Delirious about End-of-Life Delirium?

1. Delirious about End-of-Life Delirium? TNMHO Convention San Antonio, Texas April 2014 Presenter: Robert A. Friedman, MD FAAFP FAAHPM Chief Medical Officer Hospice Austin President Central Texas Palliative Care Associates

2. Disclosures • No financial or other conflicts of interest • There will be off-label discussion

3. Objectives • Recognize End-of-Life Delirium • Determine and work-up potential causes, as appropriate • Describe treatment options • Compare medication options • Develop a Plan of Care

4. Case 1 81 y.o. male with Stage 4 NSCLC • Metastatic to liver • Former smoker, has COPD • PPS 30%, but decreased intake Develops rather rapid onset of agitation and confusion • Is disoriented, paranoid, a little combative, wants to climb out of bed, but is unsteady • Family denies that patient has had recent constipation and • States that he is voiding regularly • Hasn’t slept much in the last 24 hours

5. What are we talking about? • Delirium occurs in 22-83% of patients nearing end of life • Delirium in end-of-life is frequently missed and significantly under-diagnosed by physicians • What is “confusion”? • Delirium, dementia, psychosis, obtundation, cognitive decline during the few weeks before death • Distinguish delirium from other causes of confusion • Use a validated assessment tool • Confusion Assessment Method • Delirium Rating Scale • Delirium Symptom Interview • Memorial Delirium Assessment Scale

6. Yes ma’am, that’s delirium • Presentation • Acute change in level of arousal • Onset is over hours to days • Fluctuating course • Altered LOC • Cognitive impairments • Disorganized thought processes • Incoherent slow or rapid speech • Disturbance of memory, orientation and attention • Emotional lability • Perceptual disturbances, delusions and hallucinations • Restlessness/agitation • Lethargy • Altered sleep/wake cycle • Course • Can last hours to weeks, if reversible

7. Case 1In case you’re confused or forgot 81 y.o. male with Stage 4 NSCLC • Metastatic to liver • Former smoker, has COPD • PPS 30%, but decreased intake Develops rather rapid onset of agitation and confusion • Is disoriented, paranoid, a little combative, wants to climb out of be, but is unsteady • Family denies that patient has had recent constipation and • Family states that he is voiding regularly • Hasn’t slept much in the last 24 hours

8. What do you do, what do you do? • I don’t know, I’m confused • Consider potential cause(s) of delirium • Start lorazepam 1 mg q1hr prn until calm • Start lorazepam 1 mg q4hrs prn until calm • Start haloperidol 1 mg q1hr prn until calm • Start haloperidol 1 mg q4hrs prn until calm • Start thorazine 25-50 mg q4hrs prn until calm • Educate family on terminal restlessness, begin above treatment and tell them to call back if the treatment isn’t working • Start Crisis Care • Admit to Inpatient Unit • Other

9. Types of delirium • Hyperactive: vigilance and/or agitation • Hypoactive: lethargy, somnolence or coma • Mixed: fluctuation between hyperactive and hypoactive state

10. What transpired • Started on haloperidol 1 mg q4hrs prn agitation • DRE is negative • Foley placed and results in 2 liters of urine output over several minutes • Patient calms down over 2 hours, but required a second dose of 1 mg of haloperidol 1 hour after the first dose, remains confused, but is fairly cooperative • Kept on Haloperidol 2 mg q4hrs ATC, may hold if sedated or sleeping • Intake is now minimal, mainly sips • Patient dies the next day

11. Risk factors for delirium • Increasing age • General debility • Advanced disease • Dementia/cognitive impairment • Change in environment • Impaired renal function • Depression • Pain/other symptoms • Sleep deprivation

12. Assess for reversible causes-In advanced terminal illnesses • Drug toxicity • Antichoinergics: anti-secretion drugs, anti-emetics, antihistamines, TCAs • Sedative hypnotics • Opioids • Infection • Hypotension • Hypoxia • Hypoglycemia • CNS pathology • Hypercalcemia • Elevated ammonia • Alcohol-sedative drug withdrawal • Sleep deprivation • Potential easily reversible causes • Pain • Constipation • Urinary retention

13. Case 2 78 y.o. female admitted to hospice with dx of Alzheimer’s Dementia • Also has HTN and Hypothyroidism • FAST 7d • PPS 40%, still able to feed self, but appetite is ‘fair’ and she lost 10% of her body weight over the 6 months prior to admission to hospice. BMI now 18.9 • She is developing contractures of both arms and legs in spite of passive ROM therapy at PCH and has a Stage 2 pressure ulcer over her sacrum

14. Flash forward-6 weeks She suddenly stops eating, smiling or making eye contact, and appears more lethargic What do you do? • Order CBC, Urinalysis, and CXR • Send to local ER for evaluation • Review/discuss current goals of care with patient’s medical decision maker • Educate the family that this is normal disease progression and recommend supportive care • Start on antibiotics pending lab results to cover for possible infection (UTI or pneumonia) • Discuss option of placing a PEG tube for nutritional purposes • Perform a DRE and palpate her bladder • Other

15. Formulating the work-upConsider first: • Goals of care • Disease trajectory

16. What new diagnosis does this patient have? • Urinary tract infection • Pneumonia • Poorly controlled hypothyroidism • Sepsis from pressure ulcer • Not sure • Some other diagnosis-specify

17. Case 2-What have we here? • Hypoactive delirium • Discussion with MPOA/family • Patient has a DNR and Advance Directives • MPOA states that patient would not want further hospitalizations, work-ups or treatments

18. The saga of Case 2 continues Next step • Thoughtful discussion/reality check on consequences • Your responsibilities? • Supportive care • Anticipate needs

19. Case 3 39 y.o. female with clear cell ovarian cancer diagnosed on 4/7/2010 • Declined further disease-directed therapy and was admitted to hospice in 12/2012. At that time she has metastatic disease to the peritoneum and pleura • Oncology records from 2/2012 show CA 125 of 2397 and Ca++ of 12.4, with normal albumin at 3.9 • Takes 2.5 methadone q12hrs for pain and 20 mg liquid morphine q1hr prn pain, which is adequate • She is a very private person

20. This morning mother reports: • Over the last 3 days has had increasing confusion, with restlessness, agitation and dyspnea. Patient can’t get “comfortable”

21. On-call nurse reports: • Received 20 mg morphine this morning x2, but suffered emesis immediately after on both occasions • Received promethazine 25 mg pr x 1 this morning • Appears to be having some hallucinations, (visual and auditory) • She is extremely cachectic and her abdomen is extremely distended

22. So……you order labs which show: • CBC and Urinalysis normal • Random BS 95 mg/dl • Calcium 10.3 and the rest of the chem panel is normal except for • AlkPhos520 • Albumin 1.7and protein 4.9

23. What do you do? • Haloperidol 1 mg PO/SC q4hrs prn nausea and confusion • Reassure the patient and family that this is normal disease progression and offer comfort/supportive treatment • Start Levofloxacin 500 mg qday for altered mental status changes due to possible UTI • Give IV saline and zoledronate 4 mg slow IV push • Order a new bone scan

24. Case 3 epilogue? • Her corrected calcium level is 12.1 mg/dl (Cacorrected = Caserum + 0.8(4-Albuminserum) • She is admitted to the hospice IPU • After 2L of IV saline and zoledronate 4 mg slowly IV push, her sensorium clears • She is discharged home • Routine Chem panel scheduled again in 4 weeks

25. Rewind of Case 3 • Oncologist is contact this morning and asks that patient be admitted to the hospice IPU • On-call RN assesses patient • Patient extremely restless, appears in severe pain, and concurs that patient should be transported to the IPU • You are the receiving physician and you have one Oncology note from 12/2012 in addition to the a hospice nursing “clinical summary” from time of admission to hospice, in addition to periodic updates to this summary

26. What you know-Nurse reports • Over the last 3 days has had increasing confusion, is restlessness, agitation and dyspnea. Patient can’t get “comfortable” • Received 20 mg morphine this morning x2, but suffered emesis immediately after on both occasions • Received promethazine 25 mg pr x 1 this morning • Appears to be having some hallucinations, (visual and auditory) • She is extremely cachectic and her abdomen is extremely distended

27. What would you like to know • Recent intake? • How long has her abdomen been extremely distended? • Goals of care? • Other?

28. So what happened next?

29. Medications for EOL Delirirum • Benzodizepines • Useful for alcohol-sedative drug withdrawal or anticholinergic excess • Can cause paradoxical worsening of delirium • Can be used as an adjunct to neuroleptics when severe agitation not controlled with neuroleptics alone • Neuroleptics • First-line pharmacological choice for symptom managment • Haloperidol • Best studied and agent of choice for most patients • Has a favorable side-effect profile, but has potential side effects with higher doses and prolonged use • Can be given PO/PR/SC/IV, starting doses 0.5 mg to 1 mg, can titrate hourly. Can be scheduled in divided doses.

30. Medications for EOL Delirium-continued • Other neuroleptics-Thorazine • Older typical neuroleptic • May have higher incidence of EPS, sedation, and hypotension • Some advocate its use in dying patients when sedation is desired • Atypical neuroleptics • Olanzapine, quetiapine, risperidone • Scant evidence for use with delirium • Not first line • Associated with fewer drug-induced movement disorders • ?agents of choice with NMDs • These meds are given daily to TID depending on the medication and should only be titrated over days to a week • May not work as fast as conventional antipsychotics • Quetiapine is the most sedating of this group

31. Non-pharmacologic management • Always use • Reduce or increase sensory stimulation as needed • Bed sitters • Frequent reorientation • Time permitting: CAM

32. Delirium in terminally ill patients • Is a reliable indicator of death within days to weeks • End-of-life restlessness: may include • Skin mottling and cool extremities • Mouth breathing with hyper-extended neck • Respiratory pattern changes such as Cheyne-Stokes, shallow breathing • Calling out or speaking to deceased families or friends • Other EOL phenomenon • Periods of deepening somnolence

33. References • William Breitbart; YesneAlici. Agitation and Delirium at the End of Life: “We Couldn’t Manage Him”. JAMA. 2008;300(24):2898-2910. • Diagnosis and Treatment of Terminal Delirium, 2nd ed. EPERC Fast Facts and Concepts #001. • Pharmacologic Management of Delirium; Update on Newer Agents, 2nd ed. EPERC Fast Facts and Concepts #060. • Joel S. Policzer, Jason Sobel. Management of Selected Nonpain Symptoms of Life-Limiting Illness. AAHPM UNIPAC 4, third edition, 2008. • Robert Friedman. Palliative Management of Common Non-pain Symptoms-presentations; 2008-2011. • Watson, Lucas, Hoy, and Back. Oxford Handbook of Palliative Care. New York, USA: Oxford University Press, Inc; 2005. • Woodruff. Palliative Medicine. Victoria, Australia: Oxford University Press, 4thed, reprinted in 2005. • American Psychiatric Association, Diagnostic and Statistical Manual, 4th ed, APA Press, Washington, DC 1994.

34. Questions?????????