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Delirium

Delirium. Management Therapy Care. Multiple factors and the role of opioids. Pain due to bone metastases, poor pain control Fentanyl TTS 300 ug Slight change in cognition MRI negative Morphine IV 400 mg/day good pain control

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Delirium

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  1. Delirium • Management • Therapy • Care

  2. Multiple factors and the role of opioids • Pain due to bone metastases, poor pain control • Fentanyl TTS 300 ug • Slight change in cognition MRI negative • Morphine IV 400 mg/day good pain control • Acute delirium with high fever haloperidol 12 mg/day lorazepam 12 mg/day. Full recovery • Chronic cognitive change persists repeated MRI shows meningeal metastases Gaudreau JD et al Cancer 2007; 109:2365-2373 and J Clin Oncol 2005; 23: 6712-6718

  3. Delirium subjective perception Do you feelNot at all Very confused confused Delirious 21 11 Not delirious 14 5 Bosisio, Borreani, Grassi, Caraceni Rivista Italiana di Cure Palliative vol. 4, n 1/2002

  4. The delirium experience (Breitbart et al Psychosomatics 2002; 43: 183) • 101 consecutive patients who recovered from delirium • MDAS • 53% could recall the episode • Delirium experience questionnaire • Distress level over 4 grades Crammer JL Br J Psychiatry 2002, 18: 71-75

  5. Delirium recall depends on delirium severity Breitbart et al 2002

  6. Delirium subjective distress • 80% of patients report from moderate to severe distress • Distress predictors • Pt = perceptual disturances and delusions • Spouse = performance • Nurse = D. severity and and perceptual disturbances

  7. Delirium and the family • High levels of distress in spouse and caregivers create anxiety also in the long term • How can we help ? Susan B 2003; Breitbart W 2002; Morita 2004; Morita 2007; Buss M 2007

  8. Delirium and the family • Respect for the patient’s subjective perceptions and experiences, • Coordination of care to enhance communication, • Improving communication to explain the reasons for delirium and its course. • A care giver being with the patient was associated with lower family emotional distress Morita et al JPSM 2007

  9. Therapeutic interventions • Reduce overall risk • Treat reversible causes (30-50% in pc) • Non pharmacological management • Family counselling • Drug therapy

  10. A geriatric model of risk modification • Orientation protocol • Non pharmacological protocol for night sleep management • Mobilization • Visual and auditory aids • Hydration Inouye et al 1999 Reduction of delirium incidence from 15 to 9 %. in patients ≥ 70 years of age

  11. Conscious states = wakefulness and sleep • Cholinergic n. (opioids) • Noradrenergic n. (Clonidine) • Histaminergic n. (prometazine) • Dopaminergic n. (haloperidol) • Serotonergic n. (ssri) • Gabaergic (Benzodiazepine propofol) Cortex Thalamus

  12. Evidences for pharmacological treatment are poor • Lonergan E Cochrane review 2007 • Lonergan E Cochrane review 2009 • Seitz D J Clin Psychiatry 2007 • Lacasse H Ann Pharmacother 2006 • Jackson Cochrane review 2004

  13. Drug therapy • Haloperidol • Phenotiazine neuroleptics • Atypical neuroleptics • Anthistamine • Clonidine • Sedation - Benzodiazepines

  14. Haloperidol doses Low doses 2.5 mg/24 hs 61% Intermediate 15 mg/24 hs 32% High 30 mg/24 hs 7% Olofson et al Supp Care Cancer Retrospective study 1996

  15. Haloperidol titration Time Haloperidol . 1 0.5 mg . 2 thirty minutes 0.5 mg . 3 0.5 mg . 4 1 mg . 5 1 mg . 6 1 mg . 7 2 mg . 8 2 mg . 9 2 mg . 10 5 mg . 11 5 mg . 12 5 mg Average dose 1st day = 6 +/- 4 Entire period = 5.4 +/- 3.4 mg Akechi Supp Care Cancer 1996 Prospective study

  16. Other neuroleptics Drug dose T/2 (hs) Droperidol 1-10 mg 2-3 Chlorpromazine 25-50 mg 16-30 Promazine 25 mg 15-30 Methotrimeprazine 25-50 mg 16-78

  17. Atypical neuroleptics • Antagonism on the dopamine receptors and serotonin receptors D2 D4 etc 5HT2a

  18. Lonergan et al Antipsychotics for delirium (Review) Cochrane database of systematic reviews 2007, Issue 2. http://www.cochranelibrary.com

  19. Olanzapine • 82 cancer patients assessed at 2-3 and 4-7 days • Oral olanzapine • Mean starting dose 3.0 mg (SD 0.14, range 2.5-10) • Mean final dose 6.3 mg (SD 0.5 range 2.5-20) • 30% reported sedation Breitbart W. Et al 2002 Psychosomatics

  20. Predictors of response • Logistic regression analysis - worse response OR • Age > 70 171.5 • CNS spread 74.9 • Hypoactive delirium 11.3 • Hypoxia 5.9 • History of dementia 0.34 • Delirium severity 5.03 Breitbart et al 2002

  21. Olanzapine • Skrobik Y.K. et al Intensive Care Med 2004 • ICU patients Delirium Index (5 day assessment) • 45 haloperidol vs 28 olanzapine orally • Mean daily dose olanzapine 4.54 mg, range (2.5-13) haloperidol 6.5 mg, range 1-28

  22. Benzodiazepine • Lorazepam 2 mg IV or IM repeated after 15-30 minutes (IV) • It is first choice in alcohol withdrawal delirium

  23. Effect not sufficient or contraindication to benzodiazepines • Prometazine 50 mg im, children 1-2 mg/kg (can be combined with haloperidol, benzodiazepine, opioid)

  24. If sedation is primarily desired • Lorazepam os, im, ev • 0.5-2 mg, children 0.1 mg/kg q 1-2h, to effect • Midazolam • 5-15 mg sq /im/ev, children 0.1-0.15 mg/kg, than infusion iv/sq 0.1- 0.6 mg/kg/h; Effect not sufficient or contraindication to benzodiazepines

  25. clonidine: • orally 1-5 mcg/kg q8h, or 0.1mg q 8-24 h, (titration every 24 h to maximum 0.6 mg/day) • iv infusion 0.1- 2 mcg/kg/h • iv occasional dose 2mcg/kg Pandharipande et al JAMA 2008; 298: 2644-2653

  26. Opioid-induced delirium • Oversedation - hypoactive delirium • Cognitive impairment • Hyperactive delirium

  27. Opioid-induced delirium • Dose reduction (Caraceni et al JPSM 1994) • Switch opioid (Maddocks et al JPSM 1996) • Switch route (parenteral spinal ?) • Haloperidol • Psychostimulants, (Modafinil ?) • Donepezil (Slatkin 2001, Bruera JPSM 2003) Gaudreau JD et al Cancer 2007; 109:2365-2373 and J Clin Oncol 2005; 23: 6712-6718

  28. Conclusions • Palliative care should develop more the subjective and family related areas of delirium research • Intervention strategies are still based on very limited scientific evidences • Prevention of delirium in PC • Opioid-related deliria

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