Acute organic brain syndrome: delirium – types, clinical features, etiology, and treatment

01Definition and overview

Delirium, also called an acute confusional state, is a syndrome of acute brain dysfunction. Its defining features are a disturbance of attention and awareness that develops over hours to days, is a change from the person's usual state and fluctuates through the day, with further disturbance of cognition, and evidence that a physical cause, a drug, or a drug's withdrawal is responsible. The changes in consciousness range from drowsiness to hypervigilance; they stop short of coma, where no assessment is possible.

The subtypes are set by the level of activity, and patients often move between them:

Delirium is a medical, not a psychiatric, emergency: it signals that something is wrong in the body, and the patient is cared for by the team treating the physical illness, with psychiatric or geriatric advice where needed. Delirium and dementia often coexist: dementia is the strongest risk for delirium, and delirium can reveal and speed up dementia.

02Etiology and pathophysiology

Vulnerability and precipitants

Delirium follows when an insult meets a vulnerable brain. In a person with no reserve, such as someone with advanced dementia, a minor urine infection or a new tablet is enough; a fit young adult becomes delirious only with a severe insult, such as sepsis, a major operation or a large overdose.

Some causes are found in younger patients too: delirium tremens and Wernicke's encephalopathy, hepatic encephalopathy, head injury, non-convulsive status epilepticus after a seizure, poisoning, encephalitis and hypoglycaemia. In some patients no cause is found; in many there are several.

Mechanisms

How so many causes produce the same picture is only partly understood, and the following is a simplification:

• Neurotransmitters: a lack of acetylcholine and a relative excess of dopamine. Anticholinergic drugs cause delirium, dementia with low cholinergic reserve predisposes to it, and dopamine blockers calm the hyperactive form. Noradrenaline, glutamate and GABA also change, most of all in withdrawal states.
• Inflammation: cytokines released in infection, surgery or injury act on the brain across a leaky blood–brain barrier and switch on microglia, especially in an ageing or degenerating brain.
• Energy failure: hypoxia, hypoglycaemia and poor perfusion starve neurons, which need a constant supply of oxygen and glucose.
• Stress hormones and sleep: high cortisol and a disrupted sleep–wake rhythm and melatonin secretion.
• Networks: the result is a breakdown of the connections between brain networks that sustain attention and awareness, seen as diffuse slowing on the EEG.

03Clinical features

The onset is over hours to a few days, and the picture changes through the day, often worse in the evening and at night. Lucid intervals are common, so a patient who seems well on the morning round may have been severely confused overnight; the night staff and family know.

The physical signs point to the cause: fever, a raised respiratory rate, low oxygen saturation, dehydration, a palpable bladder, a loaded rectum, signs of liver failure, a tremor and flap (asterixis) in hepatic, uraemic or carbon dioxide encephalopathy, myoclonus, focal neurological signs, neck stiffness, or the tremor, sweating and tachycardia of withdrawal.

Delirium is told from its main mimics by its acute onset, fluctuation and inattention:

Dementia with Lewy bodies is the hardest mimic, because it also fluctuates and brings visual hallucinations; the history over months and the presence of parkinsonism separate them, and delirium on top of it is common.

04Diagnosis and management

Recognising it

All older people, or anyone with other risk factors, are assessed on admission and watched every day for changes in cognition, behaviour, sleep, appetite, mobility or social contact. A brief tool confirms the suspicion:

• The 4AT takes about two minutes, needs no special training and can be done in drowsy patients. UK guidance recommends it, and across studies it found about 88 per cent of patients with delirium and was negative in about 88 per cent of those without.
• The Confusion Assessment Method (CAM) asks for an acute onset with a fluctuating course and inattention, plus either disorganised thinking or an altered level of consciousness. The CAM-ICU adapts it for ventilated patients in intensive care.

A score of 4 or more suggests delirium, with or without cognitive impairment; 1 to 3 suggests cognitive impairment; 0 makes both unlikely, unless the information on an acute change is incomplete. A screening tool is not a diagnosis: a doctor confirms delirium clinically, and the history from family or carers about the person's usual cognition and when the change began is what makes the diagnosis possible.

Finding the cause

The history covers the time course, every drug started, stopped or changed (including over-the-counter drugs and alcohol), falls, pain, bowels and bladder. The examination covers the vital signs, hydration, chest, abdomen, bladder, skin and pressure areas, and the neurological signs.

Care

1. 1

   Treat the causes

   Treat infection, correct oxygen, fluids, sodium, calcium and glucose, relieve pain, retention and constipation, and stop or reduce the drugs that can cause delirium. Give thiamine where alcohol misuse or malnutrition is possible.
2. 2

   Non-drug measures

   A calm, well-lit room, the same staff, no ward moves, a clock and calendar, gentle reorientation, glasses, hearing aids and dentures, family visits, early mobilisation, drinks and meals with help, and a quiet night without needless observations.
3. 3

   De-escalation

   For distress or agitation, a calm voice, explanation, distraction and a familiar person. Hallucinations and delusions are neither argued with nor endorsed. Restraint and sedation are a last resort.
4. 4

   A drug, only if needed

   If the patient is distressed or a danger to themselves or others and de-escalation has failed, a short course of haloperidol at the lowest dose, usually for a week or less, reviewed every day.
5. 5

   Follow-up

   Explain what happened to the patient and family, record the delirium in the discharge letter, and check cognition again after recovery, to look for dementia.

Drugs do not treat delirium: in trials, antipsychotics neither shortened it nor reduced deaths, and in palliative care they made symptoms worse than placebo. They are used only to relieve severe distress or keep people safe. Haloperidol is started at a low dose, often 0.5 mg in an older person, with an ECG for the QT interval where possible, and stopped as soon as it can be. Antipsychotics are avoided in Parkinson's disease and dementia with Lewy bodies, where they can cause severe rigidity, falls and death; if a drug cannot be avoided, a senior or specialist chooses one.

Benzodiazepines make delirium worse and cause falls and oversedation. They are the treatment for delirium in alcohol or benzodiazepine withdrawal, where they replace the missing drug, and are a choice in seizures and sometimes when an antipsychotic is ruled out. Delirium tremens and Wernicke's encephalopathy, with parenteral thiamine before glucose, are covered in alcohol use disorders.

Delirium often removes the capacity to decide on treatment. Care is then given in the patient's best interests under the local capacity law, such as the Mental Capacity Act 2005 in England and Wales, rather than under mental health legislation, and any restriction is the least needed and reviewed often.

Prevention

UK guidance asks for these measures, tailored by a trained multidisciplinary team, within 24 hours of admission for anyone at risk: aged 65 or more, with cognitive impairment or dementia, a hip fracture or a severe illness. Multicomponent programmes like this cut the incidence of delirium by about a third to a half, and falls too. Around surgery, European anaesthesia guidance adds guiding the depth of anaesthesia with processed EEG monitoring, to avoid needlessly deep anaesthesia, and advises against benzodiazepines to treat delirium after surgery. It recommends no drug for prevention: dexmedetomidine may lower the risk, but its benefit is weighed against bradycardia and hypotension. No drug, antipsychotic or cholinesterase inhibitor, is recommended to prevent delirium on general wards.

05Epidemiology

have delirium, on admission or during the stay

1 in 4older medical inpatientshave delirium, on admission or during the stay

after a hip fracture

up to 1 in 2older patientsafter a hip fracture

of older people in the community

1 to 2per centof older people in the community

Delirium is the commonest mental disorder in general hospitals. It affects roughly 1 in 5 to 1 in 3 older medical inpatients, about 15 to 50 per cent of older people after surgery, with the highest rates after hip fracture and cardiac surgery, most ventilated patients in intensive care, and most people in the last days of life. In care homes and in the community it is less common but carries a high mortality. Between a third and two thirds of cases are not recognised, most of them hypoactive. The risk rises steeply with age, dementia and frailty.

06Prognosis

Most delirium clears within days to a couple of weeks once the cause is treated, but in older people symptoms often outlast the cause, and full cognitive recovery may take months; in some patients it never comes. In older patients, delirium in hospital is linked, independently of age and illness, to:

• about twice the risk of death in the following two years;
• more than twice the risk of entering a care home;
• a much higher risk of dementia in the next few years, and a faster decline in those who already have it;
• longer stays, falls, pressure sores and loss of function.

Many patients remember the episode as frightening, and survivors of intensive care can be left with intrusive memories. Delirium recurs with the next illness, so it is a warning to avoid precipitants, such as anticholinergic drugs, in future.