Acute Confusional State

Synonyms: Acute brain failure, acute organic reaction, delirium, post-operative psychosis.

Acute confusional state or delirium is a neuropsychiatric syndrome which is difficult to exactly define but involves abnormalities of thought, perception and levels of awareness. Patients may appear confused or "not with it" when talking to them. Alternatively, it maybe their family or carer who notice the confusion.

It is very common, especially in the elderly and many of these patients subsequently do not return to their baseline function and some even require institutionalisation. It can occur acutely or subacutely and symptoms fluctuate. More disappointing is the realisation that delirium can be avoided in many cases (up to one third) and the lack of awareness is leading to a large amount of morbidity and mortality and a burden on NHS costs.¹

Delirium occurs in about 15 - 20 % of all general admissions to hospital.² Occurence rates vary from 11-42% and it is the commonest complication of hospitalisation in the elderly population.¹ The incidence is also higher in those with pre-existing cognitive impairment. The prevalence is higher in patients with malignancy and HIV.³ Despite these facts delirium remains underdiagnosed and poorly managed - up to two thirds of cases are missed in some centres.²

There is an increase in delirium with age: 0.4% in those over 18 years of age, 1.1% in those over 55, 13.6% in those over 85 years.⁴

Furthermore, patients with delirium have longer hospital stays and a higher frequency of complications e.g. infections and pressure sores.²

Risk factors for delirium^2,4,5,6,7

• Extremes of age
• Male sex
• Pre-existing cognitive deficit e.g. dementia, stroke
• Severity of dementia
• Severe co-morbidity
• Previous episode of delirium
• Operative factors e.g. type of operation - hip fracture repairs are more likely to be associated with delirium as are emergency operations
• Certain conditions - burns, AIDS, fractures, infection, low albumin, dehydration
• Drug use (implicated in nearly half of cases) and dependence e.g. benzodiazepines
• Substance misuse e.g. alcohol
• Extremes of sensory experience e.g. hypothermia or hyperthermia
• Visual or hearing problems
• Poor mobility
• Social isolation
• Stress
• Terminally ill
• Movement to a new environment
• ICU admission

High serum urea levels have also been found to be a risk factor for delirium in acutely admitted patients in one prospective study.⁸

Usually a precipitant is required along with risk factors for delirium to occur. Further, the presence of a greater number of risk factors to begin with means that only a small precipitant is necessary to trigger delirium.

• Acute infections:
  • Urinary tract infection
  • Pneumonia
  • Sepsis
  • Viral infections
  • Meningitis
  • Encephalitis
  • Cerebral abscess
  • Malaria
• Prescribed drugs:
  • Benzodiazepines
  • Analgesics e.g. morphine
  • Anticholinergics
  • Anticonvulsants
  • Anti-parkinsonism medications
  • Steroids
• Surgical:
  • Post-operative
• Toxic substances:
  • Substance misuse or withdrawal
  • Alcohol - acute intoxication or withdrawal
  • CO poisoning
  • Exposure to heavy metals
  • Barbiturate withdrawal
• Vascular disorders:
  • Cerebrovascular haemorrhage or infarction
  • Cardiac failure or ischaemia
  • Subdural haemorrhage
  • Subarachnoid haemorrhage
  • Vasculitis e.g. SLE
  • Cerebral venous thrombosis
  • Migraines
• Metabolic causes:
  • Hypoxia
  • Electrolyte abnormalities e.g. hyponatremia and hypercalcaemia
  • Hypo - or hyperglycaemia
  • Hepatic impairment
  • Renal impairment
• Vitamin deficiencies:
  • Thiamine deficiency
  • Nicotinic acid deficiency
  • Vitamin B12 deficiency
• Endocrinopathies:
  • Hypo- and hyperthyroidism
  • Hypopituitarism
  • Hypo- or hyperparathyroidism
  • Cushing's disease
  • Porphyria
  • Carcinoid
• Trauma:
  • Head injury
• Epilepsy:
  • For example, post-ictally
• Neoplasia:
  • Primary cerebral malignancy
  • Secondaries in the brain
  • Paraneoplastic syndromes
• Others:
  • Urinary retention
  • Faecal impaction
• Multiple aetiology
• Unknown aetiology

The commonest causes are medical conditions such as infections, medications or drug withdrawal.

Making an accurate assessment relies on a collateral history to determine the patients pre-morbid level of function. There are very useful cognitive function screening tools e.g. abbreviated mental test score and confusion assessment method.¹⁰ The mental tests should be performed regularly and on all high risk patients.¹⁰ However, it may not be appropriate or possible to do these tests on a sick patient.

The diagnosis of delirium is clinical. The following features may be present:

• Usually acute or subacute presentation
• Fluctuating course
• Consciousness is clouded
• Impaired cognition
• Disorientation
• Poor attention
• Memory deficits - predominantly poor short-term memory
• Abnormalities of sleep-wake cycle including sleeping in the day
• Abnormalities of perception e.g. hallucinations or illusions
• Agitation
• Emotional lability
• Psychotic ideas are common but of short duration and of simple content
• Neurological signs e.g. unsteady gait and tremor

Only some of these symptoms may be present. The symptoms may coincide with underlying dementia - which is common. The diagnosis is still clinical and criteria are set out by the DSM-IV (Diagnostic and Statistical manual of Mental Disorders) as illustrated in the next section.

1. Disturbance of consciousness with decreased clarity of awareness and difficulties of attention.
2. Change in cognition e.g. memory deficit and disorientation or presence of perceptual abnormalities. These changes are not the result of previous or evolving dementia.
3. The disturbance develops over a short period of time and fluctuates.
4. There is evidence that the disturbance is the result of a general medical condition.

• Hypoactive subtype - apathy and quiet confusion are present and easily missed. This type can be confused with depression.
• Hyperactive subtype - agitation, delusions and disorientation are prominent and it can be confused with schizophrenia.
• Mixed subtype - patients vary from hypoactive to hyperactive.

• Check airway/breathing/circulation
• Conscious level
• Vital signs e.g. pulse oximetry, pulse, blood pressure, temperature
• Capillary blood glucose
• Full cardiovascular and respiratory examination
• Full abdominal and genitourinary examination if appropriate
• Full neurological examination
• Further examination depending on suspected problem e.g. ENT or rectal examination

Delirium is commonly mistaken for the following diagnoses

• Dementia - for example, Lewy body type which typically has a fluctuating course¹
• Depression
• Bipolar disorder
• Functional psychoses e.g. schizophrenia

These should be guided by the clinical presentation and are aimed at identifying an underlying cause of the delirium. Typical investigations that can be performed include:

• Full history and include collateral history and cognition testing e.g. mini-mental state examination.
• Full examination - look for sources of infection including ears and throat, look for rashes, lymphadenopathy and check for constipation.
• Bloods - include full blood count, urea and electrolytes and creatinine (see below), glucose, calcium, magnesium, liver function tests, thyroid function tests, cardiac enzymes, vitamin B12 levels, syphilis serology, autoantibody screen and PSA.
• Creatinine - this is vital to obtain creatinine clearance or an estimated glomerular filtration rate as this may effect the handling of medications and may predispose to drug induced delirium.
• Urine dipstick and microscopy.
• Blood cultures and serology if indicated.
• ECG.
• Pulse oximetry and arterial blood gas if indicated.
• Chest X ray and possibly abdominal X ray if indicated.
• Further imaging e.g. CT scan of the brain.
• Lumbar puncture may be necessary.
• EEG - this is usually only performed if there is doubt regarding the diagnosis and shows generalised diffuse slowing in 80% of delirious patients.

• This begins with increased awareness of delirium and regular measures of cognitive function. The underlying cause needs to be treated.
• It is common for patients with delirium to be admitted to hospital to help investigate the patient and for supportive management. However, some patients can be managed in the community and moving patients to a new environment can worsen delirium.
• In delirium the features are fluctuating and some patients are lucid between episodes and can thus provide informed consent during these periods. However, if the patient is not able to provide informed consent then they can be treated in their best interests under common law.

But more specific to delirium the management can be divided into:

1. Supportive management
2. Environmental measures
3. Medical management
4. Management post-discharge

Supportive management

• Clear communication.
• Reminders of the day, time, location and identification of surrounding persons.
• Have a clock available.
• Have familiar objects from home around patients especially glasses, walking aids and hearing aids.
• Staff consistency - both doctors and nurses.
• Relaxation e.g. watch television.
• Involve family and carers.

Environmental measures

• Avoid sensory extremes (over- or under- stimulation)
• Adequate space and sleep
• Single rooms if possible
• Avoid speciality jargon
• Control excess noise
• Control room lighting and a low wattage bulb at night
• Control room temperature (aim 21-23°C)
• Use health advocates (interpreters) where needed and if possible
• Maintain competence e.g. maintain walking in ambulant patients
• Adequate nutrition and attention to continence

Medical management

• Using drugs to treat delirium can lead to adverse effects and worsening of delirium, therefore careful consideration is required.
• Antipsychotics have beneficial effects in selected patients who are agitated and their onset is relatively fast.
• Haloperidol is preferred although there is a risk of extra-pyramidal side effects (EPSEs). Small doses should be used e.g. 0.5 -2.0 mg PO/IM/IV. It may be appropriate to consider a lower dose in elderly patients e.g. 0.5 mg.This can be repeated in 30 minutes if no response.
• Lorazepam is generally the first choice of benzodiazepines as it has a a rapid onset of action and a short duration. Lorazepam can be used alone or with low doses of haloperidol if there are concerns regarding EPSEs e.g. Parkinson's disease or Lewy body dementia. A starting dose of 0.5-1 mg orally can be given 2 hourly or 0.5-1 mg IV/IM(both to a maximum of 3 mg in 24 hour period).¹⁰
• Atypical antipsychotics have also been used, however olanzapine and risperidone should be avoided in the elderly as they have been associated with an increased risk of cerebrovascular disease.¹
• In delirium resulting from alcohol withdrawal (delirium tremens) a benzodiazepine such as diazepam or chlordiazepoxide is preferred. The benzodiazepine is usually used as a reducing course. Large doses may lead to sedation and therefore close observation is required.
• Mianserin appears to have a beneficial effect in reducing non-cognitive symptoms² but further research is necessary.

Management post-discharge

• The symptoms of delirium may last longer than the underlying condition.
• This means that some patients will be discharged with persisting abnormalities.
• These abnormalities include disorientation, inattention and depression.
• Families and carers may also need to be supported and given advice and reassurance.

• Hospital acquired infections e.g. Clostridium difficile and meticillin-resistant Staphylococcus aureus
• Pressure sores
• Fractures e.g. femoral or hip fractures from falls
• Residual psychiatric and cognitive impairment
• Some progress to stupor, coma and eventual death

The mortality rate in elderly hospitalised patients in the US is estimated at 22 - 76%.³ Some patients may not recover for months and one third of patients will continue to have delirium.¹ Many patients become institutionalised after delirium.¹ A prospective cohort study in Canada discovered that symptoms of delirium persist for up to a year after an episode.¹⁴ The same study revealed that there was a worse prognosis if the episode has a protracted in-patient course. Patients with malignancy or HIV also have a worse prognosis.³

Awareness of high risk patients and subsequent close observation for delirium with prompt assessment and management can potentially reduce morbidity and mortality.

One study has looked at methods of reducing post-operative delirium in patients with multiple risk factors.¹⁵ Their results are interesting and suggest that simple factors like hyperglycaemia, poor nutritional and poor functional states (e.g. delayed mobility) - all of which are easily prevented, account for adverse clinical outcomes in a subset of patients.

Further education of medical staff and awareness is required.¹⁶ Guidelines may be effective in the management of delirium. This has been studied by one group and they reported that guidelines reinforced by teaching sessions are effective - although statistical significance was not reached.¹⁷