Abstract
Background
Episodic breathlessness (EB) or dyspnea is a common symptom with a very negative impact on the quality of life of patients with cancer and with non-oncological advanced diseases, mainly cardiorespiratory and neurological.
Objective
The purpose of this non-systematic review is to ascertain the role played by opioids in the management of episodic breathlessness.
Methods
A non-systematic literature review was done in the databases MEDLINE, COCHRANE, and DATABASE, and articles of greater scientific rigor, mainly reviews or prospective studies/randomized clinical trials published to date (August 2015), were selected. Terms used in the search included episodic breathlessness, acute breathlessness, episodic dyspnea, opioids, morphine, fentanyl, oxycodone, and breakthrough dyspnea.
Conclusions
Although the pathophysiology and mechanism of action of opioids for management of breathlessness, and specifically EB, are not fully known, there is scientific evidence, and particularly great clinical evidence, of the benefit of this drug class for dyspnea management. It is important to differentiate hospitalized patients from outpatients because venous or subcutaneous access is easier in hospitalized patients, but use of transmucosal fentanyl, especially in faster formulations like intranasal application, opens up new possibilities to manage outpatients due to its fast onset of action. The main problem is the lack of data available and the multitude of unanswered questions about opioid type, administration route, safety, and dose titration.
Similar content being viewed by others
References
Booth S, Silverter S, Todd C (2003) Breathlessness in cancer and chronic obstructive pulmonary disease: using a qualitative approach to describe the experience of patients and carers. Palliat Support Care 1:337–344
American Thoracic Society (1999) Dyspnea. Mechanisms, assessment, and management: a consensus statement. Am J Respir Crit Care Med 159:321–340
Solano JP, Gomes B, Higginson IJ (2006) A comparison of symptom prevalence in far advanced cancer, AIDS, heart disease, chronic obstructive pulmonary disease and renal disease. J Pain Symptom Manag 31:58–69
Tripodoro VA, De Vito EL (2008) Management of dyspnea in advanced motor neuron diseases. Curr Opin Support Palliat Care 2:173–179
Reddy SK, Parsons HA, Elsayem A, Palmer JL, Bruera E (2009) Characteristics and correlates of dyspnea in patients with advanced cancer. J Palliat Med 12:29–36
Williams CM (2006) Dyspnea. Cancer J 12(5):365–373
O’Driscoll M, Corner J, Bailey C (1999) The experience of breathlessness in lung cancer. Eur J Cancer Care 8:37e43
Heinzer MMV, Bish C, Detwiler R (2003) Acute dyspnea as perceived by patients with chronic obstructive pulmonary disease. Clin Nurs Res 12:85e101
Navigante AH, Castro MA, Cerchietti LC (2010) Morphine versus midazolam as upfront therapy to control dyspnea perception in cancer patients while its underlying cause is sought or treated. J Pain Symptom Manag 39(5):820–830
Bailey PH (2004) The dyspnea-anxiety-dyspnea cycle COPD patients’ stories of breathlessness: “It’s scary/when you can’t breathe”. Qual Health Res 14:760e778
Mularski RA, Reinke LF, Carrieri-Kohlman V, Fischer MD, Campbell ML, Rocker G, et al. (2013) An official American Thoracic Society workshop report: assessment and palliative management of dyspnea crisis. Ann Am Thorac Soc 10(5):S98–S106
Simon ST, Weingärtner V, Higginson IJ, Voltz R, Bausewein C (2014) Definition, categorization, and terminology of episodic breathlessness: consensus by an international Delphi survey. J Pain Symptom Manag 47(5):828–838
Simon ST, Higginson IJ, Benalia H, Gysels M, Murtagh FE, Spicer J, et al. (2013) Episodic and continuous breathlessness: a new categorization of breathlessness. J Pain Symptom Manag 45:1019–1029
Simon ST, Higginson IJ, Benalia H, Gysels M, Murtagh FE, Spicer J, et al. (2013) Episodes of breathlessness: types and patterns—a qualitative study exploring experiences of patients with advanced diseases. Palliat Med 27:524–532
Donesky D (2015) Management of acute breathlessness in the person with chronic refractory breathlessness. Curr Opin Support Palliat Care 9(3):212–216
Weingärtner V, Scheve C, Gerdes V, Schwarz-Eywill M, Prenzel R, Otremba B, et al. (2015) Characteristics of episodic breathlessness as reported by patients with advanced chronic obstructive pulmonary disease and lung cancer: results of a descriptive cohort study. Palliat Med 29(5):420–428
Simon ST, Bausewein C, Schildmann E, Higginson IJ, Magnussen H, Scheve C, et al. (2013) Episodic breathlessness in patients with advanced disease: a systematic review. J Pain Symptom Manag 45(3):561–578
Hallenbeck J (2005) Palliative care in the final days of life: “they were expecting it at any time”. J Am Med Assoc 293(18):2265–2271
Pattinson KT (2008) Opioids and the control of respiration. Br J Anaesth 100(6):747–758
Davies BL, Brundage CM, Harris MB, Taylor BE (2009) Lung respiratory rhythm and pattern generation in the bullfrog: role of neurokinin-1 and mu-opioid receptors. J Comp Physiol B 179(5):579–592
Kinkead R (2009) Phylogenetic trends in respiratory rhythmogenesis: insights from ectothermic vertebrates. Respir Physiol Neurobiol 168(1–2):39–48
Sinha SS, Goetz RR, Klein DF (2007) Physiological and behavioral effects of naloxone and lactate in normal volunteers with relevance to the pathophysiology of panic disorder. Psychiatry Res 149(1–3):309–314
Mahler DA, Murray JA, Waterman LA, Ward J, Kraemer WJ, Zhang X, et al. (2009) Endogenous opioids modify dyspnoea during treadmill exercise in patients with COPD. Eur Respir J 33(4):771–777
Scardella AT, Parisi RA, Phair DK, Santiago TV, Edelman NH (1986) The role of endogenous opioids in the ventilatory response to acute flow-resistive loads. Am Rev Respir Dis 133(1):26–31
Mustapic S, Radocaj T, Sanchez A, Dogas Z, Stucke AG, Hopp FA, et al. (2010) Clinically relevant infusion rates of mu-opioid agonist remifentanil cause bradypnea in decerebrate dogs but not via direct effects in the pre-Bötzinger complex region. J Neurophysiol 103(1):409–418
Ballanyi K, Ruangkittisakul A, Onimaru H (2009) Opioids prolong and anoxia shortens delay between onset of preinspiratory (pFRG) and inspiratory (preBötC) network bursting in newborn rat brainstems. Pflugers Arch 458(3):571–587
Woodcock AA, Gross ER, Gellert A, Shah S, Johnson M, Geddes DM (1981) Effects of dihydrocodeine, alcohol, and caffeine on breathlessness and exercise tolerance in patients with chronic obstructive lung disease and normal blood gases. N Engl J Med 305(27):1611–1616
Rosser R, Guz A (1981) Psychological approaches to breathlessness and its treatment. J Psychosom Res 25:439–447
Krajnik M, Jassem E, Sobanski P (2014) Opioid receptor bronchial tree: current science. Curr Opin Support Palliat Care 8:191–199
Burki N (2012) Acute dyspnea: is the cause cardiac or pulmonary or both? Consultant (Volume 52, Issue 11). http://www.consultant360.com/article/acute-dyspnea-cause-cardiac-orpulmonary-or-both
World Health Organization (2005) WHO definition of palliative care. Available from: http://www.who.int/cancer/palliative/definition/en/. Accessed 12 May 2012
Donesky D, Citron TL, Hilling L, Cayou C, Milic MM (2015) Additional evidence for the long-term benefits of pulmonary rehabilitation. Respir Care 60(8):1120–1129
Janssen DJ, McCormick JR (2014) Palliative care and pulmonary rehabilitation. Clin Chest Med 35:411–421
Farquhar MC, Prevost AT, McCrone P, Brafman-Price B, Bentley A, Higginson IJ, et al. (2014) Is a specialist breathlessness service more effective and cost-effective for patients with advanced cancer and their carers than standard care? Findings of a mixed-method randomized controlled trial. BMC Med 12:194
Higginson IJ, Bausewein C, Reilly CC, Gao W, Gysels M, Dzingina M, et al. (2014) An integrated palliative and respiratory care service for patients with advanced disease and refractory breathlessness: a randomised controlled trial. Lancet Respir Med 2:979–987
Schneidman A, Reinke L, Donesky D, Carrieri-Kohlman V (2014) Patient information series. Sudden breathlessness crisis. Am J Respir Crit Care Med 189:9–10
Jennings AL, Davies AN, Higgins JP, Gibbs JS, Broadley KE (2002) A systematic review of the use of opioids in the management of dyspnea. Thorax 57:939–944
López Saca JM, Centeno C (2014) Opioids prescription for symptoms relief and the impact on respiratory function: updated evidence. Curr Opin Support Palliat Care 8:383–390
Navigante AH, Cerchietti LC, Castro MA, Lutteral MA, Cabalar ME (2006) Midazolam as adjunct therapy to morphine in the alleviation of severe dyspnea perception in patients with advanced cancer. J Pain Symptom Manag 31:38e47
Charles MA, Reymond L, Israel F (2008) Relief of incident dyspnea in palliative cancer patients: a pilot, randomized, controlled trial comparing nebulized hydromorphone, systemic hydromorphone, and nebulized saline. J Pain Symptom Manag 36(1):29–38
Hui D, Xu A, Frisbee-Hume S, Chisholm G, Morgado M, Reddy S, et al. (2014) Effects of prophylactic subcutaneous fentanyl on exercise-induced breakthrough dyspnea in cancer patients: a preliminary double-blind, randomized, controlled trial. J Pain Symptom Manag 47(2):209–217
Coyne PJ, Viswanathan R, Smith TJ (2002) Nebulized fentanyl citrate improves patient’s perception of breathing, respiratory rate, and oxygen saturation in dyspnea. J Pain Symptom Manag 23(2):157–160
Benitez-Rosario MA, Martin AS, Feria M (2005) Oral transmucosal fentanyl citrate in the management of dyspnea crises in cancer patients. J Pain Symptom Manag 30:395e397
Sitte T, Bausewein C (2008) Intranasal fentanyl for episodic breathlessness. J Pain Symptom Manag 36(6):e3–e6
Gauna AA, Kang SK, Triano ML, Swatko ER, Vanston VJ (2008) Oral transmucosal fentanyl citrate for dyspnea in terminally ill patients: an observational case series. J Palliat Med 11:643e648
Harlos MS, Stenekes S, Lambert D, Hohl C, Chochinov HM (2013) Intranasal fentanyl in the palliative care of newborns and infants. J Pain Symptom Manag 46(2):256–274
AEMPS Actiq® Summary of product characteristics. http://www.aemps.gob.es/CIMA. Medicamento propiedad de Teva UK Limited
AEMPS Abstral® Summary of product characteristics. http://www.aemps.gob.es/CIMA. Medicamento propiedad de Prostrakan Limited
AEMPS Effentora® Summary of Product Characteristics. http://www.aemps.gob.es/CIMA. Medicamento propiedad de Teva Europe
AEMPSPecFent® Summary of Product Characteristics. http://www.aemps.gob.es/CIMA
Mercadante S (2012) Pharmacotherapy for breakthrough cancer pain. Drugs 72(2):191
Bausewein C, Simon ST (2014) Inhaled nebulized and intranasal opioids for the relief of breathlessness. Curr Opin Support Palliat Care 8:208–212
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflicts of interest.
Rights and permissions
About this article
Cite this article
Cabezón-Gutiérrez, L., Khosravi-Shahi, P., Custodio-Cabello, S. et al. Opioids for management of episodic breathlessness or dyspnea in patients with advanced disease. Support Care Cancer 24, 4045–4055 (2016). https://doi.org/10.1007/s00520-016-3316-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00520-016-3316-x