The Elderly Patient with Delirium

1. The Elderly Patient with Delirium Thomas Price, MD Emory University School of Medicine Division of Geriatric Medicine and Gerontology

2. Overview • Definition • Presentation • Pathophysiology • Risk Factors • Prevention • Management • Consequences

3. What’s Going On? • BT is an 85 year old man who has been admitted to the hospital for repair of a hip fracture he sustained while playing golf • He has a history of hypertension and hypercholesterolemia, both of which are treated • On review of systems, he admits to some “memory problems” and difficulty sleeping at night

4. What’s Going On? • The day after admission he undergoes total hip replacement • Blood loss is estimated at 300cc • Two units of blood transfused during the surgery • Seems to recover well the next day after surgery, is talking with his family about “getting back on the course”

5. What’s Going On? • Four days post-op his wife voices concern that he is “not himself” • He seems to ignore her at times during conversations and is not eating much • She says he is often confused, saying that he asks her if she’s “taken the dog out” when they haven’t had a dog in years

6. What’s Going On? • That night he pulls his IV line out and is witnessed trying to remove his Foley catheter by the nurse

7. Definition • DSM-IV • Disturbance of consciousness with reduced ability to focus, sustain, or shift attention. • A change in cognition or the development of a perceptual disturbance that is not better accounted for by a preexisting, established, or evolving dementia. • The disturbance develops over a short period of time and tends to fluctuate during the course of the day. • There is evidence from the history, physical examination, or laboratory findings that the disturbance is caused by the direct physiological consequences of a general medical condition. American Psychiatric Association, DSM-IV

8. Definition • Confusion Assessment Method (CAM) • Inouye et al, 1990 • 56 subjects (65-96 yrs old), 26 with delirium and 30 without, measured with CAM • Results • 94-100% sensitive • 90-95% specific • PPV 91-94%, NPV 90-100% • Interobserver reliability of CAM is high (=0.81-1.0) Inouye, SK et al. Annals of Internal Medicine 1990;113:941-948

9. Definition • Confusion Assessment Method (CAM) • All of: • Acute onset • Fluctuating course • Inattention • And one of the following: • Disorganized thinking • Altered level of consciousness Inouye, SK et al. Annals of Internal Medicine 1990;113:941-948

10. Definition - ICU Patients • Modified CAM - The CAM-ICU • Ely et al. modified CAM • Visual recognition to test attention and short-term memory • Scale based on degree of consciousness • Head nodding and hand movements as responses • Sensitivity and specificity comparable to the basic CAM Ely EW et al. Crit Care Med 2001;29(7)

11. Presentation • Types of Delirium • Hyperactive Delirium • Agitation, vigilance, hallucinations • Easiest to recognize (loud, disruptive patients) • Hypoactive Delirium • Lethargy, reduced psychomotor functioning • More likely to go unrecognized (“good patients”) • Mixed Delirium • Features of both hypo- and hyperactive delirium • Normal Consciousness Delirium • Meet CAM criteria due to disorganized thinking Flacker, JM and Marcantonio ER Drugs & Aging 1998;13(2):119-30

12. Presentation Original graphic by Thomas Price, adapted from data by Lipzin B, Levkoff SE (Br J Psychiatry 1992;161:843-5)

13. Presentation • So we can say that delirium… • Is a common complication of illness in the elderly • Is an acute change in mental status • Always fluctuates • Always features abnormal attention • Is often a “missed diagnosis”

14. Morbidity and mortality Francis and Kapoor, 1992 229 pts >70 years (223 survived hospitalization) followed up for 2 years RR of Death 1.82 (1.04-3.19) RR of Institutionalization 1.82 (1.31-2.53) RR if pt with cancer 2.61 (1.32-5.18) RR if pt with ADL dependence 2.00 (1.03-3.89) Consequences Francis J and Kapoor WN, JAGS 1992:40(6);601-606

15. Pathophysiology • Cholinergic System • Central cholinergic inhibition • Elevated serum anticholinergic activity • Endogenous anticholinergic substances • Dynorphin A • Myelin Basic Protein • Protamine Flacker, JM et al. Am Journal Geriatric Psych 1998;6(1):31-41 Flacker, JM and Lipsitz LA Journal of Gerontology 1999;54A(1):M12-16 and 54A(6):B239-246

16. Pathophysiology • Cholinergic System • Direct drug binding of receptors • Atropine, scopolamine • Muscarinic binding of drug metabolites • Furosemide, cimetidine, digoxin Flacker, JM and Lipsitz LA Journal of Gerontology 1999;54A(6):B239-246

17. Pathophysiology • Serotonin • Affects cognition, mood and wakefulness • Serotonin depletion • Phenyalanine  tryptophan  serotonin • Limited trials show branched-chain amino acid infusions reduce phenylalanine and increase cognition • Can cause delirium in both over-stimulation and deficiency • SSRIs for delirium? Flacker, JM and Lipsitz LA Journal of Gerontology 1999;54A(6):B239-246

18. Pathophysiology • Other biochemical suspects • Dopamine (activation) • GABA (increased activity) • Glutamate (increased activity) • Cortisol (excessive endogenous production) • IL-1, IL-2, Prostaglandin D2 (increased in sepsis cascade) Flacker, JM and Lipsitz LA Journal of Gerontology 1999;54A(6):B239-246

19. Risk Factors • Can be split into two categories • Predisposing factors • “Pre-hospitalization” • Can alert the physician to risk but are often unmodifiable in the acute setting • Prevention can focus on these on a “chronic” timetable • Precipitating factors • “Post-hospitalization” • Often iatrogenic • Often modifiable • Often preventable

20. Predisposing Factors • Past Medical History • Falls • Stroke • Delirium • Chronic Illness • Cognitive disorders/dementia • Poor vision or hearing • Malnutrition • Renal failure or chronic dehydration

21. Predisposing Factors • Psychosocial • Age • Male sex • Alcoholism or other drug use • Depression • Functional impairment

22. Prevention - The Short List • At risk patients - key features • Predisposing • Visual impairment • Illness severity • Cognitive impairment • BUN:Cr ratio >18 • Precipitating • Malnutrition • Use of physical restraints • More than 3 medications added • Use of a bladder catheter • Iatrogenic (adverse) event Inouye SK and Charpentier PA JAMA 1996;275(11):852-7

23. Update on Our Patient • In the morning, the attending is told the events of the previous day by his resident. “We had to restrain him and I gave him 2 mg Haldol to get him to stop yelling.” • Medications are reviewed: • Aspirin 325mg po daily • Atenolol 25mg po daily • Simvastatin 20mg po qHS • Propoxyphene/APAP (Darvocet) 1 q4h prn pain • Diphenhydramine 25mg po qHS prn sleep

24. Update on Our Patient • Physical Exam • 130/62, HR 64, RR 16, SpO2 98% RA, T 95.4 F • Patient is unrousable but responds to pain • Lungs clear, heart regular, abdomen normal • Surgical site intact, no inflammation/drainage • Foley catheter in place • Patient in wrist restraints, bruising along arms • Heavily wrapped 20 ga. IV in left arm AC hooked to 75cc/hr NS

25. Prevention • Inpatient Consultation • Inouye 1999 • 852 patients, 70 or older, admitted to general medicine unit at Yale New Haven Hospital (1995-98) • Intervention: Elder Life Program • Interdisciplinary team including geriatrician • Targeted six delirium risk factors Inouye SK et al. NEJM 1999;340(9):669-76 Data used with permission from the author.

26. Prevention • How did they do this? • Cognitive Impairment • Orientation protocols • Therapeutic activities • Sleep Deprivation • Nonpharmacologic sleep protocol • Sleep-enhancement protocol • Immobility • Early mobilization protocol • Minimal use of tethers/restraints Inouye SK et al. NEJM 1999;340(9):669-76

27. Prevention • How did they do this? • Visual Impairment • Vision protocol • Hearing Impairment • Hearing protocol • Dehydration • Early recognition protocol • Encourage PO fluids Inouye SK et al. NEJM 1999;340(9):669-76

28. Prevention • Inpatient Consultation • Marcantonio and Flacker, 2001 • 125 patients > 65 years admitted for surgical repair of hip fracture • Consultation focused on 10 specific recommendations • Consultation reduced incidence of delirium during acute hospitalization after hip fracture Marcantonio ER, Flacker JM, Wright RJ, Resnick NM JAGS 2001;49(5):516-522 Data used with permission from the author.

29. Prevention • How did they do this? Geriatric consultation focused to make recommendations on 10 specific areas • Adequate CNS oxygen delivery • Fluid/electrolyte balance • Treatment of severe pain • Elimination of unnecessary medications • Regulation of bowel/bladder function • Adequate nutritional intake • Early mobilization and rehabilitation • Prevention, early detection, and treatment of major post-operative complications • Appropriate environmental stimuli • Treatment of agitated delirium Marcantonio ER, Flacker JM, Wright RJ, Resnick NM JAGS 2001;49(5):516-522

30. Prevention • Potentially inappropriate medications included: • Sedatives (sleeping meds, benzos) • Antihistamines (diphenhydramine) • Neuroleptics (phenytoin, phenobarb) • Antiarrhythmics (digoxin) • Narcotics (meperidine, propoxyphene) • Tricyclic antidepressants • Anticholinergics (atropine, scopolamine)

31. Prevention • Nursing Programs • Milisen and Foreman, 2001 • Small study; 120 pts (mean age 80) admitted for hip fracture • Intervention included cognitive screen, pain protocol, and staff education • Results: • No significant effect on delirium incidence • Reduced duration of delirium (1 v. 4 days, P=0.03) • Reduced severity of delirium (P=0.015, scored by CAM) Milisen et al. JAGS 2001;49(5):523-32

32. Management • History and physical exam • Last bowel movement • Pulse Ox • Blood glucose • Post-void residual • Lab workup • LP not suggested as routine workup • CT or not CT?

33. Management • Delirium is almost always multifactorial in origin • Work up should approach several possible diagnoses at a time • Correcting a single derangement will rarely resolve the delirium

34. Correct Underlying Pathology • Iatrogenic Causes • Environmental • Tethers • Lighting • Noises • Lack of reorientation • Sensory impairment

35. Correct Underlying Pathology • Iatrogenic Causes • Medications • Untreated (or under-treated) pain • Constipation/impaction • Urinary retention • Nutrition (modify diet if needed)

36. Correct Underlying Pathology • Infections • Urinary tract infections • Respiratory tract infections • Cardiopulmonary events • Acute coronary event • Congestive failure • Reduced output (atrial fibrillation, SVT) • Hypoxia (PE, CHF, pneumonia)

37. Correct Underlying Pathology • Metabolic Abnormalities • Dehydration • Hypernatremia, ARF • Hypo/hyperkalemia • Anemia

38. Pharmacologic Management • Antipsychotic agents are preferred over benzodiazepines • Haloperidol • 0.25-0.5 mg IV or IM, q1-2 hrs prn • Long-term use is associated with EPS/dyskinesia • Risperidone • 0.25 - 0.5 mg PO or oral dissolvable, q8-12 hrs prn • Olanzapine • 2.5 - 5 mg IM q1h prn, 2.5 - 5 mg PO QD • Quetiapine • 12.5 - 25 mg PO q8-12 hrs prn, 12.5 - 25 mg PO BID • Ziprasidone • 10 - 20 mg PO/IM q12 hrs prn

39. Pharmacologic Management • It takes smaller doses of sedatives to “knock” an elderly patient out • Notify family of the need for use • Use of antipsychotics in long term care facilities carry additional complications

40. Update on Our Patient • Diphenhydramine-induced urinary retention diagnosed and treated - foley removed • Urinary tract infection diagnosed and treated • Propoxyphene replaced with hydrocodone/APAP • IVF stopped and IV removed

41. Update on Our Patient • Patient woke up the next day • In three days was cooperating with inpatient PT again • Some residual confusion handled well with re-direction and reinforcement • Successfully transferred to subacute rehab facility 9 days post-op with improved cognitive function

42. Caveats • Delirium can persist from days to months after treatment of the underlying cause but is often reversible • Discharge destination may need to be reconsidered upon diagnosis of delirium • Dementia and delirium often co-exist • Many patients experience some degree of permanent cognitive function loss after a delirium episode

43. Take Home Points • The cause of delirium is multi-factorial • Delirium may be preventable or its severity lessened by targeted interventions • Treatments for delirium are interdisciplinary and involve multiple approaches • Psychotropic drug therapy (at appropriate dosage) is a last resort

44. The End