2 Neuroscience2.11 Integrated neurobiology of syndromes and states
2.11.13 Delirium
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Written by Resident Doctor Committee · Published
Definition and vulnerability
Delirium is an acute, fluctuating disturbance of attention, awareness and cognition caused by physical illness, drugs or withdrawal. It can persist and carries substantial mortality.
Vulnerability and insult severity interact, so a more vulnerable brain needs a smaller trigger.
Predisposing factors are older age, dementia or other neurodegeneration, low cognitive reserve, and prior brain injury such as stroke, trauma or previous delirium.
In dementia, minor triggers such as constipation or anticholinergic medication can precipitate delirium.
Diffuse network dysfunction explains why many different causes produce similar symptoms.
Neurotransmitters
Acetylcholine supports attention, so anticholinergic drugs cause delirium; selected toxicological cases respond to specialist use of physostigmine.
Cholinesterase inhibitors are not an established treatment for delirium in general.
Antipsychotics may control severe distress or risk when other measures fail, but they do not treat the cause.
Transmitter | Change and setting |
|---|---|
Gamma-aminobutyric acid (GABA) | Raised in hepatic encephalopathy and sedative intoxication; reduced in alcohol and benzodiazepine withdrawal, with seizures |
Glutamate | Excitotoxic overactivity in hypoxia, hypoglycaemia and withdrawal |
Serotonin | Excess in serotonin toxicity; altered in hepatic encephalopathy and sepsis |
Noradrenaline | Excess in withdrawal and hyperactive delirium |
Dopamine | Dopaminergic drugs can precipitate delirium |
Inflammation
Infection, surgery and injury release interleukin-1β, interleukin-6 and tumour necrosis factor alpha, which reach the brain through barrier transport, circumventricular organs and vagal afferents.
Microglial cytokines and reactive oxygen species impair synapses, and ageing and neurodegeneration prime microglia to overreact.
Metabolic and toxic causes
Route | Typical causes |
|---|---|
Hypoxia | Cardiorespiratory failure, anaemia, carbon monoxide |
Glucose | Hypoglycaemia (injures rapidly), hyperglycaemia, ketoacidosis |
Electrolytes | Sodium, calcium or magnesium abnormalities |
Organ failure | Liver, renal or endocrine failure |
Drugs | Anticholinergics, opioids, sedatives, steroids, dopamine drugs, lithium |
Withdrawal | Alcohol, benzodiazepines |
Networks and sleep
Disrupted thalamocortical and ascending arousal systems make attention and awareness unstable.
Sleep fragments, slow-wave and rapid eye movement sleep are lost, and timing may reverse; sundowning is evening worsening.
Electroencephalogram (EEG)
The usual pattern is reduced posterior alpha with increased theta and delta, which shows diffuse dysfunction but is not specific.
Triphasic waves occur in hepatic and other encephalopathies, and fast activity accompanies withdrawal or sedatives.
EEG detects non-convulsive status epilepticus but cannot reliably separate delirium from psychiatric illness.
Motor subtypes
Subtype | Features |
|---|---|
Hyperactive | Agitation, restlessness, hallucinations; readily recognised |
Hypoactive | Drowsiness, slowing, reduced responsiveness; often missed in older people |
Mixed | Alternating patterns |
Subtypes can change within hours and are not separate diseases.
Differential diagnosis
Feature | Delirium | Dementia | Primary psychosis |
|---|---|---|---|
Onset | Hours to days | Months to years | Variable |
Course | Fluctuating | Usually progressive | Relatively sustained |
Attention | Prominently impaired | Varies by subtype | Variable |
Consciousness | Altered | Usually clear early | Usually clear |
Hallucinations | Often visual | Visual in Lewy body disease | Often auditory |
EEG | Diffuse slowing | May be slowed | Often normal |
Delirium is followed by cognitive decline and later dementia diagnosis, though cause and shared vulnerability are hard to separate.
Any acute change in mental state during physical illness or in older age needs urgent assessment for delirium.