Evidence Matters The Role of Opioids in Treating Dyspnea

Evidence Matters
Vol. 1, No. 2 • 2007
The Role of Opioids in Treating Dyspnea
Terri L. Maxwell PhD, APRN, BC-PCM
What is dyspnea?
Dyspnea is the subjective sensation of being unable to breathe and is experienced by more than 70% of
patients who receive palliative care.1 Dyspnea results when there is a mismatch between the perceived need
to breathe and the perceived ability to breathe. Dyspnea can be acute or chronic in nature and is often present
with other symptoms such as fatigue, cough, anxiety and pain.2 Underlying conditions that may be contributing
to dyspnea need to be evaluated and addressed before instituting interventions aimed only at palliating
the symptom.
What causes dyspnea?
Dyspnea is a multidimensional phenomenon with physiologic, psychological, environmental, and social
factors, making it a challenging symptom to control in many patients.3 Primary causes of dyspnea include
chronic disease (heart failure, COPD, neuromuscular disease, etc.); acute, superimposed illness (pneumonia,
pulmonary embolism, etc.); and cancer-induced complications (tumor growth, bronchial obstruction, pleural
effusions). Other causes are anemia, ascites, anxiety, and depression.
Dyspnea is generally associated with three physiologic abnormalities:
1. increased respiratory effort needed to overcome a certain load or resistance (e.g., restrictive or obstructive
lung disease, or pleural effusion);
2. increased proportion of respiratory muscle required to maintain a normal workload (e.g., neuromuscular
weakness, cancer cachexia);
3. increased ventilatory requirements (e.g., hypoxemia, hypercapnea, metabolic acidosis, anemia).1, 4
Dyspnea may result from a combination of the three previously listed abnormalities. Because so many factors
can contribute to the experience of dyspnea, accurate clinical interpretation of any patient’s dyspneic experience is very challenging.4
How do I assess dyspnea?
Similar to pain, there is no objective test to measure the sensation of dyspnea. A clinician cannot rely upon
oxygen saturation to determine who is dyspneic; patients can be very dyspneic with normal saturations.
Therefore, a patient’s self-report or signs of agitation are the best means of identifying the presence and severity
of dyspnea.
The words patients use to describe dyspnea vary depending upon the underlying disease or pathology.3
Complaints range from chest tightness to air hunger. Caregivers’ ratings of the dyspnea experiences have been
found to be similar to the patient’s self-reports. Therefore, proxy ratings of dyspnea can be an important
predictor of patient comfort and may be useful to the clinician when patient self-report is not available.5
What pharmacologic treatments should I use for hospice patients who report dyspnea?
There are a variety of pharmacologic approaches to treating dyspnea, including (but not limited to) bronchodilators,
corticosteroids, and benzodiazepines. A systematic review of the use of oral and parenteral opioids showed substantial
benefit in reducing the feeling of breathlessness in patients with advanced disease of any cause.6 For patients with
advanced disease and for patients without a chronic respiratory disorder present (e.g., COPD), opioids should be
considered first-line therapy as they have been proven to be safe and effective for the treatment of dyspnea.7
How do opioids relieve dyspnea?
The exact mechanism by which opioids alleviate dyspnea is unknown. One theory is that opioids decrease respiratory
distress both by altering the perception of breathlessness and by decreasing ventilatory response to decreasing oxygen
and rising CO2 levels. Contrary to popular belief, opioids do not improve dyspnea through inhibition of the respiratory drive; rather, opioids improve dyspnea without causing significant deterioration in respiratory function.8
Another theory of how opioids work in the management of dyspnea is that they affect receptors located in the lungs
when administered via nebulization, resulting in peripheral activity without significant systemic absorption. However, some studies suggest that these receptors have little effect on the sensation of breathlessness and results of trials
with nebulized opioids have had limited success.6, 9
Which opioid should I use and at what dose?
While the efficacy of opioids in managing dyspnea has been demonstrated in clinical studies, the optimal dosing and
route of administration is highly debated. Most clinicians agree that the best treatment is to initiate therapy with a
low dose and increase the dose slowly as needed, since respiratory drive suppression can occur if serum opioid levels
rise too quickly.
Morphine is the opioid most studied in the treatment of dyspnea; other opioids, such as hydromorphone or codeine,
are also effective.10, 11 The usual dose of morphine in the opioid naïve patient is 5 mg orally (preferred route) every 4
hours, which can be titrated upwards in 25–50% increments until symptoms are controlled.3
For patients already receiving opioid therapy, the current regimen can be increased by 25–50% depending upon the
severity of the dyspnea.3 Patients requiring at least 30 mg of oral morphine (or equivalent) daily might benefit from a
long-acting opioid preparation administered every 12 hours.3 For these patients, a dose of approximately 10% of the
total daily long-acting opioid dose should be made available for breakthrough dyspnea.12
Shouldn’t I try an anxiolytic agent first?
Anxiolytic agents such as lorazepam are often used to treat dyspnea. While they are effective in relieving the anxiety
that may contribute to shortness of breath, they work best in hospice patients who complain of anxiety associated
with breathing. Therefore, they should be used as second-line therapy or in combination with opioids because they
do not treat the dyspnea directly. To date, there is no evidence to support the routine use of anxiolytics as first-line
therapy in patients experiencing dyspnea.13
Is nebulized morphine effective in treating dyspnea? What is the correct dose?
Nebulized morphine has been used to relieve dyspnea with some success, but, at this time, evidence to support its use
is weak. Nebulized morphine should not be used in place of oral or parenteral dosing.6
Other opioids, such as fentanyl and hydromorphone,14 have also been used to control dyspnea. One study demonstrated that nebulized fentanyl improved patient perception of breathing, respiratory rate, and oxygen saturation
without adverse effects. However, the number of patients in the study was small.15
For patients who are not having adequate response to other interventions for the management of dyspnea, if a trial of
nebulized morphine is being considered, the recommended starting dose of morphine via nebulizer is 5 mg in 3 ml
NSS every 2–4 hours as needed.16 The dose can be increased in 5 mg increments until relief is achieved.16
Do opioids hasten death?
Unfortunately, many prescribers are reluctant to use morphine or other opioids to manage dyspnea due to concerns
that respiratory depression can hasten death. Studies show that the risk of respiratory depression secondary to opioid
use in terminally ill patients is very minimal when therapy is initiated at a low dose and titrated thereafter based on
patient response and tolerability.
A recent study of hospice patients demonstrated that opioid use causes an extremely small risk of hastened death in
this population.17 Ethically, there is no justification for withholding opioid treatment out of fear of potential respiratory depression.18
Conclusion:
Dyspnea is a common and distressing symptom in hospice patients
Opioids should be considered as first-line therapy
• Start low and go slow when initiating opioid therapy
• Nebulized opioids may be effective for some patients, but evidence supporting their use is lacking
• Appropriately dosed opioids should not be withheld from patients because of respiratory depression fears
•
•
HP Partners, please refer to the dyspnea algorithm on page 28 in the Hospice Pharmacia Medication Use
Guidelines, 8th Edition for more information on palliation of dyspnea.
References
1. Ripamonti C, Fulfaro F, Bruera E. Dyspnoea in patients with advanced cancer: Incidence, causes and treatments. Cancer Treat Rev.
1998;24(1):69–80.
2. Webb M, Moody LE, Mason LA. Dyspnea assessment and management in hospice patients with pulmonary disorders. Am J Hosp Palliat Med.
Jul 2000;17(4):259–264.
3. Williams CM. Dyspnea. Cancer J. Sep 2006;12(5):365–373.
4. Ripamonti C, Bruera E. Dyspnea: Pathophysiology and assessment. J Pain Symptom Manage. 1997;13(4):220–232.
5. Moody L, McMillan S. Dyspnea and quality of life indicators in hospice patients and their caregivers. Health Qual Life Outcomes. 2003;1(1):9.
6. Jennings AL, Davies AN, Higgins JPT, Gibbs JSR, Broadley KE. A systematic review of the use of opioids in the management of dyspnoea.
Thorax. Nov 2002;57(11):939–944.
7. 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. Sept 2003;327(7414):523–528.
8. Hallenbeck JL. Non-pain symptom management: Dyspnea. In: Hallenbeck JL, ed. Palliative Care Perspectives: Oxford University Press; 2003.
9. Ketzner P, Lindgren M. The use of nebulized medications for the treatment of dyspnea. PERT Program: Tip of the Month [online].
December 2004; http://www.swedishmedical.org/PERT/tips/tip_dec_04.htm. Accessed 15 March 2007.
10. Robin ED, Burke CM. Risk-benefit analysis in chest medicine. A new feature. Chest. Feb 1986;89(2):163–164.
11. Berger AM, Shuster JL, Von Roenn JH. Principles and Practice of Palliative Care and Supportive Oncology. 3rd ed: Lippincott Williams
& Wilkins; 2006.
12. Allard P, Lamontagne C, Bernard P, Tremblay C. How effective are supplementary dose of opioids for dyspnea in terminally ill patients:
A randomized, continuous sequential clinical trial. J Pain Symptom Manage. 1999;17(4):256–265.
13. Thomas JR, von Gunten CF. Clinical management of dyspnoea. Lancet Oncol. 2002;3(4):223–228.
14. Sarhill N, Walsh D, Khawam E, Tropiano P, Stahley MK. Nebulized hydromorphone for dyspnea in hospice care of advanced cancer.
Am J Hosp Palliat Med. Nov 2000;17(6):389–391.
15. 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. 2002;23(2):157–160.
16. Dyspnea. In: Weschules DJ, Baer J, Bain KT, et al., eds. Hospice Pharmacia’s Medication Use Guidelines (MUGs)TM. 8th ed. Philadelphia:
excelleRx, Inc; 2006.
17. Portenoy RK, Sibirceva U, Smout R, et al. Opioid use and survival at the end of life: A survey of a hospice population. J Pain Symptom
Manage. 2006;32(6):532–540.
18. Randall R, Downie RS. Palliative Care Ethics: A Good Companion. 1st ed. Oxford, U.K.: Oxford University Press; 1996:71–74.
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A P RIL 2007
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Evidence Matters
Dear Clinician,
Please enjoy Hospice Pharmacia’s second edition of Evidence Matters, a newsletter devoted to
sharing clinical information and promoting an evidence-based approach to palliative medicine. Our second topic is The Role of Opioids in Treating Dyspnea.
This newsletter is a production of the Quality Outcomes team at excelleRx. Our team is
dedicated to building the evidence base and improving outcomes related to chronic illness
and palliative care. We welcome your feedback and questions as well as your suggestions
for future topics.
We hope you find this publication a valuable resource.
Sincerely,
The Quality Outcomes Team • qualityoutcomes@excelleRx.com • 215.282.1724