Delirium in the Elderly

1. Delirium in the Elderly Kirsten M. Wilkins, MD Assistant Professor of Psychiatry Yale School of Medicine VA CT Healthcare System

2. 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

3. 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.

4. 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.

5. 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.

6. 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

7. 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% • At end of life up to 83% Trzepacz and Meagher 2005 Saxena and Lawley 2009 Fong et al 2009

8. 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

9. 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/cFong et al 2009 Siddiqi et al 2006

11. 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

12. Delirium Risk Factors • Age • Preexisting dementia • Recent surgery • Bone fractures • Infections • Hypoalbuminemia • Preexisting CNS structural abnormalities

13. Delirium Risk Factors • Abnormal sodium • Severe illness • AIDS, Cancer • Polypharmacy • Dehydration • Visual/hearing impairment

14. Delirium Risk Factors • Substance Abuse • Alcohol • Prescription drugs • Illicit drugs • You must ask! • Collateral informant

15. 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

16. 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

17. 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

18. 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)

19. Delirium:Differential Diagnosis • Dementia with Behavioral Disturbance • Psychotic Disorder (Schizophrenia) • Mood Disorder (Depression, Mania) • Catatonia • Others

20. 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 +++ +++ - + + ++ + + + + + - +++

21. 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

22. 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

23. Source: Matrix Advocare Network wesite

24. 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

25. Etiologies of Delirium • Urgent recognition • Wernicke’s • Hypoxia • Hypoglycemia • Hypertensive encephalopathy • Intracerebral hemorrhage • Meningitis/encephalitis • Poisoning/medications

26. 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 -“ I WATCH DEATH “

28. Etiologies of Delirium General Medical Conditions HIV/AIDS Orthopedic procedures (50%) Infectious (UTI, Pneumonia, Sepsis) Metabolic derangement Cancer (PLE, brain mets—L, B, M) Impaction, constipation, dehydration, many, many others…

29. Etiologies of Delirium • Iatrogenic and polypharmacy • Anticholinergic medications • Opioids • Benzodiazepines • Steroids • Antihistamines • Antibiotics • Many, many others…

30. 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

31. 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

32. 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

33. 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

34. 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!

35. 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

36. 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

37. 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

38. Delirium: Management • Pharmacological Therapy • Haloperidol • EPS rare when IV route used, however, IV route carries risk of QTc prolongationrisk 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

39. 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

40. Delirium: Management Atypical Antipsychotics • Risperidone 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 prn • Limited data on aripiprazole, ziprasidone (concern for QTc prolongation)

41. 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

42. Delirium: Management • Antipsychotics • Black box warning • Increased risk of death/CVAE’s in pts with dementia • Use judiciously, continue to reassess R/B ratio, taper when appropriate

43. 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

44. 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

45. 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)

47. 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

48. 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.

49. 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.