DELIRIUM: DALLA DIAGNOSI AL TRATTAMENTO - grg-bs.it · dipartimento di farmacologia sperimentale ed...
Transcript of DELIRIUM: DALLA DIAGNOSI AL TRATTAMENTO - grg-bs.it · dipartimento di farmacologia sperimentale ed...
DIPARTIMENTO DI FARMACOLOGIA SPERIMENTALE ED APPLICATA FACOLTA’ DI FARMACIA DELL’UNIVERSITA’ DI PAVIA DEPARTMENT OF DRUG SCIENCE - PHARMACOLOGY SECTION, UNIVERSITY OF PAVIA
DELIRIUM: DALLA DIAGNOSI
AL TRATTAMENTO LE PROSPETTIVE DELLA RICERCA
S.Govoni
DIPARTIMENTO DI FARMACOLOGIA SPERIMENTALE ED APPLICATA FACOLTA’ DI FARMACIA DELL’UNIVERSITA’ DI PAVIA DEPARTMENT OF DRUG SCIENCE - PHARMACOLOGY SECTION, UNIVERSITY OF PAVIA
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, under-recognised, and often fatal.
DIPARTIMENTO DI FARMACOLOGIA SPERIMENTALE ED APPLICATA FACOLTA’ DI FARMACIA DELL’UNIVERSITA’ DI PAVIA DEPARTMENT OF DRUG SCIENCE - PHARMACOLOGY SECTION, UNIVERSITY OF PAVIA
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.
DIPARTIMENTO DI FARMACOLOGIA SPERIMENTALE ED APPLICATA FACOLTA’ DI FARMACIA DELL’UNIVERSITA’ DI PAVIA DEPARTMENT OF DRUG SCIENCE - PHARMACOLOGY SECTION, UNIVERSITY OF PAVIA
Defining delirium pathophysiology, is that useful?
DIPARTIMENTO DI FARMACOLOGIA SPERIMENTALE ED APPLICATA FACOLTA’ DI FARMACIA DELL’UNIVERSITA’ DI PAVIA DEPARTMENT OF DRUG SCIENCE - PHARMACOLOGY SECTION, UNIVERSITY OF PAVIA
Defining delirium pathophysiology, is that useful? Yes, in order to find: • predictive markers • treatment targets
DIPARTIMENTO DI FARMACOLOGIA SPERIMENTALE ED APPLICATA FACOLTA’ DI FARMACIA DELL’UNIVERSITA’ DI PAVIA DEPARTMENT OF DRUG SCIENCE - PHARMACOLOGY SECTION, UNIVERSITY OF PAVIA
The literature has focused the attention mainly on two systems: • trasmitters/hormones involved in
inflammation and immune modulation
• cholinergic transmission
DIPARTIMENTO DI FARMACOLOGIA SPERIMENTALE ED APPLICATA FACOLTA’ DI FARMACIA DELL’UNIVERSITA’ DI PAVIA DEPARTMENT OF DRUG SCIENCE - PHARMACOLOGY SECTION, UNIVERSITY OF PAVIA
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 attenuated by IL-10.
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 behavioural changes compared with controls
DIPARTIMENTO DI FARMACOLOGIA SPERIMENTALE ED APPLICATA FACOLTA’ DI FARMACIA DELL’UNIVERSITA’ DI PAVIA DEPARTMENT OF DRUG SCIENCE - PHARMACOLOGY SECTION, UNIVERSITY OF PAVIA
DIPARTIMENTO DI FARMACOLOGIA SPERIMENTALE ED APPLICATA FACOLTA’ DI FARMACIA DELL’UNIVERSITA’ DI PAVIA DEPARTMENT OF DRUG SCIENCE - PHARMACOLOGY SECTION, UNIVERSITY OF PAVIA
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DIPARTIMENTO DI FARMACOLOGIA SPERIMENTALE ED APPLICATA FACOLTA’ DI FARMACIA DELL’UNIVERSITA’ DI PAVIA DEPARTMENT OF DRUG SCIENCE - PHARMACOLOGY SECTION, UNIVERSITY OF PAVIA
Gool WA et al. Systemic infection and delirium: when cytokines and acetylcholine collide, Lancet 2010; 375: 773–75
Gool WA et al. Systemic infection and delirium: when cytokines and acetylcholine collide, Lancet 2010; 375: 773–75
DIPARTIMENTO DI FARMACOLOGIA SPERIMENTALE ED APPLICATA FACOLTA’ DI FARMACIA DELL’UNIVERSITA’ DI PAVIA DEPARTMENT OF DRUG SCIENCE - PHARMACOLOGY SECTION, UNIVERSITY OF PAVIA
Defining delirium pathophysiology, is that useful? Yes, in order to find: • predictive markers
DIPARTIMENTO DI FARMACOLOGIA SPERIMENTALE ED APPLICATA FACOLTA’ DI FARMACIA DELL’UNIVERSITA’ DI PAVIA DEPARTMENT OF DRUG SCIENCE - PHARMACOLOGY SECTION, UNIVERSITY OF PAVIA
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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
DIPARTIMENTO DI FARMACOLOGIA SPERIMENTALE ED APPLICATA FACOLTA’ DI FARMACIA DELL’UNIVERSITA’ DI PAVIA DEPARTMENT OF DRUG SCIENCE - PHARMACOLOGY SECTION, UNIVERSITY OF PAVIA
Other confounders
DIPARTIMENTO DI FARMACOLOGIA SPERIMENTALE ED APPLICATA FACOLTA’ DI FARMACIA DELL’UNIVERSITA’ DI PAVIA DEPARTMENT OF DRUG SCIENCE - PHARMACOLOGY SECTION, UNIVERSITY OF PAVIA
Thomas N Robinson, Christopher D Raeburn, Erik M Angles, and Marc Moss Low Tryptophan Levels Are Associated with Post-Operative Delirium in the Elderly Am J Surg. 2008; 196: 670–674.
DIPARTIMENTO DI FARMACOLOGIA SPERIMENTALE ED APPLICATA FACOLTA’ DI FARMACIA DELL’UNIVERSITA’ DI PAVIA DEPARTMENT OF DRUG SCIENCE - PHARMACOLOGY SECTION, UNIVERSITY OF PAVIA
Post-operative Tryptophan Levels in Elderly Subjects with and without Delirium
DIPARTIMENTO DI FARMACOLOGIA SPERIMENTALE ED APPLICATA FACOLTA’ DI FARMACIA DELL’UNIVERSITA’ DI PAVIA DEPARTMENT OF DRUG SCIENCE - PHARMACOLOGY SECTION, UNIVERSITY OF PAVIA
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
DIPARTIMENTO DI FARMACOLOGIA SPERIMENTALE ED APPLICATA FACOLTA’ DI FARMACIA DELL’UNIVERSITA’ DI PAVIA DEPARTMENT OF DRUG SCIENCE - PHARMACOLOGY SECTION, UNIVERSITY OF PAVIA
Defining delirium pathophysiology, is that useful? Yes, in order to find: • treatment targets
DIPARTIMENTO DI FARMACOLOGIA SPERIMENTALE ED APPLICATA FACOLTA’ DI FARMACIA DELL’UNIVERSITA’ DI PAVIA DEPARTMENT OF DRUG SCIENCE - PHARMACOLOGY SECTION, UNIVERSITY OF PAVIA
BUT…
DIPARTIMENTO DI FARMACOLOGIA SPERIMENTALE ED APPLICATA FACOLTA’ DI FARMACIA DELL’UNIVERSITA’ DI PAVIA DEPARTMENT OF DRUG SCIENCE - PHARMACOLOGY SECTION, UNIVERSITY OF PAVIA
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 approaches are recommended
DIPARTIMENTO DI FARMACOLOGIA SPERIMENTALE ED APPLICATA FACOLTA’ DI FARMACIA DELL’UNIVERSITA’ DI PAVIA DEPARTMENT OF DRUG SCIENCE - PHARMACOLOGY SECTION, UNIVERSITY OF PAVIA
DIPARTIMENTO DI FARMACOLOGIA SPERIMENTALE ED APPLICATA FACOLTA’ DI FARMACIA DELL’UNIVERSITA’ DI PAVIA
Neurodormancy
Afferent information overload
Neurotransmitter specific
interventions
Stimulatory trasmission
L-dopa Bromocriptine Amantadine
Antidepressants Methylphenidate
Zolpidem
Baclofen
DIPARTIMENTO DI FARMACOLOGIA SPERIMENTALE ED APPLICATA FACOLTA’ DI FARMACIA DELL’UNIVERSITA’ DI PAVIA DEPARTMENT OF DRUG SCIENCE - PHARMACOLOGY SECTION, UNIVERSITY OF PAVIA
Re-thinking delirium in clinical practice in ICU: the difficulty to
intervene with drugs in absence of full knowledge of delirium
physiopathology
DIPARTIMENTO DI FARMACOLOGIA SPERIMENTALE ED APPLICATA FACOLTA’ DI FARMACIA DELL’UNIVERSITA’ DI PAVIA DEPARTMENT OF DRUG SCIENCE - PHARMACOLOGY SECTION, UNIVERSITY OF PAVIA
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
DIPARTIMENTO DI FARMACOLOGIA SPERIMENTALE ED APPLICATA FACOLTA’ DI FARMACIA DELL’UNIVERSITA’ DI PAVIA DEPARTMENT OF DRUG SCIENCE - PHARMACOLOGY SECTION, UNIVERSITY OF PAVIA
Defining delirium pathophysiology, is that useful?
DIPARTIMENTO DI FARMACOLOGIA SPERIMENTALE ED APPLICATA FACOLTA’ DI FARMACIA DELL’UNIVERSITA’ DI PAVIA DEPARTMENT OF DRUG SCIENCE - PHARMACOLOGY SECTION, UNIVERSITY OF PAVIA
Inouye SK et al. Delirium in elderly people, Lancet 2014; 383: 911–22