Delirium is not “confusion”. It is acute failure of the brain’s ability to maintain homeostasis, usually triggered by illness elsewhere in the body. When attention collapses, the cortex is signalling that its metabolic, inflammatory, or neurotransmitter environment has become unsafe.
Unlike dementia, which reflects slow structural decline, delirium develops over hours to days, fluctuates, and is usually reversible when the underlying insult is corrected.
Delirium is common, dangerous, and frequently missed — especially the quiet forms.
What Delirium Represents Mechanistically
Delirium is best understood as network-level brain dysfunction. No single pathway explains it; instead, several mechanisms converge to disrupt the brain’s ability to regulate arousal, attention, and cognition.
1. Neurotransmitter Failure: When the Signalling Balance Tips
The cortex relies on a finely tuned balance of neurotransmitters to maintain attention and organised thought. Delirium emerges when this balance is disrupted.
- Acetylcholine deficiency — the most consistent finding. Acetylcholine supports attention, working memory, and wakefulness. Anything that reduces cholinergic tone (infection, hypoxia, anticholinergic drugs) increases vulnerability.
- Dopamine excess — contributes to agitation, hallucinations, and disorganised thought. This explains why dopamine antagonists can reduce dangerous agitation, though they do not “treat” delirium.
- Other systems shift too: serotonin dysregulation, GABA withdrawal states, and glutamate excitotoxicity.
A helpful way to frame this for students: delirium is not a single neurotransmitter problem — it is a loss of coordinated signalling across multiple systems.
2. Neuroinflammation: When the Immune System Reaches the Brain
Systemic inflammation is a major driver of delirium.
Cytokines released during infection, trauma, or surgery (IL‑1, IL‑6, TNF‑Ξ±) can cross or disrupt the blood–brain barrier. Microglia become activated, altering synaptic transmission and impairing neuronal communication.
Older adults are especially vulnerable because:
- The blood–brain barrier is more permeable.
- Microglia are “primed” and overreact to small insults.
- Cerebral reserve is reduced.
This is why a mild UTI can produce profound delirium in an older adult — the inflammatory signal is amplified inside a vulnerable brain.
3. Impaired Cerebral Perfusion and Metabolism: When the Brain Runs Out of Fuel
The brain has no energy stores. It requires continuous oxygen and glucose delivery.
Hypoxia, hypotension, anaemia, hypoglycaemia, electrolyte imbalance, and organ failure all impair neuronal metabolism. When ATP production falls, neurons cannot maintain membrane potentials or reliable signalling.
Delirium is therefore the clinical expression of global cortical dysfunction.
Who Gets Delirium? Thinking in Terms of Vulnerability + Insult
Delirium is common:
- 10–20% of general medical inpatients
- Up to 50% of older hospitalised adults
- 60–80% of ICU patients
- Very common after major surgery, especially hip fracture repair
Risk is best understood as the interaction between:
- Predisposing vulnerability (age, dementia, frailty, sensory impairment, polypharmacy)
- Precipitating insult (infection, hypoxia, metabolic disturbance, drugs, pain, retention, constipation)
A robust 25‑year‑old can tolerate sepsis without delirium. A frail 85‑year‑old may become delirious from mild dehydration.
How Delirium Presents: Pattern Recognition Matters
Delirium is defined by:
- Inattention — the core feature
- Acute onset
- Fluctuating course
- Additional cognitive disturbance (memory, language, visuospatial ability)
Clinically, it appears in three patterns:
- Hyperactive — agitated, hallucinating, pulling out lines
- Hypoactive — quiet, withdrawn, sleepy (the most commonly missed)
- Mixed — fluctuating between the two
The key is not the behaviour but the loss of attention and fluctuation.
Case Vignette: Reasoning Through the Mechanisms
An 82‑year‑old woman is admitted with pneumonia. On day two she becomes disoriented, pulls out her IV line, and is agitated overnight. By morning she is drowsy and slow to respond.
Investigations show elevated CRP, mild hyponatraemia, and oxygen saturation of 91%.
This is classic delirium in a vulnerable brain, driven by:
- Neuroinflammation (infection)
- Hypoxia (impaired oxygen delivery)
- Metabolic disturbance (hyponatraemia)
The fluctuation between agitation and drowsiness reflects unstable cortical networks.
Diagnosing Delirium: A Clinical Reasoning Process
Delirium is a clinical diagnosis supported by tools such as the 4AT or CAM.
The reasoning steps are:
- Has there been an acute change?
- Is attention impaired?
- Does the course fluctuate?
- Is there an underlying medical cause?
Never diagnose delirium without searching for the precipitating factor. The diagnosis is incomplete until the cause is identified.
Common Causes: Think Physiological Stressors
Delirium is often multifactorial. Common contributors include:
- Infection (UTI, pneumonia, sepsis)
- Electrolyte disturbance (Na⁺, Ca²⁺, glucose)
- Hypoxia
- Stroke
- Drug toxicity (anticholinergics, opioids, benzodiazepines)
- Alcohol withdrawal
- Pain
- Urinary retention
- Constipation
A helpful mental model: anything that disrupts oxygen, glucose, neurotransmitters, or inflammation can precipitate delirium.
Management: Stabilise the Brain by Fixing the Body
1. Identify and Treat the Trigger
Correct the physiological insult: treat infection, optimise oxygenation, correct electrolytes, review medications.
2. Support the Brain’s Environment
Non‑pharmacological strategies are first-line:
- Orientation cues
- Family presence
- Adequate lighting
- Hydration
- Pain control
- Sleep protection
- Early mobilisation
These reduce cognitive load and stabilise arousal networks.
3. Medications
Antipsychotics may be used for severe agitation threatening safety, but they do not shorten delirium duration. Avoid benzodiazepines except in withdrawal states.
Why Delirium Matters Clinically
Delirium is associated with:
- Increased mortality
- Longer hospital stay
- Functional decline
- Institutionalisation
- Long-term cognitive impairment
Delirium is often the first sign that the brain is vulnerable. Early recognition and thorough investigation can change outcomes.
Takeaway
Delirium is acute brain failure. It reflects disrupted neurotransmission, neuroinflammation, and impaired cerebral metabolism — usually triggered by systemic illness in a vulnerable brain.
When a patient becomes suddenly confused, the brain is telling you something is wrong elsewhere in the body.
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