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
