Transcript cam to cam bi

M. Dasgupta, Nov 2014
Division of Geriatric Medicine
Department of Medicine, UWO
Faculty/Presenter Disclosure
 I have not received any commercial support related
to this topic
 I do not have any potential or perceived financial
conflict of interests related to this topic
Objectives
 Review (BRIELFY) diagnosis, relevance & risk factors
 Review studies on management issues:
 Delirium prevention in different settings

Non-pharmacologic & pharmacologic approaches
 Active treatment of delirium, in different settings

Non-pharmacologic & pharmacologic approaches
Harsh realities in studying delirium
 Harsh realities to keep in mind when studying
delirium:
 Ubiquitous & heterogenous disorder seen in
young very sick ICU patients, old frail patients and preterminal conditions
 Multiple diverse contributing factors
 Poor understanding of underlying biology/
pathophysiology
 Often very sick & therefore hard to enrol into studies
Diagnosis- a reminder
 Clinical diagnosis based on history & mental
status exam
 Delirium- DSM criteria (gold standard):
 Reduced clarity of awareness of the environment
(inability to maintain or shift attention)
 Change in cognition (memory impairment,
disorientation, language impairment, disorganized
thinking) or perceptual disturbance
 Features develop over a short period of time and
fluctuate during the day
 Often associated with disturbed sleep-wake cycle, or
altered psychomotor activity
Confusion Assessment Method
(CAM) - diagnosis:
 CAM derived from the DSM, & includes key
features of delirium (Inouye et al., Ann Intern Med 1990; 113: 941-8):
 acute onset and fluctuating course
 deficits of attention, and
 Either: disorganized thinking or altered level of consciousness
 ICU: CAM-ICU (Ely et al., JAMA 2001; 286: 2703-10)
 Original study showed CAM to have sensitivity of
94-100% & specificity of 90-95% (Inouye et al., Ann Intern
Med 1990; 113: 941-8)
 Is reliable, valid with high & low LRs (JAMA 2010; 340 (7):
779-86)
What delirium looks like
Copyright © 2007 The Royal College of Psychiatrists
Other diagnostic issues:
 Sub-syndromal delirium (some symptoms, but not
enough for full diagnosis)
 Prognosis of sub-syndromal delirium likely falls in
between full delirium and no delirium (Ouimet et al., 2007;
Marcantonio et al., 2005)
 Delirium severity scales: MDAS, DI, DRS, CAM-S
 All have been validated- i.e. Higher scores found to
correlate with prolonged delirium/worse outcomes *
 Still used primarily as research tools or to gauge
response to interventions in actively delirious people
*Kelly et al., 2001; McCusker et al., 2002; Tzepacz et al., Adamis et al., 2006; Inouye et al., 2014;
What it means/ why diagnose it?:
 Common, and possible underlying acute illnessmedical emergency!
 Poor recognition is associated with poor prognosis1
 Studies have shown delirium to be a risk factor for
adverse outcomes in the short & long-term2
 Increased LOS (cost), in-hospital complications,
institutionalization, functional decline
 future cognitive decline/ dementia and worsening cognition in
dementia 3
 death
1 BMC
2
Geriatrics 2005; 5:5; JAGS 2003; 51 (4): 443-50 Age Ageing 2006; 35: 350-64, Witlox et al., 2010:
3 Brain 2012; 135: 2809-16
Implications of delirium
 A distressing ordeal that may be remembered by
patient and family members, associated with
PTSD (O’Keefe 2005; DiMartini et al, 2007)
 Older literature suggested delirium to be
reversible, but recent studies suggest not always
reversible (aging population and greater comorbidity)
 Many have postulated that it is part of a spectrum
of cognitive impairment and is a harbinger for
future cognitive problems
Pathophysiology/ why it happens?
 RF’s: Acute/chronic illness, baseline
vulnerability & in-hospital factors
 Little known about pathophysiology –
altered neurotransmission (high dopamine,
low acetylcholine, altered serotonin/
melatonin)
 Management approaches include tackling
all of these factors
Risk/contributing factors
 Acute illness (severity), drugs, dehydration
 Baseline vulnerability- risk factors- common to all
settings baseline cognitive impairment/vulnerable brain
 depression/ psychopathology
 functional impairment/ NH residence
 visual /hearing impairment
 chronic co-morbidity
 Older age
 A frail person is at greater risk for delirium (Leung et al,
2011; Pol et al., 2011)
In-hospital factors (McCusker et al., JAGS
2001, Inouye et al., 1996, Creditor et al., 1993):
 Lack of mobility
 harmful to even vibrant & healthy
active seniors
 Urinary catheters, physical
restraints, drugs, iatrogenesis
 Sensory deprivation (lack of aids,
etc..)/ over-stimulation
 Dietary modifications/
dehydration
 Contact precautions

Decrease infection spread but may
have consequences (Morgan et al., 2009,
Day et al. 2012)
In-hospital factors
 Chaotic and stressful
environment Multiple changes in staff
(unfamiliarity)
 Lack of sleep/windows
 Impersonal environment
 Admissions at all hours, other
patients who decompensate,
vitals/ care processes
interrupting sleep, etc..
The operative setting- unique
 Elective operations- typically patients are screened &
prepared for surgery, prior to admission
 Three distinct periods to consider:
 pre-operative (patient baseline risk)
 operative period
 post-operative period
 Requires a truly multidisciplinary- team approach nursing, PT and other allied health professionals
 internists/geriatric practioners, anesthesiologists, ICU
staff, and surgeons
15
Non-pharmacologic & pharmacologic
Non-pharmacologic interventions:
 Multifaceted delirium programs have been studied,
often addressing hospital-related care issues (Holroyd-
Leduc et al., CMAJ 2010; 182 (5): 465-70; O’Mahony et al., 2011, Siddiqi et al.,
2009)
 In the medical, surgical (mainly hip OR) setting and
ICU settings




Some target prevention (i.e. exclude patients delirious on
admission)
Others directed at both prevention and treatment (i.e.
enrolled both prevalent and new, incident delirious patients
A few are directed at already delirious patients
Prevention likely better than intervening once already
delirious, and may reduce delirium by 1/3
Multi-faceted interventions:
 Treat illness & target risk factors
(mainly hospital-related):
 e.g. early mobilization, avoiding
bad drugs, regularly orienting
patients, monitoring bowel and
bladder function, applying
hearing/ visual aids if
indicated, familiar objects/
presence of family in room,
continuity of staff, optimizing
non-drug approaches to sleep,
avoiding restraints/ tubes, etc
Multifaceted Trials in the medical
setting:
 1 positive RCT (Lundstrom et al., JAGS 2005; 53: 622-8) of
medical in-patients (did not exclude prevalent
delirium):
 Randomly allocated to any ward when bed available
 intervention ward (n= 200, education, patient-centered care
plan, changing organizational care plan, monthly nursing care
guidance) vs.
 control ward (n= 200)
 found intervention patients were less likely to die, had
lower LOS, and had shorter delirium duration
Family can help
 Recent RCT (n = 287, medical in-patients, at risk for
delirium) involving family members; excluded prevalent
delirium (Martinez et al., 2012)
 Intervention (provided by family members): briefly
educating family members, provision of a clock & calendar,
avoiding sensory deprivation, presence of familiar objects,
re-orientation to time/place & current events by family
members, extended (up to 5 hours) family visiting time
 Intervention group: less likely to get delirious (RR 0.41,
NNT = 13), trend towards fewer falls (p = 0.06), no
difference in LOS
Multifaceted Trials in the medical
setting:
 S. Inouye study- Hospital Elder Life Program
(HELP)- not actually randomized (NEJM 1999, 340 (9): 66976)-
 Excluded folks delirious on admission (excluded
prevalent delirium)
 Multifaceted intervention on 852 medical in-patients at
intermediate or higher risk for delirium RCT (1 or more
of delirium risk factors present- severe illness,
dehydration, cognitive impairment, visual impairment)
Multifaceted studies in the medical
setting:
 HELP (Hospital Elder Life Program) study (NEJM 1999, 340 (9):
669-76)-
 Intervention: promotion of ambulation, orienting, non-
pharmacological sleep protocol, providing visual or auditory
aids when appropriate, monitoring and treating for
dehydration
 Found lower incidence (RR 0.66) of new delirium in
intervention group, but no difference in LOS/ LTC, etc..
 Follow-up cost studies suggest:


in patients at intermediate delirium risk (1-2 RFs), there was no
additional cost related to the intervention (Medical care 2001; 39:
740-52)
lower NH costs (JAGS 2005; 53: 405-9)
Multifaceted interventions:
 Other hospitals have adopted HELP-type programs
with benefits
 Decreased delirium & cost when HELP-type programs
adopted in US, Spanish, Italian & Australian hospitals (Caplan et
al., Intern Med J 2007; 37: 95-100; JAGS 2009; 57(11): 2029-36; Rubin et al., 2011)
 Less delirium & ADL decline in Taiwanese post-op (elective
GI) population when modified-HELP (mobility, cognition,
nutrition/hydration) instituted (J Am Coll Surg 2011; 213: 245-52)
 Adoption of HELP style/ multi-faceted program
resulted in cost savings to hospital over the next year
and increased patient/ staff job satisfaction
 Families can help with some HELP interventions
1,2,3,4
(Rosenbloom-Brunton et al., 2010)
JAGS 2009; 57(11): 2029-36; Am J Geriatr Psych 2009; 17 (9): 760-8; 1JAGS 2006; 54: 969-74; 2Ann Intern
Med 2011; 154: 746-51; 3 Age Ageing 2012; 41: 285-91; 4 Age Ageing 2012; 41: 285-91
Surgical (hip surgery) setting:
 Positive study in hip fracture (Lundstrom M, et al.
Aging-Clinical &
Experimental Research, 2007; 19 (3): 178-86)
 Did not exclude prevalent delirium
 Intervention patients- assigned to geriatric-orthopedic ward and
received comprehensive assessment (vs. orthopedic ward)
 Intervention group: fewer days of delirium, less incident delirium,
had fewer delirium complications, lower post-op LOS; no difference
on rate of institutionalization or 4-12 month mortality rates (n= 199)
 There were some baseline differences including a non statistically
significant lower percentage of prevalent delirium in intervention
(21.8%) compared to control group (30.9%), higher rate of
depression and antidepressant use (ss); but in adjusted multivariate
models this did not affect the significant effect of the intervention
 Subgroup analyses showed demented patients did better with
intervention (Stenvall et al., 2012)
Surgical setting:
 A RCT to look at the effect of a multifaceted
intervention on general outcomes after hip fracture
surgery (n= 319) (Vidan et al., JAGS 2005; 53: 1476-82):
 Intervention- geriatrician responsible for medical care, and
had comprehensive geriatric assessment (MSW, rehab MD)
vs. Control (MRP- orthopedic team)
 Intervention: lower complication & death rate, trend toward
lower LOS (p= 0.06, median difference 2 days)
 Trend towards less delirium (secondary outcome) in
intervention (p= 0.06) and were fewer pressure sores (p=
0.001), but there was a trend towards an increase in CHF in
the intervention group (p= 0.07)
 Greater chance of ADL or mobility recovery in intervention at
3 months follow-up (bigger benefit seen in non-demented or
independent ambulators prior to admission)
Surgical setting:
 Marcantonio et al., JAGS 2001; 49: 516-22:
 RCT: Proactive geriatrics consult (n=62) vs. standard care (n=
64) in hip fracture patients (included prevalent delirium)
 Intervention: optimize oxygenation, treat anemia, avoid
hypotension, monitor & treat fluid/electrolyte imbalances &
severe pain routinely, eliminate unnecessary drugs, good
bowel/bladder function/nutrition, early mobilization, etc…
 Intervention: less likely to get delirious & fewer days of severe
delirium
 But when dementia and functional level controlled for,
intervention was better (but not ss better); No effect on LOS
or duration
In-patient Geriatric consult team
 A Belgian study of traumatic hip fracture patients
(Deschodt et al., 2012)
 n= 171, mean age 80, 73% women, about 20% with
dementia history, 20% with pre-op delirium
 control (standard post-op care) or intervention - pre-op
& post-op, through day 15, intensive geriatric
consultation (CL team- geriatrician, nurse, OT, PT)
 found 30% lower incidence/occurrence of delirium and
better cognitive functioning in intervention
Non randomized studies- surgical/
other setting
 Other non-randomized control trials (e.g. before-after
design) in the hip fracture setting have been published,
that suggest multidisciplinary multifactorial intervention
programs (nursing care, maintaining oxygen saturation &
general geriatric interventions) are effective in preventing
delirium
 (Milisen et al., JAGS 2001; 49:523-32, Lundstrom et al., Scand J Caring Sci 1999; 13:
193-200, Gustafson et al., JAGS 1991; 39: 655-62)
 Negative prevention study (limited to documenting risk
factors, monitoring regularly, family education, drug
assessment & orientation) in pre-terminal cancer
population (Gagnon et al., 2012)
Fast-track procedures
 RCT suggests that fast-track procedures decrease
delirium, length of post-op stay, improve
nutritional status, with fewer complications
(patients ≥ 70, undergoing open curative colorectal
surgery)
 Fast track procedures involve less time NPO pre-op,
faster removal of foley catheter, faster mobilization, no
NG tube, no drainage tubes, avoiding narcotics (used
epidural blocks) (Jia et al., 2014)
 Similar findings in orthopedic procedures (Krenk et al.,
2012)
Never too early to start
 European study instituted preventative measures in
the ambulance and ED as an intervention (included
rapid transfer to floor from ED, ensuring good
oxygenation, IVF’s, avoiding anti-cholinergics, pain
control, optimal nutrition)- before after study showed
decreased delirium in cognitively intact persons
(Bjorkelund et al., 2010)
Uni-faceted interventions- may
not be as effective
 Liberal blood transfusions (to maintain Hgb ≥ 10) do
not help mortality, functional outcomes nor delirium
in patients undergoing hip fracture repair
 FOCUS study- 2016 patients undergoing hip fracture
repair, mean age 81- no benefits to routine transfusion
(Carson et al., 2011)
 Sub-study (within FOCUS, n = 139): no difference in
CAM-defined delirum not delirium severity scores
(MDAS) (Gruber-Baldini et al., 2013)
Other interventions- surgical
setting
 RCTs assessing by-pass/anesthetic
techniques:
 CABG- higher perfusion pressures better than
low perfusion pressure
 Depth of sedation matters- EEG- lighter
sedation better than heavy sedation
 Anesthetic agents matter- dexmedetomidine
better than benzodiazepines
Perfusion Pressure
 Recent RCT suggests that perfusion pressures during
elective/urgent CABG may affect cognition (?delirium)
risk *:
 Group assigned to high perfusion pressure (mean BP:
80-90) had better cognition post-op compared to low
pressure group (mean BP 60-70)


Outcome: change in MMSE of 10 or more points compared to
baseline)
No difference on oxygen saturation measured by infrared
spectroscopy, but higher lactate levels in low pressure group
*Siepe M et al., Eur J Cardio-Thorac Surgery 2011; 40: 200-7
Anesthetic and other considerations:
 General or local anesthetics likely don’t matter in
delirium (may
be fewer other complications with the
1
use of local)
 Nerve blockade (vs. placebo) decreases delirium and
acute pain after hip fracture surgery, based on SR (4
RCTs, 2 cohort studies) (Abou-Setta et al., 2011)
 Nerve blockade may be beneficial, end-stage cancer
patients (Arai et al., 2013)
 Recent trials have suggested a potentially beneficial
role of the α2-agonist dexmedetomidine (as a sedative)
vs. a benzodiazepine
1
Williams Russo et al., JAMA 1995; 274: 44-50; Mason et al., J Alz Dis2010; 22:
S67-79; Rodgers et al., 2000 BMJ; 321: 1-12
Role of medications: alpha-agonists
 Alpha-agonists- sedating, analgesic, sleeppromoting effects (Ann Pharmacother 2009; 43: 2064-74)
 Dexmedetomidine (α-2-agonist) (Precept) *:
 2 RCTs (ventilated ICU patients): lower duration/ occurrence of
delirium (or delirium plus coma) compared to benzodiazepines
(& 1 negative RCT)
 2 RCTs (post-op): lowered occurrence and duration of delirium &
hastened extubation
 Role of Clonidine? (pilot RCT, AAA repair, n = 30)
(Interactive Cardiovasc Thorac Surg 2010; 10: 58-62)
*JAMA 2009; 301 (5): 489-99; JAMA 2007; 298 (22): 2644-53; Intensive Care Med 2009; 35: 282-90 (negative
RCT); Anesthes. 2009; 111 (5):1075-84; Psychosomatics 2009; 50 (3): 206-17
Decreasing sedative use:
 RCT1 of older hip fracture patients
randomized to light (responsive to
verbal stimuli) vs. heavy (unresponsive
to noxious stimuli) sedation (EEG
monitored Bi-Spectral Index, BIS); used
spinal anesthesia
 included moderately demented individuals
(MMSE ≥ 15)
 Light sedation group: less delirium (NNT
4.7 overall, 3.5 if MMSE ≥ 24) & lower rate
of complications
 Confirmed in other studies (RCTs) and
surgery types 2,3
 Observational studies4 support targeted
sedation-protocols
1Mayo
Clin Proc 2010; 85 (1): 18-26; 2Brit J Anesthes 2013; 110 (S1): i98-i105; 3 J Neurosurg
Anesthesiol 2013; 25: 33-42; 4Arch Phys Med Rehabil 2010: 91: 536-42
Pharmacologic agents- prevention
 Neuroleptics- role for peri-op prevention (RCTs)?:
 RCT’s of haldol

non-cardiac , post-op ICU patients, n = 457, mean age 74 (Wang et al,
2012) - less delirium, shorter ICU stay (overall & delirious pts) (IV
Haldol bolus and 12-hr drip, < 2 mg/d);
Orthopedic surgery reduced severity, duration & LOS(Kalisvaart et al.,
2005)
 Resperidone in cardiac surgery (Prakanrattana et al., 2007)
 Olanzepine RCT (mean age 74, n = 495, cognitively intact
patients, elective orthopedic):

less delirium (NNT 4), increased d/c to home & longer time to
delirium (though had longer & more severe delirium) vs. placebo
(Larsen et al., 2010)
Neuroleptics for prevention
 Two meta-analyses found neuroleptics to decrease delirium
in the peri-operative setting, although their effect on other
hard outcomes is less clear (LOS, delirium duration or
severity) (Tesylar et al, 2013; Gilmore et al 2013)
 Neuroleptics for targeted prevention, pre-operatively
(Hakim et al., 2012)?
 One study found resperidone decreased new delirium, in older
post- cardiac OR, ICU patients , who had sub-syndromal delirium
(may be a RF for delirium 1);
 Excluded patients with dementia or depression
1
deJonghe et al., 2007
ChEI’s for prevention?- likely not:
 RCTs of prophylactic pre-op & post-op cholinesterase
inhibitors have largely been negative:
 In elective orthopedic surgeries (n = 80, young cognitively
intact study sample, with a low incidence of post-op delirium
(Liptzin et al., Am J Geriatr Psych 2005; 13: 1000-06)
 Positive trend for less delirium symptoms and lower LOS in
one study (donepezil x 4 days, n = 33, elective hip, cognitively
intact) (Sampson EL et al., Int J Geriatr Psych 2007; 22: 343-9)
 In cardiac surgery- negative study (n = 120) of rivastigmine 1.5
mg TID pre-op to POD #6 (Gamberini et al., Crit Care Med 2009; 37 (5): 17628)
 Recent negative small (n = 16) trial in hip fracture population
(Marcantonio et al., JAGS 2011; 59: S282-8)
Ramelteon/Melatonin?
 Multicenter trial of Ramelteon (melatonin agonist) in 67
older medical or ICU in-patients found to be beneficial in
preventing delirium (RR 0.09, 95% CI: 0.01-0.69) (Hatta et al.,
2014)
 RCT of melatonin in older medical in-patients (included
delirious and non-delirious on admission)- (T. Al-Aama et al., Int J
Geriatr Psychiatry. 2011; 26: 687-94. ):
 N= 145 patients, medical in-patients ≥ 65 years old (mean age 84.5);
lower occurrence of delirium in individuals randomized to 0.5 mg
of Melatonin compared to placebo (OR 0.19, 95% CI 0.06-0.62)
 Melatonin?- other studies (Sultan et al., 2010; de Jonghe et al., 2011)
Benzodiazepines- use for alcohol
withdrawl (medical setting)
 No evidence to support use of benzodiazepines in non-
alcohol withdrawl or non post-ictal delirium
(Lonergan et al., 2009, CD006379)
Non-pharmacologic & pharmacologic approaches
Delirium management (active
symptoms)
 Treat underlying cause- no RCT’s showing treatment
of underlying cause improves delirium symptoms
(case series/case reports) but unethical to not treat a treatable medical condition
 Observational study- correcting electrolyte disorder
hastened delirium recovery
(Koizumi J et al., Jpn J Psych
Neurol 1988; 42: 81-8)
 How far to look for an underlying cause? Different
recommendations by different consensus panels
Multifaceted Trials in the medical
setting:
 3 essentially negative trials (RCTs) on people
already delirious on admission:
 1 negative RCT (Pitkala et al., J Gerontol BIO MED SCI 2006; 61 (2):
176-81):

RCT on delirious medical in-patients (n= 174); intervention
(multicomponent geriatric intervention) vs. control- no
difference in LOS, 6 month MMSE slightly better in intervention
group, no difference in death/LTC at 12 months
 2 other negative RCTs (Cole et al, 1994 & 2002)
Delirium- management:
 Cole et al., CMAJ 1994; 151 (7): 965-70:
 Small RCT in already delirious medical in-patients control (n= 46: standard care), or intervention [n= 42,
geriatrician/ geriatric psychiatrist consult with daily f/u by liason
nurse (working on environmental factors, orientation, familiarity,
communication, and appropriate activities- avoiding restraints,
encourage self care, etc.)]:
 early improved cognitive functioning in intervention (no
difference at 8 weeks); slight improvement in behaviour at 8
weeks in the intervention group. However no difference in
restraint use, LOS, d/c to higher level of care, or mortality
 There was contamination (14 control patients received consult)
Delirium- management:
 Cole et al., CMAJ 2002; 167 (7): 753-9:
 Another RCT in already delirious medical in-patients control (n= 114: standard care), or intervention [n= 113,
geriatrician/ geriatric psychiatrist consult with daily f/u by liason
nurse (working on environmental factors, orientation, familiarity,
communication, and appropriate activities- avoiding restraints,
encourage self care, etc.)]:
 No statistically significant difference in intervention and control
groups in time to improvement (HR) of the DI (a severity scale);
also no difference at 8 weeks, between 2 groups in rate of
improvement of Barthel index, LOS, d/c rate to community;
dementia did not affect results of analyses
Non-pharm approaches to
management (actively delirious)
 Prior multi-faceted RCT’s- sometimes included
delirious patients, and some showed benefits in
decreasing delirium duration, LOS (maybe not as
effective as prevention)
 Other models of care (observational &
preliminary studies):
 involving dedicated unit for delirium/delirium room
suggesting possibly improved outcomes (Lu et al, 2011,
Flaherty & Little, 2011, Eeles et al., 2013)
 Cognitive rehabilitation (30 min daily) (Kolanowski et al.,
2011)
ICU setting- importance of
mobility:
 A recent RCT (Schweickert et al., lancet 2009; 373: 1874-82) involving
mechanically ventilated ICU patients, randomized to
 Intervention – early (within 1.5 days of enrollment) active PT
(with a protocol to decrease sedation during PT) vs.
 control (standard) care –

all (96% of) control patients got PT while in the ICU but started at a
later time
 Intervention patients had less time in ICU (and on a ventilator),
and shorter delirium
 Suggests a pro-active approach may be beneficial
 Prior observational studies support mobilizing (exercise
decreased use of anti-psychotics in palliative patients- Tatematsu et
al., 2011)
Bright Light Therapy?
 Sleep disorder associated with delirium
 Pilot studies show some possibilities of BLT (bright
light therapy) in decreasing delirium:
 As an adjunct to non-pharmacologic approaches (228
patients) (Chong et al., 2013)
 A pilot study, post-esophagectomy, randomised patients,
(some likely with delirium) to control (n = 12) or intervention
(n = 10; involved BLT – 2 hrs/day x 4 days, starting POD 2)
delirium assessed days 1-6; found better sleep and a suggestion
for less delirium in BLT group (Ono et al, 2011)
 Another small (n= 11) study of males, post-esophagectomy
patients suggested possible benefits of BLT in improving
night-time restlessness and faster delirium symptom
resolution (Taguchi et al., 2007)
 As an adjunct to antipsychotics in other patient populations?
(Yang et al., 2012)
Pharmacologic agents- active Rx
 Symptomatic treatment, neuroleptics- 2
RCT’s (with placebo group):
 One RCT of “selected”, hospitalised patients with “senile
delirium”(China), randomized to Olanzepine (n= 74) vs.
haldol (n= 72) vs. placebo (n= 29) (Hua et al., 2006)

Showed a higher recovery & faster resolution in haldol/ olanzepine
groups (DRS scores)
 One RCT (medical & surgical) showed faster resolution of
delirium symptom severity (DRS, especially non-cognitive
symptoms) in patients given quetiapine (versus placebo):
under-powered, small study (Tahir et al., 2010)

n = 42, needed 68 patients by sample size calculations; FDA halted
study because of general concerns of antipsychotic use in older folksmay not get better studies in this population
Treatments for already delirious
folk- neuroleptics?
 Neuroleptics- mainstay of treatment (Internat Psychogeriatr 2010;
22: 328-31)
 BUT- mostly uncontrolled, small studies in selected
populations suggesting a possible benefit of
neuroleptics in improving delirium symptoms 1
 In 10 comparator studies, on diverse populations, of
neuroleptics, 2/3 of participants responded after 2-6
days of treatment (Meagher et al., 2008)
 Many unanswered questions: e.g. timing, dosing,
effectiveness (duration/adverse outcomes),
etc...(Heymann et al., 2010)
1
Seitz et al., 2007; Flaherty et al., 2011; Ann Pharmacother 2006; 40: 1966-72; J Clin Psych 2007;
68:11-21; Psychosomatics 2004; 45: 297-301; J Am Med Dir Assoc 2008; 9: 18-28; J Psychosomatic Res
2011; 70: 197-8. Meagher et al., 2013
Treatments for already delirious
folk (ICU)- neuroleptics?
 ICU RCTs- younger non-demented patients:
 A small RCT in mechanically ventilated delirious adultsplacebo vs. quetiapine (Crit Care Med 2010; 38: 419-27)


Excluded many people (enrolled 36/258)
Less use of Haldol, lower rate of institutionalization, faster
delirium resolution in seroquel group
 A negative RCT, included delirious, non-delirious &
comatose patients (Crit Care Med 2010; 38 (2): 428-37):


mechanically ventilated, n = 101; placebo vs. haldol vs.
ziprasidone;
vast majority of patients with delirium/coma at start of trial
ChEI’s- for active treatment?
 Increased death when given to delirious ICU
patients, mean age 68 (RCT halted prematurely)
(van Eijk MM et al., Lancet 2010: 376: 1829-37)
 Role in treatment of already delirious (?): one
small (n= 15) “positive” study using exelon in
medical older in-patients (excluded many pts)exelon may hasten recovery but not ss (Overshott et al.,
2010)
 Other open label trials suggest a possible benefit
of ChEI’s in active delirium, in vascular
dementia (decreasing duration) (Moretti et al., 2004),
or post-CVA delirium (Oldenbeuving et al., 2008)
Conclusions:
 Delirium common, associated with poor prognosis and not






always reversible
Multiple contributors
Non-pharmacologic approaches work in prevention; may
help the already delirious patient (less helpful)
Newer surgical techniques may be helpful (fast-track
procedures, perfusion pressure)
Pharmacologic advances include dexemedetomidine, good
pain control, lighter sedation, possibly ramelteon or
melatonin, largely for prevention
Active treatment- neuroleptics if needed, but few good
studies to support their use
Clearly more research is needed
Case 1
 95 year old previously independent lady (living alone; some
PSW assistance, but used to apply her own Bi-PAP mask for
OSA and take her own medications)
 Admitted to hospital with cellulitis after a fall (couldn’t
ambulate)
 PMH: COPD (sporadic home O2 use), OA, OSA, prior
delirium, visually & hearing impaired, reasonable cognition
 On admission, forgetful (“where am I?”, “what am I doing
here”, “what should I do next?”), occasionally associated
with de-saturation
Case 1
 Cellulitis responded well to antibiotics
 Despite this, worsening forgetfulness throughout and very
hard to communicate
 Wrote orders to ambulate, to orient with each vital sign
measurement, tried to re-orient




Fluctuated- at times coherent, at other times not
Sometimes would not recognize son
Got delirious- took off her Bi-PAP, often de-saturated
Further hx from son- does well but likes her routines, gets
forgetful when routines are off
 Deteriorated and passed away
Case 2 Mrs. P- 76 year old woman, s/p excision of facial
SCC
 Intermittent confusion throughout hospital stay e.g. called husband telling him “I have to go to the hospital”
 e.g. at times thought her husband was her father
 PMH: HTN, DM, CRF, severe DDD, lymphoma,
DVT (x2), declining STM for 1.5 years (less able to
make meals d/t pain & ?STM)
 O/E- inattentive at times, drifting off, perseverative
(difficulty shifting); c/o severe back pain
Case 2 Present drugs: tylenol PRN, percocet PRN (not
received in days), bromazepam 6 mg QHS,
ranitidine 150 mg OD, amlodipine 7.5 mg,
thyroxine 0.1 mg, detrol 1 mg BID, dyazide,
multivits, glyburide, amitryptiline 100 mg OD,
metoprolol 75 mg BID, Coumadin
 What next?
Case 3 Ms. W- 80 year old resident of Retirement home
 PMH: mentally challenged since birth, HTN
 NSTEMI (admitted to hospital 2 months earlier- had possible
CVA/seizure- started phenytoin;
 Because unclear whether true seizure, was tapering
phenytoin- admitted to hospital with tonic-clonic seizuregiven lorazepam & phenytoin (also on other drugs)
 Developed rash- Phenytoin changed to valproic acid
 In hospital, seizures settled, developed ?pneumonia
(temperature) and mild CHF (started on antibiotics and
lasix)
 5 days after admission, despite being treated for
pneumonia and seizures, started getting more confused
Case 3 The following day, became increasingly agitated, started




yelling
Next day: started hallucinating (seeing “dead father” &
“his 3 sons”), and having decreased po intake; OT
described her as unusually aggressive and refused to
participate
Many drugs discontinued (ranitidine, trazadone, clavulin)
3 days later, accused RN of poisoning her, did not take her
pills (for 2 days), and stopped eating
What next?
Selected References:
 Abou-Setta AM, Beaupre LA, Salfee R et al. Ann Intern Med 2011; 155: 234-45
 Adamis D, Treolar A, Martin FC et al., Arch Geriatr Gerontol 2006; 43: 289-98
 Arai YCP, Nishihara M, Kobayashi K et al., J Anesth 2013; 27: 88-92
 Bjorkelund KB, Hommel A, Thorngren K-G et al. Acta Anaesthesiol Scand 2010;
54: 678-88
 Carson JL, Terrin ML, Noveck H et al., N Engl J Med 2011; 365 (26): 2453- 62
 Chong MS, Tan KT, Tay L et al., Clin Interventions Aging 2013; 8: 565-72
 Day HR, Perencevich EN, Harris AD et al. Infect Control Hosp Epidemiol 2012;
33 (1): 34-9
 De Jonghe JFM, Kalisvaart KJ, Dijkstra M et al., Am J Geriatr Psych 2007; 15: 112-
21
 DeMartini A, Dew MA, Kormos R et al., Psychosomatics 2007; 48 (5): 436-9
 Deschodt M, Braes T, Flamaing J et al., J Am Geriatr Soc 2012; 60:733-9
Selected References:
 Devlin JW, Roberts RJ, Fong JJ et al., Crit Care Med 2010; 38 (2): 419-27
 Eeles E, Thompson L, McCrow J et al., Australasian J Ageing2013; 32 (1):






60-3
Flaherty JH, Gonzales JP, Dong B; J Am Geriatr Soc 2011; 59:S269-76
Flaherty JH, Little MO. J Am Geriatr Soc 2011; 59: S295-300
Gagnon P, Allard P, Gagnon B et al. Psycho-Oncology 2012; 21: 187-95
Gilmore ML, Wolfe DJ. Gen Hosp Psychiatry 20013;
http://dx.doi.org/10.1016/ j.genhosppsych.2012.12.009
Gruber-Baldini A, Marcantonio E, Orwig D et al., J Am Geriatr Soc
2013; 61: 1286-95
Hakim SM, Othman AI, Naoum DO. Anesthesiology 2012; 116 (5): 98797
Selected References
 Hatta K, Kishi Y, Wada K et al., JAMA Psychiatry 2014; 71 (4): 397-403
 Heymann A, RadtkeF, Schiemann A et al., J Internat Med Res 2010; 38: 1584- 95
 Hua H, Wei D, Hui Y et al. Chin J Clin Rehab 2006; 10 (42): 188- 90
 Inouye SK, Kosar CM, Tommet D et al., Ann Intern Med 2014; 160: 526-33.
 Inouye S, Charpentier P. JAMA 1996; 275: 852-7
 Jia Y, Jin G, Guo S et al., Langenbecks Arch Surg 2014; 399: 77-84
 Kalisvaart KJ, De Jonghe JF, Bogaards MJ et al., J Am Geriatr Soc 2005; 53: 165866
 Kelly KG, Zisselman M, Cutillo-Schmitter T et al., Am J Geriatr Psych 2001; 9
(1): 72- 7
 Kolanowski AM, Fick DM, Clare L et al., Res Gerontol Nurs 2011; 4 (3): 161-7
 Krenk L, Rasmussen LS, Hansen TB et al. Br. J Anesthes 2012; 108 (4): 607-11
 Larsen KA, Kelly SE, Stern TA et al., Psychosomatics 2010; 51:409-18
Selected References
 Leung JM, Tsai TL, Sands LP. Anesth Analg 2011; 112:1199-201
 Liptzin et al., Am J Geriatr Psych 2005; 13: 1100-6
 Lonergan E et al., Coch Database Syst Rev 2009 Oct 7;(4):CD006379. doi:
10.1002/14651858.CD006379.pub3
 Lu JH, Chan DKY, O’Rourke F et al. Arch Gerontol Geriatr 2011; 52: 66-70
 Marcantonio ER, Kiely DK, Simon SE et al., J Am Geriatr Soc 2005; 53: 963-9
 Martinez FT, Tobar C, Beddings CI et al., Age Ageing 2012; 41: 629-34
 McCusker J, Cole M, Abrahamowicz M et al. J Am Geriatr Soc 2001; 49:1327-34
 McCusker J, Cole M, Abrahamowicz M et al. Arch Intern Med 2002; 162: 457-63
 Meagher D & Leonard M. Advances Psych Treatment 2008; 14: 292-301
 Meagher DJ, McLoughlin L, Leonard M et al., Am J Geriatr Psych 2013; 21: 122338
Selected references:
 Moretti R, Torre P, Antonella RM et al., Am J Alz Dis Oth Dement 2004;19 (6):
333-9
 O’Keefe S. Internat Psychogeriatrics 2005; 17 Suppl2: 120
 Oldenbeuving AW, deKort PLM, Jansen BPW et al., BMC Neurol 2008; 8:34;
doi.10.1186/1471-2377/8/34
 O’Mahoney R, Murthy L, Akunne A et al., Ann Intern Med 2011; 154: 746-51
 Ono H, Taguchi T, Kido Y et al. Intens Care Crit Nurs 2011; 27: 158- 66
 Ouimet S, Riker R, Bergeron N et al., Intens Care Med 2007; 33: 1007-13
 Overshott R, Vernon M, Morris J et al. International Psychogeriatrics 2010; 22
(5): 812-8.
 Pol RA, van Leeuwen BL, Visser L et al., Eur J Vasc Endovasc Surg 2011; 42: 82430
 Prakanrattana U, Prapaitrakool S, Anaesth Intensive Care 2007; 35: 714-9
Selected references
 Rosenbloom-Brunton DA, Hennemen EA, Inouye SK. J Gerontol Nurs2010; 36
(9): 22-34
 Rubin FH, Neal K, Fenlon K et al. J Am Geriatr Soc 2011; 59: 359-65
 Saczynski JS, Marcantonio ER, Quach L et al., N Engl J Med 2012; 367: 30-9
 Seitz D, Gill S, van Zyl LT. J Clin Psych 2007; 68: 11-21
 Siddiqi N, Holt R, Britton AM et al., Coch Database Syst Rev 2007, Issue 2
CD005563. doi: 10.1002/14651858. CD005563.pub2
 Stenvall M, Berggren M, Lundstrom M et al. Arch Geriatr Gerontol 2012;54:
e284-9
 Taguchi T, Yano M, Kido Y. Intens & Crit Care Nurs 2007; 23: 289-97
 Tahir TA, Eeles E, Karapareddy V et al., J Psychosomatic Res 2010; 69: 485-90
 Tatematsu N, Hayashi A, Narita K et al., Support Care Cancer 2011; 19: 765-70
Selected References
 Tesylar P, Stock VM, Wilk CM et al., Psychosomatics 2013; 54: 124-31.
 Trzepacz P, Baker RW. Psychiatry Res 1988; 23: 89-97
 Wang W, Li H-L, Wang D-X et al. Crit Care Med 2012; 40: 731-9
 Witlox J, Eurelings LSM, deJonghe JFM et al., JAMA 2010; 304 (4): 443-51
 Yang J, Choi W, Ko Y-H et al., Gen Hosp Psych 2012: 546-51