Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Seminar in Palliative Care September 26 – October 02, 2010 Salzburg, Austria in Collaboration with The EPEC-O TM Education in Palliative and End-of-life Care - Oncology Project The EPEC-O Curriculum is produced by the EPECTM Project with major funding provided by NCI, with supplemental funding provided by the Lance Armstrong Foundation. Delirium Frank D. Ferris, MD, FAAHPM Institute for Palliative Medicine at San Diego Hospice University of California San Diego University of Toronto The Butcher, Baker, and Candlestick Maker Return: Interdisciplinary Goal-Based Approaches to Delirium Recognition, Work-Up, and Management Scott A. Irwin, MD, PhD Director, Psychiatry Programs Rosene D. Pirrello, RPh Director, Pharmacy Jeremy M. Hirst, MD Assistant Director, Psychiatry Gary T. Buckholz, MD Director, Fellowship Program Frank D. ferris, MD, FAAHPM Director, International Programs © 2010 Key Topics… Definition Prevalence & consequences Many causes Assessment Common language History & exam Tools Under recognition Differential diagnoses Goals of care Diagnostic workup …Key Topics Management Non–pharmacological Pharmacological Reversible Irreversible Terminal Delirium Is... Change in mental status, impaired Attention Orientation Cognition Consciousness Reality Behavior American Psychiatric Association. (2000) Diagnostic and statistical manual of mental disorders. 943 . . . Delirium Is Develops quickly May fluctuate Underlying medical etiology NOT dementia American Psychiatric Association. (2000) Diagnostic and statistical manual of mental disorders. 943. Associated changes Day-night reversal Emotional states Non-specific neurological abnormalities Decline in functional ability Types Hyperactive Associated behavioral disturbances Hallucinations Delusional beliefs Hypoactive Quiet Mistaken for depression or fatigue Mixed – waxing and waning Delirium is Highly Prevalent and has Serious Consequences… Reported Prevalence Hospitalized elderly 14 – 56 % ICU 70 – 87 % Advanced cancer and / or end-of-life 25 – 85 % Consequences... 6 month mortality up to 25 % Increased mortality 10 – 78 % Prolonged hospitalizations …Consequences... Stress, discomfort, reduced quality of life Patients, nurses, family members Even if hypoactive Namba M, et al. (2007) Palliat Med 21: 587 Morita T, et al. (2007) J Pain Symptom Manage 34: 579 Cohen, MZ, et al. (2009) J Palliat Care 25:164 Bruera, E, et al. (2009) Cancer 15:2004 …Consequences 101 cancer patients who recovered from delirium, 54 % recalled experience Hypoactive delirium 43 % Hyperactive delirium 66 % Distress ( many reported severe ) Patients 3.2 out of 4 Spouses / caregivers 3.75 Nurses 3.09 Breitbart W, et al. (2002) Psychosomatics 43: 183 Video – Hypoactive Delirium Key points 1. Pathophysiology 2. Assessment 3. Management Delirium has Many, Many Causes… Many are Discoverable and Reversible… Medical Causes of Delirium Levenson JL, (2005) The American Psychiatric Publishing textbook of psychosomatic medicine See Appendix in Handout Medications Causing Delirium Levenson JL, (2005) The American Psychiatric Publishing textbook of psychosomatic medicine See Appendix in Handout Most Common Causes… Fluid imbalance Medications Infections Anticholinergics Hepatic / renal failure Benzodiazepines Hypoxia Opioids Steroids Hematological disturbance …Most Common Causes Hazard ratio of developing delirium ( 43 inpatients with cancer ) Benzodiazepines 2.04 if > 2 mg / day ( 1.05 – 3.97 ) Corticosteroids 2.67 if > 15 mg / day ( 1.18 – 6.03 ) Morphine equivalents 2.12 if > 90 mg / day ( 1.09 – 4.13 ) Gaudreau JD, et al. (2005) J Clin Oncol 23: 6712 Many Causes are Treatable... 237 hospice inpatients with cancer 213 ( 90 % ) had 245 episodes of delirium Causes found in 93 of the 153 who had a workup Multi-factorial in > 50 % Complete remission in 20 % Morita T, et al. (2001) J Pain Symptom Manage 22: 997 …Many Causes are Treatable 104 inpatients with advanced cancer receiving palliative care 71 had 94 episodes of delirium Reversible in 50 % Lawlor PG, et al. (2000) Arch Intern Med 160: 786 Delirium is Under–Recognized… Often Under–Recognized... 2716 hospice patients Delirium recognized in only 17.8 % of home care patients 28.3 % of inpatients Irwin SA, et al. (2008) Palliative and Supportive Care 6: 159 …Often Under–Recognized 107 end-stage cancer inpatients Delirium recognition rate : 44.9 % 20.5 % of hypoactive cases Fang CK, et al. (2008) Jpn J Clin Oncol 38: 56 Why Under–Recognized ? Complex presentation Inconsistent language Hypoactive sub-type Thought to be normal part of end-of-life Careful Assessment & Communication of Findings is Key to Successful Management of Delirium… Common Language is Essential… Assessment Clinical history, physical examination, observations over time Mental status exam Review of medication use Thorough medical and laboratory work-up to elucidate underlying cause History Context of the patient Symptoms Quality Severity Temporal profile Effect of treatments Assessment Tools… “ Gold Standard ” Experienced clinician DSM-IV criteria Three types of standardized tools 1. Screening 2. Diagnosis 3. Symptom severity Sensitivity 94 – 100 % Specificity 90 – 95 % Laurila JV, et al. (2002) Int J Geriatr Psychiatry 17: 1112 Inouye SK, et al. (1990) Ann Intern Med 113: 941 Differential Diagnoses to Consider… American Psychiatric Association. (2000) Diagnostic and statistical manual of mental disorders. 943 Differentiate Delirium From Dementia Psychotic disorders Depression Personality disorders Anxiety Developmental disorders Akathisia Dementia Slow decline in brain function > expected with normal aging May have Problems with memory, attention, language, emotions, & problem solving Confusion, hallucinations, delusions Delirium vs. Dementia Delirium Dementia Yes No Onset Hours to days Gradual Fluctuation Often No Change in alertness Depression Symptom, episode, recurrent disorder Major depression Several symptoms > 2 weeks duration Impaired function Delirium vs. Depression Delirium Depression Yes No Onset Hours to days Gradual Fluctuation Often No Change in alertness Potential Reversibility of Delirium Guides Work-up & Management… Potential Reversibility of Delirium Potentially Reversible Irreversible Patient is dying ( terminal delirium ) Goals of care Work–up / reversal unsuccessful Goals of Care Initial patient & family goals Goals can change Goals after diagnosis Diagnostic work-up vs. palliate Goals after work-up Reverse vs. palliate vs. irreversible Diagnostic Work-up May Include Chemistry Cardiac Hematology Infection Endocrine Toxicology Vitamin levels Imaging Delirium Management… Management Strategies… Ensure safety Address environment Manage based on potential reversibility & goals of care Adapted from APA Practice Guidelines 2004 American Psychiatric Association. (1999) Am J Psychiatry 156: 1 Cook IA. (2004) Available online at: http://wwwpsychorg/psych_pract/treatg/pg/prac_guidecfm …Management Strategies… Reverse Treat underlying causes Relieve Non-pharmacological Pharmacological Consult psychiatry …Management Strategies Treatment Benefits Risks Burdens Time-limited therapeutic trials Always Use Non-pharmacological Treatments… Non-Pharmacological Treatments Can Address Disordered thinking Risk of falls / injury Disorientation Dehydration Sleep disturbance Environmental factors Immobility Sensory deprivation Prevention of Delirium... 852 patients age > 70 admitted to medicine service Target Treatment Orientation Introduce care team / daily schedule each shift, oriented 1 – 3x / day Activity Cognitive stimulation 3x / day Mobility Ambulate / range of motion 3x / day Sleep Non-pharmacological sleep protocol Sensory aids Glasses, hearing aids Dehydration Rehydrate as needed …Prevention of Delirium In the treatment group Fewer episodes of delirium 62 vs. 90 ( 9.9 % vs. 15 %, p = 0.03 ) Shorter duration 105 vs. 161 days ( p = 0.02 ) Followup showed up to an 89 % reduction of risk of delirium Inouye SK, et al. (1999) N Engl J Med 340: 669 Inouye SK, et al. (2003) Arch Intern Med 163: 958 Use Pharmacological Treatments when Appropriate… & Appropriately… Pharmacological Management No medication is FDA approved for the treatment of delirium No published double-blind, randomized, placebo controlled trials No consensus among oncologists, geriatricians, psychiatrists, or palliative medicine specialists Agar M, et al. (2008) Palliat Med 22: 633 Delirium Management Decision Tree Context & Reasonable Goals of Care Potentially Reversible Irreversible Hyperactive Hypoactive Hyperactive Hypoactive Medical Rx Medical Rx Medical Rx Medical Rx Successful Unsuccessful Potentially Reversible, Hyperactive Context & Reasonable Goals of Care Potentially Reversible Hyperactive Reverse Cause Antipsychotics Antipsychotic Indications Indication Drug Anti Muscle Sedation Amnesia agitation relaxation Anti convulsant Haloperidol Chlorpromazine Risperidone Olanzapine Quetiapine 1st Line Pharmacological Treatment Double-blind RCT of 30 AIDS patients Haloperidol 0.4 ‒ 3.6 mg daily, n = 11 vs Chlorpromazine 10 ‒ 80 mg daily, n = 13 vs Lorazepam 0.5 - 10 mg daily, n = 6 Haloperidol = chlorpromazine >> lorazepam Haloperidol & chlorpromazine minimal side effects Lorazepam stopped early due to adverse events Breitbart W, et al. (1996) Am J Psychiatry 153: 231 PEARL Use 1st generation antipsychotics Do Not Use Benzodiazepines Not first-line treatment Increase confusion, disinhibition, falls Necessary for alcohol or sedative withdrawal APA Practice Guidelines 2004 American Psychiatric Association. (1999) Am J Psychiatry 156: 1. Cook IA. (2004) Available online at: http://wwwpsychorg/psych_pract/treatg/pg/prac_guidecfm Application of Pharmacological Principles Improves Management… Plasma Concentration Anti-psychotic Pharmacokinetic Guidelines Cmax SC / IM 30 min Cmax PO / PR 60 min t1/2 24 hrs 0 Half-life ( t1/2 ) Time Sample Orders… For Agitation Haloperidol – 1 mg SC q 30 min PRN If 3 doses not effective, call MD Do not exceed 100 mg in 24 hr Schedule today’s PRNs tomorrow 1 or 2 x / day + same PRN schedule Chlorpromazine – 50 mg SC q 30 min PRN If 3 doses not effective, call MD Do not exceed 2000 mg in 24 hr Schedule today’s PRNs tomorrow 1 or 2 x / day + same PRN schedule …Pharmacological Management Haloperidol = Olanzapine & Risperidone 1. Haloperidol 1 - 28 mg daily, n = 45 vs Olanzapine 2.5 - 13.5 mg daily, n = 28 2. Haloperidol 1.5 - 10 mg daily, n = 11vs Olanzapine 5 - 15 mg daily, n = 11 3. Haloperidol 1 - 3 mg daily, n = 12 vs Risperidone 0.5 - 2 mg daily, n = 12 PEARL Treat agitation like a breakthrough symptom, e.g., pain Provide breakthrough ( PRN ) doses on the Time to maximum concentration ( TCmax ) If 3 doses not effective, call MD ( time-limited trials ) Provide routine doses once every Half-life ( t½ ) Management of Severe Agitation… When is Agitation an Emergency ? Aggression to property, hostile verbal behavior Irritability, intimidation Mood lability, loud speech Motor restlessness, purposeless movements Uncooperative, intense staring Allen et al. Treatment of Behavioral Emergencies Expert Consensus, 2001 Hierarchy of Treatments Seclusion and / or Restraint Emergency Medication Show of Force Voluntary Medication Verbal Intervention Needs Check e.g., food, water, pain, etc. Severe Agitation... If imminent risk of harm to self or others Haloperidol 2 - 5 mg + Diphenhydramine* 50 - 100 mg x 1 ( protects against EPS & adds sedation ) ± Lorazepam 1 - 2 mg ( or Midazolam ) In same syringe, mix very slowly in order Lorazepam Haloperidol Diphenhydramine …Severe Agitation – Alternatives… Chlorpromazine 50 - 100 mg SC Increase dose by 50 mg once every Time to Maximum Concentration ( tCmax ) until controlled Up to 2 gm / day If SC administration painful, e.g., burning, consider IV infusion with dexamethasone Likely don’t need diphenhydramine ± Lorazepam …Severe Agitation - Alternatives Olanzapine 5 - 10 mg IM May repeat x 1 in 2 hr May repeat x 1 again 4 hr later Up to 30 mg / day ( Expensive ) Ziprasidone 10 - 20 mg IM May repeat 10 mg every 2 hr May repeat 20 mg every 4 hr Up to 40 mg / day ( Expensive ) Antipsychotics – Black Box Warnings Drug Increased Suicidal Mortality in Ideation in Warning DementiaChildren, related Adolescents, Psychosis Young adults Post injection Delirium Sedation Syndrome Haloperidol Chlorpromazine Risperidone Olanzapine Quetiapine Antipsychotics – Sudden Cardiac Death Agent(s) 1st Generation Dose in Incidence-Rate CPZ equiv Ratio Low < 100 mg Moderate 100–299 mg High > 300 mg 2nd Generation Incidence-Rate Ratio 1.31 1.59 2.01 2.13 2.42 2.86 P values significant for dose-response relationship P value not significant for 1st vs. 2nd generation risk NEJM 2009; 360 : 225 - 35 Potentially Reversible, Hypoactive Context & Reasonable Goals of Care Potentially Reversible Hypoactive Reverse Cause ? Delirium Management Decision Tree Context & Reasonable Goals of Care Potentially Reversible Irreversible Hyperactive Hypoactive Hyperactive Hypoactive Medical Rx Medical Rx Medical Rx Medical Rx Successful Unsuccessful Terminal Delirium Delirium during dying process Prospective, irreversible Altered level of consciousness Oliguria / anuria Tachycardia Cyanosis Abnormal breathing patterns Peripheral cooling Loss of swallow / gag Oral / tracheal secretions Loss of sphincter control Venous pooling / mottling Two Roads to Death Confused Tremulous Restless DIFFICULT ROAD ( Hyperactive ) Hallucinations Normal Mumbling Delirium Sleepy Myoclonic Jerks Lethargic USUAL ROAD ( Hypoactive ) Seizures Obtunded Semicomatose Comatose Dead Irreversible Terminal, Hyperactive Signs of Active Dying Irreversible Hyperactive Support Benzodiazepines, Barbiturates, Propofol Benzodiazepine Indications Indication Drug Anti Muscle Sedation Amnesia agitation relaxation Anti convulsant Lorazepam Midazolam / Antipsychotics Opioids Sample Orders to Control Agitation… Lorazepam PO / Buccal Mucosa Starting dose = 1 mg PO / Buccal q 1 h PRN If 3 doses not effective, call MD Up to 40 mg in 24 hr Schedule today’s PRNs tomorrow q 8 h + PRN doses q 1 h …Sample Orders to Control Agitation… Midazolam SC Loading dose = 0.2 mg / kg then 0.1 mg / kg q 30 min x 2 PRN Maintenance dose / hr = 25 % total dose to sedate Consider alternative if need > 10 mg / hr …Sample Orders to Control Agitation… Propofol IV Starting dose = 1 mg / kg / hr Increase by 0.5 mg / kg / hr increments every 15 – 30 min PRN Maximum for EOL = 6 mg / kg / hr …Sample Orders to Control Agitation Phenobarbital IV or SC Loading dose = 10 mg / kg May repeat x 2 within 2 – 3 hrs Continuous infusion 10 – 20 mg / hr Titrate PRN Maintenance = 600 – 2400 mg / 24 hr PEARL Treat agitation like a breakthrough symptom, e.g., pain Provide breakthrough ( PRN ) doses on the Time to maximum concentration ( TCmax ) If 3 doses not effective, call MD ( time-limited trials ) Provide routine doses once every Half-life ( t½ ) Benzodiazepines Lethal Doses Lorazepam LD 50 = 5,000 mg Midazolam LD 50 = 10,000 mg Don’t worry about Amnesia, confusion, restlessness Hypotension Respiratory depression Irreversible, Hyperactive Goals of Care or Work-up / Treatment Unsuccessful Irreversible Hyperactive Support Antipsychotics, Benzodiazepines, Barbiturates, Propofol Irreversible, Hypoactive Goals of Care or Work-up / Treatment Unsuccessful Irreversible Hypoactive Support ? Mental Health Experts Can Help Diagnoses often complex Clinicians unfamiliar with non-pharmacological treatments Clinicians often uncomfortable with pharmacological treatments, especially off-label use Develop new treatments Key Topics… Definition Prevalence & consequences Many causes Assessment Common language History & exam Tools Under recognition Differential diagnoses Goals of care Diagnostic workup …Key Topics Management Non–pharmacological Pharmacological Reversible Irreversible Terminal Summary Cases can be complex Clinicians often unfamiliar with all possible treatments Complex cases stressful