Delirium at End-of-Life: Assessment and
Treatment When Comfort is the Goal
Nancy Newman RN BSN
Contact Nancy Newman @newmannk@courses.alverno.edu
Alverno College
April 15, 2011
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Navigation
Mental
Assessment
Tools
Learner
Outcomes
Case Study
Part One
Drug Toxicity
Case Study
Part Six
What is
Delirium at
End -of- Life
Case Study
Part Two
Interventions
for drug
toxicity
Case Study
Part Seven
Metabolic
Imbalances
Causes of
Delirium at
End –of- Life
Case Study
Part Three
Case Study
Part Five
Spiritual
Distress
Interventions
Systemic
Inflammation
Case Study
Part Four
Medications for
Delirium at
End -of -Life
Case Study
Part Eight
Other
Nursing
Interventions
Learner Outcomes
 The learner will be able to assess and identify signs and
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symptoms of delirium at end-of-life
The learner will be able to distinguish between dementia and
delirium at end-of-life
The learner will understand and identify the physiology of
known causes of delirium at end-of-life
The learner will be able to identify appropriate
treatments/nursing interventions for delirium at end-of-life
The learner will be able to identify the impact of stress,
genetics and aging on delirium at end-of-life
Do you want to review delirium at endof-life?
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 If you don’t want to review delirium at end-of-life, click here
to start case study
What is delirium at end-of-life?
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 Delirium is an altered level of consciousness characterized by reduced
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attention and memory, perceptual disturbances (hallucinations and or
delusions), incoherent speech, and altered sleep/wake cycles.
(Weissman, Anbuel, & Hallenbeck, 2010, p. 56)
Delirium at end-of-life usually occurs in weeks to hours prior to
death
Other terms for delirium at end-of-life include terminal agitation,
terminal restlessness, and end-stage restlessness
Occurs in 25-85% of cancer patients prior to death (Blanchette, 2005,
p.18)
Cause may never be confirmed. May be result of interaction between
precipitating factors and other risk factors, and/or by the shut down of
different body systems during the dying process (Blanchette, 2005, p.
18)
What are common causes of delirium
at end-of-life? Select answer(s)
Medications
Yes you are right! Drug toxicity can
cause delirium at end of life.
Brain Metastasis
Yes, you are right again!
Metabolic Imbalances
Yes, you are very smart!
Hypercalcemia, hyponatremia, liver
and renal failure may cause delirium
at end-of-life.
History of Extreme Exercise
No, you are incorrect.
Other causes of delirium at end-of-life
 Constipation
 Urinary retention
 Spiritual distress
 Dyspnea
 Uncontrolled pain
 Infection
Hyperactive or Hypoactive?
 Hyperactive delirium is characterized by increased arousal
and agitation. Climbing out of bed, pulling out IV lines, foley
catheters, picking at air.
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 Hypoactive delirium is characterized by the patient being
more quiet, withdrawn, sleepy, mumbling speech.
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Delirium at end-of-life is NOT dementia
“Dementia is a loss of mental ability severe enough to
interfere with normal activities of daily living, lasting more
than six months, not present since birth, and not associated
with a loss or alteration of consciousness ( THE FREE
DICTIONARY BY FARLEX, 2011)”.
Frequently used mental assessment
tools
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 Click on link for examples of frequently assessment tools to
determine cognitive status.
 Confusion Assessment Method (CAM/ICU)
 Richmond Agitation-Sedation Scale
 Mini- Mental Status Exam
Case Study Part One
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 Mr. G. is an 80 yo male with stage IV lung cancer with metastasis
to brain and bone and renal failure. He is a home hospice patient
with a prognosis of 1-2 weeks. The patient and family have
identified the goals of care as comfort and no aggressive
treatment. He was admitted to the palliative care unit last night
for pain control and restlessness. In report you hear that his wife
reported that he had not slept the last 2 nights, c/o urge to urinate
but only “goes a little bit each time”. He is newly confused with
increasing agitation.
Does Mr. G appear to have delirium at endof-life or dementia? Select answer
Delirium at end-of-life
Yes, you are correct. Mr.
has had a rapid change in
level of consciousness
Dementia
Sorry, try again.
Case Study Part Two
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 You enter the patient’s room to do your assessment. Mr. G.
has his feet over the side of the bed and is trying to get out of
bed. His hospital gown is off. He has pulled out his IV. You
greet Mr. G. and ask him where he is going. He states he has
to go to the bathroom. When you try to help him put his
gown on, he pushes you away and yells, “Get out of my room
or I’ll call the police”.
Is Mr. G. exhibiting signs of hyperactive
or hypoactive delirium ? Select
answer
Hyperactive delirium
Yes you are correct
Hypoactive delirium
Sorry, try again
Case Study Part Three
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 You ask Mr. G. if he needs to go to the bathroom. He says
“yes “ and you help him to the bathroom. He voids 50 ml of
urine.You assist him back to bed.You ask him if he is having
any pain. He denies pain, but winces every time he moves in
the bed.You revise your question and ask Mr. G. if he is
comfortable. He shakes his head “no”. You notice that Mr.
G.’s arms are twitching intermittently.
According to Mr. G.’s case study what are
potential causes of his delirium at end-of-life ?
Select answer(s)
Urinary retention
Yes, you are correct, he has urinary
urgency and frequency
Dyspnea
Incorrect. Mr. G. has not
complained of dyspnea. You are
correct that dyspnea can cause
terminal restlessness
UTI
You are right again. The symptoms
of urinary urgency and frequency
could be due to infection
Brain Metastasis
You are correct. Mr. G. does have
lung cancer with brain metastasis
Case Study Part Four
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 You quickly review Mr. G.’s admission note and medication
list. He has been taking morphine SR 60 mg every 12 hours.
In the last 24 hours he has had liquid morphine IR 20 mg
orally every 2 hours. You remember that Mr. G.’s arms were
twitching. He has no history of seizures.
You remember that drug toxicity can
cause delirium at end-of-life
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Morphine is commonly prescribed at
end of life for pain and dyspnea
 “The principal actions of therapeutic value of morphine are
analgesia and sedation (i.e., sleepiness and anxiolysis). The
precise mechanism of the analgesic action is unknown.
However, specific CNS opiate receptors for endogenous
compounds with opioid-like activity have been identified
throughout the brain and spinal cord and are likely to play a
role in the expression of analgesic effects” (Drugs.com,
2011).
Morphine-what happens when it is
metabolized?
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Some morphine metabolites may
lead to delirium at end-of-life
 Morphine is metabolized by the liver.
 The plasma morphine metabolites are:
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 Morphine-6-glucuronide (M6G) which binds to mu opioid
receptor sites and provides analgesia and sedation
 Morphine-3-glucuroinide (M3G) M3G does not appear to have
any analgesic properties, nor does it bind to mu opioid receptors.
It can cause neuroexcitation, hyperalgesia, allodynia,
myoclonus, and terminal agitation (Maluso-Bolton, 2000, p.
12)
 To review drug metabolism click here
(Tierney, 2008)
Morphine metabolism in the liver
Liver
Cell
Morphine
UGT2B7
Normorphine
UGT1A1
UGT2B7
M-6-G
UGT1A1
Provides
analgesia, sedation
M-3-G
Causes
neuroexcitation
and restlessness
Note. From “Pathway- Codeine and Morphine Pathway” (PK) by PHARMGKB.
Copyright 2006. Adapted with permission from PharmGKB and Stanford University.
Which morphine metabolite can lead to
delirium at end-of-life ? Select answer
M-6-G
No, M-6-G provides
pain relief and
sedation
M-3-G
Yes, M-3-G can cause
neurotoxicity and
restlessness
Factors that may affect morphine
metabolism
 Age. Morphine metabolites are excreted by the kidney. Renal function
declines with age. “Numerous cross-sectional studies have documented a
steady, age-related decline in total renal blood flow of approximately 10% per
decade after 20 years of age…(Porth & Matfin, 2009, p. 44)”.
 Gender. Some studies have found that morphine has a longer onset and offset in
women (Sarton et al., 2000, p. 1253) One study found that elderly women have
higher levels of morphine metabolites than elderly men, and a reduced renal
clearance.(Wittwer & Kern, 2006,p. E350)
 Genetic mutations of the genes of the mu opioid receptor sites may increase or
decrease the effectiveness of morphine metabolism. Mutations may cause
patients to require a higher dose and/or have increased side effects. Studies
continue. (Ross, et al., 2005) (Fujita, et al., 2010)
Interventions
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 Opioid rotation (changing to a different opioid, i.e..
morphine to hydromorphone) hydration or dose reduction
 Renal failure can increase accumulation of morphine
metabolites. Hydromorphone or other opioids would be a
better choice of medication for patients with renal failure
 ALL treatment is based on therapeutic goals for
patient and family and how close pt is to death. The
benefit of treatment should outweigh the burden of
treatment
Case Study Part Five
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 The home hospice nurse had recommended lorazepam 0.5-1
mg po every hour prn for restlessness. The wife stated she
gave him 2 doses of lorazepam and he had become more
agitated with each dose. She thinks he is allergic to
lorazepam.
Lorazepam may have paradoxical side
effects
 Lorazepam may increase agitation or cognitive deficits
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Medications for hypoactive delirium at
end-of-life
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 Haloperidol PO/IV/SQ 0.5-6 mg every 4-12 hours prn.
 Add benzotropine 0.5-1 mg IV (PO TID) for extra
pyramidal symptoms (EPS)
 Use olanzopine 2.5-5 mg po if continued EPS
 (Derby & O’Mahony, 2006)
Medications for hyperactive delirium at
end-of-life
 Haloperidol IV/PO/SQ 2-10 mg every 4-12 hours prn.
 Add benzotropine 0.5-1 mg IV (PO TID) for extra
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pyramidal symptoms (EPS)
Add lorazepam 0.5-2 mg every 4 hours for sedation prn
Change lorazepam to chlorpromazine 25-50 mg IV every 412 hours if increased sedation is needed
Change lorazepam to olanzapine if regimen is not tolerated
or if EPS are an issue
(Derby & O’Mahony, 2006)
Select the interventions you would perform
Medicate with haloperidol.
Yes, you are correct.
Haloperidol is the primary
agent for treating terminal
restlessness.
Contact the physician to
check on changing opioids
Yes, you are correct. Mr. G.
has renal failure.
Medicate with lorazepam.
No you are incorrect.
Lorazepam would be given
only if haloperidol is
ineffective.
Contact the physician to
check on reducing the dose of
pain medication.
No, Mr. G.’s pain is not well
controlled.You wouldn’t
want to reduce the dose.
Case Study Part Six
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 Mr. G. is calmer since you have medicated him with
haloperidol and hydromorphone. He allows you to continue
your assessment. When you assess his abdomen you find that
his abdomen is slightly distended and firm. You can palpate
his bladder. Mr. G. mumbles, “I have to go to the bathroom,”
as you palpate his abdomen. Mr. G.’s wife reported his last
b.m. was 5 days ago.
Which interventions are appropriate for
Mr. G.? Select answer(s)
Insert a foley catheter.
No, do a bladder scan first to
ensure he needs a foley
catheter.
Perform a bladder scan.
Yes, a bladder scan will
validate the need for a foley
catheter.
Pre-medicate for a rectal
exam.
Yes, you should pre-medicate
for the exam.
Turn the bed alarm on.
Yes, the bed alarm should be
on. Mr. G. is a fall risk due to
his confusion.
Case Study Part Seven
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 The bladder scan revealed 500 mls urine.You inserted a foley
catheter. He had a b.m. after you gave him a suppository. Mr. G. is
calmer. You go to lunch and come back to find Mr. G. is restless
again. His bed alarm is going off almost continuously. You enter
Mr. G.’s room to find him pulling at his gown. He is halfway out
of the bed.You are calm and reassuring as you assist him to lay
down.You ask him where he is trying to go. Mr. G. replies, “The
priest, the priest…” over and over.
Spiritual or Existential Distress
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 “ Spiritual distress is an expression of profound disharmony
in the person’s belief or value system that threatens the
meaning of his or her life (Nursing Care Plans, 2010) ”.
Click on the pictures below to find
nursing interventions to help Mr. G.
Call the
chaplain
Ask his wife
about his
spiritual
beliefs
Offer to pray
with the patient
All images on this page are Microsoft Clip Art
Case Study Part Eight
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 You told Mr. G.’s wife that he seemed to be asking for a
priest. Mrs. G replied that she knew he hadn’t been to
church in a long time. She thought he would like to see a
priest. You contacted the chaplain department and a priest
visited Mr. G. the next day. Mr. G. is on scheduled
haloperidol and hydromorphone. He is comfortable and
peaceful as he nears the end of his life. His goals of care are
being met.
Palliative sedation/Terminal sedation
 “Terminal sedation is the use of pharmacological agents to
induce sedation to unconsciousness in order to relieve
intractable suffering” (Moluso-Bolton, T. .2000,p.18).
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Treatment in the actively dying patient
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 Remember, ALL treatment is based on therapeutic
goals for patient and family and how close pt is to
death. The benefits of treatment should outweigh
the burden of treatment.
Some interventions assist to “destress” patient and family
 Some of the symptoms of terminal restlessness may indicate
the “fight or flight” response of the sympathetic nervous
system has been activated
 Many nursing non-medication interventions assist to activate
the relaxation response of the parasympathetic nervous
system (PNS)
 “The PNS slows the heart rate, stimulates GI function,
promotes bowel and bladder elimination, and contracts the
pupil, protecting from excessive light during periods when
visual function is not vital to survival” (Porth & Matfin, 2009,
p. 1216).
Click on items to find additional
nursing interventions
Oxygen to
decrease dyspnea
Decrease stimuli,
but leave a light on
Reassure the family
and answer questions
Gentle touch or light
massage
Fan to decrease
dyspnea
Encourage family to
visit/stay with patient
Frequent
Orientation
All images on this page are Microsoft Clip Art
Metabolic imbalances that may cause
delirium at end-of-life
 Hypercalcemia- Calcium >10.5 mg/dL
 Due to bone metastasis, dehydration, certain cancers
 Hyponatremia- Serum sodium <136 meq/L
 Due to disease process or from side effects of some diuretics
 (Blanchette, 2005, p. 20)
 Note -No lab work was done on Mr. G due to his short
prognosis and goals of care
Common metabolic imbalances that
can affect delirium at end-of-life
Hypercalcemia
Serum
calcium> 10.5
mg/dL
Caused by
bone
metastasis,
dehydration,
certain
cancers
Main
neurological
symptoms due
to decreased
neuromuscular
excitability
Muscle
weakness
personality
change,
cognitive
dysfunction,
disoriented,
incoherent
speech, coma
(National Cancer
Institute, n.d.)
Hyponatremia
Serum sodium <
136 meq/L
May be caused by
disease process
and dehydration
Main symptoms
due to cerebral
edema
Fatigue,
confusion,
decreased
consciousness,
hallucinations,
convulsions,
coma,
restlessness,
Treatment with
rehydration,
biophosphonates
(biophosphonate
accumulates in
bone and inhibit
osteoclastmediatated bone
resorption)
(Cleveland Clinic,
2011)
Treatment may
include rehydration
(dependent on
cause), fluid
restriction,
medications
dependent on
underlying disorder
(GlobalRPH.com,n.d.)
(Medline Plus,2011)
*No bloodwork was done on Mr.. due to short prognosis and goals
of care
Pathophysiology of malignant
hypercalcemia
 Osteolytic hypercalcium results from bone
destruction by tumor
 “Humoral hypercalcemia is mediated by circulating
factors secreted by malignant cells without
evidence of bony disease.[8,9] It is believed that
hypercalcemia results from the release of factors by
malignant cells that ultimately cause calcium
reabsorption from bone [4]” (National Cancer
Institute, 2011).
Humoral hypercalcemia
Malignant cells
Secrete PTHrP
into circulation
Binds with skeletal and
renal receptors
Increases calcium reabsorption
from the bone into the blood
Hypercalcemia
Which factors can cause
hypercalcemia? Select answer (s)
Bone Metastasis
Yes, you are correct.
Cancer
Yes, you are correct.
Drinking a glass of milk daily
Sorry, try again.
Dehydration
Yes, you are correct.
Click on red boxes to see
pathophysiology of hyponatremia
Decreased sodium in ECF
Causes water to move into ICF
by osmosis
Increased ICF causes
swelling in cell
Edema in brain cells cause
cerebral edema
Cerebral edema causes
most of the symptoms of
hyponatremia
The impact of systemic inflammation
on delirium at end-of-life
 Systemic inflammation may occur when delirium at end-of-
life is precipitated by infection
 The acute-phase of the inflammatory response includes
symptoms of “anorexia, somnolence, and malaise, probably
because of the actions of IL-1 and TNF on the central
nervous system”( Porth & Matfin, 2009, p.389)
 The elderly are at higher risk. Recent studies have shown
that with ageing and some forms of pathology there is an
“exaggerated CNS response to stress and inflammation
results” ( MacLullich, 2008).
INFECTION
Inflammatory response is
initiated
Inflammatory response progresses to
systemic inflammatory response
Acute-phase response with
increased release of IL-2, TNF being
produced
Increase in IL-2 and TNF affects the central
nervous system and results in somnolence,
malaise, and anorexia
References
 Blanchette,H. (2005). Assessment and treatment of terminal restlessness in the
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hospitalized adult patient with cancer. MEDSURG Nursing, 14 (1), 17-23.
Cleveland Clinic. (2011). Retrieved April 9, 2011 from
http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/en
docrinology/hypercalcemia/#cesec30
Derby, S., & O’Mahony, S. (2006). Elderly patients. In Betty R. Ferrell &
Nessa Coyle (Eds.), Textbook of palliative nursing (pp. 635-657 ). New York, New
York: Oxford University Press.
Drugs.com. (2011). Retrieved March 27, 2011 from
http://www.drugs.com/pro/morphine-sulfate.html
Ely, E. (2007). CAM/ICU Worksheet. (2007). Retrieved March 27, 2011
from
http://www.mc.vanderbilt.edu/icudelirium/docs/CAM_ICU_worksheet.pdf
References
 Fujita, K., Ando,Y.,Yamamoto,Y., Miya, T., Endo, H., Sunaawa,Y., et al. (2010).
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Association of UGT2B7 and ABCB1 genotypes with morphine-induced adverse
drug reactions in Japanese patients with cancer. Cancer Chemotherapy Pharmacology,
65, 251-258.
MacLullich, A., Ferguson, K.,Miller, T., De Rooij,S., &Cummingham, C. (2008).
Unravelling the pathophysiology of delirium: A focus on the role of aberrant stress
responses. Journal of Psychosomatic Research, 65, 229-238.
McCauley,D. (n.d.). Hyponatremia. Retrieved April 5, 2011 from
http://www.globalrph.com/hyponatremia.htm
MedlinePlus. (2011). Retrieved April 5,2011 from
http://www.nlm.nih.gov/medlineplus/ency/article/000394.html
Mini-Mental Status Exam. (n.d.). Retrieved March 27, 2011 from
http://www.nmaging.state.nm.us/pdf_files/Mini_Mental_Status_Exam.pdf
References
 Moluso-Bolton, T. (2000). Terminal agitation. Journal of Hospice and Palliative
Nursing, 2 (1), 9-20.
 National Cancer Institute. (2011). Retrieved April 5, 2011 from
http://www.cancer.gov/cancertopics/pdq/supportivecare/hypercalcemia/He
althProfessional/page1
 National Cancer Institute. (n.d.). Retrieved April 5, 2011 from
http://www.cancer.gov/cancertopics/pdq/supportivecare/hypercalcemia/He
althProfessional/page3
 Nursing Care Plans. (2010). Retrieved March 29, 2011 from
http://www1.us.elsevierhealth.com/MERLIN/Gulanick/Constructor/index.
cfm?plan=50
References
 Ross,J., Rutter, D., Welsh, K., Joel, S., Goller, K., Wells, A.,et al. (2005).
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Clinical response to morphine in cancer patients and genetic variation in
candidate genes. The Pharmcogenomic Journal,5, 324-336.
Porth, C., & Matfin, G. (Eds.). (2009). Pathophysiology: concepts of altered health
states. Philadelphia: Lippincott Williams & Wilkins.
Richmond Agitation/Sedation Scale. (n.d.). Retrieved March 27, 2011 from
http://www.mc.vanderbilt.edu/icudelirium/docs/RASS.pdf
Sarton, E.,Olofsen, E., Romberg, R., den Hartigh J., Kest, B., Nieuwenhuijs,
D, et al. (2000). Sex differences in morphine analgesia: An experimental study
in healthy volunteers. Anesthesiology, 93 (5) 1245-1254.
THE FREE DICTIONARY BY FARLEX. (2011). Retrieved March 23, 2011
from
http://medical-dictionary.thefreedictionary.com/dementia
References
 Thorn C., Klein, T., & Altman, R. (2009). Codeine and morphine pathway.
Pharmacogenet Genomics ,19 (7), 556-558.
 Tierney, K. (2008,September 12). Drug metabolism. [Video file]. Retrieved
from http://www.youtube.com/watch?v=2uehdqZzKEM&feature=related
 Weissman, D., Anbuel, B., & Hallenbeck, J. Palliative care: A resource guide for
physician education, 4th Edition. Medical College of Wisconsin, 2010.
 Wittwer,E., Kern, S. (2006). Role of morphine’s metabolism in analgesia:
Concepts and controversies. American Association of Pharmaceutical Scientists
Journal, 8 (2), E348-E352.