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Oxygen for end-of-life lung cancer care: Managing dyspnea and hypoxemia

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 Review

Oxygen for end-of-life lung

cancer care: managing
dyspnea and hypoxemia
Expert Rev. Respir. Med. 7(5), 479–490 (2013)

Brian Tiep*1, Oxygen is commonly prescribed for lung cancer patients with advancing disease. Indications
Rick Carter2, include hypoxemia and dyspnea. Reversal of hypoxemia in some cases will alleviate dyspnea.
Finly Zachariah1, Oxygen is sometimes prescribed for non-hypoxemic patients to relieve dyspnea. While some
patients may derive symptomatic benefit, recent studies demonstrate that compressed room
Anna C Williams1,
air is just as effective. This raises the question as to whether to continue their oxygen. The
David Horak1, most efficacious treatment for dyspnea is pharmacotherapy–particularly opioids. Adjunctive
Mary Barnett1 and therapies include pursed lips breathing and a fan blowing toward the patient. Some patients
Rachel Dunham1 may come to require high-flow oxygen. High-flow delivery devices include masks, high-flow
1
City of Hope National Medical Center, nasal oxygen and reservoir cannulas. Each device has advantages and drawbacks. Eventually, it
Duarte, California, USA may be impossible or impractical to maintain a SpO2 > 90%. The overall goal in these patients
2
Lamar University, Texas, USA
is comfort rather than a target SpO2. It may eventually be advisable to remove continuous
*Author for correspondence:
btiep@coh.org oximetry and transition focus to pharmacological management to achieve patient comfort.

KEYWORDS: adjunctive therapy • benzodiazepines • dyspnea • high-flow oxygen • lung cancer • opioids • oxygen
• pharmacotherapy

dyspnea, recent studies have concluded that oxy-

Oxygen therapy in context of end-of-life
care
Clinicians commonly prescribe oxygen for
lung cancer patients with end stage disease.
Indications for oxygen typically include hypo-
xemia and dyspnea. Prescribing oxygen for
hypoxemic patients is well founded and justi-
fied by studies performed in patients with
chronic lung disease–particularly those with
COPD [1,2]. Most of these studies determined
that oxygen therapy over time improved sur-
vival in the chronic lung disease population.
Dyspnea was not often addressed as a primary
endpoint. In patients with lung cancer at the
end of life, the treatment goal is to abolish
dyspnea and assure patient comfort [3,4]. It is
important to recognize that some patients are
hypoxemic but not dyspneic, while others may
be dyspneic but not hypoxemic [5]. Hence,
dyspnea is not synonymous with hypoxemia
and the treatment for hypoxemia may not
relieve dyspnea.
Dyspnea, a perception, often occurs in the
non-hypoxemic patients [6]. While it may seem
intuitive to prescribe oxygen for patients with
gen is no more effective than compressed ambi-
ent air in relieving dyspnea [7]. Accordingly,
oxygen may not be recommended for patients
displaying dyspnea on the basis of evidence to
support it. However, some patients in those
studies derived symptomatic benefit from both
oxygen and medical air [7,8]. This raises the ques-
tion as to whether it is justifiable for those
patients to receive oxygen, despite the fact that
compressed ambient air will work just as well.
On the other hand, some studies have demon-
strated that administering oxygen does not
relieve dyspnea in a number of hypoxemic and
non-hypoxemic patients [9]. These data, point to
the premise that dyspnea is in fact a multidimen-
sional sensation and for some supplementing
with either air or oxygen may have benefit while
others may not gain relief from either.
Oxygen is not the only treatment option, nor
is it the most efficacious remedy for relieving
dyspnea. Opioids are very effective in alleviating
the discomfort of dyspnea whether the patient is
hypoxemic or not [10]. Additionally, benzodiaze-
pines have been successful in calming anxiety
that often accompanies dyspnea [11].

www.expert-reviews.com 10.1586/17476348.2013.816565
2013 Informa UK Ltd ISSN 1747-6348 479

 Review Tiep, Carter, Zachariah et al.
This review will address the treatment of dyspnea as a com-
ponent of palliative care for patients with advanced lung cancer
and where oxygen may be positioned in the overall treatment
plan. Oxygen is one option that should be considered as part
of a comprehensive palliative management plan, and may be
both rational and reasonable even if it does not reverse or pre-
vent tissue hypoxia. The goal of care is palliation rather than
arterial oxygenation [5]. That fact should be kept in mind as
the decision to include or continue oxygen is being considered.
Oxygen therapy will be presented along with portable and sta-
tionary systems for prescribing oxygen.
Approaching the end of life
It is generally recognized that the most likely outcome for
advanced stage lung cancer is that the death will occur as a
consequence of the cancer and/or its sequella [4]. It is often not
apparent as to when the end of life for a lung cancer patient is
imminent. Likewise, it is not always clear as to when to make
the transition from treatment targeting tumor regression to
providing comfort to the patient and family as the central med-
ical delivery focus [12].
A reasonable expectation for patients with advanced lung
cancer is that active treatments including radiation and chemo-
therapy will lead to tumor regression. As tumors become
smaller in size, patients and family grasp for hope that they
will beat their cancer and live a long life [4]. In fact, some
patients with advanced stage disease do live several years seem-
ingly unaffected by their cancer. However, at some point their
cancer returns with local or distant metastases. Other lines of
tumor-targeted therapy are then offered–again ushering hope
for tumor regression. Finally, at some point it becomes obvious
that the cancer will prevail. Commonly it is at this junction
that therapeutic attention turns to symptomatic relief as
patients experience increasing pain, nausea, fatigue and dysp-
nea. Dyspnea is especially prevalent in patients with co-existing
COPD or other lung conditions [6].
Many patients and their caregivers become fearful that death
will occur by suffocation. Simple reassurance is often insuffi-
cient for this very worrisome concern. When life-preserving
treatment ceases, it is common for patients and their families
to assume that the healthcare team is giving up and no longer
fighting the cancer [4]. Actually, symptomatic care (available all
along) now becomes central. Included in symptomatic care
may be some very active interventions including radiation or
laser to reopen an obstructed bronchus or thoracentesis to drain
a pleural effusion. Also, non-invasive positive pressure ventila-
tion (NPPV) for respiratory assistance may be appropriate for
relieving respiratory discomfort [13].
Palliative medicine
The focuses of palliative medicine are to prevent/reduce suffering
and improve quality of life. It is specifically designed to assist
patients with serious or life threatening illness, and centers on
symptom management in the context of whole person care for
the patient and their family. Palliative medicine comprises four
480
domains: physical, psychological, social and spiritual [4]. Accord-
ingly, a multidisciplinary team is involved. Palliative care is
provided, keeping with the patient and family desires and prefer-
ences. It is not just provided at end of life when symptoms can
be overwhelming, but is ideally integrated into all stages of can-
cer care, as early as the time of diagnosis and includes bereave-
ment support once a patient passes away [14]. If included within
the medical model, it creates a continuum of care that manages
all aspects of the life of the patient.
As cancer advances, patients and their families become terri-
fied that the end of life will be rampant with pain and suffoca-
tion. Both pain and dyspnea can be abated or relieved in most
cases [15]. Knowing that suffocation can be averted may go far
to relieve the suffering of anticipation. It is therefore crucial
that clinicians understand dyspnea, how to assess its etiologies
and what treatment options are most effective [16]. This may
include oxygen therapy provided specifically for dyspnea relief
and not for correction of arterial hypoxemia as commonly
indicated.
The prevalence of dyspnea in advanced lung cancer can be
as high as 70%. The presence and intensity of dyspnea will
depend on multiple factors including anxiety and comorbid-
ities [17]. It is debilitating and has a major impact on the will
power to live. It is a frequent cause of reduced activity levels
and participation in living. It tends to be a prognostic indicator
of mortality. Dyspnea prevention and relief are therefore signif-
icant components of palliative care–particularly at the end of
life. Pain is also very common in cancer patients, and may
travel similar neurological paths as dyspnea. Pain has been
shown to amplify dyspnea [18]. Thus, controlling of pain may
help in the control of dyspnea.
Many patients wish to remain physically active and partici-
pate in meaningful activities and relationships to the extent
possible as the end of life nears. Pulmonary rehabilitation pro-
vides tools that can be helpful with the reasonable goal of max-
imizing quality of life that is so valued at this critical juncture.
Hospice is a subset under the umbrella of palliative medicine,
and is an important and even crucial component of the contin-
uum of care, allowing for aggressive symptom management
and whole person care at the end of life.
Dyspnea
Dyspnea is a multidimensional process; it is a subjective symp-
tom that is experienced by the patient and communicated to
the clinician. Dyspnea may occur at any stage of the disease
and must be addressed [19]. Dyspnea may be caused by two
major threats: 1) increased work of breathing, which is the per-
ceived imbalance between the body’s demand for ventilation
and its ability to meet it and 2) suffocation, which is an intense
desire to breathe coupled with the lack of ability to do so [10].
Dyspnea may be the direct result of impairment in the work of
breathing, hypoxemia, CO2 retention, airway obstruction,
restriction, interstitial impairment, lack of lung volume, or it
may be caused by a failure of circulatory transport mechanics
and/or energetic mechanisms [20].
Expert Rev. Respir. Med. 7(5), (2013)
 Oxygen for end-of-life lung cancer care: managing dyspnea & hypoxemia
There is no direct measure of dyspnea beyond symptom
scores, although indications on physical examination include
tachypnea and halting speech [20]. Arterial blood gas abnormal-
ities hypoxemia and hypercapnia, as well as alterations in pH
in either direction provide important information helpful in
understanding a cause for dyspnea and its ultimate relief. How-
ever, these findings may be loosely correlated or completely
unconnected. In assessing dyspnea, it is reasonable to try to dis-
cern dyspnea intensity and the distress places on the patient
and the patient’s ability to function. Also, the language of
dyspnea yields important new insights, and is becoming a key
diagnostic tool for understanding and evaluating dyspnea [21-23].
Hence, the clinician must be in tune to the patient’s descrip-
tion, such as ‘I feel like I am suffocating’ or ‘I can not catch
my breath’ [19–22]. Those descriptors provide clues as to the
cause of their dyspnea and enhance the ability to manage it.
Dyspnea on exertion reflects both patient effort and a failing
attempt to achieve adequate ventilatory support for that effort.
It reflects the burden of increased work of breathing.
Dyspnea varies in intensity in response to an interface of
physiology, psychology, psychosocial, environmental and care-
giver impacts. The overall impact is frightening and conjures
the feeling of impending death. The fear of dyspnea becomes a
driving factor in both lung cancer, as well as, that experienced
by patients with severe lung disease in exacerbation. If broncho-
spasm is involved, bronchodilators may provide rapid and
ongoing relief. Oxygen for the patient, who is hypoxemic, par-
ticularly worsening on exertion, will likely improve their ability
to exert with less dyspnea by improving oxygenation and
reducing the work of breathing [9]. Successful treatment of
dyspnea can be achieved first by determining the underlying
cause and then targeting treatment [10].
Assessment of dyspnea
Dyspnea can be described in terms of quality, intensity, triggers
and relievers. Quality is described as ‘air hunger’, ‘suffocation’,
‘unable to take a deep breath’ or ‘chest tightness’ [20]. Intensity
can be assessed on a scale of 1–10 as in the Borg Score, or by
use of a visual analogue scale. A number of other dyspnea scales
are available to both assess and determine the impact of dyspnea
on the patient’s ability to function [19]. Triggers and relievers
provide information directly useful in treating the patient.
Management of dyspnea
The goal of managing dyspnea is complete relief of this fright-
ening symptom, thus enabling an enriched quality of life.
Ideally, addressing the cause of the dyspnea and resolving that
pathology would be ideal [20]. Examples would be: the treat-
ment of bronchospasm with bronchodilators (and steroids),
thoracentesis to remove a large pleural effusion, anticholinergics
to reduce secretions or radiation to shrink an obstructing
lesion. However, this is often not possible or practical at the
very end of life.
Pharmacological management is largely based on opioids–
particularly morphine derivatives. Oral (sublingual) morphine
www.expert-reviews.com
Review
derivatives are rapid and effective with convenient dosing. Sys-
temic opioids are particularly effective over the long term - uti-
lizing a slowly escalating dosing protocol [10]. Opioid receptors
are found not only in respiratory centers in the brain, but
peripherally as well [24]. The peripheral location provides a basis
for utilizing nebulized fentanyl (25 mcg of fentanyl citrate in
2 ml of saline) [25]. While nebulized fentanyl shows promise,
nebulized morphine has not been shown to have benefit in alle-
viating dyspnea [26]. In prospective double-blinded randomized
placebo-controlled trials, nebulized morphine had no effect on
dyspnea and only one of seven studies showed a minor benefit
in exercise tolerance. In contrast, a number of uncontrolled tri-
als and case studies, predominantly in advanced cancer showed
subjective improvement in dyspnea, paroxysmal coughing and
breathing pattern [27]. Oral transmucosal fentanyl citrate
showed promise in a small study of four patients as another
potentially safe (and easy to administer) alternative to alleviate
dyspnea [28].
Opioids have the usual side-effects of constipation, nausea
and sedation, but by slow escalation of opioids, respiratory cen-
ter suppression and sedation can be minimized or averted.
Among the side-effects, constipation is typically the only persis-
tent one, and an adequate bowel regimen should always be
advised when opioids are administered [16].
Morphine dosing of 2.5 mg (oral elixir comes as 10 mg/
5ml, 20 mg/5ml or 100 mg/5ml) every 4 h as needed for dysp-
nea is a good starting place for opioid naı̈ve patient [14]. If a
patient continues to have severe dyspnea, the dose may be
doubled. The dosing interval may also be shortened, consider-
ing peak effect of short-acting morphine is between 30–90 min
and duration is approximately 4 h [29]. Further titration needs
to balance comfort with side-effects. The highest risk for seda-
tion and elevations in PaCO2 occurs when basal or long-acting
doses are utilized. If oral formulations of opioids do not pro-
vide adequate relief because of slow onset, use of a patient con-
trolled anaesthesia (PCA) pump enables patients to self-
administer their medication in the home setting with subcuta-
neous catheter in place. Onset of subcutaneous morphine is
around 5–10 min. If a patient has renal insufficiency, consider
using dilaudid or fentanyl as alternative opioids to prevent
build-up of metabolites.
Benzodiazepines are not generally effective in relieving dysp-
nea except when the patient is experiencing a significant degree
of anxiety. One exception is a study using midazolam (Versed)
in cancer patients [27]. In this study, midazolam was at least as
effective as morphine in reducing dyspnea with adequate dos-
ing [30]. While the evidence for first line use is weak, benzodia-
zepines may serve as a second line treatment when opioids are
not fully effective or the patient has a strong anxiety compo-
nent [31]. In general, benzodiazepines are useful adjuncts to
opioids when anxiety becomes a major co-conspirator.
Pain and dyspnea not only coexist, but also can be mutually
reinforcing [18]. Opioids may be rejected by the patient or fam-
ily for the treatment of dyspnea but might be embraced for
pain control. Providing opioids for pain control will also be
481
 Review Tiep, Carter, Zachariah et al.
effective at relieving dyspnea, thereby enabling its acceptance
by the patient for relieving dyspnea. Furosemide and prometha-
zine are two other agents which may have some utility in treat-
ing dyspnea. Nebulized furosemide (20–40 mg) was seen to
have benefit in a number of small studies [27,32,33]. Oral prome-
thazine (25 mg) has conflicted reports of success in dyspnea [34].
Further studies are needed to determine whether these treat-
ments should be generally recommended to alleviate dyspnea
and whether they should be given alone or in conjunction
with opioids.
While opioids, particularly morphine and fentanyl are the
most consistent and reliable treatment for dyspnea; palliative
sedation via a non-opioid may be necessary to lower the level
of consciousness in the case of refractory dyspnea [35]. When a
patient has underlying pain, opioids are continued during
palliative sedation.
Adjunctive therapies for dyspnea
A fan blowing air past the face can sometimes relieve dyspnea,
whether or not associated with hypoxemia [36]. Vibration can
calm dyspnea, as well as distraction with music. Pulmonary
rehabilitation has a variety of tools to help the patient to feel
better-both symptomatically and about themselves [37]. These
include exercise training such as walking, ergonomics, techni-
ques to manage depression and anxiety and breathing techni-
ques. Pursed lips breathing may be useful in improving oxygen
uptake and CO2 elimination for the same ventilatory effort,
and thereby reduce the work and energy cost of breathing [38].
Relaxation techniques can help to relieve the anxiety compo-
nent while avoiding sedation. Modification of activity levels
with efficiency training, wheel chairs, walkers and bathroom
aids may increase autonomy and self-efficacy. When patients
have a buildup of secretions, chest physiotherapy and cough
training along the bronchodilators can mobilize and clear
secretions [39].
Cancer and COPD frequently co-exist [40]. Treatments speci-
fied for COPD including bronchodilators will often make a
difference and give the patient a sense of self-efficacy. Gluco-
corticoids are administered to relieve inflammatory airway
obstruction and are particularly efficacious during a COPD
exacerbation. Diuretics may help resolve dyspnea for patients in
fluid overload. A thoracentesis will enable the patient with a
pleural effusion to breathe with greater inspiratory volume and
less restriction.
Oxygen therapy can minimize dyspnea for some patients
with advanced lung cancer. Oxygen for dyspneic patients who
are hypoxemic is generally accepted on the basis of the noctur-
nal oxygen therapy trial (NOTT) and MRC studies performed
on COPD patients [1,2]. Oxygen for patients who are dyspneic
but non-hypoxemic is shown to be no more effective than
compressed ambient air [7]. The question arises as to whether
to provide non-hypoxemic patients with oxygen if they have
received it and felt symptomatic benefit from it. Is it a reason-
able option to simply inform the patient that the benefit they
experience is placebo and that compressed ambient air will
482
work just as well [7,41]? Perhaps it is a better option to proceed
with oxygen, as a chronological part of an interim strategy to
start them on medications, then wean them off the oxygen as
the medication takes effect. As such, the patient will not feel
deprived of a therapy, which they feel relieves their dyspnea.
Oxygen therapy
Oxygen therapy merges physiology and technology in prevent-
ing tissue hypoxia [42]. This section will review causes of hypo-
xemia, indications for oxygen and appropriate devices and
methodologies along with their interface with the patient.
Clinicians should always be aware of patient and family pre-
conceptions, and take these factors into account in planning
care. Physiological efficacy may not be the only important fac-
tor; practical considerations will emerge as oxygen is chronolog-
ically integrated into the overall care plan.
Hypoxemia
Oxygen is persistently required to meet the metabolic needs of
living tissue. Oxygen enters the body through the lungs; how-
ever several physiological steps are involved in the transport
and utilization of oxygen at the cellular level [101]. Pulse oxime-
try measures oxygenated hemoglobin, but an adequate supply
of hemoglobin is necessary to carry the oxygen to the tissues; a
competent circulatory system provides the transportation and
the tissue interfaces must be intact and functional for transfer-
ence of oxygen from the lung to the blood and then to the
cell. Metabolically active cells participate by taking up and uti-
lizing oxygen in the mitochondria to create the energy for cel-
lular metabolism. With the overall oxygen transport system in
mind, adequate prevention of tissue hypoxia requires attention
to the entire pathway. Advancing metastatic disease can exert
its damage anywhere along the transport path.
Hypoxemia may be caused by a variety of ventilatory pathol-
ogies: ventilation/perfusion mismatch, diffusion deficit, right-
to-left shunts or alveolar hypoventilation-any of which may be
present in advanced disease. Remedial action for specific etiolo-
gies may prevent or reverse hypoxemia. In addressing hypoxe-
mia the treatment seems intuitive: enrich the inspired oxygen
with supplemental oxygen to increase the driving pressure for
oxygen. This solution is often adequate. However, when deal-
ing with a right to left shunt, such as severe atelectasis or shunt
through a highly vascular tumor [102], the challenge is arduous.
With the rest of the transport stages intact, the physiological
goal of oxygen therapy for the hypoxemic patient will be met
by the titration of oxygen to SpO2 > 90%. As the disease pro-
gresses, it may become more difficult to achieve this endpoint.
Thus, our attention turns to patient comfort in preventing or
relieving dyspnea.
Oxygen for the hypoxemic patient
Oxygen is considered standard for patients with lung disease
who are hypoxemic. It is prescribed to prevent tissue hypoxia
and improve survival [1,2,100]. Hypoxemia is defined as
PaO2 £ 55 mmHg or SpO2 £ 88% (via oximetry) during
Expert Rev. Respir. Med. 7(5), (2013)
 Oxygen for end-of-life lung cancer care: managing dyspnea & hypoxemia Review

wakeful rest, sleep, or exertion. Oxygen flow is titrated to
achieve PaO2 > 60 mmHg or SpO2 >90%. These are accept-
able standards for COPD and are based on studies performed
in the 1970s that showed oxygen to significantly improve sur-
vival. [1,2] Thus, the rationale for providing oxygen is to meet
the physiological goal of preventing tissue hypoxia and improv-
ing survival. For patients with lung cancer, that standard has
been generally accepted. As lung cancer advances and curative
or tumor regression treatment is no longer possible, the goal of
care becomes symptomatic relief. Oxygen is prescribed with the
expectation that it will relieve or prevent dyspnea. If dyspnea is
caused by hypoxemia, oxygen will often meet that expectation–
at least initially. As the disease progresses, oxygen requirements
may grow to the point of requiring high flow oxygen delivery
systems. Eventually, a target SpO2 > 90% may become
unachievable, even with the highest flow systems. As this stage
arrives, it is obvious that other measures are necessary (perhaps
overdue) to prevent dyspnea and the patient feeling suffocation
(FIGURE 1A). The goal of care that includes oxygen has already
transitioned to patient comfort, which can be achieved with the
use of opioids and anxiolytics. Oxygen at this time has become
adjunctive to these medications.
From the viewpoint of treating dyspnea in the hypoxemic
patient, it is reasonable to begin medications at an earlier stage,
as opioids will eventually assume the dominant role. Continual
measurement using pulse oximetry becomes unnecessary and
counterproductive [16]. At the very end of life, oxygen may
even be discontinued as the hypoxemic patient is breathing
comfortably from medication. This transition will depend on
the desires and comfort levels of the patient and family.
Oxygen for the non-hypoxemic patient
Clinicians and non-clinicians have regarded oxygen as a remedy
or protector from the ravages of many illnesses including can-
cer. Hence, when the patient becomes dyspneic, we often turn
to oxygen. Some patients are able to derive symptomatic relief
and reassurance from oxygen to relieve dyspnea and gain a sense
of reassurance that they will not suffocate [3]. It is tempting to
provide these patients with oxygen, despite the fact their dyspnea
is not due to hypoxemia. Some patients do not feel better with
oxygen, and yet it is difficult not to include oxygen even for
these patients. Several recent studies have shown that there is no
measurable advantage between administering oxygen or medical
compressed air. Abernethy et al. [7] addressed this issue very well

A B

Hypoxemic Non-hypoxemic

Opioids
Previously No Still
O2 ± anxiolytic ±
No Dyspnea
relieves dyspnea RX O2 on O2
adjunctive†
Yes
Yes O2
Opioid ± No
relieves dyspnea Stop O2 Trial of O2‡
RX O2 anxiolytic

Yes
Continue O2‡
Dyspnea No Continue
returns O2
Opioids
Yes ± anxiolytic ±
Start opioid ± adjunctive†
anxiolytic

Dyspnea
Dyspnea No Try controlled
control adjunctive†

Yes Taper O2
Taper O2 if possible
if possible

Figure 1. Oxygen for lung cancer patients end-of-life.

†
Adjunctive measures: fan, pursed lips breathing, distraction
‡
Oxygen is not more effective than ambient air. However, oxygen rather than air is appropriate if the patient derives symptomatic benefit.
Other adjunctive measures should be tried.

www.expert-reviews.com 483
 Review Tiep, Carter, Zachariah et al.
in a randomized controlled trial. Interestingly, they discovered
that both oxygen and room air provided symptomatic benefit for
a subset of their patients. These results are also demonstrated in
patients with advanced cancer [32]. While oxygen was no better
than room air, there is no place in the care of these patients to
prescribe compressed room air. However, some patients will
benefit from a fan blowing air across their facial cheeks (dis-
cussed in section of adjunctive treatments) [43]. This option may
provide the patient with the comfort and reassurance of oxygen.
Again, this option should be considered in conjunction with
pharmacological management (FIGURE 1B).
Some patients and their families want oxygen and are reas-
sured by its presence while others are content to reject it.
There are disadvantages to oxygen therapy, particularly in the
patient who does not want it. It is a constant reminder of the
fact that the patient is very ill and possibly close to death. It
is also uncomfortable and restrictive for some. Oxygen, like
all other therapeutic options, is provided with the rationale
that the benefits must outweigh the disadvantages. It may be
unnecessary or even counterproductive to focus on achieving
a target SpO2 [20]. As such, it may be anxiety provoking to
constantly monitor and record pulse oximetry and this should
be avoided.
Hazards of oxygen therapy
Overall, oxygen therapy is safe and effective in the treatment of
hypoxemic patients. However, there are pitfalls. These include
risk of accidents related to oxygen storage and handling, [44]
CO2 retention, [101] oxygen toxicity and absorptive atelecta-
sis [42]. Accidents are preventable by proper instructions and
monitoring of patients and families. While obvious to avoid,
some patients have experienced critical injuries by lighting a
cigarette as oxygen is flowing into their noses. Oxygen itself is
not explosive but can greatly increase the heat and volume of a
burning flame.
CO2 retention is a consideration mainly for COPD patients,
who are presently experiencing some CO2 retention [101]
PaCO2 normally capnostatically controls ventilation. For some
COPD patients, the CO2 drive is suppressed, which decreases
their ventilatory drive and work of breathing. Their ventilation
is then controlled and determined by the hypoxic ventilatory
drive. By administering oxygen to these patients–particularly in
high concentrations–the ventilatory drive will be suppressed.
The result would be hypercapnia and respiratory acidosis.
Oxygen-induced hypercapnia does rarely occur, but it does not
typically cause respiratory acidosis [101]. When CO2 retention
does occur, it appears to be due to an increase in the physio-
logical dead space, and does not usually lead to CO2 narcosis.
There is an occasional exception, but it is relatively rare. By
titrating oxygen to SpO2 in the low 90% range, this situation
can be averted.
Oxygen toxicity may occur due to long term exposure to
high oxygen concentrations (FiO2 > 50%). In patients who
have had certain chemotherapeutic agents including bleomycin
or patients on amiodarone, high oxygen concentrations can
484
potentiate toxicity and cause pulmonary fibrosis [45]. In another
concern, high oxygen concentrations may potentially lead to
absorptive atelectasis, as well as the attenuation of hypoxic vaso-
constriction. This can cause further ventilation/perfusion mis-
match [101]. While this can occur even at low flows, special
caution is advised for patients requiring high flow oxygen.
Finally, oxygen therapy is inconvenient and is an admission
of critical deterioration, both for the patient and family. There
are some patients who will flatly reject oxygen partly on this
basis and will desire alternatives.
Oxygen systems
Oxygen is available as compressed gas (under high pressure),
liquid oxygen (supercooled to its liquid state) or oxygen con-
centrator (extracted from room air). Each system supplies oxy-
gen, but each has inherent advantages and disadvantages [42].
The choice of systems will depend on the needs of the patient.
Practical considerations include cost, availability, ease of use,
portability and delivery to the home. Each system includes a
stationary (home-based) component, as well as a portable com-
ponent for those who remain ambulatory. The development of
oxygen conserving technology, along with miniaturization of
tanks and delivery devices, has enabled the development of
highly portable systems that allow patients the opportunity to
leave their home and even travel [46].
Oxygen delivery methods
Standard low flow oxygen with portable component
Lung cancer patients with low flow requirements may utilize
oxygen systems and delivery methods that are in common use
by patients with COPD and other chronic lung diseases that
cause hypoxemia. Each of these devices and systems have a
portable component so that the patient may be up and active,
visit their physicians, go to restaurants and shopping with their
families, and enjoy quality lives. The options for these patients
are numerous, and the alternatives will depend on device avail-
ability, cost, their activity level and other factors including cos-
metic considerations [46].
Continuous flow nasal cannulas
Nasal cannulas comprise dual nasal prongs, and provide low
flow oxygen entrained in a much higher delivery volume of
ambient air. As such, each liter flow setting enriches inspired air
about 3–4%. Thus, a flow setting of 2 l/min provides FiO2 of
about 28%. The delivery model used to calculate the inspired
oxygen volume is based on a breath cycle of 3 sec for a patient
ventilating at 20 breaths/min. Given an inspiratory/
expiratory ratio of 1:2, one second is devoted to inhalation; the
last half of that time is spent on inhalation that fills the dead-
space of the upper and bronchial airways, but does not partici-
pate in alveolar gas exchange. Thus, the 1st half sec becomes
the window of opportunity for gas exchange. Most of the
remaining delivery is wasted to room ambience. The devices
that follow are designed to improve upon the efficiency of
standard nasal oxygen delivery [42].
Expert Rev. Respir. Med. 7(5), (2013)
 Oxygen for end-of-life lung cancer care: managing dyspnea & hypoxemia
Reservoir cannulas
Reservoir nasal cannulas (Oxymizer and Pendant) store oxygen
during exhalation in order to add that previously wasted vol-
ume to the next inhalation. [47,48] The reservoir cycles between
storage on exhalation and delivery upon inhalation, by a tech-
nology called fluidics. Oxygen is supplied continuously to the
reservoir. However, because 18–20 ml of oxygen is stored dur-
ing exhalation, that volume is added to supply oxygen-delivered
immediately with the next breath. This increases the effective
delivery flow of oxygen by about 2 l/m. Basically, these reser-
voir cannulas improve upon the efficiency of nasal oxygen by a
factor of two to fourfold at low flows, so that 0.5 l/m is equiv-
alent to 2 l/m and 2 l/m is equivalent to 4 l/m compared to
standard flow cannulas. Reservoir cannulas were originally
designed for patients with standard flow requirements, but
found to be efficacious for patients with a high flow require-
ment. [49,50] High-flow reservoir cannula delivery will be dis-
cussed in the section on high flow oxygen.
Demand (pulsed) oxygen delivery
Demand pulse delivery devices function by sensing the very
beginning of inhalation and delivering a bolus of oxygen within
the opportunity for gas exchange-mentioned above in the section
of standard nasal cannula [46]. The most efficient of these devices
can improve delivery efficiency by a factor of sevenfold by avoid-
ing delivery during exhalation and the last part of inhalation
(dead-space). The most efficient of these devices are electronically
controlled. Pneumatically driven devices are less efficacious, but
they do not require a battery. This technological development
has enabled the introduction of highly portable devices including
the portable oxygen concentrator. Some demand oxygen delivery
devices have a motion sensor that increases the volume of the
delivery pulse in response to physical activity where the demand
for oxygen is increased [51]. This enables the patient to go about
their daily lives without having to change settings.
Transtracheal catheters
Transtracheal oxygen (TTO) is delivered through a small stoma
in the neck into the trachea [52,53]. Oxygen flows down the tra-
chea toward the carina. Oxygen delivered by this technique
bypasses about 50 ml of upper airway dead-space, and is there-
fore also more efficient than standard nasal oxygen. It has also
been found to reduce the work of breathing, dyspnea and
tension-time index of the diaphragm [54,55]. The most common
advantage of TTO is for the ambulatory patient who wishes to
avoid nasal oxygen–often for cosmetic reasons. However, high
flow TTO has been introduced that now provides a high flow
option, which will be discussed in that section. The efficiency
of delivery can be further improved by pulsing the oxygen
through the transtracheal catheter using a demand oxygen
delivery device [56].
Oxygen for patients with high flow requirement
As the lung cancer progresses, adequate oxygenation may become
increasingly difficult to achieve. Standard low flow nasal cannula
www.expert-reviews.com
Review
oxygen is delivered at £ flows up to 6 l/m. For patients requiring
higher flows, the options available include masks; nasal high flow
warmed and humidified, reservoir cannulas and noninvasive pos-
itive pressure ventilation (NPPV) [57] (FIGURE 2).
Mask oxygen
The simple mask delivers oxygen at the efficiency similar to the
standard nasal cannula. The volume of the mask is
100–300 ml delivering FiO2 up to 40–50%. The actual FiO2
that the patient receives is highly variable and depends on
breathing pattern and facial structure. Venturi masks operate
under high flow delivering a stable mixture of oxygen and
ambient air. This device is usually considered when there is a
specific concern about CO2 retention. It can deliver FiO2 up
to 50%. A non-rebreather mask supplies highly concentrated
oxygen. It can deliver FiO2 up to 90%. These masks require a
tight seal at the face, which can be rather uncomfortable [57].
Nasal high flow oxygen
Mask oxygen tends to be uncomfortable. Accordingly, high-
flow warmed and humidified nasal oxygen has now gained
favor as a more comfortable alternative [57]. It is also more effi-
cacious than mask oxygen at the higher flows, since nasal HFO
is stored in the nasopharynx during exhalation and adds to oxy-
gen enrichment upon inhalation [58]. Mouth breathing for
patients on nasal oxygen is often believed to be disadvanta-
geous. However, mouth breathing on HFO actually stores oxy-
gen in both their oral cavity and nasopharynx for a larger
delivery bolus on inhalation [59]. The driving flows can be
adjusted from 10–40 l/min. HFO delivers oxygen mixtures of
24–100%, creating FiO2’s of nearly 90%. [60,61] High-flow oxy-
gen for dyspneic hypoxemic patients may relieve symptoms via
a CPAP mechanism in addition to treating hypoxemia. The
disadvantage of this system is that it is noisy and requires a
large supply of oxygen–making it impractical for home use.
High flow transtracheal catheters
High flow transtracheal catheters deliver oxygen (sometimes
warmed and humidified) directly into the trachea. They reduce
the work and energy cost of breathing and assist CO2 elimina-
tion. TTO is a particularly useful option if the patient has just
been decannulated and still has a small and viable stoma [62].
Some bench studies have demonstrated FiO2 similar to non-
rebreather masks.
Reservoir cannulas
Reservoir cannulas (Oxymizer and Pendant) provide an alterna-
tive to nasal HFO. [49,50,57,63] They incorporate smaller supply
tubing and are less cumbersome and noisy. They require a
reduced amount of oxygen as compared to HFO in order to
achieve the same level of oxygenation. Accordingly, these devices
are practical and convenient for patients requiring higher flow
to be discharged home–particularly to home hospice. Reservoir
cannulas improve the efficiency of delivery by storing oxygen in
the 20 ml reservoir during exhalation-ready to be inspired upon
485
 Review Tiep, Carter, Zachariah et al.

Hypoxemia

Nasal O2 ≤ 6 l/m

Simple mask

SpO2 > 90% Continue nasal O2

Non-rebreather mask

High flow nasal

High flow devices

Reservoir cannula

Comfortable Continue HF device

Transtracheal oxygen

Nasal CPAP Add opioid ±

Change device
anxiolytic
NPPV
Device: mask or reservoir
D/C home
cannula; consider liquid O2

Continue O2 + RX opioid

Figure 2. High flow oxygen for lung cancer patients. Practical considerations at home limit high flow oxygen. Liquid oxygen and res-
ervoir cannulas may be good options.

the next inhalation along with the supply flow. At high flows,
the nasopharynx provides an additional 40 ml of storage space.
Thus, a total storage on exhalation of 60 ml for early inspira-
tory delivery is possible. Again, mouth breathers also store oxy-
gen in the mouth, thus adding to the reservoir effect [59].
Patients requiring HFO have been adequately oxygenated at
supply flows of ‡ 8 l/min [50].
The disadvantage of reservoir cannulas, as compared with
nasal HFO, is that the oxygen is not warmed and humidified
beyond that which is provided with the bubble humidifier. One
study indicated that this might make a difference in a mask set-
ting [64]. Some patients may therefore find reservoir cannulas to
be uncomfortable, due to the drying effect. However, given the
lower flows required for the reservoir cannulas, patients who tol-
erate the lack of added humidity have the option of a more
convenient and practical home system. For those opting for
home hospice, reservoir cannulas may present a viable choice.
Noninvasive positive pressure ventilation & nasal continuous posi-
tive airway pressure
Some patients have obstructive sleep apnea and are accustomed
to nasal CPAP. This provides them with comfort, support and
reassurance that they won’t stop breathing when they sleep [13].
Also, there is a feeling of improvement due to the supportive
benefits of nasal CPAP. Oxygen can be bled into the mask and
conduit of the CPAP, which improves oxygenation while sup-
porting ventilation. It is therefore reasonable for these patients
to continue use of these devices if they desire. Another group
of patients who might benefit from NPPV are those who were
formerly intubated and have opted to discontinue invasive ven-
tilatory support. NPPV can provide an intermediate stage in
discontinuing high-level ventilatory support [65].
Since the goal of this ventilatory support is comfort, CPAP
or NPPV should be discontinued if it does not relieve dyspnea,
or the patient is no longer alert. However, if it does relieve
dyspnea but the patient feels claustrophobic, a benzodiazepine
may help to alleviate anxiety.
NPPV interfaces & settings
Full-facemasks are common for inpatient applications, but nasal
masks or pillows are often more comfortable. A clinician, who is
familiar with mask interfaces and inspiratory and expiratory posi-
tive airway pressure settings, should initially adjust the pressure
settings. [66,67] While the patient usually triggers inspiration, a
backup rate setting is sometimes utilized. This may be inappro-
priate for the dying patient who simply requires symptom relief.
Conclusions
Oxygen is commonly prescribed for patients with advanced
stage lung cancer nearing the end of their lives. The main

486 Expert Rev. Respir. Med. 7(5), (2013)

 Oxygen for end-of-life lung cancer care: managing dyspnea & hypoxemia Review

Hypoxemia
Dyspnea
Anemia
O2 transport
Circulatory
Cellular level
Treatable cause Treat causes
Consider
Bronchial obstruction
adjunctive
palliative and Pleural effusion
Comfortable
pulmonary Pericardial effusion
rehab options Oxygen Hypoxemic
Lymphangitic spread
as appropriate Cancer
********** Phrenic nerve paralysis
Exercise, purse Continue to Metastasis
lips energy - treat causes Pain
efficiency self Opioids Still dyspneic
mgmt active Fatigue
life fan + other Radiation fibrosis
position sit up
adjuncts CPAP
Benzodiazepine Anxiety COPD
NPPV.
Consider Asthma
stopping all but Lung fibrosis
comfort
Adjust Co-morbidity Pneumonia
medications as
death is medication Still dyspneic Cardiac
imminent consider O2
Renal
Anxiety
Continue present care.
Goal = comfort

Figure 3. Dyspnea management for advanced lung cancer.

indications are hypoxemia and dyspnea. For the hypoxemic
patient, oxygen can prevent tissue hypoxia and in some cases
can relieve dyspnea. If the patient is severely hypoxemic, then
dementia is a possibility, and maintaining an adequate SpO2
could enable the patient to communicate with their family. For
patients who require high flow oxygen, they should be pre-
scribed a high flow system. If dyspnea remains regardless of the
SpO2, the parallel use of opioids may be required to ameliorate
the dyspnea.
For the patient who is not hypoxemic and is not dyspneic,
there is no role for oxygen. For the patient who is non-hypoxemic
but is dyspneic, oxygen is not the first treatment choice because it
is no more effective than compressed room air. For the patient
who is non-hypoxemic but is dyspneic and has derived sympto-
matic benefit from oxygen, oxygen is recommended as a transi-
tory treatment while pharmaceutical options are brought up to
speed. Consider adjunctive measures such as pulmonary rehabili-
tation tools to manage dyspnea including pursed lips breathing.
Also, a fan blowing air toward the patient’s face may provide a
level of dyspnea relief for symptomatic patients as a therapeutic
alternative to being tethered to the oxygen.
The treatment for dyspnea begins with an assessment of cause,
which could lead to targeted treatment. Examples include: bron-
chodilators for bronchospasm, thoracentesis for pleural effusions,
steroids, antibiotics and bronchodilators for COPD exacerbations.
Nonspecific effective treatment for dyspnea is based on steroids,
and anxiolytic treatment is based on benzodiazepines (FIGURE 3).
The goal of oxygen therapy at the end of life is patient com-
fort. This is especially true for the patient for whom it is
becoming increasingly difficult to achieve a target SpO2 > 90%.
In these patients, continuous monitoring of pulse oximetry is
not only counterproductive but can be disquieting. It does not
contribute to life quality during this precious time at the end of
life. The focus should center entirely on keeping the patient
comfortable. Opioid medications can easily provide this relief.
The overall goal at end of life is to provide the patient and
family with comfort, quality and confidence during this time.
Expert commentary
Providing skillful and empathetic care as the patient approaches
the end of life can be as challenging as actively treating the
cancer. The patient and loved ones are informed that options
for cure and tumor regression have been exhausted and the dis-
ease is progressing. At this time attention is directed toward
assuring comfort and living quality to the extent possible. Oxy-
gen was prescribed at an earlier stage of care to prevent hypoxe-
mia and tissue hypoxia. At this stage, the goal of administering
oxygen is to assist in patient comfort. Some non-hypoxemic
patients feel better and reassured by the presence of oxygen
while other feel burdened by it. Those who feel benefit should
be maintained on oxygen in an end-of-life setting.
Oxygen may relieve dyspnea and prevent feelings of suffoca-
tion, however pharmacological management occupies center
stage. Opiates modulate the respiratory drive by alleviating

www.expert-reviews.com 487
 Review Tiep, Carter, Zachariah et al.

dyspnea while easing pain and anxiolytics lessen dyspnea-
associated anxiety. Continuous oximetry and extraneous medi-
cations are removed in favor of comforting medications. The
entire experience should be palliative and enriching for the
patient and loved ones at this last major life transition.
Five year view
The future for patients with advancing diseases may come from
several directions. Targeted therapies may improve our ability
to actively manage lung cancer to enable patients to live longer
lives with quality. Pharmacological advances may provide alter-
natives to the present opioids to effectively manage dyspnea
while avoiding somnolence that patients presently experience.
Non-pharmacological management techniques may enable
patients to more effectively manage their advancing disease.
The tools of pulmonary rehabilitation may be honed to enable
patients to experience more quality lives and participate in their
own care. More invasive techniques may maintain open airways
longer than presently available. Non-invasive respiratory assist
devices may lighten the ventilatory workload and thereby allevi-
ate dyspnea. The most important advances will be both in pre-
vention and effective treatment of the underlying disease.
Financial & competing interests disclosure
B Tiep is the inventor of several oxygen delivery devices and receives royal-
ties for some of them through CHAD Therapeutics Inc., division of Inovo,
which is a division of Drive Medical Inc. He is a consultant for CHAD
Therapeutics and Nonin Medical Inc. The authors have no other relevant
affiliations or financial involvement with any organization or entity with
a financial interest in or financial conflict with the subject matter or
materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.

Key issues
• Overall goal of care at the end of life is comfort. Control of dyspnea and pain are important components.
• The indications for oxygen therapy for advanced lung cancer patients are to prevent hypoxemia and relieve dyspnea.
• Oxygen therapy for the hypoxemic patient will often but not always alleviate dyspnea.
• Oxygen therapy for the dyspneic non-hypoxemic patient is no more effective than compressed room air in relieving dyspnea.
• Non-hypoxemic patients who gain symptomatic relief from oxygen should continue on it as a transition to pharmacotherapy.
• The cornerstone basic treatment for dyspnea is pharmacotherapy – particularly opioids.
• There are adjunctive therapies available for dyspnea management that include pursed lips breathing and fan blowing air toward the
patient.
• Patients who require high flow oxygen have several systems and delivery devices open to them including non-rebreather masks, high-
flow nasal oxygen and reservoir cannulas.
• In some patients, there is a point beyond which it is not possible or practical to reach target oxygen saturation. For those patients it is
advisable to rely more heavily on pharmacological management.
• Continuous monitoring of pulse oximetry at the end of life can be disquieting and counterproductive. It should not be the focus of
attention for the patient or family.

References 2 Medical Research Council Working Party. inhibitory controls in humans”. J.

Papers of special note have been highlighted as:
• of interest
•• of considerable interest
1 Nocturnal Oxygen Therapy Trial Group.
Continuous or nocturnal oxygen therapy in
hypoxemic chronic obstructive lung disease:
a clinical trial. Ann. Intern. Med. 93(3),
391–398 (1980).
• This is a companion study to the British
MRC study (see [2]) which shows that
hypoxemic COPD patients have better
survival if they use their oxygen
continuously versus 12 hours per day.
The overall conclusion of the two studies is
that hypoxemic patients have better
survival the greater number of hours per
day that they use their oxygen.
Long term domiciliary oxygen therapy in
chronic hypoxic cor pulmonale complicating
chronic bronchitis and emphysema. Lancet
1(8222), 681–686 (1981).
• This is a companion study with the
NOTT (Reference 1) which shows that
hypoxemic COPD patients have better
survival if they use their oxygen at least
15 hours per day versus no oxygen.
The overall conclusion of the two studies is
that hypoxemic patients have better
survival the greater number of hours per
day that they use their oxygen.
3 Banzett RB, Gracely RH, Lansing RW.
When it’s hard to breathe, maybe pain
doesn’t matter. Focus on “Dyspnea as a
noxious sensation: inspiratory threshold
loading may trigger diffuse noxious
Neurophysiol. 97(2), 959–960 (2007).
4 Griffin JP, Nelson JE, Koch KA et al.;
American College of Chest Physicians.
End-of-life care in patients with lung
cancer. Chest 123(1 Suppl.), 312S–331S
(2003).
•• Excellent and thoughtful review on
end-of-life care.
5 Maunder RJ. JPM Patient Information.
Oxygen therapy at the end of life. J. Palliat.
Med. 9(4), 1030–1031 (2006).
• This study demonstrates that some patients
with dyspnea are not hypoxemic while
others are hypoxemic but not breathless.
6 Dudgeon DJ, Lertzman M, Askew GR.
Physiological changes and clinical
correlations of dyspnea in cancer
outpatients. J. Pain Symptom. Manage 21(5),
373–379 (2001).

488 Expert Rev. Respir. Med. 7(05), (2013)

 Oxygen for end-of-life lung cancer care: managing dyspnea & hypoxemia Review

7 Abernethy AP, McDonald CF, Frith PA
et al. Effect of palliative oxygen versus room
air in relief of breathlessness in patients with
refractory dyspnoea: a double-blind,
randomised controlled trial. Lancet
376(9743), 784–793 (2010).
•• This is an adequately powered study that
showed that oxygen offered no additional
benefit to breathing compressed room air
in relieving refractory dyspnea.
8 Moore RP, Berlowitz DJ, Denehy L et al.
A randomised trial of domiciliary,
ambulatory oxygen in patients with COPD
and dyspnoea but without resting
hypoxaemia. Thorax 66(1), 32–37 (2011).
9 Currow DC, Agar M, Smith J,
Abernethy AP. Does palliative home oxygen
improve dyspnoea? A consecutive cohort
study. Palliat. Med. 23(4), 309–316 (2009).
10 Hallenbeck J. Pathophysiologies of dyspnea
explained: why might opioids relieve
dyspnea and not hasten death? J. Palliat.
Med. 15(8), 848–853 (2012).
• This reference is one of several that brings
pharmacological perspective to the
management of dyspnea – the central role
of opioids.
11 Clemens KE, Klaschik E. Dyspnoea
associated with anxiety–symptomatic therapy
with opioids in combination with lorazepam
and its effect on ventilation in palliative care
patients. Support Care Cancer 19(12),
2027–2033 (2011).
12 Reinke LF, Engelberg RA, Shannon SE et al
. Transitions regarding palliative and
end-of-life care in severe chronic obstructive
pulmonary disease or advanced cancer:
themes identified by patients, families, and
clinicians. J. Palliat. Med. 11(4), 601–609
(2008).
13 Levy, M., Tanios MA, Nelson D et al.
Outcomes of patients with do-not-intubate
orders treated with noninvasive ventilation.
Crit. Care Med. 32(10), 2002–2007 (2004).
14 Davis CL. ABC of palliative care.
Breathlessness, cough, and other respiratory
problems. BMJ 315(7113), 931–934
(1997).
15 Bruera E, Neumann CM. Management of
specific symptom complexes in patients
receiving palliative care. CMAJ 158(13),
1717–1726 (1998).
16 Thomas JR, von Gunten CF. Management
of dyspnea. J. Support Oncol. 1(1), 23–32
(2003); discussion 32–34.
17 Reuben DB, Mor V. Dyspnea in terminally
ill cancer patients. Chest 89(2), 234–236
(1986).
18 Nishino T, Shimoyama N, Ide T, Isono S.
Experimental pain augments experimental
dyspnea, but not vice versa in human
volunteers. Anesthesiology 91(6), 1633–1638
(1999).
19 Williams AC, Grant M, Tiep B, Kim J,
Hayter J. Dyspnea management in
early-stage lung cancer: a palliative
perspective. J. Hospice Palliat. Nursing
14(5), 332–340 (2012).
20 Mahler DA, O’Donnell D. Dyspnea:
mechanisms, measurement, and
management. In: Lung Biology in Health
and Disease (2nd Edition). Taylor & Francis,
Boca Raton xvii, 472 (2005).
21 Harver A, Mahler DA, Schwartzstein RM,
Baird JC. Descriptors of breathlessness in
healthy individuals: distinct and separable
constructs. Chest 118(3), 679–690 (2000).
22 Elliott MW. The language of breathlessness.
Monaldi Arch. Chest Dis. 53(6), 664–668
(1998).
23 Elliott MW, Adams L, Cockcroft A et al.
The language of breathlessness. Use of
verbal descriptors by patients with
cardiopulmonary disease. Am. Rev. Respir.
Dis. 144(4), 826–832 (1991).
24 Zebraski SE, Kochenash SM, Raffa RB.
Lung opioid receptors: pharmacology and
possible target for nebulized morphine in
dyspnea. Life Sci. 66(23), 2221–2231
(2000).
25 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. 23(2), 157–160 (2002).
26 Bruera E, Sala R, Spruyt O, Palmer JL,
Zhang T, Willey J. Nebulized versus
subcutaneous morphine for patients with
cancer dyspnea: a preliminary study. J. Pain
Symptom. Manage. 29(6), 613–618 (2005).
27 Kallet RH. The role of inhaled opioids and
furosemide for the treatment of dyspnea.
Respir. Care 52(7), 900–910 (2007).
28 Gauna AA, Kang SK, Triano ML,
Swatko ER, Vanston VJ. Oral transmucosal
fentanyl citrate for dyspnea in terminally ill
patients: an observational case series.
J. Palliat. Med. 11(4), 643–648 (2008).
29 Zeppetella G. Dynamics of breakthrough
pain vs. pharmacokinetics of oral morphine:
implications for management. Eur. J. Cancer
Care (Engl.) 18(4), 331–337 (2009).
30 Navigante AH, Castro MA, Cerchietti LC.
Morphine versus midazolam as upfront
therapy to control dyspnea perception in
cancer patients while its underlying cause is
sought or treated. J. Pain Symptom Manage.
39(5), 820–830 (2010).
31 Simon ST, Higginson IJ, Booth S,
Harding R, Bausewein C. Benzodiazepines
for the relief of breathlessness in advanced
malignant and non-malignant diseases in
adults. Cochrane. Database Syst. Rev. (1),
CD007354 (2010).
32 Kohara H, Ueoka H, Aoe K et al. Effect of
nebulized furosemide in terminally ill cancer
patients with dyspnea. J. Pain Symptom.
Manage. 26(4), 962–967 (2003).
33 Currow DC, Ward AM, Abernethy AP.
Advances in the pharmacological
management of breathlessness. Curr. Opin.
Support Palliat. Care 3(2), 103–106 (2009).
34 Viola R, Kiteley C, Lloyd NS et al. The
management of dyspnea in cancer patients:
a systematic review. Support Care Cancer
16(4), 329–337 (2008).
35 Mercadante S, Porzio G, Valle A et al.
Palliative sedation in patients with advanced
cancer followed at home: a systematic
review. J. Pain Symptom. Manage. 41(4),
754–760 (2011).
36 Galbraith S, Fagan P, Perkins P, Lynch A,
Booth S. Does the use of a handheld fan
improve chronic dyspnea? A randomized,
controlled, crossover trial. J. Pain Symptom.
Manage. 39(5), 831–838 (2010).
37 Hodgkin JE, Celli BR, Connors GL.
Pulmonary Rehabilitation : Guidelines to
Success (4th Edition). Mosby/Elsevier, St.
Louis, Mo. xiv, 583 (2009).
38 Tiep BL, Burns M, Kao D, Madison R,
Herrera J. Pursed lips breathing training
using ear oximetry. Chest 90(2), 218–221
(1986).
39 Ozalevli S, Ilgin D, Kul Karaali H, Bulac S,
Akkoclu A. The effect of in-patient chest
physiotherapy in lung cancer patients.
Support Care Cancer 18(3), 351–358
(2010).
40 Yang IA, Relan V, Wright CM et al.
Common pathogenic mechanisms and
pathways in the development of COPD and
lung cancer. Expert Opin Ther Targets 15(4),
439–456 (2011).
41 Booth S, Wade R. Oxygen or air for
palliation of breathlessness in advanced
cancer. J. R. Soc. Med. 96(5), 215–218
(2003).
42 Tiep BL. Portable Oxygen Therapy :
Including Oxygen Conserving Methodology.
Futura Pub. Co., Mount Kisco, NY xvii,
490 (1991).
43 Schwartzstein RM, Lahive K, Pope A,
Weinberger SE, Weiss JW. Cold facial

www.expert-reviews.com 489
 Review Tiep, Carter, Zachariah et al.
stimulation reduces breathlessness induced
in normal subjects. Am. Rev. Respir. Dis.
136(1), 58–61 (1987).
44 West GA, Primeau P. Nonmedical hazards
of long-term oxygen therapy. Respir. Care
28(7), 906–912 (1983).
45 Donat SM, Levy DA. Bleomycin associated
pulmonary toxicity: is perioperative oxygen
restriction necessary? J. Urol. 160(4),
1347–1352 (1998).
46 Tiep B, Carter R. Oxygen conserving
devices and methodologies. Chron. Respir.
Dis. 5(2), 109–114 (2008).
47 Tiep BL, Nicotra B, Carter R, Belman MJ,
Mittman C. Evaluation of a low-flow
oxygen-conserving nasal cannula. Am. Rev.
Respir. Dis. 130(3), 500–502 (1984).
48 Carter R, Wautelet F, Delwiche JP,
Prignot J, Dubois P. Evaluation of the
pendant oxygen-conserving nasal cannula
during exercise. Chest 89(6), 806–810
(1986).
47 Collard P, Wautelet F, Delwiche JP,
Prignot J, Dubois P. Improvement of
oxygen delivery in severe hypoxaemia by a
reservoir cannula. Eur. Respir. J. 2(8),
778–781 (1989).
50 Sheehan CJ, O’Donohue WJ. Use of a
reservoir nasal cannula in hospitalized
patients with refractory hypoxemia. Chest
110(4), S1 (1996).
51 Tiep B, Murray R, Barnett M, Carter R.
Auto-adjusting demand oxygen delivery
system that minimizes SaO2 swings between
rest and exertion. Chest
126 Abstract(4) (2004).
52 Heimlich HJ, Carr GC. The micro-trach.
A seven-year experience with transtracheal
oxygen therapy. Chest 95(5), 1008–1012
(1989).
53 Hoffman AM, Viel L. A percutaneous
transtracheal catheter system for improved
oxygenation in foals with respiratory distress.
Equine. Vet. J. 24(3), 239–241 (1992).
54 Wesmiller SW, Hoffman LA, Sciurba FC,
Ferson PF, Johnson JT, Dauber JH.
490
View publication stats
Exercise tolerance during nasal cannula and
transtracheal oxygen delivery. Am. Rev.
Respir. Dis. 141(3), 789–791 (1990).
55 Christopher KL, Schwartz MD.
Transtracheal oxygen therapy. Chest 139(2),
435–440 (2011).
56 Tiep BL, Christopher KL, Spofford BT,
Goodman JR, Worley PD, Macy SL. Pulsed
nasal and transtracheal oxygen delivery.
Chest 97(2), 364–368 (1990).
57 Garvey C, Tiep B, Carter R, Barnett M,
Hart M, Casaburi R. Severe
exercise-induced hypoxemia. Respir. Care
57(7), 1154–1160 (2012).
• This is a good overall review of high flow
oxygen.
58 Tiep B, Barnett M. High flow nasal vs high
flow mask oxygen delivery: Tracheal gas
concentrations through head extension
airway model. Respir. Care 47(9), 1079
(2002).
59 Wettstein RB, Shelledy DC, Peters JI.
Delivered oxygen concentrations using
low-flow and high-flow nasal cannulas.
Respir. Care 50(5), 604–609 (2005).
• This study showed that patients on high
flow nasal oxygen may achieve greater
oxygenation if they are breathing with
their mouths open in spite of the fact that
oxygen is delivered through the nose.
60 Rello J, Pérez M, Roca O et al. High-flow
nasal therapy in adults with severe acute
respiratory infection: a cohort study in
patients with 2009 influenza A/H1N1v.
J. Crit. Care 27(5), 434–439 (2012).
61 Peters SG, Holets SR, Gay PC. Nasal high
flow oxygen therapy in do-not-intubate
patients with hypoxemic respiratory distress.
Respir. Care 58(4), 597–600 (2013).
62 Nomori H, Horio H, Suemasu K. Assisted
pressure control ventilation via a
mini-tracheostomy tube for postoperative
respiratory management of lung cancer
patients. Respir. Med. 94(3), 214–220
(2000).
63 Dumont CP, Tiep BL. Using a reservoir
nasal cannula in acute care. Crit. Care
Nurse. 22(4), 41–46 (2002).
64 Chanques G, Constantin JM, Sauter M
et al. Discomfort associated with
underhumidified high-flow oxygen therapy
in critically ill patients. Intensive Care Med.
35(6), 996–1003 (2009).
65 Schettino G, Altobelli N, Kacmarek RM.
Noninvasive positive pressure ventilation
reverses acute respiratory failure in select
“do-not-intubate” patients. Crit. Care Med.
33(9), 1976–1982 (2005).
66 Gay PC, Hess DR, Hill NS. Noninvasive
proportional assist ventilation for acute
respiratory insufficiency. Comparison with
pressure support ventilation. Am. J. Respir.
Crit. Care Med. 164(9), 1606–1611
(2001).
67 Hess DR. The mask for noninvasive
ventilation: principles of design and effects
on aerosol delivery. J. Aerosol. Med. 20
(Suppl. 1), S85–S98 (2007); discussion
S98–S99.
Websites
101 Celli B, McNee W. American Thoracic
Society/European Respiratory Society.
Standards for the diagnosis and management
of patients with COPD 2004. [Website]
2004 2005 January 18, 2013]; Guidelines
for managment of COPD].
www.thoracic.org/clinical/copd-guidelines/
resources/
102 Wang T, Kernstine K, Tiep B,
Venkataraman K, Horak D, Barnett M.
Intrapulmonary shunting through tumor
causing refractory hypoxemia. ATS Clinical
Cases 2007 2007.
www.thoracic.org/clinical/ats-clinical-cases/
pages/intrapulmonary-shunting-through-
tumorcausing-refractory-hypoxemia.php.
Expert Rev. Respir. Med. 7(05), (2013)