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Delirium- the good, the bad & the ugly: a riveting (?) update

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1 Delirium- the good, the bad & the ugly: a riveting (?) update
M. Dasgupta, Nov 2014 Division of Geriatric Medicine Department of Medicine, UWO

2 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 This slide must be visually presented to the audience AND verbalized by the speaker.

3 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

4 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 pre-terminal conditions Multiple diverse contributing factors Poor understanding of underlying biology/ pathophysiology Often very sick & therefore hard to enrol into studies

5 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

6 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: ) Original study showed CAM to have sensitivity of % & 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): )

7 What delirium looks like
Copyright © 2007 The Royal College of Psychiatrists

8 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;

9 What it means/ why diagnose it?:
Common, and possible underlying acute illness- medical 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 Geriatrics 2005; 5:5; JAGS 2003; 51 (4): Age Ageing 2006; 35: , Witlox et al., 2010: 3 Brain 2012; 135:

10 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 co-morbidity) Many have postulated that it is part of a spectrum of cognitive impairment and is a harbinger for future cognitive problems

11 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

12 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)

13 In-hospital factors (McCusker et al. , JAGS 2001, Inouye et al
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)

14 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..

15 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

16 Management options- Prevention?
Non-pharmacologic & pharmacologic

17 Non-pharmacologic interventions:
Multifaceted delirium programs have been studied, often addressing hospital-related care issues (Holroyd-Leduc et al., CMAJ 2010; 182 (5): ; 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

18 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

19 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

20 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

21 Multifaceted Trials in the medical setting:
S. Inouye study- Hospital Elder Life Program (HELP)- not actually randomized (NEJM 1999, 340 (9): )- 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)

22 Multifaceted studies in the medical setting:
HELP (Hospital Elder Life Program) study (NEJM 1999, 340 (9): )- 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: ) lower NH costs (JAGS 2005; 53: 405-9)

23 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: ; JAGS 2009; 57(11): ; 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: ) Adoption of HELP style/ multi-faceted program resulted in cost savings to hospital over the next year and increased patient/ staff job satisfaction 1,2,3,4 Families can help with some HELP interventions (Rosenbloom-Brunton et al., 2010) JAGS 2009; 57(11): ; Am J Geriatr Psych 2009; 17 (9): 760-8; 1JAGS 2006; 54: ; 2Ann Intern Med 2011; 154: ; 3 Age Ageing 2012; 41: ; 4 Age Ageing 2012; 41:

24 Surgical (hip surgery) setting:
Positive study in hip fracture (Lundstrom M, et al. Aging-Clinical & Experimental Research, 2007; 19 (3): ) 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)

25 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: ): 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)

26 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

27 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

28 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: , Gustafson et al., JAGS 1991; 39: ) Negative prevention study (limited to documenting risk factors, monitoring regularly, family education, drug assessment & orientation) in pre-terminal cancer population (Gagnon et al., 2012)

29 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)

30 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)

31 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 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)

32 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

33 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

34 Anesthetic and other considerations:
General or local anesthetics likely don’t matter in delirium (may be fewer other complications with the use of local) 1 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

35 Role of medications: alpha-agonists
Alpha-agonists- sedating, analgesic, sleep-promoting effects (Ann Pharmacother 2009; 43: ) 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): ; JAMA 2007; 298 (22): ; Intensive Care Med 2009; 35: (negative RCT); Anesthes. 2009; 111 (5): ; Psychosomatics 2009; 50 (3):

36 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:

37 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)

38 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

39 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: ) 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): ) Recent negative small (n = 16) trial in hip fracture population (Marcantonio et al., JAGS 2011; 59: S282-8)

40 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: ) (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: ): 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 ) Melatonin?- other studies (Sultan et al., 2010; de Jonghe et al., 2011)

41 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)

42 Management of active delirium
Non-pharmacologic & pharmacologic approaches

43 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

44 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): ): 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)

45 Delirium- management:
Cole et al., CMAJ 1994; 151 (7): : 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)

46 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

47 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)

48 ICU setting- importance of mobility:
A recent RCT (Schweickert et al., lancet 2009; 373: ) 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)

49 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)

50 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 folks- may not get better studies in this population

51 Treatments for already delirious folk- neuroleptics?
Neuroleptics- mainstay of treatment (Internat Psychogeriatr 2010; 22: ) 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: ; J Clin Psych 2007; 68:11-21; Psychosomatics 2004; 45: ; J Am Med Dir Assoc 2008; 9: 18-28; J Psychosomatic Res 2011; 70: Meagher et al., 2013

52 Treatments for already delirious folk (ICU)- neuroleptics?
ICU RCTs- younger non-demented patients: A small RCT in mechanically ventilated delirious adults- placebo vs. quetiapine (Crit Care Med 2010; 38: ) 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): ): mechanically ventilated, n = 101; placebo vs. haldol vs. ziprasidone; vast majority of patients with delirium/coma at start of trial

53 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: ) 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)

54 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

55 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

56 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

57 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

58 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?

59 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 seizure- given 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

60 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?

61 Selected References: Abou-Setta AM, Beaupre LA, Salfee R et al. Ann Intern Med 2011; 155: Adamis D, Treolar A, Martin FC et al., Arch Geriatr Gerontol 2006; 43: 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: Carson JL, Terrin ML, Noveck H et al., N Engl J Med 2011; 365 (26): Chong MS, Tan KT, Tay L et al., Clin Interventions Aging 2013; 8: 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: 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

62 Selected References: Devlin JW, Roberts RJ, Fong JJ et al., Crit Care Med 2010; 38 (2): 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: S Gagnon P, Allard P, Gagnon B et al. Psycho-Oncology 2012; 21: Gilmore ML, Wolfe DJ. Gen Hosp Psychiatry 20013; j.genhosppsych Gruber-Baldini A, Marcantonio E, Orwig D et al., J Am Geriatr Soc 2013; 61: Hakim SM, Othman AI, Naoum DO. Anesthesiology 2012; 116 (5):

63 Selected References Hatta K, Kishi Y, Wada K et al., JAMA Psychiatry 2014; 71 (4): Heymann A, RadtkeF, Schiemann A et al., J Internat Med Res 2010; 38: Hua H, Wei D, Hui Y et al. Chin J Clin Rehab 2006; 10 (42): Inouye SK, Kosar CM, Tommet D et al., Ann Intern Med 2014; 160: 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: 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): Larsen KA, Kelly SE, Stern TA et al., Psychosomatics 2010; 51:409-18

64 Selected References Leung JM, Tsai TL, Sands LP. Anesth Analg 2011; 112: Liptzin et al., Am J Geriatr Psych 2005; 13: Lonergan E et al., Coch Database Syst Rev 2009 Oct 7;(4):CD doi: / CD 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: McCusker J, Cole M, Abrahamowicz M et al. J Am Geriatr Soc 2001; 49: McCusker J, Cole M, Abrahamowicz M et al. Arch Intern Med 2002; 162: Meagher D & Leonard M. Advances Psych Treatment 2008; 14: Meagher DJ, McLoughlin L, Leonard M et al., Am J Geriatr Psych 2013; 21:

65 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 / /8/34 O’Mahoney R, Murthy L, Akunne A et al., Ann Intern Med 2011; 154: Ono H, Taguchi T, Kido Y et al. Intens Care Crit Nurs 2011; 27: Ouimet S, Riker R, Bergeron N et al., Intens Care Med 2007; 33: Overshott R, Vernon M, Morris J et al. International Psychogeriatrics 2010; 22 (5): Pol RA, van Leeuwen BL, Visser L et al., Eur J Vasc Endovasc Surg 2011; 42: Prakanrattana U, Prapaitrakool S, Anaesth Intensive Care 2007; 35: 714-9

66 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: 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 CD doi: / CD 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: Tahir TA, Eeles E, Karapareddy V et al., J Psychosomatic Res 2010; 69: Tatematsu N, Hayashi A, Narita K et al., Support Care Cancer 2011; 19:

67 Selected References Tesylar P, Stock VM, Wilk CM et al., Psychosomatics 2013; 54: 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): Yang J, Choi W, Ko Y-H et al., Gen Hosp Psych 2012:

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