Delirium: Agitation and Restlessness at the End of Life

Transcription

1 Delirium: Agitation and Restlessness at the End of Life Gail Gazelle, MD, FACP, FAAHPM Assistant Clinical Professor of Medicine, Harvard Medical School Hospice Medical Director Life and Career Coach Course Materials & Disclosure Course materials including handout(s) and conflict of interest disclosure statement are available to download with this course. This presentation is for educational and informational purposes only. It is not intended to provide legal, technical or other professional services or advice. Why spend time on this topic? One of the most devastating occurrences in end-of-life care If caught early, can usually be successfully treated Survivors often view it as the single most painful expression of the dying experience Interferes with intimate conversations and meaningful good-byes Leaves survivors at risk for a complicated grief response 1

2 Objectives for this course Contrast the difference between delirium and dementia Describe the risk factors associated with delirium Identify early warning signs of delirium Improve clinical management of delirium Early Descriptions Hippocrates: 400 BCE they move the face, hunt in empty air, pluck nap from the bedclothes all these signs are bad, in fact deadly Celsus: 1 st Century CE Sick people lose their judgement and talk incoherently when the violence of the fit is abated, the judgement presently returns Delirium Delirare: to be crazy De lira: to leave the furrows 2

3 Delirium Common in the terminally ill: Up to 80% of people experience delirium during the final week of life 15 30% of hospitalized cancer patients experience some delirium Delirium Early recognition is THE KEY step for appropriate management Delirium: The First Step is Recognition Dad just isn t himself anymore he takes everything so seriously, gets irritable and angry at the slightest change But she was so calm just a few days ago He seems worse in the afternoon I don t know why but last night things got really bad It s the strangest thing. Yesterday, she was reading a book to her grand-daughter and now she s slumped in bed speaking gibberish. I must be imagining things I wonder what could be causing this? 3

4 DSM-IV Criteria: Delirium Disturbance in consciousness Attention, level of wakefulness Change in cognition e.g., memory, orientation, language Develops over a short period of time Caused by the direct physiological consequences of a general medical condition Agitation and Delirium Delirium: an acute organic mental disorder characterized by confusion, disorientation, restlessness, agitation, incoherence, fear, anxiety, excitement waxing and waning level of consciousness occasionally hallucinations (usually visual) Agitation and Delirium Physical: the hallmark is movement agitation, fidgeting, tossing and turning, pacing, jerking, twitching, fumbling, purposeless movements 4

5 Agitation and Delirium Fragmented sleep/wake cycle Night-time awakenings Often first signs of delirium at night-- SUNDOWNING Delirium may be worse at night, but some studies show morning worsening Delirium: The Wind-Up Early signs (the wind-up): Restlessness, anxiety, sleep disturbance, irritability Attention decreased (easily distractible) Altered arousal and psychomotor abnormality Sleep-wake disturbance (usually worsens at night) SUNDOWNING Impaired memory (can t register new information) Delirium: The Wind-Up Early signs (the wind-up): Disorganized thinking and speech Disorientation time, place, person Perceptions altered misperceptions, illusions, delusions, hallucinations Emotional lability Education of the family is KEY 5

6 Clinical Subtypes Hyperactive Confusion, agitation, hallucinations, myoclonus Hypoactive Confusion, somnolence, withdrawn More likely to be under-diagnosed Mixed Goals of Care Awake, alert, calm, cognitively intact, able to communicate coherently with family and caregivers Work-up of delirium must be balanced between likelihood of facilitating calm state and minimizing invasive or burdensome procedures and stress Delirium is Very Distressing for Patients and Caregivers 154 patients with cancer and delirium 53% recalled delirium Mean delirium-related distress on 0-4 scale, was 3.2 for patients, 3.75 for spouses and caregivers Delusions were the most predictive of distress No difference in distress between hypoactive and hyperactive delirium Breitbart et al. Psychosomatics,

7 Delirium is Very Distressing for Patients and Caregivers 76% witnessed delirium or confusion 38% witnessed these symptoms daily Sense of fear and helplessness May contribute to caregiver risk for Major Depressive Disorder and quality of life impairments (in aggregate with prevalence and frequency of other distressing events) Am J Geriatric Psychiatry. 2003; 11: 309 The Differential Diagnosis: What else could it be? Terminal Anguish Dementia Extrapyramidal symptoms (EPS) Multifocal myoclonus Terminal Anguish vs Delirium Terminal Anguish: Tormented state of mind Often after long-standing spiritual / psychological distress Usually no hallucinations Usually no delusions No impaired consciousness Can be attentive Guilt may be a prominent theme 7

8 Terminal Anguish vs Delirium Terminal Anguish rather than delirium should be suspected in the absence of hallucinations, delusions, or cognitive failure Highlights the need to make every effort to deal with spiritual and psychological distress before the patient deteriorates Dementia vs Delirium Dementia: Slowly progressive, chronic onset Short-term memory is lost Gradual loss of cognitive ability Sleep-wake cycles less impaired Less movement and vocalization problems Dementia vs Delirium Features Delirium Dementia Onset Acute Insidious over months to years Course Fluctuating Progressive Duration Days to weeks Months to years Consciousness Altered Clear Attention Impaired Normal except in severe dementia Psychomotor activity Increased or decreased Reversibility Sometimes Rarely Often normal 8

9 Delirium Risk Factors Elderly Renal failure Dehydration Dementia Poor pain control Opioids, steroids, anti-depressants Many other meds Cancer Delirium Risk Factors Patient with guilt and remorse Poor nutritional status History of drug/alcohol dependence History of post-traumatic stress disorder Veterans Domestic abuse or incest survivors Other tragedies Not in home setting Delirium: Case example Sharon is a 77 year old woman with colon cancer with liver metastases. She has been on hospice for a month, gradually eating less and becoming weaker to the point of being too weak to get out of bed. On a routine visit, her husband looks more tired than usual. When you mention this, he tells you that it was a strange night. While he was sleeping, Sharon had gotten up and taken clothes out of the closet. When he awoke in the morning, she was asleep on the floor and there were 3 mixed up outfits arranged on the bed. 9

10 Delirium: Differential Diagnosis Drugs (Side effects, O.D., withdrawal) Emotion (Mania, Anxiety, Depression), Encephalopathy, Environmental change, Electrolyte imbalance Low Oxygen or Hearing/Seeing (Ischemia, CHF, PE, COPD), Liver failure Infection, Intracranial event or metastasis Retention, Renal failure Intake (Malnutrition, Dehydration), Immobility, Impaction Uremia Metabolic (Thyroid, Organ Failure, Electrolytes, Calcium, SAIDH), Metastases to the brain Q: Which of the following medications can cause delirium? 1. Lorazepam 2. Hyoscyamine 3. Dexamethasone 4. All of the above 5. None of the above Pharmacologic Causes of Delirium Anticholinergics Opioids Benzodiazepines Corticosteroids Dopaminergic agonists Anticonvulsants Digoxin Other antiarrhythmics 10

11 What causes delirium? Medications the most common cause Opioids Corticosteroids Benzodiazepines Scopolamine Hyoscyamine Hydroxyzine Diphenhydramine Tricyclic antidepressants H2 blockers NSAIDs Metoclopramide Compazine Alcohol/drug withdrawal Delirium: Case example Sharon s abdominal and back pain have been gradually worsening. She had been maintained on MSContin 20mg three times a day. Due to increasing pain, this was recently increased to 40mg three times a day Drugs: Opioids Opioid toxicity the metabolites Morphine and hydromorphone (Dilaudid) have a toxic metabolite causes neuroexcitatory side effects Morphine and hydromorphone metabolites accumulate with any significant degree of renal impairment More common if dehydrated Treatment: Reduce by 25% or rotate opioids sometimes changing the opioid may improve the delirium 11

12 Other Drug-Related Deliriums Steroids Withdrawal of drugs Substance withdrawal Nicotine Alcohol Other illicit drugs Electrolytes Hyponatremia (low sodium) Hypo- or Hyperglycemia Hypercalcemia (Bones, Moans, Groans) Moans (Constipation) Groans (Abdominal pain nausea, vomiting) Eventually leads to delirium and coma Delirium: (things not in the acronym) The Psychological and Spiritual Unfinished business Spiritual distress Anxiety Fear of dying Burden of sins Inability to trust Guilt Control Issues 12

13 Q: Delirium is reversible in what percentage of cases? 1. ~50% 2. ~25% 3. ~10% 4. ~1% Delirium Management The First Step: Identification Delirium normally requires a thorough assessment and search for an underlying cause but in hospice patients... The etiology is multifactorial and may not be found in over 50% Even when found, it may not be reversible or treatable A diagnostic work-up may be limited by the setting (home) Our focus is on comfort and most diagnostic tests are burdensome Delirium: Case example Sharon is failing more rapidly. She has difficulty clearing her secretions and is started on a scopolamine patch. Over the next few days, Sharon becomes more agitated. She begins reaching out as if she is trying to catch invisible things in the air. She becomes paranoid, accusing her husband of giving me medication that is going to kill me What do you recommend to help her? 13

14 Agitation and Delirium: Management Social: Strong psychosocial support from the team A subdued, calm, safe environment Familiar environment A calm presence family is usually best Decrease stimulation Crowd control Reduce any sense of isolation Give the caregiver breaks Agitation and Delirium: Management Psychological: --Strong psychosocial support from the team Family education and support Aromatherapy Relaxation tapes Music therapy Counseling for the family (counseling for the patient is usually difficult at this stage) 14

15 Agitation and Delirium: Management Spiritual: Chaplain involvement Access resources Prayer Scripture reading Prepare family for imminent death Support and value this near death transition Q. Which of the following is an appropriate initial intervention for delirium? 1. Music during turns/personal care 2. Minimize ambient sound (alarms, bells, voice) 3. Aromatherapy such as lavender with bed bath 4. Spiritual interventions such as prayer, ritual, meditation 5. Cognitive behavioral therapy for PTSD 6. Engaging family or familiar people in care 7. All of the above Antipsychotics In Delirium The Cochrane Collaboration 2005 Review of drug therapy for delirium in terminally ill patients Multi-database search ( ) for prospective studies w/ or w/o randomization and/or blinding Of 13 studies only one met criteria: Breitbart W, et al: A double-blind trial of haloperidol, chlorpromazine and lorazepam in the treatment of delirium in hospitalized AIDS patients Further research essential 15

16 Antipsychotics In Delirium Methods: 30 patients with AIDS 3 arm blinded study using lorazepam, haloperidol or chlorpromazine Doses doubled At intervals Results: haloperidol & chlorpromazine effective; lorazepam worsened delirium Am J Psych 1996; 153(2): Antipsychotics In Delirium Antipsychotic Agent Chlorpromazine Haloperidol Sedation EPS Anticholinergic ++ + Orthostatic Hypotension = very high incidence, +++ = high incidence, ++ = moderate incidence, + = low incidence Drug Facts and Comparisons (Oct 2003) Antipsychotics In Delirium Choose based on level of behavior If need sedation, consider chlorpromazine If more hypoactive, consider haloperidol Titrate medication if initial dose is not effective Consider switching medication if: Lengthy treatment anticipated Lack of response despite increased dose Paradoxical response 16

17 Delirium: Case example Sharon is failing more rapidly. She has difficulty clearing her secretions and is started on a scopolamine patch. Over the next few days, Sharon becomes more agitated. She begins reaching out as if she is trying to catch invisible things in the air. She becomes paranoid, accusing her husband of giving me medication that is going to kill me What do you recommend to help her? Antipsychotics In Delirium Haloperidol (Haldol) Possible hypotension, prolongation of the QTc interval Possible adverse effects EPS/dystonic reactions Neuroleptic malignant syndrome Nursing homes unwilling to use. Bad reputation Q. What is NOT a first line medication for delirium? 1. Haloperidol 2. Chlorpromazine 3. Morphine 4. Risperidone 17

18 Antipsychotics In Delirium Haloperidol (Haldol) Considered the first-line drug of choice Breitbart, J of Clinical Oncology, (11): 1206 Antipsychotics In Delirium Haloperidol: mg po q6h prn for mild delirium mg po q6h prn for moderate/severe delirium In severe delirium, can be given every hour (PO, IM, IV) until controlled, then q 6 hours Titrate upward by mg every 6 hours Maximum dose can be >20mg/d Delirium: Case example Sharon is started on Haldol 0.5mg three times a day and 1mg at bedtime. For the next three days, she is calm during the day and sleeps through the night. 18

19 Antipsychotics In Delirium Ativan (Lorazepam) 0.5 mg to 2.0 mg (PO, SL) q 4-6 hours prn (Maximum typically 8 mg/d) liquid may be used sublingually or bucally in those patients who can not swallow Possible adverse effects -- MAY cause paradoxical agitation Delirium: Case example Sharon is becoming more agitated. There are now periods when she screams for hours at time. Last night, it took her husband and her 3 grown sons to hold her keep her from climbing out of bed. She is now getting Haldol 2mg SL every 6 hours and 5mg at bedtime Antipsychotics In Delirium Thorazine mg q 4 12 hours prn more sedating than Haldol PO bioavailability low and highly variable PR recommended if patient able/willing PO:PR:IV/IM = 4:2:1 More orthostatic hypotension than Haldol Risk of arrhythmias Prolongation of the QT interval 19

20 Delirium: Case example You decide to d/c the Haldol and start Thorazine. Sharon is started on 25-50mg q6h and mg at bedtime. Medications In Delirium Phenobarbitol VERY sedating medication In many cases does not cause excessive sedation Can cause paradoxical agitation Many drug interactions Decreases levels of benzos Can put patients on methadone into withdrawal Antipsychotics In Delirium Second-generation antipsychotics Risperidone (Risperdol) Least sedating in this class Most likely to cause orthostatic hypotension Starting dose mg q12h Olanzapine (Zyprexa) More sedating Starting dose mg q12h Quetiapine (Seroquel) Starting dose mg po q8h 20

21 Antipsychotics In Delirium Second generation antipsychotics CANNOT RAPIDLY TITRATE THE DOSE Possible adverse effects Diabetes Dyslipidemia Weight gain Premature death Mechanism unclear Antipsychotics: FDA Black Box Warning Antipsychotics in dementia: Both typical and atypical antipsychotics carry increased risk of death in people with dementia Sudden cardiac death Lipid abnormalities Palliative Benefits of Parental Hydration in Terminal Cancer Randomized control trial of 51 terminally ill cancer patients with dehydration 1000 mls/day versus 100 mls/day either IV of subcutaneous Examined for hallucinations, myoclonus, fatigue and sedation 73% of hydration patients versus 49% of placebo patients had improvement (p=0.005) Low burden May be palliative role for hydration in terminally ill cancer patients Bruera E et al. J Clin Oncol, 2005:23:

22 Delerium related to Dementia: Acetylcholinesterase Inhibitors donepezil, rivastigmine, galantamine, memantine 2008 Cochrane review: No evidence from controlled trials to support use of cholinesterase inhibitors in delirium The Cochrane Library 2009 Delirium: Case example Sharon has been on Thorazine 25-50mg q6h and mg at bedtime for the past week. She has been resting calmly. Although she is sleeping more of the day and night, she has periods of being lucid and interacting with her family. After four days of taking no fluid or nutrition, she quietly dies. Her family expresses their gratitude for all the care and support the hospice team provided. Agitation and Delirium: Summary The key is awareness and prevention Aggressive spiritual and psychological counseling for those at risk Try to keep the patient in familiar environment Use the least amount of medicine that achieves symptom relief Be alert to those at increased risk Be alert for early symptoms 22

23 Agitation and Delirium: Summary Delirium is very common near end of life Often misdiagnosed as depression or ignored Workup must be balanced against burdens, likelihood of reversal Treat readily reversible etiologies Very distressing for patients and family Intensive family support Agitation and Delirium: Summary Treat aggressively in all spheres of the patient s life (social, psychological, spiritual) Treat aggressively with antipsychotics For difficult cases, don t be afraid to manage aggressively More manageable if caught early! Course Evaluation & Post-Test Thank you for viewing this course on the Hospice Education Network. To conclude this course and to obtain a certificate of completion, you must finish the evaluation and post-test. 23

24 Delirium: Agitation and Restlessness at the End of Life Gail Gazelle, MD, FACP, FAAHPM Assistant Clinical Professor of Medicine, Harvard Medical School Hospice Medical Director Life and Career Coach 24