmucosal fentanyl citrate in the management of dyspnea crises in cancer patients. J. Pain Symptom Manage. 30(5), 395-397 (2005).
33. Dudgeon D. Breathlessness in advanced cancer. In: Dyspnoea in Advanced Disease. Booth S, Dudgeon D (Eds). Oxford University Press, Oxford, UK 75-98 (2006).
34. Argyropoulou P, Patakas D, Koukou A et al. Buspirone effect on breathlessness and exercise performance in patients with chronic obstructive pulmonary disease. Respiration 60, 216-220 (1993).
35. Singh NP, Despars JA, Stansbury DW et al. Effects of buspirone on anxiety levels and exercise tolerance in patients with chronic airflow obstruction and mild anxiety. Chest 103, 800-804 (1993).
36. Gysels M, Bausewein C, Higginson IJ. Experiences of breathlessness: a systematic review of the qualitative literature. Palliat. Support. Care 5(3), 281-302 (2007).
37. Eimer M, Cable T, Gal P et al. Effects of clorazcpate on breathlessness and exercise tolerance in patients with chronic airflow obstruction. J. Fam. Pract. 21, 359-362 (1985).
38. Woodcock AA, Gross ER, Geddes DM. Drug treatment of breathlessness: contrasting effects of diazepam and promethazine in pink puffers. BMJ 283, 343-346 (1981a).
39. O'Neill PA, Morton PB, Stark RD. Chlorpromazine - a specific effect on breathlessness? Br. J. Pharmacol. 19, 793-797 (1985).
40. Man GCW, Hsu K, Sproule BJ. Effect of alprazolam on exercise and dyspnea in patients with chronic obstructive pulmonary disease. Chest 90, 832-836 (1986).
41. Rice KL, Kronenberg RS, Hedemark LL, Niewoehner DE. Effects of chronic administration of codeine and promethazine on breathlessness and exercise tolerance in patients with chronic airflow obstruction. Br. J. Dis. Chest 81, 287-292 (1987).
42. Ventafridda V, Spoldi E, De Conno F. Control of dyspnea in advanced cancer patients. Chest 98, 1544-1545 (1990).
43. McIver B, Walsh D, Nelson K. The use of chlorpromazine for symptom control in dying cancer patients. J. Pain Symptom Manage. 9, 341-345 (1994).
44. Navigante AH, Cerchietti LCA, Castro MA, Lutteral MA, Cabalar ME. Midazolam as adjunct therapy to morphine in the alleviation of severe dyspnea perception in patients with advanced cancer. J. Pain Symptom Manage. 31, 38-47 (2006).
45. Davis CL. ABC of palliative care. Breathlessness, cough, and other respiratory problems. Br. Med. J. 315, 931-934 (1997).
46. Brenes GA. Anxiety and chronic obstructive pulmonary disease: prevalence, impact, and treatment. Psychosomatic Med. 65, 963-970 (2003).
47. Mueller RA, Lundberg DB, Breese GR, Hedner J, Hedner T, Jonason J. The neuropharmacology of respiratory control. Pharmacol. Rev. 34, 255-285 (1982).
48. Zigmund AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatrica Scandinavia 67, 361-370 (1983).
49. Stone P, Kurowski A, Tookman A. Nebulized frusemide for dyspnoea. Palliat. Med. 8, 258 (1994).
50. Shimoyama N, Shimoyama M. Nebulized furosemide as a novel treatment for dyspnea in terminal cancer patients. J. Pain Symptom Manage. 23(1), 73-76 (2002).
51. Kohara H, Ueoka H, Aoe K et al. The effect of nebulized furosemide in terminally ill cancer patients with dyspnoea. J. Pain Symptom Manage. 26(4), 962-967 (2003).
52. Nishino T, Ide T, Sudo T, Sato J. Inhaled furosemide greatly alleviates the sensation of experimentally induced dyspnea. Am. J. Respir. Crit. Care Med. 161(6), 1963-1967 (2000).
53. Moosavi SH, Binks AP, Lansing RW, Topulos GP, Banzett RB, Schwartzstein RM. Effect of inhaled furosemide on air hunger induced in healthy humans. Respir. Physiol. Neurobiol. 156, 1-8 (2007).
54. Ventresca PG, Nicol GM, Barnes PJ et al. Inhaled furosemide inhibits cough induced by low chloride content solutions but not by capsaicin. Am. Rev. Resp. Dis. 142, 143-146 (1990).
55. Bianco S, Vaghi A, Robuschi M, Pasargiklian M. Prevention of exercise-induced bronchoconstriction by inhaled frusemide. Lancet 2, 252-255 (1988).
56. Ong KC, Kor AC, Chong WF, Earnest A, Wang YT. Effects of inhaled furosemide on exertional dyspnea in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 169, 1028-1033 (2004).
57. Jensen D, Amjadi K, Harris-McAllister V, Webb KA, O'Donnell DE. Mechanisms of dyspnoea relief and improved exercise endurance after furosemide inhalation in COPD. Thorax 63(7), 606-613 (2008).
58. Hinckley JB. Inhaled furosemide in the treatment of acute exacerbations of asthma. Acad. Emerg. Med. 7, 1167 (2000).
59. 2 in ventilated quadriplegics. Respir. Physiol. 90, 19-30 (1992).
60. 2-induced air hunger in normal subjects. Respir. Physiol. 103, 19-31 (1996).
61. Welsh MJ. Electrolyte transport by airway epithelia. Physiol. Rev. 67, 1143-1184 (1987).
62. - channels regulate citric acid cough in guinea pigs. J. Appl. Physiol. 101, 635-643 (2006).
63. Sudo T, Hayashi F, Nishino T. Responses of tracheobronchial receptors to inhaled furosemide in anesthetized rats. Am. J. Respir. Crit. Care Med. 162, 971-975 (2000).
64. Laveneziana P, Galarducci A, Binazzi B, Stendardi L, Duranti R, Scano G. Inhaled furosemide does not alleviate respiratory effort during flow-limited exercise in healthy subjects. Pulm. Pharmacol. Ther. 21, 196-200 (2008).
65. MRC Working Party. Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Lancet 1, 681-686 (1981).
66. Domiciliary Oxygen Therapy Services. Clinical guidelines and advice for prescribers. A report of the Royal College of Physicians of London. 49, (1991).
67. Leach RM, Bateman NT. Domiciliary oxygen therapy. Br. J. Hosp. Med. 51, 47-54 (1994).
68. Eaton T, Garrett JE, Young P et al. Ambulatory oxygen improves quality of life of COPD patients: a randomised controlled study. Eur. Resp. J. 20, 306-312 (2002).
69. Bruera E, de Stoutz N, Velasco-Leiva A, Schoeller T, Hanson J. Effects of oxygen on dyspnoea in hypoxaemia terminal-cancer patients. Lancet 342, 13-14 (1993).
70. Philip J, Gold M, Milner A, Di Iulio J, Miller B, Spruyt O. A randomized, double-blind, crossover trial of the effect of oxygen on dyspnea in patients with advanced cancer. J. Pain Symptom Manage. 32, 541-549 (2006).
71. Uronis HE, Currow DC, McCrory DC, Samsa GP, Abernethy AP. Oxygen for relief of dyspnoea in mildly- or non-hypoxaemic patients with cancer: a systematic review and meta-analysis. Br. J. Cancer 98, 294-299 (2008).
72. Booth S, Wade R. Oxygen or air for Palliation of breathlessness in advanced cancer. J. R. Soc. Med. 96, 215-218 (2003).
73. Booth S, Wade R, Johnson M et al. The use of oxygen in the palliation of breathlessness. A report of the expert working group of the Scientific Committee of the Association of Palliative Medicine. Resp. Med. 98(1), 66-77 (2004).
74. Spathis A, Wade R, Booth S. Oxygen in the palliation of breathlessness. In: Dyspnoea in Advanced Disease. Booth S, Dudgeon D (Eds). Oxford University Press, Oxford, UK (2005).
75. Currow D, Fazekas B, Abernethy A. Oxygen use - patients define symptomatic benefit discerningly. J. Pain Symptom Manage. 34(2), 113-114 (2007).
76. Laude EA, Duffy NC, Baveystock C et al. The effect of helium and oxygen on exercise performance in chronic obstructive pulmonary disease: a randomized crossover trial. Am. J. Respir. Crit. Care Med. 173(8), 865-870 (2006).
77. Ahmedzai SH, Laude E, Robertson A, Troy G, Vora V. A double blind, randomized, controlled Phase II trial of Heliox28 gas mixture in lung cancer patients with dyspnoea on exertion. Br. J. Cancer 90, 366-371 (2004).
78. Kallet RH. The role of inhaled opioids and furosemide for the treatment of dyspnea. Resp. Care 52, 900-910 (2007).
79. Uronis HE, Currow DC, Abernethy AP. Palliative management of refractory dyspnea in COPD. Int. J. Chron. Obstruct. Pulmon. Dis. 1(3), 289-304 (2006).
80. Abernethy A, Uronis H, Wheeler JL, Currow D. Pharmacological management of breathlessness in advanced disease. Prog. Palliat. Care DOI: 10.1007/s00520-008-0562-6 (2008) (Epub ahead of print).
81. Adams L, Lane R, Shea SA, Cockcroft A, Guz A. Breathlessness during different forms of ventilatory stimulation: a study of mechanisms in normal subjects and respiratory patients. Clin. Sci. (Lond.) 69, 663-672 (1985).
82. 2 in mechanically ventilated quadriplegics. Respir. Physiol. 76, 53-67 (1989).
83. 2 persists after complete neuromuscular block in humans. Respir. Physiol. 81, 1-17 (1990).
84. Chen Z, Eldridge FL, Wagner PG. Respiratory-associated rhythmic firing of midbrain neurones in cats: relation to level of respiratory drive. J. Physiol. 437, 305-325 (1991).
85. Chen Z, Eldridge FL, Wagner PG. Respiratory-associated thalamic activity is related to level of respiratory drive. Respir. Physiol. 90, 99-113 (1992).
86. Gandevia SC, Killian K, McKenzie DK et al. Respiratory sensations, cardiovascular control, kinaesthesia and transcranial stimulation during paralysis in humans. J. Physiol. 470, 85-107 (1993).
87. Spengler CM, Banzett RB, Systrom DM, Shannon DC, Shea SA. Respiratory sensations during heavy exercise in subjects without respiratory chemosensitivity. Respir. Physiol. 114, 65-74 (1998).
88. Moosavi SH, Golestanian E, Binks AP, Lansing RW, Brown R, Banzett RB. Hypoxic and hypercapnic drives to breathe generate equivalent levels of air hunger in humans. J. Appl. Physiol. 94, 141-154 (2003).
89. Moosavi SH, Banzett RB, Butler JP. Time course of air hunger mirrors the biphasic ventilatory response to hypoxia. J. Appl. Physiol. 97, 2098-2103 (2004).
90. Campbell EJ, Gandevia SC, Killian KJ, Mahutte CK, Rigg JR. Changes in the perception of inspiratory resistive loads during partial curarization. J. Physiol. 309, 93-100 (1980).
91. Gandevia SC. The perception of motor commands or effort during muscular paralysis. Brain 105, 151-159 (1982).
92. el-Manshawi A, Killian KJ, Summers E, Jones NL. Breathlessness during exercise with and without resistive loading. J. Appl. Physiol. 61, 896-905 (1986).
93. Demediuk BH, Manning H, Lilly J et al. Dissociation between dyspnea and respiratory effort. Am. Rev. Respir. Dis. 146, 1222-1225 (1992).
94. Lansing RW, Im BS, Thwing JI, Legedza AT, Banzett RB. The perception of respiratory work and effort can be independent of the perception of air hunger. Am. J. Respir. Crit. Care Med. 162, 1690-1696 (2000).
95. 2) and V(E). Respir. Physiol. 122, 45-60 (2000).
96. Killian KJ, Mahutte CK, Campbell EJ. Resistive load detection during passive ventilation. Clin. Sci. (Lond.) 59, 493-495 (1980).
97. Killian KJ, Gandevia SC, Summers E, Campbell EJ. Effect of increased lung volume on perception of breathlessness, effort, and tension. J. Appl. Physiol. 57(3), 686-691 (1984).
98. Eldridge FL, Chen Z. Respiratory-associated rhythmic firing of midbrain neurons is modulated by vagal input. Respir. Physiol. 90, 31-46 (1992).
99. Harty HR, Mummery CJ, Adams L et al. Ventilatory relief of the sensation of the urge to breathe in humans: are pulmonary receptors important? J. Physiol. 490(Pt 3), 805-815 (1996).
100. Vovk A, Binks AP. Raising end-expiratory volume relieves air hunger in mechanically ventilated healthy adults. J. Appl. Physiol. 103, 779-786 (2007).
101. Binks AP, Moosavi SH, Banzett RB, Schwartzstein RM. 'Tightness' sensation of asthma does not arise from the work of breathing. Am. J. Respir. Crit. Care Med. 165, 78-82 (2002).
102. Burki NK, Dale WJ, Lee LY. Intravenous adenosine and dyspnea in humans. J. Appl. Physiol. 98, 180-185 (2005).
103. Burki NK, Alam M, Lee LY. The pulmonary effects of intravenous adenosine in asthmatic subjects. Respir. Res. 7, 139 (2006).
104. Burki NK, Sheatt M, Lee LY. Effects of airway anesthesia on dyspnea and ventilatory response to intravenous injection of adenosine in healthy human subjects. Pulm. Pharmacol. Ther. 21, 208-213 (2008).
105. Li W, Daems E, Van de Woestijne KP, et al. Air hunger and ventilation in response to hypercapnia: effects of repetition and anxiety. Physiol. Behav. 88, 47-54 (2006).
106. Alpher VS, Nelson RB 3rd, Blanton RL. Effects of cognitive and psychomotor tasks on breath-holding span. J. Appl. Physiol. 61, 1149-1152 (1986).
107. Von Leopoldt A, Mertz C, Kegat S, Burmester SDB. The impact of emotions on the sensory and affective dimension of perceived dyspnea. Psychophysiology 43, 382-386 (2006).
108. von Leupoldt A, Seemann N, Gugleva T, Dahme B. Attentional distraction reduces the affective but not the sensory dimension of perceived dyspnea. Respir. Med. 101, 839-844 (2007a).
109. von Leupoldt A, Taube K, Schubert-Heukeshoven S, Magnussen H, Dahme B. Distractive auditory stimuli reduce the unpleasantness of dyspnea during exercise in patients with COPD. Chest 132, 1506-1512 (2007b).
110. 2 ventilatory responsiveness in humans. Pulm. Pharmacol. Ther. 15, 363-368 (2002).
111. Stone P Rix, Kurowska A, Tookman. Re: nebulized furosemide for dyspnea in terminal cancer patients. J. Pain Symptom. Manage. 24, 274-275 (2002).