Transcript Diapositiva 1

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
• 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
Delirium subjective perception
Do you feel
confused
Not at all
Very 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)
• 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 recall depends on delirium severity
100
100
90
80
70
60
55
50
% of patients
recalling
40
30
20
16
10
0
severe
Breitbart et al 2002
moderate
mild
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
4
Average
distress
score
3,5
3
2,5
2
1,5
1
0,5
0
Patient
Spouse
Nurse
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 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
•
•
•
•
•
Reduce overall risk
Treat reversible causes (30-50% in pc)
Non pharmacological management
Family counselling
Drug therapy
A geriatric model of risk modification
• Orientation protocol
• Non pharmacological protocol for night
sleep management
• Mobilization
• Visual and auditory aids Inouye et al 1999
• Hydration
Reduction of delirium incidence
from 15 to 9 %.
in patients ≥ 70 years of age
Conscious states = wakefulness and sleep
• Cholinergic n.
(opioids)
Cortex
• Noradrenergic n.
(Clonidine)
Thalamus
• Histaminergic n.
(prometazine)
• Dopaminergic n.
(haloperidol)
• Serotonergic n.
(ssri)
• Gabaergic
(Benzodiazepine
propofol)
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
•
•
•
•
•
•
Haloperidol
Phenotiazine neuroleptics
Atypical neuroleptics
Anthistamine
Clonidine
Sedation - Benzodiazepines
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
Time
.1
. 2 thirty minutes
.3
.4
.5
.6
.7
.8
.9
. 10
. 11
. 12
Haloperidol
0.5 mg
0.5 mg
0.5 mg
1 mg
1 mg
1 mg
2 mg
2 mg
2 mg
5 mg
5 mg
5 mg
Akechi Supp Care Cancer 1996
Prospective study
Average dose 1st day = 6 +/- 4
Entire period = 5.4 +/- 3.4 mg
Other neuroleptics
Drug
dose
T/2 (hs)
Droperidol
Chlorpromazine
Promazine
Methotrimeprazine
1-10 mg
25-50 mg
25 mg
25-50 mg
2-3
16-30
15-30
16-78
Atypical neuroleptics
• Antagonism on the dopamine receptors
and serotonin receptors
D2 D4 etc
5HT2a
Drug
Daily dose
t/2 (hs)
Clozapine
25-100 mg
8
Olanzapine (also
injectable)
5-10 mg
30
Risperidone
0.5-2 mg
3-20
20-30*
Quetiapine
100-300 mg
3-6
Ziprasidone
120-160 os
15-60 im
7
Clinical experience
in delirium
-
Passik 1999
Sipahimalani 1998
Meehan 2002 (IM)
Breitbart 2002
Skrobik 2004
Ravona-Springer 1998
Sipahimalani 1997
Schwartz 2000
Torres 2001
Leso 2002
Lonergan et al Antipsychotics for delirium (Review) Cochrane database of
systematic reviews 2007, Issue 2. http://www.cochranelibrary.com
Olanzapine
– 82 cancer patients
assessed at 2-3 and 4-7
days
– Oral olanzapine
– Mean starting dose 3.0
mg (SD 0.14, range 2.510)
– Mean final dose 6.3 mg
(SD 0.5 range 2.5-20)
– 30% reported sedation
20
18
16
14
12
MDAS
score
10
8
6
4
2
0
T0
Breitbart W. Et al 2002 Psychosomatics
T1
T2
Predictors of response
• Logistic regression analysis - worse
response
OR
– Age > 70
– CNS spread
– Hypoactive delirium
– Hypoxia
– History of dementia
– Delirium severity
Breitbart et al 2002
171.5
74.9
11.3
5.9
0.34
5.03
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
• Lorazepam 2 mg IV or IM repeated after
15-30 minutes (IV)
• It is first choice in alcohol withdrawal
delirium
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
• 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
• 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
• Oversedation - hypoactive delirium
• Cognitive impairment
• Hyperactive delirium
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
• 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