302 Delirium: causes outside the brain Flashcards
What is the definition of delirium according to the DSM-V?
A. Disturbance in attention (i.e., reduced ability to direct, focus, sustain, and shift attention) AND awareness (reduced orientation to the environment).
B. Develops over a short period (usually hours to a few days), represents a change from baseline attention and awareness, and tends to fluctuate in severity during the course of a day.
C. An additional disturbance in cognition (e.g., memory deficit, disorientation, language, visuospatial ability, or perception).
D. Criteria A and C are NOT explained by another pre-existing, established, or evolving neurocognitive disorder and do not occur in the context of a coma
E. Evidence from history, examination, or investigations that the disturbance is a direct physiological consequence of another medical condition, substance intoxication or withdrawal, or exposure to a toxin, or is due to multiple aetiologies
Which impairments may feature in delirium?
- Global disturbance of cognition
Eg. Illusions, delusions, hallucinations
-Psychomotor disturbance
Eg. hypoactive (65%), hyperactive (25%), mixed (10%)
-Emotional dysregulation
-Circadian rhythm
-Impairment of consciousness and attention
What are some differences between delirium and dementia?
Delirium is abrupt, dementia is insidious
Delirium only lasts hours to weeks, dementia lasts years
Alertness, orientation, behaviour, speech, thoughts, and perceptions are impaired in delirium but not in early dementia
What are some predisposing factors to delirium?
-Older age
-Dementia and cognitive impairment
-Frailty
-Previous delirium
-Male gender
-Sensory (visual or hearing) impairment
-Depression
-Alcohol dependence
-Previous stroke
-Other neuroimaging findings – general atrophy, greater white matter disease
What factors can be acute insults for the onset of delirium?
-Medications
Eg. hypnotics, sedatives, opiates, toxicity and withdrawal
-Environment
-ICU
-Surgery!
-Restraint, catheterisation
-Others
Eg. VITAMIN D, Systems based approach
What are the causes of delirium?
Remains unclear, usually multiple causes
Eg. Hypoxia, Hypoglycaemia, Metabolic abnormalities, Stroke, Drugs affecting the CNS
What makes the ageing brain vulnerable to delirium?
1) Neuronal loss
2) Neuroinflammation: Microglia & astrocytes - exaggerated pro-inflammatory responses to secondary inflammatory stimuli
3) Brain connectivity impaired: Degeneration cholinergic and noradrenergic neuronal populations
4) Vascular changes: Impaired brain perfusion Increased permeability blood brain barrier (increased exposure to systemic drugs)
All reduce physiological reserve and increase vulnerability to disruptions in energy or oxygen supply and effects of inflammatory molecules
What are some pathophysiological processes involved in delirium?
Ageing brain – Neuronal ageing hypothesis
Cerebral metabolic insufficiency hypothesis – including oxidative stress
Neuroendocrine dysregulation
Circadian rhythm dysregulation
Neurotransmitter dysregulation
Neural Network disconnectivity
What is the Cerebral metabolic insufficiency hypothesis for delirium?
The brain is largely reliant on oxygen and large amounts of energy, when the needs are unmet it leads to delirium
What is the neuroendocrine hypothesis to delirium?
Stress activates HPA (hypothalamo-pituitary-adrenal) axis leading to glucocorticoid release from adrenals
Acts to maintain homeostasis during stress event
Delirium = physiological reaction to stress mediated by abnormally high glucocorticoids
Failure of resolution – chronic exposure to glucocorticoids:
Hippocampal dysfunction
Aberrant stress response – neuronal dysfunction – increased risk cell death with repeated stress events
Similar effect seen with exogenous steroids which can trigger delirium
What is the circadian rhythm dysregulation hypothesis for delirium?
Melatonin – from pineal gland – circadian rhythms including sleep-wake cycle
Here – disruptions in 24hour circadian cycle, usual stages of sleep and variations natural light exposure => disturbances in normal sleep and may => delirium
Potential role in melatonin in delirium prevention
What is the neurotransmitter hypothesis for delirium?
Alterations in NT production, function and/or availability implicated in delirium
The most commonly described changes:
-Reduced availability of acetylcholine
-Reduced noradrenaline (sleepy), increased noradrenaline (emotional responses – fear/threat)
-Increased GABA
(NB GABA is elevated by benzos (may worsen delirium but also role in Rx))
-Increased dopamine
Which drugs are associated with delirium in relation to neurotransmitters?
-Opioids (increase dopamine and glutamate activity and reduce ACh availability)
-Benzodiazepine (sedative, increase GABA)
-Anti-histamine (decreased histamine, anticholinergic)
-H2 receptor antagonist (decrease histamine)
-Steroids (Reduce GABA, increase dopamine)
-Tricyclic antidepressant (anti-cholinergic)
-Anti-Parkinson (increase dopamine, some have anti-cholinergic effects)
-Bladder drugs – oxybutynin, tolterodine, solifenacin (anti-cholinergic)
Renal and hepatic dysfunction and polypharmacy increases risk of drug-drug interactions, drug level accumulation, toxicity
How does neuroanatomical network connectivity contribute to delirium?
Brain areas connected in functional networks and ‘talk’ to each other:
-To maintain adequate processing of sensory information and motor responses
-To preserve attention and intact consciousness
Impaired neural network connectivity may be final driver in delirium
Vulnerabilities + stressors => failure of functional connectivity in neural networks => profound failure of normal brain function
How is delirium identified?
Confusion Assessment Method- 4
4ATs test (≥4 possible delirium, 88% sens/specificity):
-Alertness
-Cognition (orientation)
-Attention (months backwards)
-Acute change/fluctuating course
