DELIRIUM: DALLA DIAGNOSI AL TRATTAMENTO LE PROSPETTIVE DELLA RICERCA

(1)

DIPARTIMENTO DI FARMACOLOGIA SPERIMENTALE ED APPLICATA FACOLTA’ DI FARMACIA DELL’UNIVERSITA’ DI PAVIA

DEPARTMENT

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AVIA

DELIRIUM: DALLA DIAGNOSI

AL TRATTAMENTO

L

E

PROSPETTIVE

DELLA

RICERCA

(2)

Inouye SK et al. Delirium in elderly people, Lancet

2014; 383: 911–22

Delirium is an acute disorder of

attention and cognition in

elderly people that is common,

serious, costly,

(3)

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Inouye SK et al. Delirium in elderly people, Lancet

2014; 383: 911–22

Delirium can be thought of as

acute brain failure—ie, a

multifactorial syndrome analogous

to acute heart failure—and might

provide a novel approach to

elucidation of brain functioning

and pathophysiology.

(4)

Defining delirium pathophysiology,

is that useful?

(5)

DEPARTMENT

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Defining delirium pathophysiology,

is that useful?

Yes, in order to find:

• predictive markers

(6)

The literature has focused the attention

mainly on two systems:

• trasmitters/hormones involved in

inflammation and immune

modulation

(7)

Cerejeir

a

J. et

al.

Neuroimm

unom

odul

ation

2014;21:72

–

78

(8)

Elevated levels of TNF-α or IL-1 (but not IL-6 or

IFN-γ) in the CNS following acute systemic

inflammation are responsible for a cluster of

transient and stereotyped changes known as

‘sickness behaviour’. This syndrome mimics the

symptoms experienced by humans during a viral

or bacterial infection and manifests with

decreased levels of social exploration, locomotor

activity and sweetened liquid or food intake. Aged

mice show enhanced production of

pro-inflammatory cytokines in the brain after LPS

stimulation and this translates into a more severe

sickness. In contrast, the symptoms are

(9)

Role of microglia

and toll-like

receptor 4 in the

pathophysiology

of delirium Jalleh

R et al. Medical

Hypotheses 79

(2012) 735–739

TLR4

deficient

mice had

less

stress-induced

behaviour

al changes

compared

with

controls

(10)

(11)

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Cac

cial

anza

et

(12)

Gool WA et al. Systemic infection and delirium: when

cytokines and acetylcholine collide, Lancet 2010; 375:

773–75

(13)

Gool WA et

al. Systemic

infection and

delirium:

when

cytokines and

acetylcholine

collide,

Lancet 2010;

375: 773–75

(14)

Hshieh et

al. J

Gerontol A

Biol Sci

Med Sci .

2008 July ;

63(7):

764–772.

(15)

Hshieh et

al. J

Gerontol A

Biol Sci

Med Sci .

2008 July ;

63(7):

764–772.

(16)

(17)

DEPARTMENT

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Defining delirium pathophysiology,

is that useful?

Yes, in order to find:

(18)

(19)

van

Mu

nster

BC

et

al.

,

Lo

ng

itu

din

al

ass

ess

ment

of

ser

um

antich

olinergic

activit

y

in

deli

rium

of

th

e

elderly

, Jo

urnal

of

Psy

chiatric

R

ese

ar

ch

46 (2012)

133

9 -1345

(20)

Watne LO et al.

Anticholinergic

Activity in

Cerebrospinal Fluid

and Serum

inIndividuals with

Hip Fracture with

and without

Delirium, J Am

Geriatr Soc 62:94–

102, 2014

(21)

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(22)

Thomas N Robinson, Christopher

D Raeburn, Erik M Angles, and

Marc Moss

Low Tryptophan Levels Are

Associated with Post-Operative

Delirium in the Elderly

(23)

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Post-operative Tryptophan Levels in Elderly

Subjects with and without Delirium

(24)

Do nutrients play a role in delirium?

Clinicians should always be vigilant and

reflect on the possibility of nutritional

deficiencies as causal agents or

contributors to delirium and consider

testing for and treating underlying

nutritional deficiencies (B vitamins,

dehydration, hypoglycemia) or excesses

(hypertriglyceridemia, hyperglycemia).

Sanford and Flaherty, Curr Opin Clin Nutr Metab Care

2014, 17:45–50

(25)

DEPARTMENT

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Defining delirium pathophysiology,

is that useful?

Yes, in order to find:

(26)

(27)

DEPARTMENT

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Inouye SK et al. Delirium in elderly people, Lancet

2014; 383: 911–22

No convincing evidence shows that

pharmacological prevention or treatment is

effective. Drug reduction for sedation and

analgesia and nonpharmacological

(28)

(29)

Neurodormanc

y

Afferent

information

overload

Neurotransmitter

specific

interventions

Stimulatory

trasmission

L-dopa

Bromocriptine

Amantadine

Antidepressants

Methylphenidate

Zolpidem

Baclofen

(30)

Re-thinking delirium in clinical

practice in ICU: the difficulty to

intervene with drugs in absence of

full knowledge of delirium

physiopathology

(31)

R

eade

EC

et

al.

N

Engl

J

Med

201 4;37

0:44

4 -54.

(32)

In conclusion, tramadol, which is a commonly

used analgesic in surgical settings, has the

potential to lead to delirium. It is important for

surgeons to have a high index of suspicion in

order to be able to recognize promptly

this uncommon but serious adverse effect of the

drug and withdraw the offending agent along with

having effective liaisoning with their psychiatric

colleagues for appropriate management.

Ghosh S. et al., Acute Delirium due to Parenteral

Tramadol, Case Reports in Emergency Medicine

2013

(33)

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Defining delirium pathophysiology,

is that useful?

(34)

Inouye SK et al. Delirium in elderly people, Lancet

2014; 383: 911–22

(35)

DEPARTMENT

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Conclusions: nothing practical,

but: avoid sedative and