Delirium and The Relationship To Anticholinergic Burden

1. Delirium and The Relationship To Anticholinergic Burden Miki Finnin, Pharm. D., BCPS, CGP CEO/Pharmacist Medication Advisors, PLLC

2. Definition of Delirium • A disturbance in consciousness with reduced ability to focus, sustain or shift attention that occurs over a short period of time and tends to fluctuate over the course of a day • Acute brain failure • Evidence of an underlying general medical condition

4. Case “A” You are the overnight provider and are called by the nurse to evaluate “Mrs. A” who has pulled out her IV and is insisting on leaving the hospital because “nothing is being done”. A quick review of the chart shows: • 100 yr old lady with h/o CAD, CHF, DM, GERD, urinary incontinence and depression admitted for CHF exacerbation secondary to non compliance • Meds – ASA, beta blocker, ACEI, nifedipine, lasix, KCL, oxybutinin, cimetidine, paroxitine

5. Why Bother? • Common problem • Serious complications • Often unrecognized • May be preventable

6. Prevalence in Elderly • Hospitalized 10 – 52% • Hospitalized with dementia 32 – 86% • Postoperative 15 – 53% • ICU 70 – 87% • NH/Post-acute care 20 – 60% • Palliative care up to 83% Inouye S. N Engl J Med 2006; 354 :1157-65.

7. Prevalence in Elderly • Complicates more than 2.3 million hospitalized older adults annually • Associated with 17.5 million hospital days • > 4 billion in excess annual health care expenditures Inouye S. Am J Med 1994; 97(3) : 278-88. Rizzo, et al. Medical Care 2001; 39(7):740.

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9. Duration of Delirium • Transient phenomenon • May last weeks to months

10. Vulnerability-Trigger Interaction • Complex interaction among various degrees of insult and different levels of patient vulnerability • Hence the wide range of prevalence 10 -86%

11. Vulnerability Factors • Cognitive impairment • Depression • Alcohol abuse • Sensory deprivation • > 2 assisted ADL’s • Anticholinergic • Dehydration • Sodium abnormality • Vascular risk factors

12. Risk Factors • Intrinsic Factors • Vision impairment (<20/70) • Cognitive impairment (MMSE < 24) • Severe illness (APACHEII > 16) • BUN/CR ratio > 18 Inouye S, et al. JAMA 1996; 275(11):852-7. • Precipitating Factors • Restraint use • Malnutrition • 3 new medications • Bladder catheterization • Any iatrogenic event

14. Tipping Point • Patient had requested a sleep-aid because of insomnia and was given Tylenol PM

15. Adverse Drug Events • Potential for interaction • 2 drugs 6% • 5 drugs 50% • > 6 drugs nearly 100% • 70 – 80% of adverse drug events in the elderly are dose related • 30 – 50% are preventable Carbonin P, et al. JAGS 1991; 39:1093-99.

16. Anticholinergic Burden • Drugs with no anticholinergic effects were rated “0” • Mildly anticholinergic drugs were scored as “1” • Moderately anticholinergic drugs were rated “2” • Highly anticholinergic drugs were scored as “3” Rudolph JL, et al. Arch Intern Med 2008; 168(5):508-13.

17. Cumulative Anticholinergic Burden Imipramine Cimetidine Diphenhydramine Codeine Ipratropium Coumadin Amitryptilline Haldol Quetiapine Alprazolam Meclizine Nifedipine Meperidine Prednisone Paroxitine Lasix Triamterene Digoxin Han L, et al. J Am Geriatr Soc 2008; 56(12):2203-10. Rudolph JL, et al. Arch Intern Med 2008; 168(5):508-13.

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19. Common Problem Drugs • Anticholinergic medications increase delirium risk • Diphenhydramine • Odd ration (OR) of catheter placement 2.5 • OR delirium 1.8 • Psychoactive medications increase ADEs • Non-steroidals, cardiac medications Agostini JV, et al. Arch Intern Med 2001; 161:2091-7. Han L, et al. Arch Intern Med 2001; 161:1099-105.

20. Case “A” You are the overnight provider and are called by the nurse to evaluate “Mrs. A” who has pulled out her IV and is insisting on leaving the hospital because “nothing is being done”. A quick review of the chart shows: • 100 yr old lady with h/o CAD, CHF, DM, GERD, urinary incontinence and depression admitted for CHF exacerbation secondary to non compliance • Meds – ASA, beta blocker, ACEI, nifedipine, lasix, KCL, oxybutinin, cimetidine, paroxitine, Tylenol PM

22. Recognition of Delirium • RN’s recognize only 50% of cases • MD’s recognize only 20% of cases Classic Presentation wildly agitated patient presents in only 25% of cases

23. Confusion Assessment Method (CAM) – Diagnostic Algorithm • Acute onset and fluctuating course • Inattention • Disorganized thinking • Altered level of consciousness

24. The CAM Instrument 1. [Acute Onset] Is there evidence of an acute change in mental status from the patient’s baseline? 2A. [Inattention] Did the patient have difficulty focusing attention, for example, being easily distractible, or having difficult keeping track of what was being said? 2B. (If present or abnormal) Did this behavior fluctuate during the interview, that is, tend to come and go or increase and decrease in severity? 3. [Disorganized thinking] Was the patient’s thinking disorganized or incoherent, such as rambling or irrelevant conversation, unclear or illogical flow of ideas, or unpredictable switching from subject to subject?

25. The CAM Instrument 4. [Altered level of consciousness] . Overall, how would you rate this patient’s level of consciousness? (Alert [normal]; Vigilant [hyperalert, overly sensitive to environmental stimuli, startled very easily], Lethargic [drowsy, easily aroused]; Stupor [difficult to arouse]; Coma; [unarousable]; Uncertain) 5. [Disorientation] Was the patient disoriented at any time during the interview, such as thinking that he or she was somewhere other than the hospital, using the wrong bed, or misjudging the time of day? 6. [Memory impairment] Did the patient demonstrate any memory problems during the interview, such as inability to remember events in the hospital or difficulty remembering instructions?

26. The CAM Instrument 7. [Perceptual disturbances] Did the patient have any evidence of perceptual disturbances, for example, hallucinations, illusions or misinterpretations (such as thinking something was moving when it was not)? 8A. [Psychomotor agitation] At any time during the interview did the patient have an unusually increased level of motor activity such as restlessness, picking at bedclothes, tapping fingers or making frequent sudden changes of position? 8B. [Psychomotor retardation]. At any time during the interview did the patient have an unusually decreased level of motor activity such as sluggishness, staring into space, staying in one position for a long time or moving very slowly? 9. [Altered sleep-wake cycle]. Did the patient have evidence of disturbance of the sleep-wake cycle, such as excessive daytime sleepiness with insomnia at night?

27. The CAM Instrument Feature 1: Acute Onset or Fluctuating Course This feature is usually obtained from a family member or nurse and is shown by positive responses to the following questions: Is there evidence of an acute change in mental status from the patient’s baseline? Did the (abnormal) behavior fluctuate during the day, that is, tend to come and go, or increase and decrease in severity? Feature 2: Inattention This feature is shown by a positive response to the following question: Did the patient have difficulty focusing attention, for example, being easily distractible, or having difficulty keeping track of what was being said?

28. The CAM Instrument Feature 3: Disorganized thinking This feature is shown by a positive response to the following question: Was the patient’s thinking disorganized or incoherent, such as rambling or irrelevant conversation, unclear or illogical flow of ideas, or unpredictable switching from subject to subject? Feature 4: Altered Level of consciousness This feature is shown by any answer other than “alert” to the following question: Overall, how would you rate this patient’s level of consciousness? (alert [normal]), vigilant [hyperalert], lethargic [drowsy, easily aroused], stupor [difficult to arouse], or coma [unarousable])? • The diagnosis of delirium by CAM requires the presence of features 1 and 2 and either 3 or 4.

29. The CAM Instrument • Sensitivity of 94% (95% CI = 91 – 97%) • Specificity of 89% (95% CI = 85 – 94%) Wei L, et al. JAGS 2008; 56(5):823-30.

30. Causes of Delirium 44% of delirium is due to medications Thus the TOP 3 causes of delirium are: • Medications • Medications • Medications

31. Diagnosis

32. Medical Vs. Psychiatric 2/3 cases of delirium have an underlying medical cause and so a work-up must be initiated

33. Assessment • Vital signs • Examine the patient • UA • Cr, Na, K, Ca, Glu • CBC with diff • Meds review esp. Antichol, BDZ • Remove tethers

34. Non-Pharmacological Interventions • Pacing – allow to pace as long as safe • Social isolation – talk to the agitated patient to distract them • Night-lite to orient • Keep daytime light as bright as possible • Pet therapy • 1:1 observation – have family visit and stay with patient

35. Treatment • Antipsychotics • Anticonvulsants • Benzodiazepines

37. A Little Evidence for Pre-Op Haldol • 430 hip fracture patients aged 70+ at risk for post-op delirium • Visual impairment • APACHE II >16 • MMSE < 25 • BUN/Cr > 18 • Randomized to receive haloperidol 1.5 mg daily started pre-op and continued until 3 days post surgery Kalisvaart K, et al. JAGS 2005; 53:1658-66.

38. Results