by Daniel Johnson MD, University of Colorado Health Sciences Center, Denver, CO.
Ms. Y is an 82 y/o woman admitted to inpatient hospice with advanced metastatic lung cancer and COPD. Despite treatment with steroids, nebulized albuterol and atrovent, IV morphine, lorazepam and oxygen, she remains short of breath at rest. Ms. Y accepts her poor prognosis, and appears at peace both socially and spiritually. She states "I just want to be more comfortable [in her breathing] for whatever days I have left." She complains of fatigue, increasing somnolence and constipation - especially following recent increases in her morphine. Her pain is well controlled. You want to provide her relief, but are concerned about the increasing side effects of the IV opioids. You wonder, "is there a role for nebulized opioids in treating Ms. Y's dyspnea?"
Multiple studies have examined the use of morphine and other narcotics in the treatment of breathlessness in seriously or terminally ill patients. There is a growing interest in the use of nebulized opioids for dyspnea - especially in cases where systemic side effects of oral/ parenteral opioids make further narcotic dosage escalation less desirable. While the physiologic mechanism(s) by which opioids relieve dyspnea are poorly understood, nebulized opioids may provide an advantage over oral/parenteral routes through direct drug delivery to lung opioid receptors with decreased systemic absorption.1
While numerous authors have reported case series describing the effective relief of dyspnea using nebulized morphine, hydromorphone and fentanyl, few blinded, well-controlled clinical trials exist. A recent Cochrane collaborative systematically reviewed the use of opioids for the palliation of dyspnea in terminal illness. Based on 18 randomized double-blind, controlled trials (9 of which studied nebulized opioids) the group concluded that 1) there was evidence to support the use of oral or parenteral opioids to palliate breathlessness, although the number of patients involved in the studies were small, and 2) there was no evidence to support the use of nebulized opioids. The group recommended further research with larger numbers of patients, using standard protocols and with quality of life measures.2
Is the use of nebulized opioids for the relief of dyspnea safe? While most studies report few or no significant adverse reactions to nebulized opioids, at least one study describes a case of respiratory depression requiring mechanical ventilation following the administration of nebulized morphine.3 Bronchospasm has been reported with the use of nebulized opioids, particularly at higher doses. Fentanyl may be associated with less bronchospasm.4 The first dose should be administered in a supervised setting where medical or nursing intervention is available in case of bronchospasm or other adverse effect. When utilizing morphine, the IV formulation should be used rather than the oral elixir.5
There is no consensus on the most appropriate starting dose or schedule, the best steps for dose titration, or the optimal design and length of a therapeutic trial. Some suggested doses by one review include:5
|Morphine Sulfate||20 mg diluted to 5 mls w/ saline||Up to 4 times/hr||Up to 100 mg 4 times/hr||Risk of bronchospasm|
|Fentanyl Citrate||50 mcg diluted to 5 mls w/ saline||Up to 4 times/hr||Up to 100 mcg 2 times/hr||Less risk of bronchospasm|