1. U13: Cancer and Aging: Interventions to Prevent Delirium Sharon K. Inouye, M.D., M.P.H. Professor of Medicine Beth Israel Deaconess Medical Center Harvard Medical School Milton and Shirley F. Levy Family Chair Director, Aging Brain Center Hebrew SeniorLife 1

2. DSM5 CRITERIA FOR DELIRIUM Disturbance in attention and awareness (reduced orientation to the environment) Disturbance develops acutely and tends to fluctuate An additional disturbance in cognition, (e.g., memory deficit, language, visuoperceptual) Not better explained by a preexisting dementia Not in face of severely reduced level of arousal or coma Evidence of an underlying organic etiology or multiple etiologies Used with permission. American Psychiatric Association, 2013 2

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4. Why is delirium important? Common problem Serious complications Often unrecognized Typically multifactorial etiology Up to 40% cases preventable 4

5. In U.S. hospitals today 5 older patients become delirious every minute 2.6 million older adults develop delirium each year 5 U.S. Dept HHS, AoA Report, Profile of Older Americans 2011

6. 6 Delirium is common Delirium Rates Hospital: Prevalence (on admission)14-24% Incidence (in hospital) 6-56% Postoperative:15-53% Intensive care unit:70-87% Nursing home/post-acute care:20-60% Palliative care:up to 80% Mortality Hospital mortality:22-76% One-year mortality:35-40% Ref: Inouye SK, NEJM 2006;354:1157-65; Lancet 2014; 383:911-922

7. Delirium rates in cancer patients Review of literature 10-50%: cancer patients undergoing surgery (7 studies) 30-90%: advanced cancer patients receiving palliative or terminal care (10 studies) 7

8. Delirium has serious complications Delirium associated with: –Increased morbidity and mortality –Functional and cognitive decline –Increased rates of dementia –Institutionalization –Increased LOS and healthcare costs –Post-traumatic stress disorder –Caregiver burden 8

9. 9 Delirium is expensive Hospital costs (> $8 billion/year) Post-hospital costs (>$150 billion/year) Rehospitalization Institutionalization Rehabilitation Home care Caregiver burden Ref: Leslie DL, et al. Arch Intern Med 2008;168:27-32

10. Causes in Cancer Patients Multifactorial Multimorbidity (multiple chronic conditions) Drugs –Chemotherapeutic agents –Steroids (Decadron) –Antiemetics (Compazine) –Anticholinergics (Benadryl) –Narcotics –Other psychoactive drugs (anxiety, depression, sleep) Infections (UTI, pneumonia) Metabolic derangements (↓Na, renal) Pain, sleep deprivation

12. Medications Associated with Delirium [2012 AGS Beers Criteria: Potentially Inappropriate Medications for Elderly] All tricyclic antidepressants Anticholinergics (eg, diphenhydramine) Benzodiazepines Corticosteroids H 2 -receptor antagonists Meperidine Sedative hypnotics Thioridazine/chlorpromazine 12

13. Delirium is a preventable medical condition Previous studies documented at least 30-40% of delirium is preventable Multiple successful strategies: – Hospital Elder Life Program (Inouye 1999, 2000; Chen 2012) – Proactive geriatric consultation (Marcantonio 2001) – Exercise and rehabilitation interventions (Caplan 2006, Schweickert 2009) 13

14. 14 NONPHARMACOLOGIC DELIRIUM PREVENTION: HOSPITAL ELDER LIFE PROGRAM (HELP) Considered gold standard of multicomponent interventions—included in AGS and NICE guidelines Targeted at 6 delirium risk factors Risk Factor Intervention Cognitive Impairment………………………………….Reality orientation Therapeutic activities protocol Sleep Deprivation…………………………………….. Nonpharmacological sleep protocol Sleep enhancement protocol Immobilization………………………………………… Early mobilization protocol Minimizing immobilizing equipment Vision Impairment…………………………………….. Vision aids Adaptive equipment Hearing Impairment………………………………….. Amplifying devices Adaptive equipment and techniques Dehydration…………………………………………… Early recognition and volume repletion Inouye SK. N Engl J Med 1999;340:669-76.

15. 15 HELP Impact on Outcomes ReferenceNo. of Patients Rate in HELPRate in ControlsImprovement with HELP PREVENTION OF DELIRIUM Rubin 2011>7,00018%41%23% Chen 20111790%17% Caplan 2007376%38%32% Rubin 200670426%41%15% Inouye 199985210%15%5% REDUCED COGNITIVE DECLINE (MMSE decline by 2+ points) Inouye 20001,5078%26%18% REDUCED FUNCTIONAL DECLINE (ADL decline by 2+ points) Inouye 20001,50714%33%19% DECREASED HOSPITAL LENGTH OF STAY Rubin 2011>7,0005.3 days6.0 days0.7 days Caplan 20073722.5 days26.8 days4.3 days Rubin 2006704--- 0.3 days REDUCED INSTITUTIONALIZATION Caplan 20073725%48%23% DECREASED FALLS Inouye 2009--2%4%2% Inouye 2009--3.8/1000 p-y11.4/.1000 p-y7.6/1000 p-y Inouye 2009--1.2/1000 p-y4.7/1000 p-y3.5/1000 p-y Caplan 2007376%19%13% DECREASED SITTER USE Caplan 200737330 hours644 hours314 hours 15

16. 16 HELP Impact on Costs ReferenceNo. of Patients Impact on Cost Rubin 2011>7,000>$7.3 million per year savings in hospital costs (> $1000 savings per patient) Rizzo 2001852$831 cost savings per person-yrs in hospital costs Leslie 2005801$9,446 savings per person-yrs in long-term nursing home costs Caplan 2007111$121,425 per year savings in sitter costs 16 Many HELP studies have included oncology patients No studies have looked at oncology patients alone

17. DELIRIUM MANAGEMENT: NONPHARMACOLOGIC InterventionResultsReference Proactive geriatric consultation Decreased incidence of delirium Marcantonio 2001 Systematic detection and specialized care Trend towards cognitive improvement Cole 2002 Delirium RoomReduced use of sedative drugs Flaherty 2003 Comprehensive Geriatric Assessment Reduced delirium severity and duration Pitkala 2006 Delirium Abatement Program Improved detection of delirium by nurses in post- acute setting Marcantonio 2010

18. PHARMACOLOGIC APPROACHES Drug treatment may reduce agitation but prolong delirium and cognitive decline Conclusion reached by several systematic review and guideline panels: No recommendation for drug treatment for prevention or management of delirium at this time Ref: NICE 2010, VA HSRD 2011 18

19. Gaps in our Knowledge Only 2 studies focusing strictly on cancer patients only Gagnon P, 2012 [Psychooncology 2012;21: 187-94] –Educational intervention for physicians and families –Concurrent cohort design; N=1516 advanced CA –Not effective for delirium prevention Hempenius L, 2013 [PLoS One 2013;8: e64834] –Preoperative geriatric consultation with daily RN visit –RCT; N=260 scheduled for elective surgery for CA –Not effective for delirium prevention Interventions may have lacked potency 19

20. Challenges: Nonpharmacologic studies Studies can be challenging!!! Intervention of inadequate potency Adherence with intervention not assured Unblinded outcome assessment Absence of control group Lack of balanced allocation to study groups 20

21. Consider appropriate outcomes Review of ASCO’s 2014 Meaningful Outcomes in Clinical Trials Oncology trials focus on survival –PFS=progression free survival Patient-centered outcomes –Health-related quality of life –Delirium/Cognition –Physical functioning –Social and role functioning –Sxs: Fatigue, nausea, weight loss, depression 21

22. 22 How to define “effectiveness”? Choose your endpoints carefully Delirium: [do not overweight agitation] –Shortening duration and/or severity –Decrease delirium recurrence Not delirium alone: –Reduce adverse clinical outcomes (both short- and long-term): mortality, LOS, costs, readmission, NH placement –Return to functional independence NB: Large sample size may be needed

23. Approaches to Address the Gaps Randomized clinical trials of nonpharmacological preventive strategies –Pros: a gold standard approach and yield definitive answers about effectiveness –Cons: can be expensive, involving restrictive populations, and often not completely real world solutions 23

24. Approaches (continued) Pragmatic trials of proven approaches, like HELP –Pros: can be applied in a real-world setting –Cons: can also be expensive, since large sample sizes needed to see effects Answers may be less definitive and may not be considered gold standard Confounding factors may influence results strongly 24

25. Approaches (continued) Quality improvement trials (before/after) –Pros: can be useful for interventions where effectiveness and cost-effectiveness already well-established like HELP. Convincing local evidence. Inexpensive, rapid turnaround. –Cons: would not be considered a gold standard approach Results may not be generalizable to other settings or populations Historical studies susceptible to temporal trends, confounding, and co-interventions 25

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27. 27 Add life to years, not years to life.

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