1. Delirium: New Ways to Understand and Manage It Barbara Kamholz, M.D. Durham VA Medical Center Duke University

2. Recognition: D- 33-95% of cases MISSED—either misdiagnosed as depression, psychosis, or dementia, or not appreciated at all Inouye, Bair, 1998

3. Determining Features of Delirium Acute or subacute onset Fluctuating intensity of symptoms Can vary within seconds to minutes Can be very difficult to detect Inattention

4. Attention Most basic cognitive organizing function Not a static property: an active, selective, working process that should continuously adapt appropriately to incoming internal or external stimuli

5. Inattention A cognitive state that DOES NOT meet the requirements of the person’s environment, resulting in a global disconnect: inability to fix, focus, or sustain attention to most salient concern Hypoattentiveness, hyperattentiveness Days of week backward, immediate recall

7. Phenomenological Findings Most frequent: Sleep-wake cycle abnormalities and inattention Least frequent: Disorientation Inattention was associated with severity of other cognitive disturbances but not with non-cognitive items Psychosis: Perceptual disturbances or delusions; not both –Neither associated with cognitive impairment Meagher,D. Br J Psychiatry, 2007

8. Summary of Signs Acute or Subacute Change in Mental Status Overall: GROSS DISTURBANCE OF ABILITY TO INTERACT WITH ENVIRONMENT-”Fuzzy Interface”

9. Poor Executive Function Poor insight Can’t address own personal needs/identify clinical problems Can’t plan and execute complex and rational behavior (incontinence, failure to eat) Disinhibition + poor insight =danger to self and others

12. Summary of Signs, con’t Cognitive Signs: –Inattention, disorganized, fragmented thought patterns, poor memory, disorientation, and depressed level of consciousness

13. Delirium and Dysphoria Affective Signs: Dysphoria »Quiet delirium resembles depression: unmotivated, slow, withdrawn, undemanding; Up to 42% of cases referred to consultation psychiatry for depression are delirious (Farrell, 1995) »Depressed patients are NOT classically inattentive »60% are dysphoric; 52% have thoughts of death (Farrell 1995)

14. Delirium, Dysphoria, and Sensory/Perceptual Problems Affective Signs, con’t Fearfulness: Few have systematized paranoid ideations…”guardedness” Anxiety: Often found premorbidly Labile affect Sensory/Perceptual Distortions Hallucinations differ from common psychotic symptoms (illusory) Erratic sensory and motor losses (speaking, hearing, walking, swallowing, inaccurate appreciation of pain)

15. It is Not Dementia… Dementia is chronic and less globally dysfunctional and chaotic; delirium generally overshadows dementia Temporal onset, fluctuation, inattention, lability, disordered thoughts, perceptual disorders, sleep/wake problems did differentiate (Trzepacz, ANPA poster, 2002) BOTH warrant a “vulnerable patient” approach

16. Summary of Signs, con’t Behavioral signs: –Hyperactive: Impulsive, irrational, agitated, with chaotic activity –Hypoactive: Withdrawn, uncommunicative, unmotivated –Most are mixed

17. CHANGE! CHANGE….behavior, affect, cognition, sensory capability, motoric function, executive function, signs of psychosis…

18. Hyper vs Hypoactive Delirium Many attempts at correlation of phenomenology with etiology Older age strongly and independently associated with hypoactive delirium at p<.001; no older pts experienced hyperactive delirium (Peterson J, J Am Ger Society 54:2006) Extra care needed in evaluating delirium in older patients!

20. Confusion Assessment Method (“CAM”) 1) Acute onset and fluctuating course 2) Inattention 3) Disorganized Thinking 4) Altered Level of Consciousness Criteria: 1 AND 2 necessary; and 3 OR 4 Most Widely Accepted Diagnostic Instrument ICU Version using pictorial attention assessment tool: “CAM-ICU” Inouye 1990; Ely 2002

21. Clinical Delirium Scales Neecham Memorial DSI DRS-98

22. Three Modes of Assistance with Recognition Clinical examination Nursing staff notes/observations Prediction by risk factors

23. Nursing Chart Notations/Nursing Input Perez (1984) noted that physicians indicated possible delirium in only 34% of referrals, but non-psychiatric health personnel recorded signs of delirium in 93% of cases – with the first recording made most commonly by nurses.

24. Chart Notations/Nursing Input Chart Screening Checklist (Kamholz, 1999) Composed of commonly charted behavioral signs (Sensitivity= 93.33%, Specificity =90.82% vs CAM) 97.3% of diagnoses of delirium made by nurses’ notes alone using CSC 42.1% of diagnoses made by physicians’ notes alone using CSC

25. Prediction by “Risk Factor Analysis” Helps “narrow the field” and improve the ODDS of correct diagnosis But it must be specific, not a compendium Inouye’s work critical in devising a two phase model—baseline risk (population of interest) and precipitating factors (potentially treatable causes) Inouye, 1998

26. Inouye Predisposing/Precipitating Factor Methods 281 patients in 2 cohorts, all over 70 13 clinical variables were used; those involving relative risks of 1.5 or greater were used in the multivariable proportional hazards model.

30. And Again… Francis J, J American Geriatric Society, 45:1997

31. Conceptual Problem….Every Study has Different Risk Factors! Fever, high BUN/Creatinine, abnormal sodium, azotemia, psychoactive drug use, neuroleptics or narcotics, male gender, fractures, infections, hypokalemia, hyperglycemia, hypotension, alcohol use, depression, postoperative pain, scopolamine, withdrawal, dehydration, etc…

32. Conceptual Problem….Every Study has Different Risk Factors! Few specific causes: ….a combination and quantity (“enough”) of risk factors are needed to increase the odds of developing delirium

33. Frailty The concept of frailty has been invoked to identify individuals who are not just disabled but are approaching, at risk for, disequilibrium and deterioration 61% of frail patients in acute decompensation present with delirium Jarrett “Illness Presentation in Elderly Patients” Arch Int Med 1995

34. Physiological Definitions 1) Recent weight loss, self reported exhaustion, poor grip strength, slow walking speed, low physical activity  3/5 Predictor of hospitalization, disability, mortality Walston J, JAGS 54:2006 2) Primary component is sarcopenia (muscle weakening/wasting) with atherosclerosis, cognitive impairment, and malnutrition its primary causes Morley J, Gerontol A Biol Sci Med 57:2006

35. The Canadian Argument If enough variables are considered (including social support, economic security, disease burden, prior disabilities, etc.) the specific ones do not matter. It is the percentage…that predicts “higher likelihood” of frailty Deficit accumulation, not chronological age Rockwood, K J Gerontol A Biol Sci Med Sci. 62:2007

36. The Physics of Disequilibrium Evidence from other biosystem investigations that at about 70% loss of function or reserve there is an abrupt break with a homeodynamic state Result is an unstable, unpredictable system with significant vulnerability States “far from equilibrium” characterized by large reaction to small insults Bortz WM, “The Physics of Frailty” JAGS 1993 “Que Cheng-Li, “Equilibrium, Homeostasis and Complexity” Annales CRMCC 1998

37. How Do States of Global Vulnerability Develop? Age associated decrease in homeodynamism (dynamic range of physiological solutions, redundant systems, or “reserves”) Loss of dendritic branching, loss of variability of heart rate, decrease of latency, amplitude and range of EEG frequencies, trabecular loss in bone, etc. Too little variation=less ability to adapt Lipsitz L, “Loss of Complexity and Aging” JAMA, 1992

38. Progression to Delirium The most impaired patients are basically using all of their physiological reserves and cerebral resources at all times They decompensate when these reserves are exhausted  body cannot effectively supply the brain with needed oxygen and glucose Geriatric syndrome presentations (delirium, falls)

39. Implications for Delirium “Diffuse vulnerability” implied by the concept of frailty can account for the ‘multiple pathways’ to delirium ….these are patients who are broadly vulnerable, for whom “fixing one thing” will not do; they remain vulnerable at least through the course of delirium and often afterwards …..multiple entry points

40. Frailty (Jarrett,P,Arch Intern Med. 155:1995)

41. So, to Practicalities…. Modified risk factor model helps recognition, helps focus treatment in all phases despite variability of evidence-based risk factors identified “Consensus” Baseline Risks: Age Cognitive Impairment Multiple Medical Problems

42. Precipitating Risk Factors: Systemic, not CNS Infections – UTI, Pneumonia Metabolic – Hyper, hyponatremia; high BUN, low H/H, low 02 sats, high Ca++ Medications (39%)– BENZODIAZEPINES, Anticholinergics, Opiates, Antidepressants, High dose antipsychotics (>3 mg/d haloperidol), Steroids –Plasma esterases are significantly lower in delirium (White S, Age Ageing 34:2005)

43. Example.… 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 should you do?

44. Example #2 A 59 year old man functional man with a lifetime history of bipolar disorder and no other medical comorbidities was initially treated 3 months PTA with lithium, valproate, and risperidone in slowly escalating doses. He has a 1 month history of steadily declining mental status, now being completely dependent in ADLs. He appears cognitively very slowed on admission, struggling with attention questions. Li+ level is 2.15. What do you do now?

45. Example #2, con’t Okay, lithium and risperidone are stopped and valproate is reduced to ¼ prior dose (500 mg/day). Over the next 10 days he improves only slowly and gradually. What do you do now?