Acute confusion and delirium

Delirium is an acute disturbance of attention and awareness that develops over hours to days, fluctuates through the day, and is accompanied by a further change in cognition (memory, orientation, language, perception), caused by an underlying medical condition, drug, withdrawal or toxin. It is a medical emergency in the sense that it marks serious illness, and it is frequently missed.

Clinical relevance. Delirium raises the risk of falls, prolonged admission, institutional care, new dementia and death. It is common in hospitalised older adults and after surgery.

Subtypes. Hyperactive (agitated, hallucinating), hypoactive (drowsy, withdrawn, most often missed) and mixed.

Mechanisms. Acute failure of widespread brain networks from inflammation, neurotransmitter imbalance (acetylcholine deficiency, dopamine excess), metabolic stress and sleep disruption.

Risk factors. Predisposing: age over 65, dementia, previous delirium, frailty, sensory impairment, polypharmacy, alcohol misuse. Precipitating: infection, drugs, metabolic disturbance, pain, urinary retention, constipation, dehydration, surgery, hospital admission, sleep deprivation, restraint and catheters.

Key distinctions. Delirium has acute onset with fluctuation and inattention. Dementia is chronic and progressive with preserved alertness until late. Both often coexist, and a change from baseline is the anchor, taken from an informant.

History from an informant. Baseline cognition and function, time of onset, fluctuation, sleep reversal, hallucinations, new falls, reduced intake, fever, urinary symptoms, cough, pain, constipation, recent surgery, new or stopped drugs, alcohol intake and last drink.

Drug history. New or increased anticholinergics (oxybutynin, amitriptyline, hyoscine, chlorphenamine), benzodiazepines and sedatives, opioids, corticosteroids, antiparkinsonian drugs, H2 blockers, fluoroquinolones, lithium, digoxin, antiepileptics, serotonergic drugs and antipsychotics. Withdrawal from alcohol, benzodiazepines, baclofen and opioids.

Bedside assessment of attention. Months of the year backwards starting from December (7 or more correct months is normal), serial sevens, or digit span.

4AT screening tool (score 0 to 12; 4 or more suggests possible delirium, 1 to 3 possible cognitive impairment, 0 makes both unlikely):

• Alertness: normal 0; clearly abnormal 4
• Orientation (age, date of birth, place, year): no errors 0; one error 1; two or more errors or untestable 2
• Attention (months backwards): 7 or more correct 0; fewer than 7 or refuses 1; untestable 2
• Acute change or fluctuating course over the last 2 weeks and still present: no 0; yes 4

Confusion Assessment Method. Delirium is present with acute onset and fluctuating course plus inattention, plus either disorganised thinking or altered level of consciousness.

Examination. Temperature, blood pressure, pulse, respiratory rate, oxygen saturation, glucose, hydration, chest, abdomen, bladder (palpable), rectal examination for impaction, skin and pressure areas, wounds, focal neurological signs, meningism, asterixis, tremor, rigidity, clonus, hyperreflexia, pupils, and signs of alcohol withdrawal.

Red flags

• Fever with neck stiffness or rash
• New focal deficit, head injury, or anticoagulation with a fall
• Reduced consciousness, seizures
• Hypoxia, hypotension, hypoglycaemia
• Fever with rigidity or clonus after a new drug (neuroleptic malignant syndrome or serotonin syndrome)
• Alcohol withdrawal with hallucinations, tremor and autonomic instability
• Severe agitation with risk of harm

Special groups. Older adults: any acute change is delirium until shown otherwise. Post-operative patients: hypoxia, pain, drugs, urinary retention. Pregnancy: eclampsia and Wernicke encephalopathy with hyperemesis. Region specific: cerebral malaria and HIV related CNS disease.

Precipitating causes of delirium

• Infection: urinary tract infection (not asymptomatic bacteriuria alone), pneumonia, cellulitis, sepsis, bacterial meningitis, encephalitis, malaria, intra-abdominal sepsis
• Drugs and toxins: anticholinergic toxicity, opioids, benzodiazepines, corticosteroids, lithium and digoxin toxicity, serotonin syndrome, neuroleptic malignant syndrome, carbon monoxide
• Withdrawal states: alcohol (delirium tremens), benzodiazepines, baclofen, opioids
• Metabolic and endocrine: hypoglycaemia, hyperglycaemia, hyponatraemia, hypernatraemia, hypercalcaemia, uraemia, hepatic encephalopathy, hypoxia, hypercapnia, thyroid disease, adrenal insufficiency, Wernicke encephalopathy, vitamin B12 deficiency
• Cardiovascular and respiratory: myocardial infarction, heart failure, arrhythmia, pulmonary embolism, shock
• Neurological: stroke, subdural haematoma, non-convulsive status epilepticus, post-ictal state, encephalitis (including autoimmune), brain tumour, hypertensive encephalopathy
• Surgical, pain and environmental: post-operative state, urinary retention, faecal impaction, uncontrolled pain, sleep deprivation, sensory deprivation, dehydration

Conditions that mimic or coexist with delirium

• Dementia (Alzheimer disease, vascular dementia, dementia with Lewy bodies, frontotemporal dementia)
• Depression with psychomotor retardation, mania, acute psychosis, catatonia
• Receptive aphasia from a left temporal lesion
• Transient global amnesia, post-ictal state

Reasoning. Delirium is a clinical diagnosis made at the bedside. The work is to identify and correct every precipitating factor, since delirium is usually multifactorial.

First line.

Vital signs, oxygen saturation, glucose, hydration status, bladder scan, rectal examination, ECG, chest radiograph, urinalysis (interpret with care: positive dipsticks are common in older adults without infection, so treat only with urinary symptoms or systemic signs and no other source), blood tests: full blood count, urea, electrolytes, creatinine, calcium, glucose, liver function, C reactive protein, thyroid function, vitamin B12 and folate.

Add blood cultures, lactate, troponin, malaria test, HIV test, ammonia, drug levels (lithium, digoxin, phenytoin, valproate), toxicology and ethanol as relevant.

Targeted tests. CT head for focal signs, head injury, fall on anticoagulants, reduced consciousness, or no cause after initial assessment. Lumbar puncture for fever with meningism or suspected encephalitis (after CT when indicated; do not delay antibiotics). EEG for suspected non-convulsive seizures or when the cause is unclear (diffuse slowing supports delirium). MRI brain for suspected stroke, encephalitis or Wernicke encephalopathy.

Limitations. Screening tools cannot diagnose delirium in a patient with severe dementia or very poor attention without clinical review. Normal CT does not exclude encephalitis or small infarcts. After recovery, reassess cognition to find underlying dementia.

Treat the cause. Antibiotics for infection, correct metabolic derangement, stop or reduce culprit drugs, relieve retention and constipation, treat pain, correct hypoxia, and give thiamine when alcohol misuse or malnutrition is likely: thiamine 500 mg IV every 8 hours for 3 days, before or with glucose.

Non-drug measures (first line and for all patients). Quiet well lit room with a clock and calendar, regular reorientation, glasses and hearing aids in place, family or familiar staff, uninterrupted sleep at night with daytime light and mobilisation, oral fluids and nutrition (IV fluids when oral intake fails), avoid physical restraint, tethers and catheters when possible, and a single consistent care team.

Drug treatment for distress or risk of harm only, when non-drug measures fail. Evidence that antipsychotics shorten delirium is limited; they are used for short term control of severe agitation or distressing psychosis.

• Haloperidol 0.5 mg orally or IM in older adults (1 to 2 mg in younger adults), repeated after 1 hour if needed; maximum 3 mg in 24 hours in older adults and 5 mg in 24 hours in other adults. Check ECG and electrolytes first and avoid if QTc is over 500 ms (caution over 450 ms in men and 470 ms in women); correct potassium and magnesium. Contraindicated in Parkinson disease and dementia with Lewy bodies, in which it can cause severe rigidity. Review daily and stop within 3 to 7 days once settled. Watch for dystonia, akathisia, hypotension and neuroleptic malignant syndrome.
• Quetiapine 12.5 to 25 mg orally at night, increased by 12.5 to 25 mg daily if needed; maximum 100 mg daily in older adults. Use in Parkinson disease and dementia with Lewy bodies.
• Lorazepam 0.5 mg orally or IV, repeated after 1 to 2 hours; maximum 2 mg in 24 hours in older adults. Use for alcohol or benzodiazepine withdrawal, or when antipsychotics are contraindicated. Otherwise avoid, because benzodiazepines can worsen delirium.

Alcohol withdrawal delirium (delirium tremens). Diazepam 10 mg IV over 2 minutes, repeated every 10 to 15 minutes until the patient is calm and lightly sedated (large cumulative doses may be needed; monitor airway and respiratory rate). Oral diazepam 10 to 20 mg every 1 to 2 hours is used for milder symptoms. Thiamine 500 mg IV every 8 hours for 3 days, correction of magnesium, potassium and glucose, and fluid replacement. Add haloperidol only for hallucinations that persist despite adequate benzodiazepine.

Monitoring. 4AT or Confusion Assessment Method each shift, vital signs, fluid balance, glucose, sodium, and QTc when antipsychotics are used.

Referral and escalation. Medical team for all inpatients; neurology for suspected encephalitis or non-convulsive status; geriatric or liaison psychiatry review for prolonged or complex delirium; intensive care for airway compromise, uncontrolled alcohol withdrawal, or severe sepsis.

Admission criteria. Most patients need admission to find and treat the cause. Discharge is reasonable only for mild delirium with a clear reversible cause treated, a safe environment and reliable supervision.

Follow up and safety netting. Persisting confusion over 4 weeks needs reassessment. Check cognition after resolution (at 4 to 12 weeks) for dementia. Advise relatives to return for recurrent confusion, drowsiness, fever, fall, new weakness, or reduced intake.