Delirium

Delirium is an acute, fluctuating disturbance of attention, awareness, and cognition. It develops over hours to a few days as a direct physiological consequence of an acute medical condition, medication effect, substance intoxication or withdrawal, or a combination of these.

It is among the commonest and most significant complications of acute hospital care, and is frequently preventable. It is particularly common in older adults and those with pre-existing cognitive impairment.

Delirium carries well established morbidity and mortality, both directly and through its association with subsequent functional and cognitive decline. This makes prevention, prompt recognition, and systematic treatment of the precipitating cause or causes critical. Distinguishing delirium from major neurocognitive disorder is essential (see that condition).

Pathophysiology and classification

• Delirium is a final common pathway of acute, global cerebral dysfunction from a diverse range of precipitating insults. Proposed mechanisms include neuroinflammation, neurotransmitter imbalance (particularly cholinergic deficiency and dopaminergic excess), and disruption of neural network connectivity.
• Individual susceptibility reflects the interplay between baseline predisposing vulnerability (advanced age, pre-existing cognitive impairment, frailty, sensory impairment, and significant comorbidity) and the severity of the acute insult. A minor insult can precipitate delirium in a highly vulnerable individual, whereas a more substantial insult may be needed in a robust, lower vulnerability individual.
• Delirium is classified by motor subtype:
  • Hyperactive: agitation, restlessness, and increased psychomotor activity. It is generally the most readily recognised.
  • Hypoactive: lethargy, reduced responsiveness, and decreased psychomotor activity. It is frequently underrecognised and misattributed to depression, fatigue, or simply "settling", despite carrying an equal, or in some studies greater, prognostic significance than the hyperactive subtype.
  • Mixed: fluctuating between hyperactive and hypoactive features.
• The hypoactive subtype is subtle and easily overlooked, so recognising it is an important, frequently missed opportunity for earlier identification and treatment.
• Common precipitating causes:
  • Infection (particularly urinary tract infection and pneumonia, though any significant infection can precipitate delirium).
  • Metabolic derangement (including hyponatraemia, hypercalcaemia, hypoglycaemia, and renal or hepatic impairment).
  • Medication effects (particularly anticholinergic, sedative, and opioid medications, and any recent medication change).
  • Significant pain, urinary retention or faecal impaction, and hypoxia.
  • In the postoperative setting, the combined stress of surgery, anaesthesia, and analgesic medication.
• Delirium frequently reflects the cumulative contribution of multiple concurrent precipitants rather than a single, isolated cause.

• The core presentation is an acute, fluctuating disturbance of attention (difficulty focusing, sustaining, or shifting attention) and awareness. It develops over hours to days and is a clear change from baseline cognitive function. There is also disturbance in at least one further cognitive domain (memory, orientation, language, visuospatial ability, or perception).
• Symptom severity fluctuates over the day, frequently worsening in the evening and overnight (sometimes termed "sundowning", though the term is used loosely and inconsistently). Lucid intervals occur in which the individual may appear relatively normal.
• This fluctuation is a useful feature distinguishing delirium from the generally more stable presentation of major neurocognitive disorder (see that condition).
• Perceptual disturbances may accompany the core disturbance, particularly in the hyperactive subtype. These include visual or, less commonly, auditory hallucinations and delusional beliefs (frequently persecutory).
• Psychomotor disturbance ranges from marked agitation and restlessness to significant lethargy and reduced responsiveness, reflecting the motor subtype present.
• Sleep-wake cycle disturbance, with disrupted nocturnal sleep and frequent daytime drowsiness, and emotional lability are further common features.
• A collateral history from family members or familiar carers is essential. It establishes baseline cognitive function and confirms the acute, recent change. Without this baseline, it is often difficult to recognise an acute delirium superimposed on a chronic cognitive impairment.

• Diagnosis is clinical, based on the core features. Validated screening tools support structured assessment and improve recognition, particularly of the frequently underrecognised hypoactive subtype.
• The Confusion Assessment Method requires acute onset and fluctuating course, plus inattention, plus either disorganised thinking or altered level of consciousness.
• Once delirium is recognised, the central diagnostic priority is a full search for the precipitating cause or causes. This means a thorough history and examination and investigation directed at common precipitants: full blood count, renal and liver function, electrolytes including calcium, glucose, inflammatory markers, urinalysis and, where indicated, urine culture, chest radiography, and a full medication review.
• Further, more specific investigation (including blood cultures, arterial or venous blood gas, or neuroimaging) is directed by the clinical context and initial findings.
• Carefully exclude an underlying major neurocognitive disorder as the primary explanation. Attend to the acuity and pattern of onset, and use collateral history to confirm or exclude a recent change from a previously stable baseline.
• The distinction matters because the mechanism and prognosis differ, and delirium is frequently reversible whereas major neurocognitive disorder is generally progressive and irreversible (see that condition).
• Delirium can, and frequently does, occur superimposed on a pre-existing major neurocognitive disorder. It is one of the commonest precipitants of acute deterioration in a patient with known dementia.
• A pre-existing dementia diagnosis should never be used to explain away an acute change in cognitive status without proactive assessment for, and treatment of, a potential acute precipitating cause.

• Identifying and treating the precipitating cause or causes is the central management priority. Treat any infection promptly, correct metabolic derangement, and review contributing medication (discontinue or reduce the dose where appropriate).
• Give adequate analgesia for undertreated pain, and treat urinary retention or faecal impaction where relevant. This addresses the causative process rather than relying on symptomatic management alone.
• Non-pharmacological, supportive management is the foundation of care for the delirium itself. Provide a calm, appropriately lit and quiet environment, and frequent reorientation (visible clocks, calendars, and clear, simple communication).
• Ensure use of the hearing aids or visual aids the individual normally uses, as sensory impairment affects delirium risk and severity. Maintain a consistent, familiar care team and environment where feasible.
• Promote a normal sleep-wake cycle through daytime light exposure and by minimising unnecessary nocturnal disturbance. Encourage early mobilisation, ensure adequate hydration and nutrition, and involve family or familiar carers in reassurance and reorientation.
• Together these form the core of structured delirium prevention and management protocols, shown to substantially reduce delirium incidence and severity in appropriately implemented care settings.
• Reserve pharmacological management for significant distress, agitation, or risk to the patient or others that persists despite adequate non-pharmacological measures, while the precipitating cause is being actively addressed.
• Low dose haloperidol is a commonly used option where pharmacological treatment is genuinely required. Use it cautiously: its adverse effects include extrapyramidal symptoms and, of particular relevance, corrected QT interval prolongation.
• Avoid haloperidol in Parkinson disease or dementia with Lewy bodies, given the marked sensitivity to antipsychotic medication in these conditions (see Parkinson plus syndromes).
• Benzodiazepines are generally avoided because they can worsen confusion and paradoxically exacerbate agitation. Reserve them for delirium related to alcohol or benzodiazepine withdrawal, where they are the appropriate treatment of the cause.
• Avoid physical restraint wherever possible, given clear evidence of limited effectiveness and potential for harm and worsening of agitation and distress.
• Use any pharmacological or physical intervention only as a last resort, at the lowest effective intensity and for the shortest necessary duration. Document the rationale, alternatives considered, and ongoing reassessment.
• Proactive prevention is a highly effective, evidence based way to reduce delirium incidence. Systematically identify at risk individuals (particularly on admission to hospital, given the burden of hospital acquired delirium) and implement multicomponent non-pharmacological prevention strategies. Structured programmes substantially reduce delirium rates in appropriately implemented settings.
• Plan discharge and communication carefully. Document the delirium episode and its resolution, and arrange follow up, given the association between delirium and subsequent new or accelerated cognitive decline. Explain this association to the patient and family and the importance of ongoing monitoring.