Delirium in the Elderly

Kirsten M. Wilkins, MDAssistant Professor of PsychiatryYale School of MedicineVA CT Healthcare System

Case 1:

A 79 year old man with dementia, DMII, CAD, COPD, and acute renal failure but no other psychiatric history was admitted for pneumonia. After a 3 week hospital course complicated by delirium, hyponatremia, and UTI, he has been less agitated, more cooperative and more oriented for 2 days in association with decreased wbc and lessened oxygen requirements. You are consulted for acute suicidal ideation.

What initial plan would be best? a. Assign a sitter (1:1), evaluate patient for antidepressant, provide

supportive psychotherapy to address prolonged hospitalizationb. Assign a sitter (1:1), check urinalysis, do a chest x-ray, begin

SSRIc. Transfer to psychiatry for further cared. Evaluate for a sitter (1:1), check urinalysis, do a chest x-ray,

discuss with primary team

Case 1 - Discussion

Answer = D: Evaluate for a sitter (1:1), check urinalysis, do a chest x-ray, discuss with primary team

Delirium must be ruled out first in this case…it offers more morbidity than depression in this setting and this patient is at higher risk for having delirium. Suicidal ideation is common in delirium. Adding an antidepressant may worsen the picture—better to wait 2-3 days to rule out delirium, as that delay will not greatly impact treatment of depression; but, misdiagnosing as depression may result in failing to search for the cause of the delirium.

Delirium

DSM-IV-TR CriteriaDisturbance of consciousness with reduced

ability to focus, sustain, or shift attention.A change in cognition (memory deficit,

disorientation, language disturbance) or the development of a perceptual disturbance (i.e. auditory or visual hallucinations) that is not better accounted for by a preexisting dementia.

Delirium

DSM-IV-TR Criteria, cont. The disturbance develops over a short time

(hours to days) and fluctuates during the day.

There is evidence that the disturbance is caused by the direct physiological consequences of a general medical condition or substance.

Delirium

DELIRIUM IS ALSO KNOWN AS….acute confusional stateacute mental status changealtered mental statusbrain failurehepatic encephalopathyorganic brain syndrome toxic or metabolic encephalopathy

Delirium: Epidemiology

Prevalence depends on populationGreater in med/surg population

Community 0.4 - 2%General hospital admissions ~20% On admission 10 – 15% elders

During hospitalization up to 40%At end of life up to 83%

Trzepacz and Meagher 2005

Saxena and Lawley 2009

Fong et al 2009

Delirium: Epidemiology

Higher rates seen with…Post-op (ortho, cardiothoracic, vascular) ICU admission

Poor functional recovery Increased hospital lengths of stayIncreased likelihood of NH placement

Up to 60% NH pts have deliriumTrzepacz and Meagher 2005

Mittal et al 2011

Delirium - Impact

Increased morbidityPoorer recovery from medical illness Increased need for walking devices6x increased risk of decubitus ulcers or

aspiration pneumoniaIncreased risk of future cognitive decline10-33% mortality rate in hospitalIncreased risk of mortality even months

after d/c Fong et al

2009

Siddiqi et al 2006

Case 2:

Consult requested for 85 yo female with h/o dementia recently admitted to SNF, following hospitalization for hip fracture/repair , complicated by post-op infection. Pt noted by staff to be disoriented, “sundowning,” and resistant to care and PT. Per staff, family concerned that her dementia is “much worse” than before her surgery despite apparently successful surgery and resolution of her infection. Which of the following may explain her symptoms?

A) Opioid pain medications B) Ongoing symptoms of delirium C) New cognitive “baseline” D) Old age E) A, B, and C

Delirium Risk Factors

AgePreexisting dementiaRecent surgeryBone fracturesInfectionsHypoalbuminemiaPreexisting CNS structural abnormalities

Delirium Risk Factors

Abnormal sodiumSevere illness

AIDS, CancerPolypharmacyDehydrationVisual/hearing impairment

Delirium Risk Factors

Substance AbuseAlcoholPrescription drugs Illicit drugs

You must ask!Collateral informant

Delirium: Presentation

Three types Hyperactive

Better recognized More attention to treatment Associated with improved outcome

Hypoactive Little recognized Depression is primary differential Associated with poor outcomes

Mixed

Delirium: Presentation

Cognitive Symptoms Inattention Memory impairment Disorientation

Behavioral Symptoms Agitation or hypoactivity Resistance to care Sleep-wake disturbance

Psychiatric Symptoms Paranoia, delusions Hallucinations (often visual), illusions Affective lability

Disrupted Sleep-wake Cycle

Insomnia

Napping

Being awake at night, limited light and external cues leads to disorientation and paranoia which may cause agitation

Caution with sedative medications due to concerns of worsening delirium

Affective Lability

Mood may fluctuate widely in a very short period of time (minutes/hours)

Anxiety/panic/fear/angerApathy/sadness - commonly mistaken

for depressionEuphoria (esp. if steroid-induced)

Delirium:Differential Diagnosis

Dementia with Behavioral DisturbancePsychotic Disorder (Schizophrenia)Mood Disorder (Depression, Mania)CatatoniaOthers

Delirium versus Dementia

DELIRIUMimpaired memory +++

impaired thinking +++

clouding of consciousness +++

major attention deficit +++

fluctuation of course/day +++

disorientation +++

vivid perceptual disturbance ++

incoherent speech ++

disrupt sleep/wake cycle ++

nocturnal exacerbation ++

lack of insight ++

acute or sub acute onset ++

impaired judgment +++

DEMENTIA

+++

+++

-

+

+

++

+

+

+

+

+

-

+++

Delirium

Generally divided into 4 major types:Delirium secondary to general medical

conditionDelirium secondary to substance

intoxicationDelirium secondary to substance withdrawalDelirium secondary to multiple etiologies

Delirium

“Rarely is delirium caused by a single factor; rather, it is a multifactorial syndrome, resulting from the interaction of the vulnerability on the part of the patient (ie, predisposing conditions—cognitive impairment, severe illness, visual impairment) and hospital-related insults (ie, medications and procedures).” –Inouye et al 2007

Source: Matrix Advocare Network wesite

Case 2:

Consult requested for 85 yo female with h/o dementia recently admitted to the SNF, following hospitalization for hip fracture/repair , complicated by post-op infection. Pt noted by staff to be disoriented, “sundowning,” and resistant to care and PT. Per staff, family concerned that her dementia is “much worse” than before her surgery despite apparently successful surgery and resolution of her infection.

What initial plan would be best? A) Send her to the ER B) Review chart including medication list, talk to staff/family, physical and

mental status exams C) Begin routine haloperidol 0.5 mg TID for agitation D) Begin lorazepam 1 mg with dinner for sundowning behaviors

Etiologies of Delirium

Urgent recognitionWernicke’sHypoxiaHypoglycemiaHypertensive encephalopathy Intracerebral hemorrhageMeningitis/encephalitisPoisoning/medications

Etiologies -“ I WATCH DEATH “

I = Infection

W = Withdrawal A = Acute Metabolic T = Trauma C = CNS Pathology H = Hypoxia

D = Deficiencies (especially vitamin)

E = Endocrinopathies

A = Acute Vascular T = Toxins H = Heavy metals

Etiologies of Delirium

General Medical ConditionsHIV/AIDS Orthopedic procedures (50%) Infectious (UTI, Pneumonia, Sepsis)Metabolic derangementCancer (PLE, brain mets—L, B, M) Impaction, constipation, dehydration, many,

many others…

Etiologies of Delirium

Iatrogenic and polypharmacy Anticholinergic medications Opioids Benzodiazepines Steroids Antihistamines Antibiotics Many, many others…

Delirium: Neurobiology

Best established neurotransmitter dysfunction: reduced cholinergic activity

Increased dopamine may also play a roleLow and excessive serotoninLow and excessive GABA

Trzepacz and Meagher 2005

Delirium: Neurobiology

Direct injury to the neurons Metabolic Ischemic Alters synthesis/release of neurotransmitters

Stress response Trauma, surgery, infection release of

proinflammatory cytokines, elevated cortisol Direct neurotoxic effects Alters neurotransmitter levels

Mittal et al 2011

Diagnosis of Delirium

Delirium is a clinical diagnosisHistory and physical examination

(attention to VS)Mental Status ExamRating Scales-consider on admission

Confusion Assessment MethodDelirium Rating ScaleMMSE/Clock

Diagnosis of Delirium

Lab tests cannot diagnose delirium but may support dx CBC, CMP, UA, urine tox, TSH, B12, ammonia CXR, EKG, LP if indicated Neuroimaging

EEG Generalized slowing in delirium, nonspecific Triphasic waves in hepatic encephalopathy Low voltage fast activity in EtOH or BZD w/d

Delirium: Management

Identification and reversal of cause is the definitive treatment

The search must be thorough, as in the diagnosis and treatment of any other organ system failure. Delirium is brain failure!

Delirium: Management

Monitor VS and I/O Ensure good oxygenationD/C nonessential medications

Minimize opioids, benzos, etcRepeat PE, further lab, radiologic studies

if cause not yet identified

Delirium: Management

Behavioral/Environmental StrategiesReorientation, calendars, clocksRoom near nursing stationLights on/off during day/nightWindowsFamily/familiarityHearing aids, glassesAvoid restraints

Delirium: Management

Pharmacological TherapyNothing FDA-approvedAntipsychotics are treatment of choice for

agitation compromising care or safetyHaloperidol best studied, widely used

Virtually no anticholinergic effectsVirtually no hypotensive effectsRisk of EPS (akathisia), rare with IV route

Delirium: Management

Pharmacological TherapyHaloperidol

EPS rare when IV route used, however, IV route carries risk of QTc prolongationrisk of TdP

Risk greatest with higher doses over shorter periods of time, in pts with QTc >450

Monitor EKG and electrolytes (K, Mg)Monitor for akathisia

Delirium: Management

Antipsychotic Dosing in Elderly Use clinical judgment depending on severity of symptoms for starting

dose: Haloperidol

0.5mg mild 1mg moderate 2mg severe

Assess response to initial dose and repeat as needed, monitoring for effectiveness and adverse effects

Day one: order prn Day two and beyond: assess total drug needed previous day and

schedule that amount over the next day. Reassess daily continuing process until delirium resolves.

Once symptoms have remitted, continue effective dose for 48 hours, then slowly taper and discontinue over 1-5 days, depending on severity and duration of delirium up to that point. Avoid abrupt discontinuation after first day or two of mental clarity to avoid risk of rebound symptoms

Delirium: Management

Atypical AntipsychoticsRisperidone 0.25-0.5 po bid prn

ODT available

Olanzapine 2.5 mg qhs IM/ODT available Caution: sedating, anticholinergic

Quetiapine 25 mg po bid prnLimited data on aripiprazole, ziprasidone

(concern for QTc prolongation)

Delirium: Management

Cochrane Review 2007Meta-analysis compared efficacy and

adverse effects (3 trials included)No difference in efficacy or adverse effects

between low dose haloperidol and risperidone and olanzapine

High dose haloperidol (>4.5 mg/d) greater incidence of SE, mainly EPS

Lonergan 2007

Delirium: Management

AntipsychoticsBlack box warning Increased risk of death/CVAE’s in pts with

dementiaUse judiciously, continue to reassess R/B

ratio, taper when appropriate

Case 3:

70 yo male with no reported psychiatric history admitted for elective surgery. Doing well post-op until development of acute confusion, agitation, paranoia, trying to pull out lines and demanding to leave AMA. Exam reveals a diaphoretic, tremulous man with tachycardia and elevated BP. Which are part of the initial treatment plan?

A) Begin olanzapine 5 mg q4h routine for agitation B) Transfer directly to psychiatry C) Ensure safety of patient/staff D) Obtain collateral information and history from family, review chart/meds,

complete physical and mental status examinations E) Initiate alcohol detox protocol with lorazepam F) Check CMP, CBC, UA, urine tox, ammonia

Delirium: Management

Pharmacological TherapyBenzodiazepines

Primarily indicated in EtOH or benzodiazepine withdrawal delirium

Adjunct to neuroleptics in treatment of severe agitation

Lorazepam preferred given its reliable absorption from po/IM/IV routes

Generally avoided as may WORSEN delirium--especially hepatic encephalopathy

Prognosis

VariableFull recovery (unlikely at time of hospital d/c

in the elderly, may take several weeks)Persistent cognitive deficits (new “baseline”)Stupor, coma, death (the presence of

delirium indicates a more serious medical illness, affecting the central nervous system)

Prevention

30-40% cases preventableRisk factor intervention (Inouye 1999)

Standardized protocols for 6 risk factors:Reduced incidence of deliriumDecreased total # of days and # of episodes

No difference in:Severity of deliriumRecurrence of delirium

Fong 2009

Inouye et al1999

Conclusion

Delirium is common in the geriatric population Dementia is a risk factor for delirium – patients

frequently have both Recognizing delirium, and distinguishing the

syndrome from primary psychiatric conditions is critical

Delirium can present in a variety of ways and can be a result of a number of etiologies

Awareness of the hypoactive subtype of delirium is important – avoid confusing it with depression

Antipsychotic medications are useful in the management of symptoms of delirium; benzodiazepines are useful in cases of alcohol or benzodiazepine withdrawal, only.

References

Trzepacz PT, Meagher DJ. Delirium. In: Levenson JL, ed. Textbook of Psychosomatic Medicine. Arlington, VA: American Psychiatric Publishing, 2005:91-130.

Saxena S, Lawley D. Delirium in the Elderly: a clinical review. Postgrad Med J. 2009;85(1006):405-413.

Fong TG, Tulebaev SR, Inouye SK. Delirium in elderly adults: diagnosis, prevention and treatment. Nat Rev Neurol. 2009;5(4):210-220.

Mittal V, Muralee S, Williamson D, et al. Delirium in the elderly: a comprehensive review. Am J Alzheimer’s Dis Other Dement. 2011 Mar;26(2):97-109.

Siddiqui N, House AO, Holmes JD. Occurrence and outcome of delirium in medical in-patients: a systematic literature review. Age Ageing. 2006;35(4):350-364.

Lonergan E, Britton AM, Luxenberg J. Antipsychotics for delirium. Cochrane Database of Systematic Reviews 2007, Issue 2. Art. No.: CD005594. DOI: 10.1002/14651858.CD005594.pub2

Inouye SK, Bogardus ST Jt, Charpentier PA, et al. A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med. 1999;340(9):669-676.