Journal of Pain & Palliative Care Pharmacotherapy

ISSN: 1536-0288 (Print) 1536-0539 (Online) Journal homepage: https://www.tandfonline.com/loi/ippc20

Nebulized Fentanyl for Dyspnea: A Retrospective

Chart Review

Elizabeth A. Higgins, Aaron M. Young, Joan Cain, Jennifer D. Dulin, Margaret

M. Miller, Amanda N. Overstreet, Leigh Vaughan & Patrick J. Coyne

To cite this article: Elizabeth A. Higgins, Aaron M. Young, Joan Cain, Jennifer D. Dulin, Margaret
M. Miller, Amanda N. Overstreet, Leigh Vaughan & Patrick J. Coyne (2020): Nebulized Fentanyl for
Dyspnea: A Retrospective Chart Review, Journal of Pain & Palliative Care Pharmacotherapy

To link to this article: https://doi.org/10.1080/15360288.2019.1708529

Published online: 10 Jan 2020.

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JOURNAL OF PAIN & PALLIATIVE CARE PHARMACOTHERAPY
https://doi.org/10.1080/15360288.2019.1708529

ARTICLE

Nebulized Fentanyl for Dyspnea: A Retrospective Chart Review

Elizabeth A. Higgins , Aaron M. Young, Joan Cain, Jennifer D. Dulin, Margaret M. Miller,
Amanda N. Overstreet, Leigh Vaughan and Patrick J. Coyne

ABSTRACT ARTICLE HISTORY

Nebulized fentanyl is well established for analgesia but its use for dyspnea requires further Received 21 August 2019
investigation. The aim of our study was to determine the effectiveness of nebulized fentanyl Accepted 13 December 2019
in treating patients with dyspnea and to determine if there were harmful side effects
KEYWORDS
described by patients or their providers. We used a convenience sample of patients from
Dyspnea; fentanyl;
July 1 2014 to July 1 2018 and performed a retrospective chart review. We found that 360 nebulized; opiod;
doses of nebulized fentanyl were given to 73 patients during that time period. Of the 73 palliative care
patients evaluated, 32 patients (43.8%) were female and forty-one were male (56.1%). The
median age was 67 and the median length of stay was 9 days. There were no documented
findings of bronchospasm, hypotension, or allergic reaction in any of the medical records
reviewed. Patients treated with nebulized fentanyl for dyspnea showed a mean decreased
respiratory rate of 4.3 breaths/min and a mean increased oxygen saturation of 2.3%. Also,
71% of patients with documented responses experienced an improvement in their dyspnea.
Our preliminary data suggest that nebulized fentanyl has limited side effects and may have
a role in the treatment of dyspnea. Further research is necessary to determine its efficacy.

Introduction with or without hospice. Nebulized fentanyl is

Dyspnea, the subjective sensation of shortness of
breath, can be disabling and affects more than
50% of patients at the end of life (1). Systemic
administration of opioids is the most well
established pharmacologic treatment for the
management of dyspnea in patients with
advanced illness, and both the American College
of Physicians and the American Thoracic Society
recommend their routine use (2,3). The adminis-
tration of inhaled opioids is attractive due to
their limited systemic absorption (4). Other
potential advantages of inhalation therapy include
rapid relief; no need for IV access; ease of admin-
istration; patient preference to oral or parenteral
administration, and amenability to home therapy
absorbed quickly as it is highly lipophilic (5) and
works as well as intravenous fentanyl for the
relief of pain (6). Descriptive studies and case
reports have yielded promising results for the use
of nebulized fentanyl for the relief of breathless-
ness (7–9). A recent randomized, double blind,
placebo-controlled, cross-over study compared
inhaled fentanyl citrate with placebo in 12 stable
COPD patients over the age of 40 with a history
of cigarette smoking, showed that fentanyl citrate
was associated with significant and potentially
clinically important improvements in exercise
tolerance in patients with COPD (10).
The use of nebulized fentanyl for the treatment
of dyspnea has already become common at our

Elizabeth A. Higgins, MD is with the Division of General Internal Medicine, Geriatrics and Palliative Care, Medical University of South Carolina, Charleston,
South Carolina, USA; Aaron M. Young, MBA is with the Division of General Internal Medicine, Geriatrics and Palliative Care, Medical University of South
Carolina, Charleston, South Carolina, USA; Joan Cain, FNP is with the Division of General Internal Medicine, Geriatrics and Palliative Care, Medical
University of South Carolina, Charleston, South Carolina, USA; Jennifer D. Dulin, MD is with the Division of General Internal Medicine, Geriatrics and
Palliative Care, Medical University of South Carolina, Charleston, South Carolina, USA; Margaret M. Miller, PhD is with the CHFA, Denver, Colorado, USA;
Amanda N. Overstreet, DO is with the Division of General Internal Medicine, Geriatrics and Palliative Care, Medical University of South Carolina,
Charleston, South Carolina, USA; Leigh Vaughan, MD is with the Division of General Internal Medicine, Geriatrics and Palliative Care, Medical University of
South Carolina, Charleston, South Carolina, USA; Patrick J. Coyne MSN, ACHPN, ACNS-BC, FAAN, FPCN is with the Division of General Internal Medicine,
Geriatrics and Palliative Care, Medical University of South Carolina, Charleston, South Carolina, USA.
CONTACT Elizabeth A. Higgins, MD higginel@musc.edu Division of General Internal Medicine, Geriatrics and Palliative Care, Medical University of
South Carolina, Charleston, SC 29425, USA.
The data that support the findings of this study are available from the corresponding author, [EH], upon reasonable request.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/ippc.
ß 2020 Taylor & Francis Group, LLC
2 E. A. HIGGINS ET AL.

institution following the publication of a study about the effectiveness or harm of the nebulized
showing that nebulized fentanyl citrate was safe treatments. Coders also recorded the patient’s age,
and effective in improving respiratory rates, oxy- gender, diagnosis, length of stay, and whether the
gen saturation, and breathing in 35 patients com- patient was on systemic opioids. Coders also
plaining of dyspnea (11). Our institution is a logged whether the patient had a palliative care
700-bed medical center, which includes a nation- consult. SPSS was used to calculate a paired t-test
ally recognized children’s hospital, a National (p < 0.05) to compare the respiratory rates and
Cancer Institute designated cancer, a Level I oximetry levels pre- and post-treatment of one
trauma center, a psychiatric hospital, and South group of patients receiving nebulized fentanyl.
Carolina’s only transplant center. In order to add
to the body of knowledge of nebulized fentanyl
Results
for the treatment of dyspnea, we performed a
retrospective chart review in our electronic health We found that 360 doses of nebulized fentanyl
record (EHR). The aim of our investigation was were given to 73 patients during the time period
to determine the effectiveness of nebulized fen- of July 2014-July 2018. No doses were adminis-
tanyl in treating patients with dyspnea and to tered in 2014 and two were given in both 2015
discover if there were harmful side effects and 2016. Most doses were given in 2017 (121
described by patients or their providers by doses) and 2018 (235 doses). 73 patient medical
reviewing reports of respiratory rates, oximetry records were reviewed. Of the 73 patients eval-
levels, and patient or provider observations. uated, 32 (43.8%) patients were female and 41
(56.1%) were male. The median age was 67 years
Methods and the median length of stay was nine days. The
indication for receiving nebulized fentanyl for all
We used a convenience sample and searched our
patients was dyspnea. Diagnoses causing the
EHR from July 1, 2014 (the origin of our EHR) to
symptom of dyspnea varied. Patients received an
July 1, 2018. The inclusion criteria were all patients
average of four doses of nebulized fentanyl dur-
at our institution who had an order for fentanyl
ing their admission. 89% of patients (n ¼ 65)
for inhalation use only. Nebulized fentanyl at our
were on oxygen and 89% (n ¼ 65) had palliative
institution is compounded from preservative-free
care consults. Most of the patients (83.6%;
fentanyl citrate 100 mcg/2 ml vials. No patients
n ¼ 61) were on systemic opioids (Table 1).
were excluded from the chart review search, but
qualitative data from patients that had no docu- Table 1. Patient demographic information.
mented response could not be reported. Prior to Patient characteristic N. of patients (%)
data abstraction, coders were carefully trained in a Sex
1:1 session on how to search an EHR for documen- Male 41 (56)
Female 42 (58)
tation. Coders then coded several patient records Age (years)
<40 9 (12)
for practice. Practice records were not included in 40–60 13 (18)
the data set. Coders extracted data onto an Excel 60–80 42 (58)
>80 9 (12)
spreadsheet and included the patient’s name and Diagnosis
medical record number, order time and date, dose, Various cancers 26 (12)
COPD 7 (18)
and frequency. Hospital admission and discharge Pulmonary edema 5 (58)
dates were also noted. The coders examined the Pneumonia 5 (12)
Interstitial lung disease 4 (5)
medical records for indications for the use of nebu- Other/combinations 26 (36)
Length of stay (days)
lized fentanyl and the results (if any) of the treat- 1–5 22 (30)
ment. Coders reviewed all notes for each patient’s 5–10 20 (27)
11–20 16 (22)
specific encounter leading up to each administra- 21–30 8 (11)
tion of nebulized fentanyl. Coders looked for evi- 7 (10)
Systemic opioids
dence of pre- and post- respiratory rates, oximetry Yes 61 (84)
levels, and for patient or provider observations No 12 (16)

Figure 1. Data collection flow chart.
Table 2. Respiratory rate and oximetry results.
Mean (bmp)
RR pretreatment 23
RR post-treatment 20.4
Cohen’s d ¼ 0.49 p < 0.001
Mean
02 Sat pretreatment 94.8%
02 Sat post-treatment 96.1%
Cohen’s d ¼ 0.30 p < 0.001
RR ¼ respiratory rate.
O2 Sat ¼ oxygen saturation (%).
Overall patient response was documented in 42
cases (57.5%). Of the patients whose response was
recorded, patient-reported dyspnea was improved
in 30 cases (71.4%), and neutral/no effect was
reported in 11 patients (26.2%) (Figure 1). One
patient reported a general body adverse reaction to
the fentanyl. Chart notes state that she tried one
treatment of inhaled fentanyl but that, per nursing,
“she didn’t like the way it made her feel.” The
same patient did receive nebulized fentanyl several
months later, which resulted in “some relief.”
Providers reported no adverse reactions of
bronchospasm, hypotension, or allergic reaction in
any of the medical records reviewed. Respiratory
rates pre- and post-treatment were available for 78
administrations of the nebulized fentanyl.
Oximetry results pre- and post-treatment were
available for 60 administrations. There was a sig-
nificant difference in respiratory rate between the
pretreatment (M ¼ 23.0, SD ¼ 5.76) and post-
treatment (M ¼ 20.4, SD ¼ 5.30) results;
t(77)¼4.349, p < 0.001. There was also a significant
difference in oxygen saturation between the pre-
treatment (M ¼ 94.9, SD ¼ 4.39) and post-treat-
ment (M ¼ 96.1, SD ¼ 3.61) results; t(59)¼-2.343,
p ¼ 0.022. These results suggest that nebulized fen-
tanyl significantly decreased respiratory rate while
increasing oxygen saturation when used to treat
patients experiencing dyspnea (Table 2).
JOURNAL OF PAIN & PALLIATIVE CARE PHARMACOTHERAPY 3
N. of Patients Std. Deviation Std. Error Mean
78 5.76 0.65
78 5.29 0.60
N. of patients Std. deviation Std. error mean
60 4.39 0.57
60 3.61 0.47
Discussion
Dyspnea can be a disabling symptom with a sig-
nificant impact on quality of life. Systemically
administered opioids have been the mainstay of
treatment for dyspnea but concerns about adverse
effects can limit their use. One study found
inhaled opioids to be the least invasive, most
accepted, and most preferred route of drug deliv-
ery by patients with chronic diseases who experi-
ence dyspnea (12). Nebulized opioids may work
locally in the airways and lungs with only small
amounts of the drug being absorbed systemically,
therefore producing fewer, if any, side effects (5).
The evidence for nebulized morphine in the
treatment of dyspnea remains mixed whereas a
potential benefit for nebulized fentanyl and
hydromorphone has been suggested (13,14).
Fentanyl’s lipophilic properties and rapid mucosal
absorption make it an attractive alternative to
morphine. Unlike morphine, fentanyl does not
cause histamine release and has not been shown
to cause bronchospasm (15). In addition, a 25-
mcg dose of fentanyl citrate administered from a
100 mcg/2 ml vial is reasonably inexpensive. The
average wholesale price for one 2 ml vial is cur-
rently $2.32.
Retrospective chart reviews are usually hypoth-
esis generating for future controlled trials and are
valuable for furthering research of medication
4 E. A. HIGGINS ET AL.
therapies. Our retrospective chart review found a
statistically significant decrease in respiratory rate
and increase in oxygen saturation after the
administration of nebulized fentanyl. This
improvement in oxygen saturation and decrease
in respiratory rate was also noted by Coyne et al.
(11). These changes can potentially be explained
by higher tidal volumes and therefore improved
minute ventilation and less ventilation/perfusion
mismatch. We were reassured by the finding that
only one patient reported an adverse reaction
to the fentanyl.
Retrospective reviews have inherent constraints
and biases. For example, our data abstracters
were not blinded to the aim of the review and
may have been biased in their data collection.
We were also limited by the lack of documented
patient-reported response to fentanyl in 31
(42.5%) of the charts we reviewed. Our findings
cannot determine causation, only association, and
the patients making up our sample may not be
applicable to every population.
Conclusion
Our retrospective chart review found that
patients treated with nebulized fentanyl for
dyspnea showed a significant decrease in respira-
tory rate and increase in oxygen saturation. In
addition, 71.4% of patients with a documented
response reported improved symptoms of
dyspnea. This information, combined with only
one documented adverse reaction, suggests that
inhaled fentanyl could be a safe and effective
treatment for patients experiencing dyspnea.
Further research including randomized controlled
studies is needed to conclusively determine the
safety and effectiveness of nebulized fentanyl for
the treatment of dyspnea. Further work is also
needed to determine which diagnoses may benefit
the most and to determine the efficacy and safety
of the chronic use of nebulized fentanyl.
Disclosures
This research received no specific funding/
grant from any funding agency in the public,
commercial, or not-for-profit sectors. The authors
have no conflicts of interest to declare.
Acknowledgements
This research received no specific funding/grant from any
funding agency in the public, commercial, or not-for-profit
sectors. The authors have no conflicts of interest to declare.
We wish to thank Jeni Hayes, PharmD, MSPharm, BCPS
for her assistance in searching our electronic health record.
We are also grateful to Hannah Coyne, Hannah Epstein
and Conrad Williams for their expert review.
ORCID
Elizabeth A. Higgins http://orcid.org/0000-0003-
4123-4148
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