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Interferes with symptom assessment and control Untreated Delirium can progress into dementia or worsen
pre-morbid cognitive disorders
Subtypes of Delirium
Delirium is a disturbance of arousal and cognition.
Subtypes of delirium are based on the type of motoric or arousal disturbance: Hyperactive
Hypoactive
Mixed
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Subtypes of Delirium
In 12 studies, the prevalence of each of the subtypes of delirium has varied widely A meta-analysis of these studies suggest the following average prevalence for each subtype:
Hypoactive: 48% (ranges: 15-71%) Hyperactive: 24% (ranges: 13-46%) Mixed: 36% (ranges: 11-55%)
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Breitbart, et al, Psychosomatics, 2002 ; DiMartini, et al. 2007; Cohen et al, 2009
Hallucinations: (MDAS# 7)
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70% 51%
Boettger, Passik, Breitbart, Pall Supp Care, 2012 E pub ahead of print
Delirium is reversible
Terminal Delirium
Delirium is irreversible
Indirect (contd) Treatment side effects from Chemotherapeutic agents, steroids, biological response modifiers Radiation Opioids Anticholinergics Antiemetics Infection Hematologic abnormalities Nutritional deficiencies Paraneoplastic syndromes
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Minimize Use of immobilizing catheters, IV lines, physical restraints Monitor closely for dehydration Monitor fluid and electrolyte balance Monitor Nutrition Control pain Minimize medications facilitate sleep hygiene Re-orient frequently Inouye S, NEJM 2000
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Non-Pharmacological Multi-component Prevention Programs for Delirium in Medical Settings Use of Non-Pharmacologic interventions in the prevention of delirium can reduce incidence in non-terminally ill. They all include elimination of medications These interventions can result in faster improvement of delirium and cognition but no change in mortality risk after delirium
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0.5-5 q2-12h 10-75 q4-8h 12.5-50 q4-12h 12.5-50 q4-8h 0.5-5 q12h 10-50 q8-12h
Quetiapine
Ziprasidone Aripiprazolee
25-150 q12h
20-80 q12h 10-15 qd
PO
PO/IM PO
10-50 q1h
IV
Cancer Patients
William Breitbart,M.D. Annie Tremblay, M.D. Christopher Gibson, Ph.D. Memorial Sloan-Kettering Cancer Center
Under 50
51-60
61-70
Over 70
X2= 22.8 p .001
Hypoactive Hyperactive
Baseline
Time 1
Time 2
F= 9.51 p .003
Olanzapine Dosage
Mean olanzapine dosage:
Baseline : 3.0 mgs (SD=0.14) range = 2.5 to 10 mgs
T2 (day2-3):
T3 (day4-7):
4 Double or single blind RCTS of Atypical antipsychotics in ICU or post-operative settings. Girard et al (2010)- haloperidol vs ziprasidone in ICU. Bothe effective for delirium, no differences in adverse effects Devlin , et al (2010)- quetiapine plus prn haloperidol vs placebo, demonstrated benefit, but more somnolence Tahir, et al (2010)- quetiapine vs placebo. Quetiapine group responded 82% faster. No differences in adverse effects. Grover, et al (2011)- single blind, haloperidol vs risperidone, vs olanzapine. All improved delirium, no differences between drugs
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QT Interval Prolongation Torsade des Pointes QTc prolongation beyond 500msec ECG should be monitored daily during delirium RX Consider interactions with other agents that prolong QT
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Atypical antipsychotic drugs , pre- 2005,carry warnings for : increased risk of stroke or CV events; increased risk of death from stroke; Prolonged QTc interval with risk of fatal cardiac arrhythmias; Association with hyperglycemia and onset of diabetes, ketoacidosis, coma and death
Prolonged QTc interval and cardiac deaths also black boxed with
haloperidol. Wang et al NEJM 2005
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Int Psychogeriatr. 2009 Jun;21(3):588-92. Epub 2009 Apr 16. 326 elderly hospitalized patients were identified with delirium at an acute care community hospital. In elderly medical inpatients with delirium, administration of APs was not associated with a statistically significant increased risk of mortality
Short-Term Use of Atypical Antipsychotics in the Medically Ill: Assessment of Adverse Metabolic Effects and QTc Prolongation
Yesne Alici-Evcimen, MD*, Chris Nelson, PhD**, William Breitbart, MD **
*University of Pennsylvania, Department of Psychiatry, Section on Geriatric Psychiatry **Memorial Sloan-Kettering Cancer Center, Department of Psychiatry and Behavioral Sciences8
PSYCHOSOMATICS, in Press
No significant change in fasting blood sugar, body weight for any atypical or for olanzapine specifically No significant change in QTc interval between baseline and end
of treatment within 30 days
International Palliative Care Network Lecture Series 2012
Evidence Based Recommendations on Delirium Management in Cancer I - Breitbart & Alici, JCO 2012
Current evidence is supportive of short-term use of antipsychotics in the treatment of symptoms of delirium with close monitoring for possible adverse effects especially in elderly patients with multiple medical comorbidities. The longest clinical and research experience and safety/efficacy data available is for haloperidol. Low-dose haloperidol is still considered the gold standard in treatment of delirium. There is growing evidence for the efficacy of atypical antipsychotics in the management of delirium as well. The choice of antipsychotic medication for the treatment of delirium should be based on the clinical presentation of the patient and the adverse effect profile of each antipsychotic drug, given that none of the antipsychotics were found to be superior to others in comparison trials
Evidence Based Recommendations on Delirium Management in Cancer II - Breitbart & Alici, JCO 2012
II. It is strongly recommended to implement nonpharmacologic interventions in the routine care of patients who are at risk for delirium and of patients with established delirium, based on the evidence from non-oncology settings. There are no known risks associated with the use of nonpharmacologic interventions. III. There is no evidence to support the use of cholinesterase inhibitors in treatment or prevention of delirium in patients with cancer. IV. Psychostimulants cannot currently be recommended in the treatment of patients with cancer with delirium. V. Current evidence is not supportive of the use of antipsychotics for the prevention of delirium in patients with cancer. VI. The evidence supporting the use of intravenous dexmedetomidine for the prevention of delirium has been mixed and is limited to patients in intensive care settings only; there is currently no evidence to support its use in patients with cancer as a treatment for delirium.
Conclusions
Palliative Care practitioners must be familiar with the proper assessment,
diagnosis, and management of delirium.
Antipsychotic use in delirium is generally time limited and brief . New evidence
suggests low incidence of many adverse effects when use is limited to 30 days or less
Monitoring QTc interval and EPS is necessary Non-pharmacologic interventions should be optimized
Acknowledgements
Dr. Breitbarts research work has been supported over the last 25 years by grants from the National Cancer Institute, the National Institute of Mental Health, the National Institute of Nursing Research, the National Center for Complementary and Alternative Medicine, Project on Death in America-Open Society Institute, the Fetzer Foundation, the Kohlberg Foundation, the Kornfeld Foundation, and the American Cancer Society
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