Delirium in cancer palliative care

1
Delirium in cancer palliative care
Augusto Caraceni
Chief of Palliative Care, Pain
Therapy Rehabilitation Fondazione IRCCS National
Cancer Institute Milan, Italy
2
In the beginning

• 29 April 1965 to Dr RobertTwycross
• .... I hope we will continue to reduce this
  figure when we have St Christophers and when we
  learn more about the relief of mental suf fering
  and confusion, which as you see remain the big
  problem
• 16 August 1976 To Prof. Exton Smith
• the confusion which many patients experience
  we agreed that, all too often, this is and
  remains somewhat of a mistery

David Clark Cicely Saunders Founder of the
Hospice movement selected letters
1959-1999 Oxford University Press 2002
3
A problem of definition ?

• Ippocrates frenitis
• Celsus (25 b.C 50 a.C.) and then Areteus from
  Cappadocia delirium
• Greiner 1817 Verdunkelung des Bewusstseins
  (Obnubilation of consciousness)
• Chaslin 1895 La confusion mental primitive
• Lipowski 1990

4
Lipowski and the modern concept

• Delirium is a transient organic mental syndrome
  of acute onset, characterized by global
  impairment of cognitive functions, a reduced
  level of consciousness, attentional
  abnormalities, increased or decreased psychomotor
  activity, and a disordered sleep-wake cycle

Lipowski Z.J. Delirium acute confusional states
OUP 1990
5
Delirium DSM IV diagnostic criteria

• Disturbance of consciousness (i.e reduced clarity
  of awareness of the environment) with reduced
  ability to focus, sustain and shift attention
• Change in cognition or the development of
  perceptual disturbances
• Develops in hours to days and fluctuates
• Is caused by the direct physiological consequence
  of a general medical condition

Diagnostic and statistical manual of mental
disorders (DSM) IV TR APA 2000
6
Consciousness (awareness of self and environment)
as a filter controlling the quality and quantity
of stimuli reaching consciousness
taste
smell
touch
sound
sight
Environment
pain
memories
Body
Unconscious
breathing
hopes
body position sense
fears
hunger
From Averil Stedeford in Bates TD (Ed)
Contemporary Palliation of Difficult Symptoms
Ballieres and Tindall,
London 1987, Br J Hosp Med 1978 20 (6)
694-698, 703-704
7
Consciousness and attention

• We are always conscious of something. The ability
  of the brain to have different levels of
  awareness of stimuli and experience is dependent
  on attention which can be viewed as the gateway
  to awareness

8
Pathogenesis, the ascending reticular activating
system Moruzzi and Magoun 1949
Reproduced from Magoun 1952
9
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
10
Pathological states of consciousness
Clinical condition Wakefulness Awareness
Coma Absent Absent
Vegetative state Present Absent
Delirium Abnormal Abnormal
11
Epidemiology of delirium comparing oncology with
palliative care with elderly populations
Population Authors Prevalence Incidence
70 Francis (1990) 16.0 06.0
65 Levfkoff (1992) 10.5 31.3
70 Inouye (1993) 25.0
70 Inouye (1996) 18.0
Oncology Ljubisavjevic (2003) 18.0
Oncology Gaudreau (2005) 16.5
Hospice Minagawa (1999) 28.0
PC Unit Lawlor(2000) 42.0 45.0
Homecare Caraceni(2000) 28.0 -
Dying patient Massie et al.(1983) 85
From Caraceni Simonetti The Lancet Oncology In
Press
12
Differential diagnosis
Clinical Aspect DELIRIUM DEMENZA ACUTE PSYCHOSIS
onset acute insidious acute
24 hour course fluctuating stable stable
Level of consciousness reduced spared spared
Attention abnormal Initially spared Can be abnormal
Cognitive functions abnormal abnormal Can be compromised
Hallucinations Often visual Usually absent Usually auditory
Delusions Poorly organized impersistent Often absent Complex and persistent
Psychomotor activity Increased, reduced, mixed, fluctuating Normal Variable with bizzarre behaviour
Involuntary movements asterixis, myoclonus or tremors Usually absent Absent
EEG abnormal abnormal normal
13
Prodromal symptoms and signs
Insomnia Vivid dreams , nightmeres Agitation Irrit
ability Distractability Ipersensitivity to
sounds, lights Anxiety/depression
Concentration difficulties Difficulties in
marshalling own thought Unusual
behaviours Behaviour changes Hypo hyperactivity
14
Clinical assessment

• Assessement of the level of consciousness
• Assessment of cognitive functions
• Hallucinations
• Delusions
• Incoherent thought
• Written and spoken language
• Neurologic signs

15
Should specific delirium scales be used routinely
in palliative care?

• Diagnostic instruments
• CAM (Confusion Assessment Method)
  Inouye et al Ann Int Medicine 1999, Ryan et al
  Pall Med 2009)
• Delirium symptom interview
  (Albert et al , J Geriatr Psych
  Neurol 1992)
• Nursing delirium screening scale
  (Gaudreau et al J Pain Sympt Manage 2005)
• Descriptive, assessing severity, specific
• DRS , MDAS
• Non specific of delirium but assessing cognitive
  functions in general
• MMSE

16
Screening for delirium

• In the MMSE 4 items over 20 are sufficient to
  screen for delirium
• Orientation to year
• Orientation to date
• backward spelling
• copy design

• NUDESC
• Disorientation
• Behaviour
• Communication
• Illusion Hallucination
• Psychomotor

Fayers PM et al J Pain Sympt Manage 2005 30
41-50
Gaudreau et al. The nursing delirium screening
scale J Pain Sympt Manage 2005 29 368-375
17
Delirium scales

1. DRS and DRS-revised-98 (Trzepacz et al 1988,
   2001)
2. Memorial delirium assessment scale (Breitbart et
   al 1997)
3. Confusional state evaluation (Robertson et al
   1997)
4. Cognitive test for delirium (ICU) (Hart et al
   1996)
5. Delirium Index (Mc Cusker et al 1998)
6. Delirium writing test (Aakerlund and Rosenberg
   1994)
7. Communication capacity scale and Agitation
   distress scale (Morita et al 2001) (Morita JPSM,
   2003 26 827-834)
8. Delirium assessment scale (OKeefe et al 1994)
9. Intensive care delirium screening checklist
   (Dubois et al 2001)
10. Delirium severity scale (Bettin et al 1998)

From Caraceni A and Grassi L, Delirium acute
confusional states in palliative medicine OUP
2003
18
Temporal onset 0-3 Perceptual disturbances 0-3 Ha
llucinations type 0-3 Delusions 0-3 Psychomotor
behavior 0-3 Cognitive status 0-4 Physical
disorder 0-2 Sleep wake cycle dist. 0-4 Lability
of mood 0-3 Variability of symptoms 0-4
max 32
DELIRIUMRATING SCALE
Trzepacz P Psych Res 1987 J Neuropsychiatry Clin
Neurosci 2001 13 229-242
19
Level of consciousness 0-3 Disorientation 0-3 Sho
rt term memory 0-3 Digit span 0-3 Attention 0-
3 Thought 0-3 Perceptual disturbances 0-3 Delusi
ons 0-3 Psychomotor activity 0-3 Sleep-wake
cycle dist. 0-3 Max 30
MEMORIAL DELIRIUM ASSESSMENTSCALE
Breitbart et al JPSM, 1997

20
Writing abnormalities
Macleod Whitehead Palliative Medicine 1997
11 127
Tremors
Perseveration
21
Writing abormalities
22
Causes of delirium in cancer patients
Structural Brain metastases Meningeal
metastases Non cancer related (vascular,
infectious) Non structural Metabolic
encephalopathy Systemic Infectio Hematologi
c disorders (DIC) Nutritional Toxicity of
chemotherapy or radiation therapy Toxicity of
other drugs Paraneoplastic neurologic
syndromes Alcohol and drug withdrawal
23
Seizures

• It is possible that seizures present with
  clinical features which overlap with delirium

24
Delirium EEG slowing
Non convulsive status epilepticus
25
Structural causes of delirium in cancer patients
1
2
3
4
5
26
Screening of causes
Toxic drug screening and history Sepsis
Temperature, coltures, leucocyte,
PCR Glucose oxydative blood gases
metabolism Electrolytes Na, K, Mg, Ca,
Cl Renal function Uremia, Creatinine cl. Liver
function Ammonio Cofactor deficiency B1,
B12 Tyroid (endocrine) T3, T4, TSH, others
? Epilepsy EEG Paraneoplastic syndrome
Specific autoantiboides
27
Pathogenesis-etiology

• Multiple factors are almost always identified
• Drug toxicity and concurrent or predisponsing
  factors (the soil concept)

28
Risk factors in cancer patients at multivariate
analysis

• Age
• Previous cognitive failure
• Severity of associated illness
• Functional impairment
• Renal function
• Metabolic abnormalities
• Low albumin

• Bone metastases
• Liver metastases
• History of delirium
• Metastasis to CNS
• Opiods
• Benzodiazepines
• Fever infection

Caraceni Simonetti Lancet Oncology IN PRESS
29
A multifactor model

• Risk factors
• Vision impairment
• Severity of illness
• Cognitive impairment
• BUN/creatinine ratio

• Precipitating factors
• Physical restrains
• Malnutrition
• gt 3 medications
• Bladder catheter
• Any iatrogenic event

Inouye and Charpentier JAMA 1996
30
(No Transcript)
31
Multifactor model with baseline vulnerability and
precipitating factors
High vulnerability
Noxious insult
Less noxious insult
Low vulnerability
Inouye and Chapentier JAMA 1996
32
Precipitating factors in 40 reversible episodes

• Factor Prob. Poss. Total
• Opioids 35 3 38
• Psy. Drugs 8 5 13
• Dehydration 18 8 26
• Nonresp. Infection 10 2 12
• Alcohol withdrawal 2 2 4
• Intracranial cause 3 0 3
• Hypoxia 12 1 13
• Metabolic 5 6 11
• Hematologic 4 1 5
• Totals 98 28 126

Lawlor et al Arch Int Med 2000
33
Precipitating factors and reversibility in PC
Type of factor Reversed Non rev. Hazard r.
(95 C.I.) Psychoactive d. 38 (95) 15 (48)
6.65 (1.5-29) Dehydration 26 (65) 8
(26) 1.5 (.7-3.2) Hypoxia 11 (28) 22
(71) 0.32 (.15-.7) Miscellaneous 7 (18) 7
(23) Nonresp. Infection 10 (25) 8
(26) Metabolic 10 (25) 18 (58) Hematologic 5
(13) 7 (23)
Lawlor P. et al 2000 Arch Int Med
34
Delirium reversibility in hospice
Total 121 Cases reversible irreversible
33 (27) 88 (73) survival 39/- 69 16
/- 10 organ failure attention
vigilance
Leonard et al Pall Med 2008 22 848-854
35
Delirium and prognosis

• Delirium is independently associated with reduced
  survival at 12 month (McCusker 2002)
• In advanced cancer patients it is independently
  associated with worse prognosis to 30 days
  (Caraceni et al Cancer 2000)
• PaP score (Maltoni et al JPSM 1999)
• Il 50 of delirium episodes in PC are reversible
  (Lawlor Arch Int Med 2001)

36
Impact of delrium on survival curves after the
beginning of palliative care programmes A, B and
C identify three different prognostic groups
according to the PaP score

• - - delirious
• ___ not delirious

Caraceni et al Cancer 1999