Delirium in the Elderly

Kirsten M. Wilkins, MD
Assistant Professor of Psychiatry Yale School of Medicine VA 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 hospitalization b. Assign a sitter (1:1), check urinalysis, do a chest x-ray, begin SSRI c. Transfer to psychiatry for further care d. 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 caseit 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 picturebetter 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 Criteria
Disturbance 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 state acute mental status change altered mental status brain failure hepatic encephalopathy organic brain syndrome toxic or metabolic encephalopathy

Delirium: Epidemiology

Prevalence depends on population

Greater in med/surg population

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

During hospitalization up to 40%

Trzepacz and Meagher 2005 Saxena and Lawley 2009 Fong et al 2009

At end of life up to 83%

Delirium: Epidemiology

Higher rates seen with

Post-op (ortho, cardiothoracic, vascular) ICU admission

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

Up to 60% NH pts have delirium

Trzepacz and Meagher 2005 Mittal et al 2011

Delirium - Impact

Increased morbidity
Poorer recovery from medical illness Increased need for walking devices 6x increased risk of decubitus ulcers or aspiration pneumonia

Increased risk of future cognitive decline 10-33% mortality rate in hospital Increased 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

Age Preexisting dementia Recent surgery Bone fractures Infections Hypoalbuminemia Preexisting CNS structural abnormalities

Delirium Risk Factors

Abnormal sodium Severe illness

AIDS, Cancer

Polypharmacy Dehydration Visual/hearing impairment

Delirium Risk Factors

Substance Abuse
Alcohol Prescription drugs Illicit drugs

You must ask!

Collateral informant

Delirium: Presentation
Three types

Hyperactive

Better recognized More attention to treatment Associated with improved outcome Little recognized Depression is primary differential Associated with poor outcomes

Hypoactive

Mixed

Delirium: Presentation

Cognitive Symptoms

Inattention Memory impairment Disorientation

Agitation or hypoactivity Resistance to care Sleep-wake disturbance Paranoia, delusions Hallucinations (often visual), illusions Affective lability

Behavioral Symptoms

Psychiatric Symptoms

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/anger Apathy/sadness - commonly mistaken for depression Euphoria (esp. if steroid-induced)

Delirium: Differential Diagnosis

Dementia with Behavioral Disturbance Psychotic Disorder (Schizophrenia) Mood Disorder (Depression, Mania) Catatonia Others

Delirium versus Dementia

DELIRIUM
impaired 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 condition Delirium secondary to substance intoxication Delirium secondary to substance withdrawal Delirium 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 recognition
Wernickes Hypoxia Hypoglycemia Hypertensive encephalopathy Intracerebral hemorrhage Meningitis/encephalitis Poisoning/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 Conditions
HIV/AIDS Orthopedic procedures (50%) Infectious (UTI, Pneumonia, Sepsis) Metabolic derangement Cancer (PLE, brain metsL, 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 role Low and excessive serotonin Low and excessive GABA

Trzepacz and Meagher 2005

Delirium: Neurobiology

Direct injury to the neurons

Metabolic Ischemic Alters synthesis/release of neurotransmitters

Trauma, surgery, infection release of proinflammatory cytokines, elevated cortisol Direct neurotoxic effects Alters neurotransmitter levels
Mittal et al 2011

Stress response

Diagnosis of Delirium
Delirium is a clinical diagnosis History and physical examination (attention to VS) Mental Status Exam Rating Scales-consider on admission

Confusion Assessment Method Delirium Rating Scale MMSE/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 Generalized slowing in delirium, nonspecific Triphasic waves in hepatic encephalopathy Low voltage fast activity in EtOH or BZD w/d

EEG

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 oxygenation D/C nonessential medications

Minimize opioids, benzos, etc

Repeat PE, further lab, radiologic studies if cause not yet identified

Delirium: Management

Behavioral/Environmental Strategies
Reorientation, calendars, clocks Room near nursing station Lights on/off during day/night Windows Family/familiarity Hearing aids, glasses Avoid restraints

Delirium: Management

Pharmacological Therapy
Nothing FDA-approved Antipsychotics are treatment of choice for agitation compromising care or safety Haloperidol best studied, widely used

Virtually no anticholinergic effects Virtually no hypotensive effects Risk of EPS (akathisia), rare with IV route

Delirium: Management

Pharmacological Therapy

Haloperidol
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 1mg 2mg

mild moderate 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 Antipsychotics

Risperidone 0.25-0.5 po bid prn

ODT available IM/ODT available Caution: sedating, anticholinergic

Olanzapine 2.5 mg qhs

Quetiapine 25 mg po bid prn Limited data on aripiprazole, ziprasidone (concern for QTc prolongation)

Delirium: Management
Cochrane Review 2007 Meta-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

Antipsychotics
Black box warning Increased risk of death/CVAEs in pts with dementia Use 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 Therapy

Benzodiazepines
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

Variable
Full 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 preventable Risk factor intervention (Inouye 1999)

Standardized protocols for 6 risk factors:

Reduced incidence of delirium Decreased total # of days and # of episodes

No difference in:
Severity of delirium Recurrence 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 Alzheimers 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.