Robert Pope. “Visitors”
Edward (Ted) St. Godard MA MD CCFP
Consulting Physician
WRHA Palliative Care
tstgodard@wrha.mb.ca
I am funded as an
independent
contractor by the
WRHA
At the end of session, participants will
 Be able to identify the medical
condition known as delirium;
 Appreciate the importance of this
recognition;
 Have an approach to delirium
management
 Nurses are in an optimal position to
detect fluctuating symptoms of delirium
Agar et al. Palliative Medicine. September, 2011.
 Silent, unspoken piece of nursing
practice, impacting on workload
 Nurses deal with the unpredictable and
fluctuating condition of delirious
patients, which may be a signal of
impending ‘chaos’
Agar et al. Palliative Medicine. September, 2011.
 Under-detection of delirium relates to a
lack of knowledge of the criteria for
identifying delirium…
 failure to relay or communicate detected
symptoms at onset…
Agar et al. Palliative Medicine. September, 2011.
Global cerebral dysfunction
 “Brain Failure”
 Early signs often mistaken as
anger, anxiety, depression, psychosis

A) Change in consciousness with reduced
ability to focus, sustain or shift attention
 B) Change in cognition (e.g., memory,
disorientation, change in language,
perceptual disturbance) that is not dementia

C) Abrupt onset (hours to days) with
fluctuation
 D) Evidence of medical condition judged to be
etiologically related to disturbance

…a disturbance in consciousness with
inattention and problems in cognition and/or
a disturbance in perception that develop over
hours to days with organic causes.
Delirium
Dementia
Impaired memory
Impaired memory
Impaired judgement
Impaired judgement
Impaired thinking
Impaired thinking
Disorientation
Disorientation
Delirium
Dementia
Abrupt onset
Insidious, progressive
Decreased LOC
Alert, LOC intact
Sleep/wake cycle

Minimal

Delirium
Dementia
Reversible?
Irreversible
PREVENTABLE?

In up to 50 % of patients with advanced cancer,
delirium can be reversed
Kang JH et al. “Comprehensive approaches to managing delirium
in patients with advanced cancer.” Cancer Treat Rev
(2012)
60
40
20
Rev
Non Rev
0
Hypoxia
Infect
Metabol
Other
Dehyd
Opioids
Lawlor P, Gagnon B, Mancini I, Pereira J, et al. Arch Intern Med 2000



Hypoactive
confusion, somnolence,  alertness
Hyperactive
agitation, hallucinations, aggression
Mixed (>60%)
features of both
Lawlor P, Gagnon B, Mancini I, Pereira J, et al. Arch Intern Med 2000



80 % in medical intensive care units (ICU)
28 % in patients following hip fracture
22 % in general medical inpatients
Partridge et al. “The delirium experience: what is the effect on patients, relatives and staff
and what can be done to modify this?” Int J Ger Psych. October 2012 (online)
 Most frequent neuropsychiatric
complication in patients with
advanced CA
 Up to 85 % of patients delirious prior
to death
Bruera et al. JPSM 2010; 39;2: 186-196
 ~ 42% patients in PC program
delirious on admission
 50% of episodes reversible
 “Terminal delirium” in 88 %
Lawlor et al. Arch Intern Med 2000;
160:786
 Delirium/terminal restlessness (55%)
 Dyspnea (27%)
 Pain (18%)
 Nausea/vomiting (4%)
Eisenchlas. Current Opinion in Supportive and Palliative
Care 2007, 1:207–212
 Delirium number one reason for requests
Fainsinger RL et al. “A multicentre international study of sedation for
uncontrolled symptoms in terminally ill patients.” Palliat Med 2000;14:257–
65.
 “We’d rather see dad dead than like this.”
 “S/he would be horrified by this.”
 73/99 patients (74%) remembered
delirious episode
 Of these, 81 % recalled experience as
distressing
 Family stress > patients’ recalled
stress
Bruera et al. JPSM 2010; 39;2: 186-196
 Interferes with Sx assessment and Tx
 Increases morbidity and mortality
 Hinders communication within
families
Bruera et al. JPSM 2010; 39;2: 186-196
D/D
Pain
Dyspnea
Delirium
Ax/Tx Challenges
Worsening Delirium
 Delirium mediated by failure in central
cholinergic transmission?
 Acetylcholine final common
neurotransmitter pathway leading to
delirium?
White et. al. “First Do no Harm…” JPM. 10 (2); 2007: 345-351
Relative acetylcholine deficiency and
dopamine excess could mediate the
characteristic symptoms of delirium
 Delirium can be evoked by dopamine agonists
and anticholinergic medications

Moyer. American Journal of Hospice and Palliative Medicine
28(1), 2011. 44- 51
Kang JH et al. Comprehensive approaches to managing delirium in
patients with advanced cancer. Cancer Treat Rev
(2012)
 Dopamine/acetylcholine inverse relationship
 Haloperidol first line treatment for delirium
 Haloperidol D2 antagonist:
 ? Haloperidol increase levels acetylcholine?
White et. al. “First Do no Harm…” JPM. 10 (2); 2007: 345-351
Kang JH et al. Comprehensive approaches to managing delirium in
patients with advanced cancer. Cancer Treat Rev
(2012)
Sometimes successfully treated with
dopamine receptor antagonists and possibly
by cholinesterase inhibitors
 High serum anticholinergic activity in
patients with delirium

Moyer. American Journal of Hospice and Palliative Medicine
28(1), 2011. 44- 51
Υ-aminobutyric acid (GABA)-ergic
benzodiazepines seem to cause delirium
 Neuroinflammatory processes drives upregulation of GABA receptors
 GABA receptor versus microglial activation
versus apoptosis

C.G. Hughes et al. “Future Directions in Delirium
Management and Research.” Best Practice & Research
Clinical Anaesthesiology. 26 (2012) 395–405

Predisposing

Precipitating

Predisposing factors:
 Prevalence increases with age
 Male > female
 Visual impairment
 Depression
White et. al. “First Do no Harm…” JPM. 10 (2); 2007: 345-351

Predisposing factors:







Functional dependence
Immobility
Hip fracture
Dehydration
Alcoholism
Stroke
Severity of physical illness
White et. al. “First Do no Harm…” JPM. 10 (2); 2007: 345-351
All of our patients!
 Inverse relationship between the
preexisting vulnerability of the patient,
and the severity of the insult necessary
to precipitate delirium
 Most patients nearing EOL have multiple
predisposing factors
 Most of these are beyond our control

Predisposing

Precipitating
 Impractical, given our patient population
(frail, usually old)
 Imperative to minimize precipitating
factors





‘lyte derangements (dehyd’n,
hypo/hypernatremia)
Infx (UTI, resp., skin/soft tissue [sacral ulcers])
Metabolic (hyper/hypoglycemia, hypercalcemia,
uremia)
Low perfusion, hypoxia
Withdrawal
•
•
•
•
•
Anti-cholinergics (Gravol, TCAs, anti-secretories);
BZDs
Opioids
Steroids
Cipro, lasix (?) ranitidine, and on and on….
 Drug withdrawal:
 EtOH, Bzd, opioid, “street drugs”
 Prophylactic haldol
 Prophylactic olanzepine
 Prohylactic cholinesterase inhib.s
Gagnon et al. Psycho‐Oncology 21: 187–194 (2012)
 Maintain sensorium: hearing aids, eye
glasses
 Orientation (clocks, calendars,
conversation)
Gagnon et al. Psycho‐Oncology 21: 187–194 (2012)
 No good evidence for benefit from
screening hospitalized patients
Greer N et al. Delirium: screening, prevention, and diagnosis – a systematic review of the
evidence 2011 Internet.
“Cured yesterday of her disease, she
died last night of her doctor.”
paraphrasing
Jonathon Swift
(you know, Gulliver’s Travels)
 Medication sole precipitant of
delirium in 12 – 39 % healthy patients
Alagiakrishnan et al. Postgrad Med J, 2004; 88: 388-393
 Drug toxicity, drug withdrawal
 Start low, go slow
 Very often, less is more
 Analgesics: Uncontrolled pain is risk
factor for delirium
 “Rome wasn’t built in a day”
 Balance pain against dose
 Titrate gently
 Analgesics: Titrate gently
 Don’t be afraid to decrease
Ax/Tx Challenges
Worsening Delirium
 Sedatives:
“A benzodiazepine will never help your
thinking.”
Dr. Mike Harlos
 Lorazepam is an independent risk
factor for delirium, increasing risk by ~
20 % (not to mention falls, etc.)
Panpharpande et al. Anesthesiology. 2006; 104:21
Kang JH et al. Comprehensive approaches to managing delirium in
patients with advanced cancer. Cancer Treat Rev
(2012)
Sedatives:
 Try not to be the one who starts bzd, but
don’t be the one who abruptly stops it
 Better a tired patient in AM than a delirious
patient in AM

 “Anxiety,” “restlessness?”
-- how about
company? Going for a walk-about?
 More staff, fewer sedatives, less
delirium?
 Drugs cheap, one-on-one expensive
 Value?
 Does vigorous hydration decrease
delirium incidence?
 Hyd’n reversed or improved 30 – 70 %
delirium cases
Thomson et al. Current Op Supp Pal Care.
2009; 3:72-78
Name it
Claim it
Tame it
 “A little fluffy”
 “Loopy”
 “A little off”
 “Not quite right”
 “Fruit-cake”
MMSE?
 CAM?
 Intuition?
 Do something;
 Name it….

 Change in consciousness with reduced
ability to focus, sustain or shift attention
 Engage in conversation?
 Months of year backward?
 Clinical suspicion
 Drs. cause delirium?
 Can Drs/nurses prevent it, reverse it, or
reduce its impact?
 Who better?
 Two simultaneous pathways
 Seek and treat cause (thus reverse?)
 Manage behaviours (“supportive care”)
 Human intervention better than
pharmacological
Supportive measures







Hydrate?
Avoid restraints
Mobilize
Reduce noise, etc.
Orient
Reassure
One-on-one
Investigations

MEDICATION REVIEW

Bloodwork
U/A
Imaging



Meds:
 Eliminate any psychoactive med possible:
 Metoclopramide, cipro? Baclofen?
Ranitidine? Lasix? others?

Meds:
 Analgesia:
 Good pain control? Consider dose
reduction?
 Sub-optimal pain control? Opioid rotation
IF investigations reveal pathology that can
reasonably be thought to be causing
delirium; AND IF the pathology can be
treated; AND IF it is in keeping with goals
of care; trial treatment
 Does patient behaviour compromise
care, or put patient, staff, or others at
risk?
 If “yes,” can a bedside sitter safely help?
 If “no,” low-dose neuroleptic and/or lowdose bzd
 Haloperidol remains standard of care
 Powerful
 Oral and parenteral
 Limited anti-cholinergic, sedative
properties
White et. al. “First Do no Harm…” JPM. 10 (2); 2007: 345-351
No significant differences in response in
double-blind RCT comparing risperidone
and haloperidol
 Similar evidence finding minimal
differences in efficacy between olanzapine
and risperidone

Bourne et. al. “Drug Treatment of Delirium.” Journal
Psychosomatic Research. 65; 2008: 273 - 282
Kang JH et al. “Comprehensive approaches to managing delirium
in patients with advanced cancer.” Cancer Treat Rev
(2012)
 Methylphenidate can improve
cognitive and psychomotor function in
hypoactive delirium
 Methylphenidate can cause agitation,
aggravation, psychosis
Bourne et. al. “Drug Treatment of Delirium.” Journal
Psychosomatic Research. 65; 2008: 273 - 282
 Delirium is bad
 Hard on patients, families, staff
 Often preventable, often iatrogenic
 Nurses optimally located
 Occasionally reversible
At the end of this session, you will
 Understand the importance of context in the
interpretation of pain
 Appreciate at a basic level the physiology of pain
and some principles of analgesia
 Have an approach to pain management that
always bears in mind the above points
11/11 65 %
12/12 91 %
Think about
pain….

Palliative care is an approach that improves the
quality of life of patients and their families facing
the problem associated with life-threatening
illness, through the prevention and relief of
suffering by means of early identification and
impeccable assessment and treatment of pain
and other problems, physical, psychosocial and
spiritual.
the prevention and relief of suffering…..
…by means of early identification and
impeccable assessment and treatment
of pain and other problems, physical,
psychosocial and spiritual.
Loeser, JD. “Perspectives on Pain.”
Clinical Pharmacology and
Therapeutics. Padgham, ed.
Baltimore: University Park Press.
1980. p 314
Loeser, JD. “Perspectives on Pain.”
Clinical Pharmacology and
Therapeutics. Padgham, ed.
Baltimore: University Park Press.
1980. p 314
Multi-disciplinary Team?
Pain or
Suffering?
Both?
Neither?
“…an unpleasant sensory and
emotional experience associated
with actual or potential tissue
damage or described in terms of
such damage.”
Merskey H, Bogduk N. 2nd ed Seattle, WA: IASP Press; 1994.
“…what ever the experiencing
person says it is, existing whenever
s/he says it does.”
Merskey H, Bogduk N. 2nd ed Seattle, WA: IASP Press; 1994.
Pain confers a survival benefit; we are “hardwired” to experience it
Asthenia
Anorexia
Pain
Nausea
Constipation
Sedation/Confusion
% Patients
Dyspnea
0
10
20
30
40
50
60
70
80
Bruera 1992 “Why Do We Care?” Conference; Memorial Sloan-Kettering
90
Seow H et al. “Trajectory of performance status and symptom scores for
patients with cancer during the last six months of life.” J Clin Oncol 2011;
29:1151.
Nociceptive
visceral
superficial
Neuropathic
somatic
deep
neuralgic
dysesthetic
hyperalgesia
bony
Adapted from Jovey R, 2002
NOCICEPTORS
• Sensory receptors
• Preferentially sensitive to
noxious stimuli (tissue
damaging/threatening)
• Chemical, thermal,
mechanical
SOMATIC PAIN
• Nociceptive
• Aching, often constant
• Often worse with mvt
• Well localized
• Tender
– bone & soft tissue
– chest wall
– post-surgery incision
VISCERAL PAIN
•
•
•
•
Constant or crampy
Dull, aching
Poorly localized
Often referred
– CA pancreas
– Bowel obstruction
– Infiltration/compression/distension
Pain initiated or caused by
primary lesion or dysfunction
in the nervous system
International Association for the Study
of Pain
NP DESCRIPTORS
Burning, Itching,
Shooting, Shocklike, Electric,
Lancinating
“Pins and needles,”
tingling, numb
NP DESCRIPTORS
“Pins and needles,”
tingling, numb
Pharmacologic treatment
Anticonvulsants – gabapentin, pregabalin
 TCAs (esp. if depression)
 NMDA receptor antagonists: ketamine,
dextromethorphan, methadone
 Steroids
 Opioids


Up to 90% of patients with
cancer pain could have their pain
alleviated by following the
treatment guidelines of the WHO
analgesic ladder
Fitzgibbon et al. “Parenteral Ketamine as an Analgesic Adjuvant
for Severe Pain.” J Pall. Med. 8(1) 2005
Adjuvant Rx may be
added at any step
Strong opioid
+ Step 2
Weak opioid
+ Step 1
Acetaminophen
& NSAIDs
Mild pain
(0-3)
Severe
(7-10)
Moderate
(4-6)
By the clock
By the ladder
Adjuvant Rx may be
added at any step
Strong opioid
+ Step 2
Weak opioid
+ Step 1
Acetaminophen
& NSAIDs
Mild pain
(0-3)
Severe
(7-10)
Moderate
(4-6)
By the clock
By the ladder
TOXIC
Serum
[ drug ]
Therapeutic
Sub-therapeutic
Time
TOXIC
Serum
[ drug ]
Therapeutic
Sub-therapeutic
Time
TOXIC
Serum
[ drug ]
Therapeutic
Sub-therapeutic
4 hours
4 hours
Life in the
Bloodstream

Think about drug, dose, route
Steady
decline
at home
Accelerated deterioration begins,
pain worsening, pt. admitted,
medications changed
Rapid decline due to illness
progression with
diminished reserves
Family thinking what?
Every family is
the Addams
family
???????
Too much medication
Not enough….
“It’s all the
morphine
you’re
giving
her…..”
Popular
misconception
held by families,
lay public, and
professionals
“’By the way, palliative care
shortens your life,’ [xxxx]
suggested.”
“Increasing overall opioid dosage was
associated with improved survival compared
with no change or decreasing overall dosage
(mean survival 14.0 12.7 days versus 9.3 9.8
versus 9.1 11.4, days respectively, P 5 .01).”
Azoulay et al. “Opioids, Survival, and Advanced Cancer
in the Hospice Setting.” J Am Med Dir Assoc. Feb. 2011; 12: 129
-134
“Opioid usage, even at high
dosages, had no effect on survival
among advanced cancer patients
in a hospice setting.”
Azoulay et al. “Opioids, Survival, and Advanced Cancer
in the Hospice Setting.” J Am Med Dir Assoc. Feb. 2011; 12: 129
-134
“Among patients with metastatic non–
small-cell lung cancer…, As compared with
patients receiving standard care, patients
receiving early palliative care had less
aggressive care at the end of life but
longer survival.”
Temel et al. “Early Palliative Care for Patients with
Metastatic Non–Small-Cell Lung Cancer.” N Engl J Med. 2010;
363:733 -42
SUB-Q MORPHINE
Bruera et al. J Pain Symptom Manage. 1990; 5:341-344
64 woman resents to ED with “severe” pain;
 Hydromorph Contin 24 mg PO bid;
 Hydromorphone IR 6 mg Q1H prn, taking
“several” times daily;
 “Confused” per family




Pain “everywhere”;
Poor historian, “muddled,” family report fairly
rapid escalation of opioids past 3-4/7;
O/E: vitals unremarkable, dry MM, decreased BS
R>L, no adventitia, normal HS. Very tender over
R rib cage (without compressing), abdo benign,
DTR unremarkable, no tremors or twitches;





ACP “M”;
B/W shows creatinine increased from previous, at
195, dry, corrected Calcium 2.5;
U/A benign;
CXR no obvious rib fractures;
AXR abundant stool, no a/f levels, no free air
 Pain “everywhere” (pathophysiology?);
 Family report fairly rapid escalation of
opioids past 3-4/7;
 Poor historian, “muddled”;
 Creatinine up

Potentially fatal neuropsychiatric syndrome of:






Cognitive dysfunction
Delirium
Hallucinations
Myoclonus/seizures
Hyperalgesia / allodynia
Early recognition is critical
Normal Renal Fcn
Renal Insufficiency
Osborne et al. “The Pharmacokinetics of morphine and morphine
glucuronides in Kidney Failure.” Clin Pharmacol Ther 54:158-167,
1993
Opioid
tolerance
Mild myoclonus
(eg. with sleeping)
Delirium
Opioids
Increased
Severe myoclonus
Seizures,
Death
Hyperalgesia
Agitation
Misinterpreted
as Pain
Opioids
Increased
Misinterpreted
as Disease-Related Pain

Switch opioid (rotation) and/or reduce dose

Hydrate

Bzd prn?



Not everyone has pain ;
Treating pain with scheduled opioids is
appropriate and safe;
Avoid long-acting formulations;


Watch out for pain that “doesn’t make
sense,” as it might be warning you of OIN
Pain and suffering are distinct, and not
always related as closely as we think
PAIN
POSSIBLE
Suffering?
At the end of the session, you will
• Have a basic understanding of respiration
• Be aware of the complex mechanisms
underlying dyspnea
• Have an approach to the management of
dyspneic patients
“Subjective experience of breathing
discomfort that consists of
qualitatively distinct sensations that
vary in intensity.”
American Thoracic Society. “Dyspnea:
Mechanisms, Assessment, and Management, a
Consensus Statement.” Am J Respir Crit Care
Med. 1999; 159: 321 - 340
DYSPNEA
• Physical and emotional
components (anxiety, panic,
chronic fear)
• Often no measurable physical
correlates (RR ? SaO2 ? ABG)
Tachypnea ≠ dyspnea
Universal response is to
decrease activity to whatever
degree necessary
Dudgeon, D. “Managing Dyspnea and Cough.”
Hematology/Oncology Clinics of North America.
2002; 16: 557-577
A
B
C
D
“Subjective experience of breathing
discomfort that consists of
qualitatively distinct sensations that
vary in intensity.”
American Thoracic Society. “Dyspnea:
Mechanisms, Assessment, and Management, a
Consensus Statement.” Am J Respir Crit Care
Med. 1999; 159: 321 - 340
Months
Without eating
Days
Without drinking
Minutes
Without breathing
• Dyspnea, like pain, is protective. As
pain alerts us to actual or impending
tissue damage, dyspnea alerts us to
threat.
• “Hardwired” to protect
• 60 % lung Ca patients
• Nearly 90 % once near death
• 50 % described dyspnea as
severe
Muers MF, Round CE. “Palliation of symptoms in non-small cell lung cancer: a
study by the Yorkshire Regional Cancer Organization thoracic group.” Thorax
1993;48:339– 43.
Reuben DB, Mor V. “Dyspnea in terminally ill cancer patients.”
Chest. 1986; 89(2): 234-6.
• Abnormality of blood gases, especially
hypercapnia (PaCO2 > 50 mmHg) and, to a
lesser extent, hypoxia (PaO2 < 60 mmHg);
• Amount of work that must be performed
by respiratory muscles to provide adequate
ventilation;
• State of mind.
Guyton and Hall. Textbook of Medical Physiology. 491
Mahler. “Understanding
Mechanisms …Dyspnea.”
Current Opinion in
Supportive and Palliative
Care .2011, 5:71–76
• Integrates information about:
o Degree of effort required
o Mechanical response achieved
o O2/CO2 pH status
In order to answer two questions:
1.Is the mechanical response
normal relative to the degree of
effort expended?
2.Is the current effort sustainable?
If not, dyspnea
Dyspnea occurs when there is a
mismatch between ventilation and
the demand set by chemical drive
Buchanan and Richerson. “Role of Chemoreceptors in
Mediating Dyspnea.” Respiratory Physiology and
Neurobiology. 2009; 167: 9 – 19
Oxygen
Carbon
Dioxide
CO2 + H2O
HCO3- + H+
• Tachypneic?
• Hypoxic?
• Anxious/afraid?
• Diaphoretic?
• Unconscious?
“Subjective experience of breathing
discomfort that consists of
qualitatively distinct sensations that
vary in intensity.”
American Thoracic Society. “Dyspnea:
Mechanisms, Assessment, and Management, a
Consensus Statement.” Am J Respir Crit Care
Med. 1999; 159: 321 - 340
1.Assess the symptom
2.Determine the cause
3.Treat the cause
4.Treat the symptom
• Remember:
oTachypnea is not dyspnea;
oAssess distress, not just
apparent intensity
• Thoracic
• Non-malignant
• Malignant
• Paramalignant
• Extra-thoracic
•
•
•
•
•
Cachexia;
Anemia;
Ascites;
Hepatomegaly
‘Lyte derangement
•
•
•
•
•
•
•
Anti-tumour: chemo/RT, etc.
Infection
CHF
SVCO
Pleural effusion
Pulmonary embolism
Airway obstruction
• Goal of interventions:
o Minimize production of symptom
(pre-medicate, energy mgmt.,
breathing techniques)
o Diminish perception of symptom
(meds, fan, distraction)
• Goal of interventions:
o Modify the experience of the
symptom (address meaning, help
with mood/fear/anxiety)
• Non-pharmacological
oOpen window?
oCool facial stimulation (fan)
oPositioning
oPulmonary rehab?
• Pharmacological
oOxygen
oOpioids
oNebulized furosemide
oAnti-inflammatory tx
oBenzodiazepines?
Bruera 1993
• 14 dyspneic, hypoxic (SaO2 < 90%)
cancer inpatients
• RCT, 2 x blind, placebo, crossover
• 5 L/min air by NP vs O2
• no ∆ in VAS from baseline with air,
significant improvement with O2
Bruera et al. Lancet. 1993; 342: 13 -14
Bruera 1993
Conclusion: O2 substantial
benefit in hypoxic dyspneic
cancer patients
Bruera et al. Lancet. 1993; 342: 13 -14
Bruera 2003
• 33 dyspneic, non-hypoxic cancer pts
• RCT, single blind, placebo, cross-over
• 5 l/min air vs O2 for 6 MW test
• No difference in dyspnea, fatigue, or
distance walked
Bruera et al. Pall Med. 2003; 17: 659 - 63
Bruera 2003
Conclusion: O2 of no benefit over
air to exercising non-hypoxic
cancer pts
Bruera et al. Pall Med. 2003; 17: 659 - 63
• O2 no better than air in nonhypoxic patient
• O2 better than air if hypoxic
Normal
O2
CO2 Resp. Drive
COPD
O2
CO2 Resp. Drive
COPD
O2
CO2
Resp. Drive
Giving pts. with COPD
supplementary O2 can actually
suppress their resp. drive (and kill
them with kindness)
• Anxiety is significantly
correlated with intensity of
dyspnea
• Limited evidence supporting
BZD role
Bruera, E. et al. “The Frequency and Correlates of
Dyspnea in patients with Advanced Cancer.” J Pain
Symptom Mgmt. 2000; 19: 357-62
“Milk of the poppy…”
• Used for analgesia for
centuries
• Used since at least 19th
century for breathlessness
• Now a degree of reticence
• Naloxone versus saline in exercising COPD
patients;
• Naloxone group more dyspnea;
• Endogenous opioids blunt dyspnea
Mahler DA, Murray JA, Waterman LA, Ward J, Kraemer WJ,
Zhang X, Baird JC: “Endogenous opioids modify dyspnoea
during treadmill exercise in patients with COPD.” Eur Respir
J 2009; 33:771.
• Cochrane:
o 18 RDBPC crossover trials
o 9 nebulized, 9 systemic, 14 single dose
o Primarily COPD
• Conclusion: significant benefit for systemic,
but not for nebulized opioids
Jennings et al. “Opioids for the Palliation of
Breathlessness in Terminal Illness.” Cochrane.
Database of Systemic Reviews. 2001
Early use of opioids may
prolong survival, by reducing
physical and psychological
distress
Twycross, R. “Morphine and Dyspnea.” Pain Relief in
Advanced Cancer. New York: Churchill Livingston, 1994.
383- 99
• ↓ Medullary sensitivity/response to
hypercarbia/hypoxia
• ↓ Cortical resp. awareness
• ↓ Metabolic rate/ventilatory demand
• Vasodilation (improved cardiac fcn)
• Analgesia: ↓ pain-induced resp. drive
• Anxiolysis
• Narrow therapeutic index
• Watch:
oRate of dose change
oPrevious exposure?
Bruera, E. “Effects of Morphine on Dyspnea.”
J Pain Symptom Mgmt. 1990; 5: 341-4
• Pinpoint pupils
• Gradual slowing of the respiratory
rate
• Breathing is deep (though may be
shallow) and regular
“…fear has been shown to be largely unfounded.
Examining changes in respiratory parameters…in
dyspneic palliative care patients…demonstrated
significant decrease in respiratory rate and
improvement in dyspnea with titration with
morphine or hydromorphone but no significant
changes in other respiratory parameters,
indicating no opioid-induced respiratory
depression.”
Kamal et al. “Dyspnea Review for the Palliative Care
Professional.” J Pall Med. 2012; 15 (1): 106 - 114
“…demonstrated benefits, and the lack of
edvidence of accelerated death, have led
the American College of Chest
Physicians…to recommend that physicians
titrate oral and/or parenteral opioids”
Kamal et al. “Dyspnea Review for the Palliative Care
Professional.” J Pall Med. 2012; 15 (1): 106 - 114
Bruera et al. J Pain Symptom Manage. 1990; 5:341-344
• Dyspnea can’t be measured,
and often can’t be observed
• Oxygen is a drug; balance
benefit vs cost ($ and other)
• Opioids work
If you want a wise answer, ask
a reasonable question
Goethe
Who questions much, shall learn much, and
retain much
Francis Bacon
Our solar system consists of one
star, and some debris….
Carl Sagan