TNMHO ConventionSan Antonio, Texas

April 2014

Presenter: Robert A. Friedman, MD FAAFP FAAHPMChief Medical Officer Hospice Austin

President Central Texas Palliative Care Associates

Delirious about End-of-Life Delirium?

Disclosures

No financial or other conflicts of interest There will be off-label discussion

Objectives1. Recognize End-of-Life Delirium2. Determine and work-up potential causes,

as appropriate3. Describe treatment options4. Compare medication options5. Develop a Plan of Care

Case 181 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

What are we talking about?Delirium occurs in 22-83% of patients nearing

end of lifeDelirium in end-of-life is frequently missed and

significantly under-diagnosed by physiciansWhat is “confusion”?

Delirium, dementia, psychosis, obtundation, cognitive decline during the few weeks before deathDistinguish delirium from other causes of confusionUse a validated assessment tool

Confusion Assessment Method Delirium Rating Scale Delirium Symptom Interview Memorial Delirium Assessment Scale

Yes ma’am, that’s deliriumPresentation

Acute change in level of arousal Onset is over hours to days

Fluctuating courseAltered LOCCognitive 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

CourseCan last hours to weeks, if reversible

Case 1In case you’re confused or forgot81 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

What do you do, what do you do?1. I don’t know, I’m confused2. Consider potential cause(s) of delirium3. Start lorazepam 1 mg q1hr prn until calm4. Start lorazepam 1 mg q4hrs prn until calm5. Start haloperidol 1 mg q1hr prn until calm6. Start haloperidol 1 mg q4hrs prn until calm7. Start thorazine 25-50 mg q4hrs prn until calm8. Educate family on terminal restlessness, begin above

treatment and tell them to call back if the treatment isn’t working

9. Start Crisis Care10. Admit to Inpatient Unit11. Other

Types of deliriumHyperactive: vigilance and/or agitationHypoactive: lethargy, somnolence or comaMixed: fluctuation between hyperactive

and hypoactive state

What transpiredStarted on haloperidol 1 mg q4hrs prn agitationDRE is negativeFoley placed and results in 2 liters of urine

output over several minutesPatient 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 sipsPatient dies the next day

Risk factors for deliriumIncreasing ageGeneral debilityAdvanced diseaseDementia/cognitive impairmentChange in environmentImpaired renal functionDepressionPain/other symptomsSleep deprivation

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

Case 278 y.o. female admitted to hospice with dx of

Alzheimer’s DementiaAlso has HTN and HypothyroidismFAST 7dPPS 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

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 CXRSend to local ER for evaluationReview/discuss current goals of care with patient’s

medical decision makerEducate the family that this is normal disease progression

and recommend supportive careStart on antibiotics pending lab results to cover for

possible infection (UTI or pneumonia)Discuss option of placing a PEG tube for nutritional

purposesPerform a DRE and palpate her bladderOther

Formulating the work-upConsider first:Goals of careDisease trajectory

What new diagnosis does this patient have?Urinary tract infectionPneumoniaPoorly controlled hypothyroidismSepsis from pressure ulcerNot sureSome other diagnosis-specify

Case 2-What have we here?Hypoactive deliriumDiscussion with MPOA/family

Patient has a DNR and Advance DirectivesMPOA states that patient would not want

further hospitalizations, work-ups or treatments

The saga of Case 2 continuesNext stepThoughtful discussion/reality check on

consequencesYour responsibilities?

Supportive careAnticipate needs

Case 339 y.o. female with clear cell ovarian cancer

diagnosed on 4/7/2010Declined 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

This morning mother reports:

Over the last 3 days has had increasing confusion, with restlessness, agitation and dyspnea. Patient can’t get “comfortable”

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

So……you order labs which show:CBC and Urinalysis normalRandom BS 95 mg/dlCalcium 10.3 and the rest of the chem

panel is normal except forAlk Phos 520Albumin 1.7 and protein 4.9

What do you do?Haloperidol 1 mg PO/SC q4hrs prn nausea

and confusionReassure 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

Case 3 epilogue?Her corrected calcium level is 12.1 mg/dl

(Cacorrected = Caserum + 0.8(4-Albuminserum)She is admitted to the hospice IPUAfter 2L of IV saline and zoledronate 4 mg

slowly IV push, her sensorium clearsShe is discharged homeRoutine Chem panel scheduled again in 4

weeks

Rewind of Case 3Oncologist is contact this morning and asks

that patient be admitted to the hospice IPUOn-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

What you know-Nurse reportsOver 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

What would you like to knowRecent intake?How long has her abdomen been extremely

distended?Goals of care?Other?

So what happened next?

Medications for EOL DelirirumBenzodizepines

Useful for alcohol-sedative drug withdrawal or anticholinergic excess

Can cause paradoxical worsening of deliriumCan be used as an adjunct to neuroleptics when severe

agitation not controlled with neuroleptics aloneNeuroleptics

First-line pharmacological choice for symptom managment

HaloperidolBest studied and agent of choice for most patientsHas a favorable side-effect profile, but has potential side effects

with higher doses and prolonged useCan be given PO/PR/SC/IV, starting doses 0.5 mg to 1 mg, can

titrate hourly. Can be scheduled in divided doses.

Medications for EOL Delirium-continuedOther neuroleptics-Thorazine

Older typical neurolepticMay have higher incidence of EPS, sedation, and

hypotensionSome advocate its use in dying patients when sedation is

desiredAtypical 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

Non-pharmacologic managementAlways useReduce or increase sensory stimulation as

neededBed sittersFrequent reorientationTime permitting: CAM

Delirium in terminally ill patientsIs a reliable indicator of death within

days to weeksEnd-of-life restlessness: may include

Skin mottling and cool extremitiesMouth breathing with hyper-extended neckRespiratory pattern changes such as Cheyne-

Stokes, shallow breathingCalling out or speaking to deceased families

or friendsOther EOL phenomenonPeriods of deepening somnolence

References1. William Breitbart; Yesne Alici. Agitation and Delirium at the End of

Life: “We Couldn’t Manage Him”. JAMA. 2008;300(24):2898-2910.2. Diagnosis and Treatment of Terminal Delirium, 2nd ed. EPERC Fast

Facts and Concepts #001.3. Pharmacologic Management of Delirium; Update on Newer Agents,

2nd ed. EPERC Fast Facts and Concepts #060.4. Joel S. Policzer, Jason Sobel. Management of Selected Nonpain

Symptoms of Life-Limiting Illness. AAHPM UNIPAC 4, third edition, 2008.

5. Robert Friedman. Palliative Management of Common Non-pain Symptoms-presentations; 2008-2011.

6. Watson, Lucas, Hoy, and Back. Oxford Handbook of Palliative Care. New York, USA: Oxford University Press, Inc; 2005.

7. Woodruff. Palliative Medicine. Victoria, Australia: Oxford University Press, 4th ed, reprinted in 2005.

8. American Psychiatric Association, Diagnostic and Statistical Manual, 4th ed, APA Press, Washington, DC 1994.

Questions?????????