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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
Delirium
  • Management
  • Therapy
  • Care
multiple factors and the role of opioids
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

d elirium subjective perception
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

the delirium experience breitbart et al psychosomatics 2002 43 183
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

delirium subjective distress
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
delirium and the family
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

delirium and the family1
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

therapeutic interventions
Therapeutic interventions
  • Reduce overall risk
  • Treat reversible causes (30-50% in pc)
  • Non pharmacological management
  • Family counselling
  • Drug therapy
a geriatric model of risk modification
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

conscious states wakefulness and sleep
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

evidences for pharmacological treatment are poor
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
drug therapy
Drug therapy
  • Haloperidol
  • Phenotiazine neuroleptics
  • Atypical neuroleptics
  • Anthistamine
  • Clonidine
  • Sedation - Benzodiazepines
haloperidol doses
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

haloperidol titration
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

other neuroleptics
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

atypical neuroleptics
Atypical neuroleptics
  • Antagonism on the dopamine receptors and serotonin receptors

D2 D4 etc

5HT2a

slide18

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

olanzapine
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

predictors of response
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

olanzapine1
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
benzodiazepine
Benzodiazepine
  • Lorazepam 2 mg IV or IM repeated after 15-30 minutes (IV)
  • It is first choice in alcohol withdrawal delirium
slide23

Effect not sufficient or contraindication to benzodiazepines

  • Prometazine 50 mg im, children 1-2 mg/kg (can be combined with haloperidol, benzodiazepine, opioid)
if sedation is primarily desired
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

slide25
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

opioid induced delirium
Opioid-induced delirium
  • Oversedation - hypoactive delirium
  • Cognitive impairment
  • Hyperactive delirium
opioid induced delirium1
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

conclusions
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