Download Delirium - Palliative Care - University of British Columbia

Delirium
How Emergency Physicians Can
Make a Big Difference
Alan Bates, MD, PhD, FRCPC
Consultant Psychiatrist
St. Paul’s Hospital and the BC Cancer Agency
Clinical Assistant Professor
Department of Psychiatry
University of British Columbia
In 1959…
 Engel and Romano
 “…while most physicians have a strong bias
toward an organic etiology of mental
disturbances, … they seem to have little
interest in … the one mental disorder
presently known to be based on
derangement of cerebral metabolism.”
 “… deficiencies in the education of many
physicians ill equip them to recognize any
but the most flagrant examples of
delirium…”
In 1959…
 Engel and Romano continued
 “Only … a management problem on a
medical or surgical service is likely to result
in a psychiatric consultation.”
 “[The psychiatrist] … seeing the patient in
the home territory of the “organic”
specialists … is less likely or able to pursue
an understanding of the underlying
physiologic derangements, which are
generally conceived to be the proper domain
of the internist.”
In 1959…
 Engel and Romano continued
 “Unhappily, the unfortunate patient’s
malfunctioning brain rests in limbo, an object
of attention and interest neither to the
medical man nor to the psychiatrist.”
 “Not only does the presence of delirium
often complicate and render more difficult
the treatment of a serious illness, but also it
carries the serious possibility of permanent
irreversible brain damage.”
In 1959…
 Engel and Romano continued
 “With increasing life expectancy … we are
now beginning to see an increasing
incidence of so-called senile and
arteriosclerotic dementias.”
 “The physician who is greatly concerned to
protect the functional integrity of the heart,
liver, and kidneys … has not yet learned to
have similar regard for the functional
integrity of the brain.”
From Cresswell III et al.
Organic
Functional
< 12 or > 40 years old
12 – 40 years old
Sudden
Gradual
Consciousness
Decreased
Normal
Hallucinations
Visual
Auditory
Course
Fluctuates
Continuous
Orientation
Disoriented
Scattered thoughts
Abnormal
Normal
No
Yes
Age
Onset
Vitals
Psych Hx
DSM-5 Criteria
 Disturbance in attention and awareness
 Develops over short time, change from
baseline, fluctuates in severity over
course of a day
 An additional cognitive disturbance (e.g.
memory, orientation, language,
visuospatial, perception)
 Not another neurocognitive disorder, not
coma
 Direct consequence of another medical
condition
Meagher et al., 2007
 100 palliative care patients
 Attention – 97% (e.g. distractibility, digit span)
 Sleep-wake cycle – 97% (?cause of fluctuation,
early)
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Long-term memory – 89%
Short-term memory – 88%
Orientation – 76% (misses ¼)
Visuospatial ability – 87%
Motor agitation – 62% (early)
Motor retardation – 62% (early)
Language – 57%
Perceptual – 50% (motor agitation = retardation)
Incidence
 Hospitalized elderly patients – 25% (van
Blanken et al., 2005)
 ICU – 70% at some point (McNicoll et al., 2003)
 30% of critically ill children (Smith et al., 2013)
 Post-operative delirium in patients over
60 after cardiac surgery – 52% (Rudolph et al.,
2009)
 Terminal illness – 88% (Massie etl al., 1983; Lawlor et
al., 2000)
Incidence and detection - ER
 Elie et al., 2000
 10% of 447 ER patients over 65 delirious
 Detection by ED physician
 Sensitivity: 35%, Specificity: 99%
 Han et al., 2014
 12% of 406 ER patients over 65 delirious
 Detection by ED physician using CAM-ICU
 Sensitivity: 72% (better than RAs)
 Specificity: 99%
 Han et al., 2014
 CC of “altered mental status”: 38% sensitivity,
99% specificity (when not coma, non-verbal etc.)
Impact
(reviewed by Maldonado et al., 2009)
 Clear immediate increase in suffering of
patient and family
 Increased morbidity and mortality
 Prolonged hospital stays
 Increased cost of care
 Increased hospital-acquired complications
 Poor functional and cognitive recovery
 Decreased quality of life
 Increased placement in intermediate- and
long-term care facilities
Impact – ER specific
 Han et al., 2010 / 2011
 628 ER patients over age 65
 17% delirious
 6-month mortality:
 37% in delirious group
 14% in non-delirious group
 Median length of stay:
 2 days for delirious
 1 day for non-delirious
Distress
 Rate of diagnosable PTSD was 9.2% at 3
months post-ICU in 238 post-ventilated
patients with a strong association
between PTSD and recall of delusional
memories (Jones et al., 2007)
 Delirium is even more distressing for
spouses than for patients (Breitbart et al., 2002)
Milbrandt et al., 2004
 224 consecutive mechanically ventilated
ICU patients (after excluding 51 with
coma leading to death)
 82% developed delirium, mean duration
2 days
Barrough, 1601
“It commeth to passe also that the
soporiferous diseases being ended, there
ensueth forgetfulnesse: which when it
chanceth then a cold distempure is the
cause that the memorie is perished or
grievously hurt.”
Maclullich et al., 2009
 Reviewed 9 recent studies with total of 2025
patients
 8/9 studies found a significant association
between delirium and cognitive impairment
 What is the relationship?
 CNS insult causes both in parrallel?
 Premorbid dementing process unmasked in form of
delirium by stress/insult?
 Delirium causes things like dehydration, poor
nutrition, suboptimal care etc. and this leads to longterm cognitive impairment?
 Delirium is a neurotoxic state?
 Delirium management is neurotoxic?
Witlox et al., 2010
 Meta-analysis of elderly patients with delirium
 Delirium associated with increased risk of death
(38% vs. 28% in controls at average follow-up of
23 months)
 Delirium associated with increased risk of
institutionalization (33% vs. 11% in controls at
average follow-up of 15 months)
 Delirium associated with increased risk of
dementia (63% vs. 8% in controls at average
follow-up of 4 years)
 Above results are independent of age, sex,
comorbid illness, illness severity, and baseline
dementia
Risk factors
 Infection
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Withdrawal
Acute metabolic
Trauma
CNS (structural)
Hypoxia
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Deficiency of vitamins
Endocrine
Acute vascular
Toxins/Medications (Lexicomp is your friend)
Heavy metals
Deleriogenic Medications
 Anticholinergic
 e.g. diphenhydramine, hydroxyzine, atropine, amitriptyline,
imipramine, paroxetine, doxepin, furosemide, prochlorperazine
 Benzodiazepines
 Barbiturates
 Opiates
 Especially meperidine
 ? Morphine > Hydromorphone > Oxycodone (rotation can help)
 Incontinence meds
 e.g. oxybutynin
 Cardiac meds
 e.g. digitalis, quinidine, procainamide, lidocaine, beta-blockers
 GI meds
 H2-blockers (e.g. cimetidine, ranitidine), PPIs, metoclopramide
 Many others: e.g. phenytoin, steroids
Cardiac Surgery Risk
Factors
 Giltay et al. (2006): 8139 consecutive
patients undergoing CABG and/or valve
procedure
 Post-op psychotic symptoms associated
with age, renal failure, dyspnea, heart
failure, and LVH pre-operatively and
hypothermia, hypoxemia, low hematocrit,
renal failure, high sodium, infection, and
stroke perioperatively
Sockalingam et al. 2005
van der Mast et al., 1996
 “Of all the reported differences in the
studies, only year of publication is
significantly related to the incidence of
delirium after cardiac surgery, the later
publications showing a tendency towards
a lower incidence.”
 “… a cautious conclusion may be drawn
that no strong risk factor has been
identified…”
Pathophysiology:
Neurotransmitters
(Reviewed by Trzepacz, 1994)
 Acetylcholine
 Anticholinergic drugs induce delirium
 Correlation between poor cognitive function
and serum anticholinergic level
 Serum anticholinergic levels decrease as
delirium resolves
 Reversal of anticholinergic delirium with
physostigmine
Pathophysiology:
Neurotransmitters
(Reviewed by Trzepacz, 1994)
 Dopamine
 Effective treatment with dopamine receptor
blockers like loxapine or haloperidol
 Norepinephrine
 Glutamate
 Serotonin
 GABA
 Histamine
Pathophysiology
(Maldonado, 2008)
Pathophysiology
Wrist
actigraphy
 Osse et al. (2009):
motor activity at the
wrist over five 24hr
cycles after elective
cardiac surgery
Jacobson et al., 2008
 Elderly delirious postoperative patients:
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Fewer nighttime minutes resting
Fewer minutes resting over 24hrs
Greater mean activity at night
Smaller change in activity from day to night
 Delirium may be simultaneous
wakefulness and sleep
 REM intrusion into wakefulness might cause
visual hallucinations
Slatore et al., 2012
 Assessed sleep quality and screened for
delirium in veterans referred to hospice
(55% had cancer) using the Pittsburgh
Sleep Quality Index (PSQI) and the
Confusion Assessment Method (CAM)
 Sleep quality was significantly worse in
33 participants who became delirious
than in 42 who did not
 Hazard ratio for developing delirium of
2.37 for every point of worse sleep on the
PSQI (where 1 = very good; 4 = very
bad)
Glymphatic
system
 Xie et al. (2013)
demonstrated that
sleep is associated with
a 60% increase in the
interstitial space
causing striking
increase in exchange
between CSF and
interstitial fluid
 Increased rate of β–
amyloid clearance
Definitive treatment:
 Find the underlying cause or causes and
treat it/them
Non-pharmacological
interventions (Inouye et al., 1999)
 In a study of 852 elderly patients admitted to
a general medical service, Inouye et al.
reduced the incidence of delirium from 15%
to 9% with a number of non-pharmacological
interventions including promotion of sleep
with sleep inducing stimuli (e.g. relaxation
tapes, warm milk) and a sleep promoting
environment (e.g. through noise reduction)
Patel et al., 2014
 Screened for ICU delirium before (n=167)
and after (n=171) implementing
measures to promote sleep
 Noise and light reduction at night, minimize
care that interrupts sleep at night, reduce
daytime sedation when possible, address
pain early, early mobilization
 Found reduced incidence (14% vs. 33%)
and duration (1.2 vs. 3.4 days) of delirium
Maldonado et al., 2009
 90 patients who underwent valve
procedures randomly assigned to post-op
sedation with dexmedetomidine,
propofol, or midazolam
(From Aantaa & Jalonen, 2006)
Maldonado et al., 2009
 Incidence of delirium was 50% for both
propofol and midazolam groups and only
3% for dexmedetomidine group
 Possible benefits of dexmedetomidine:
not GABAergic, not anticholinergic,
sedating, promotes physiologic sleep
pattern without significant respiratory
depression, lowers opioid requirements
Melatonin
 Al-Aama et al. (2011) demonstrated
decreased incidence of delirium in older
adult patients on a general medicine unit
who received 0.5mg of melatonin nightly
 Evidence that melatonin could actually aid in
treating ongoing delirium is mostly limited to
case studies (e.g. Hanania and Kitain, 2002)
 Other findings suggest melatonin isn’t helpful
(e.g. Ibrahim et al., 2006)
Haloperidol
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Standard treatment in most places
Relatively little anticholinergic effect
Little effect on orthostatic hypotension
Less sedation good for hypoactive delirium
Risk of QT prolongation
Relatively high risk of extrapyramidal effects
 No difference between IV and PO
 Menza et al. (1987) and Maldonado (2000) both seriously
flawed
 Are reports of EPS with IV (Blitzstein & Brandt, 1997)
 Small doses (e.g. 0.5mg IV BID or 1mg IV
QHS)
Chlorpromazine
 The double-blind randomized trial by Breitbart
et al. (1996) is frequently cited as evidence
haloperidol should be chosen over other
antipsychotics
 However, the findings showed the superiority of
both haloperidol and chlorpromazine (a
sedating low-potency antipsychotic) over
lorazepam while showing equal effectiveness
between the two antipsychotics
 Sedating antipsychotic with IV option
 An example of dosing: chlorpromazine 25mg IV
Q6H standing (give over 30min; hold for SBP <
90; hold for sedation)
Methotrimeprazine
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Also sedating and can be given SC or IV
Significant analgesic effect
Need to be cautious of hypotension
e.g. 5 - 10mg Q1H PRN for agitation
Can go as high as 50mg Q4H
Quetiapine
 When we use low dose quetiapine at night,
it’s primarily acting as an antihistamine
 Maneenton et al. (2013) found no difference
between 25-100mg/day of quetiapine HS
and 0.5-2mg/day of haloperidol HS in a
double-blind, randomized trial of delirious
patients eliciting CL consult
 e.g. quetiapine 25mg PO QHS
 e.g. quetiapine 50mg PO QHS
 Caution re orthostatic hypotension
Olanzapine
 A number of studies also support use of
olanzapine (e.g. Breitbart et al., 2002;
Skrobik et al., 2004; Grover et al., 2011)
 e.g. Olanzapine oral dissolving 2.5mg QHS
 e.g. Olanzapine oral dissolving 5mg QHS
 Promotes appetite
 Reduces nausea
 Promotes sleep
 Pro-cholinergic at lower doses, but becomes
anticholinergic at larger doses
Loxapine
(Bates et al., submitted)
 In 31 patients over 55 with post-operative
delirium referred to the CL service, loxapine
was associated with a mean decrease of
8.48 on the DRS-98-R over the first 2 days
of treatment
 Only 3 participants had a worsening of
delirium, and each of those 3 showed
improvement from day 2 to day 4
 Mean number of days to resolution of
delirum (DRS < 10) was 3.2
 There was not a significant increase in QTc
Loxapine
(Bates et al., submitted)
Terminal Illness
 Delirium interferes with identification of
sources of distress like pain
 How much should one investigate?
 Definitive etiology discovered in less than 50%,
and often irreversible when found (Bruera et al. 1992)
 However, Tuma and DeAngelis (1992) report
68% can be improved even when 30-day
mortality is 31%
 Lawlor et al. (2000):
 49% reversibility in advanced cancer patients
admitted to palliative care
 Reversibility associated with opioids, other meds, and
dehydration being primary causes
Terminal Illness
 Some view delirium as natural part of dying
process
 Some worry that antipsychotic will make
patient more delirious
 Evidence is that antipsychotic generally safe
and effective at reducing distress
 “Unfortunately, the hallucinations in delirium are
rarely sugarplum fairies.”