Delirium

Synonyms: acute confusional state, acute brain failure, acute organic reaction, postoperative psychosis

What is delirium?¹

Delirium (sometimes called acute confusional state) is an acute, fluctuating syndrome of encephalopathy causing disturbed consciousness, attention, cognition, and perception. It usually develops over hours to days. Behavioural disturbance, personality changes, and psychotic features may occur.

Subtypes of delirium

• 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.

How common is delirium? (Epidemiology)²

The incidence and prevalence of delirium vary depending on the diagnostic criteria used, the population studied, and the study setting:¹

• The prevalence in the general population (across all healthcare settings) is about 0.4%.

• The prevalence in the community is thought to be between 1–2% but may be as high as 14% in people aged over 85 years.

• The prevalence among people aged 65 years and over living in long-term care is 10–40%.

• Delirium is thought to affect up to 50% of older people (over 65 years) in hospital, 30% of older people (over 65 years) in emergency departments, complicate 17–61% of major surgical procedures, and occur in 70–87% of Intensive Care Unit admissions.

• One review found that the prevalence of persistent delirium (continuing until or after discharge) in hospital patients (aged over 50 years) was 44.7%. The combined proportions of persistent delirium at 1, 3, and 6 months after discharge from hospital were 32.8%, 25.6%, and 21%.

• The prevalence of delirium in the palliative setting is estimated to be present in 6–74% of people in palliative care units and up to 88% in those people in the weeks leading up to death. The most common subtype is hypoactive delirium.

Risk factors for delirium^{3 4}

Delirium typically occurs in people with predisposing risk factors when new precipitating factors (such as some medications or infection) are added. The following are risk factors which are associated with an increased risk of delirium:

• Age 65 years or older.

• Male sex.

• Pre-existing cognitive deficit - eg, dementia, stroke.

• Severity of dementia.

• Multiple comorbidities.

• Previous episode of delirium.

• Operative factors - eg, 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.

• Current hip fracture or severe illness.

• Drug use (implicated in nearly half of cases) and dependence - eg, benzodiazepines.

• Substance misuse - eg, alcohol.

• Extremes of sensory experience - eg, hypothermia or hyperthermia.

• Visual or hearing problems.

• Poor mobility.

• Social isolation.

• Stress.

• Terminally ill.

• Movement to a new environment.

• ICU admission.

• Urea/creatinine abnormalities.

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.

Delirium causes (aetiology)¹

• Acute infections:
  

  • Urinary tract infection.

  • Pneumonia.

  • Sepsis.

  • Viral infections.

  • Meningitis.

  • Encephalitis.

  • Cerebral abscess.

  • Malaria.

• Prescribed drugs:

  • Benzodiazepines.

  • Analgesics - eg, morphine.

  • Anticholinergics.

  • Anticonvulsants.

  • Anti-Parkinsonism medications.

  • Steroids.

• Surgical:
  

  • Postoperative.

• Toxic substances:
  

  • Substance misuse or withdrawal.

  • Alcohol - acute intoxication or withdrawal.

  • Carbon monoxide (CO) poisoning.

  • Exposure to heavy metals.

  • Barbiturate withdrawal.

• Vascular disorders:
  

  • Cerebrovascular haemorrhage or infarction.

  • Cardiac failure or ischaemia.

  • Subdural haemorrhage.

  • Subarachnoid haemorrhage.

  • Vasculitis - eg, systemic lupus erythematosus (SLE).

  • Cerebral venous thrombosis.

  • Migraines.

• Metabolic causes:
  

  • Hypoxia.

  • Electrolyte abnormalities - eg, hyponatraemia and hypercalcaemia.

  • Hypoglycaemia or hyperglycaemia.

  • Hepatic impairment.

  • Renal impairment.

• Vitamin deficiencies:
  

  • Thiamine deficiency.

  • Nicotinic acid deficiency.

  • Vitamin B12 deficiency.

• Endocrinopathies:
  

  • Hypothyroidism and hyperthyroidism.

  • Hypopituitarism.

  • Hypoparathyroidism or hyperparathyroidism.

  • Cushing's syndrome.

  • Porphyria.

  • Carcinoid syndrome.

• Trauma:
  

  • Head injury.

• Epilepsy:
  

  • For example, postictally.

• Neoplasia:
  

  • Primary cerebral malignancy.

  • Secondaries in the brain.

  • Paraneoplastic syndromes.

• Others:
  

  • Urinary retention.

  • Faecal impaction.

• Multiple aetiology.

• Unknown aetiology.

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

Delirium symptoms¹

Making an accurate assessment relies on a collateral history to determine the patient's premorbid level of function. There are very useful cognitive function screening tools - eg, the abbreviated mental test score and the confusion assessment method.³ The mental tests should be performed regularly and on all high-risk patients. However, it may not be appropriate or possible to do these tests on a sick patient.

There is often an indication of an underlying precipitating factor such as infection or an adverse drug reaction. The presenting features are typically a sudden change in behaviour that may be reported. Symptoms are typically intermittent or fluctuate in severity). Lucid intervals usually occur during the day with the worst disturbance at night. Falling and loss of appetite are often warning signs for delirium. Behaviour changes (over hours to days) may include:

• Altered cognitive function: disoriented, memory and language impairment, worsened concentration, slow responses, and confusion. May be unable able to recall details of current illness, instructions, or names.

• Inattention: easily distractible and difficulty focusing and moving attention from one thing to another. Unable to maintain a conversation or follow reasonable commands.

• Disorganised thinking: may have disorganised, rambling, or irrelevant conversation, unclear or illogical flow of ideas, and difficulty expressing needs and concerns.

• Altered perception: paranoid delusions, misperceptions, or visual or auditory hallucinations.

• Altered physical function:

  • Hyperactive delirium: increased sensitivity to immediate surroundings with agitation, restlessness, sleep disturbance, wandering and hypervigilance.

  • Hypoactive delirium: lethargic, reduced mobility and movement, lack interest in daily activities, reduced appetite, and quiet and withdrawn.

  • Mixed delirium: combination of hyperactive and hypoactive features.

• Altered social behaviour: intermittent and labile changes in mood and/or emotions (eg fear, paranoia, anxiety, depression, irritability, apathy, anger, or euphoria). Behaviour may be inappropriate, and may not co-operate with reasonable requests or become withdrawn.

• Altered level of consciousness: clouding of consciousness, reduced awareness of surroundings, and sleep-cycle disturbances (daytime drowsiness, night-time insomnia, disturbed sleep, or complete sleep cycle reversal). May be subtle, and initially only apparent as lethargy or distractibility.

Only some of these symptoms may be present. The symptoms may coincide with underlying dementia - which is common.

Assessment^{3 4 1}

At presentation, assess people at risk for recent (within hours or days) changes or fluctuations that may indicate delirium. These may be reported by the person at risk, or a carer or relative. These changes may affect:

• Cognitive function: for example, worsened concentration, slow responses, confusion

• Perception: for example, visual or auditory hallucinations

• Physical function: for example, reduced mobility, reduced movement, restlessness, agitation, changes in appetite, sleep disturbance

• Social behaviour: for example, difficulty engaging with or following requests, withdrawal, or alterations in communication, mood and/or attitude.

If any of these changes are present, the person should have an assessment. Also be particularly aware for changes that may indicate hypoactive delirium, which are often missed, such as withdrawal, slow responses, reduced mobility and movement, worsened concentration and reduced appetite.

The assessment should include:

• Check:
  

  • Airway/breathing/circulation.

  • Conscious level.

  • Vital signs - eg, 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 the suspected problem - eg, ENT or rectal examination.

There are several assessment methods available for the diagnosis of delirium. If indicators of delirium are identified, NICE recommends a health or social care practitioner who is competent to do so should carry out an assessment using the 4AT. The 4A’s test (4AT) is a short, four-item tool designed for use in clinical practice. The four items are alertness, cognition (a short test of orientation), attention (recitation of the months in backwards order), and the presence of acute change or fluctuating course (see the link to the 4A's test in Further Reading for more information).

Differential diagnosis¹

Delirium is commonly mistaken for the following diagnoses:

• Dementia - for example, Lewy body type, which typically has a fluctuating course.

• Depression.

• Bipolar disorder.

• Functional psychoses - eg, schizophrenia.

• Thyroid disease.

• Non-convulsive epilepsy.

• Charles Bonnet syndrome.

Investigations^{3 4}

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, including collateral history and cognition testing - eg, mini mental state examination.

• Full examination - look for sources of infection, including the ears and throat; look for rashes, lymphadenopathy and check for constipation.

• Bloods - include FBC, U&Es and creatinine, glucose, calcium, magnesium, LFTs, TFTs, cardiac enzymes, vitamin B12 levels, syphilis serology, autoantibody screen and PSA. Creatinine is vital to obtain an estimated glomerular filtration rate (eGFR), as this may indicate impaired renal function and affect the handling of medications, and may predispose to drug-induced delirium.

• Urine dipstick testing and microscopy.

• Blood cultures and serology, if indicated.

• ECG.

• Pulse oximetry and arterial blood gas, if indicated.

• CXR and possibly abdominal X-ray, if indicated.

• Further imaging - eg, CT scan of the brain.

• Lumbar puncture may be necessary.

• Electroencephalography (EEG) - this is usually only performed if there is doubt regarding the diagnosis.

Delirium treatment and management^{3 4}

• 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.

• If the patient becomes violent or is a danger to themself, it may be possible to manage them initially using verbal and non-verbal de-escalation techniques.⁵

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

• Supportive management.

• Environmental measures.

• Medical management.

• 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. Treat impacted earwax and ensure the person has functioning spectacles, or that hearing aids are available and used if needed.

• Staff consistency - both doctors and nurses.

• Relaxation - eg, watch television.

• Involve the family and carers.

Environmental measures

• Avoid sensory extremes (over- or under-stimulation).

• Adequate space and sleep; patients should be encouraged to maintain a normal sleep/wake cycle. The use of hypnotics to aid sleep is usually discouraged and these may contribute to delirium. Melatonin has been tried but data are lacking to support its routine use.⁶

• Single rooms if possible.

• Avoid speciality jargon.

• Control excess noise.

• Control room lighting and have a low-wattage bulb at night.

• Control room temperature (aim for 21-23°C).

• Use health advocates (interpreters) where needed and if possible.

• Maintain competence - eg, maintain walking in ambulant patients.

• Adequate nutrition. Many patients with delirium may not eat as much as usual and will need assistance with their oral intake. Offer foods rich in calories and that are known to be favoured by the patient. Record and monitor the patient's weight, and consider referral to a dietician, based on locally agreed pathways.

A note on managing wandering: the delirious patient may have a tendency to wander. It is common to think of restraining and/or sedating the patient in these circumstances. However, this may only worsen the situation. The management should aim to keep the patient safe, using the least restrictive management - eg, think of causes of agitation or wandering (eg, need for the toilet). These causes should be rectified; if this is not possible, using distraction may help. Relatives or carers may be helpful in this scenario.

Medical management⁷

Correct underlying precipitants including:

• Infection: whilst infection is a common cause of delirium, it is not the only cause and is not present in all cases. Urinary tract infection, in particular, is commonly over-diagnosed in this scenario.

• Constipation: many older patients with delirium who do not eat or drink much may become constipated. Laxatives should be prescribed to constipated patients in line with local policy, and taking into account patient preferences - eg, whether they are capable of the volume of liquid necessary for some laxatives.

• Urinary retention: this is commonly missed in older people. It is not uncommon to still pass urine, and indeed have urinary frequency and urgency, in the presence of significant post-void residual urine volumes. Urinary retention may contribute to agitation. Underlying contributory factors such as constipation, use of anticholinergic drugs and immobility should be addressed. If a catheter is required, it should be used only while the person is unwell, and plans for its removal should be considered part of the process of insertion.

• Dehydration and electrolyte abnormalities: many (although not all) patients with delirium are dehydrated and a clinical assessment of volume status should be undertaken; this will probably include assessment of postural changes in blood pressure. Severely dehydrated patients or those with hypotension or suspicion of acute kidney injury should have blood tests and usually be referred to secondary care for further assessment. Patients with mild dehydration or who are not currently dehydrated should be encouraged with oral rehydration. This may be achieved by offering fluids and recording intake, aiming for an intake adequate to restore and/or maintain hydration. Another strategy may be to offer small sips of fluids - eg, 60 ml with each interaction with the patient.

• Pain: regular paracetamol is a part of many multi-component interventions for delirium. A weak opioid should be considered on a prn basis and analgesia titrated to pain, whilst being mindful of common side-effects of opioid analgesia. This means that drugs like tramadol, Oramorph®, buprenorphine and codeine can be useful - but close surveillance will be needed to respond quickly to the possibility of making confusion worse.

• Medication: consider whether a medication has been stopped or started recently. See below for further information.

Optimise treatment of comorbidities as symptoms caused by sub-optimally managed conditions - eg, COPD or diabetes - may increase agitation.

Pharmacological 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, particularly those who are aggressive and do not respond to verbal and non-verbal de-escalation techniques.

• Haloperidol or olanzapine are preferred, using the lowest possible dose for the shortest possible time (normally a week or less). The dose should be titrated gradually until symptoms are controlled. It should be noted that neither drug has a UK licence for this use so normal considerations regarding the use of unlicensed medicines should apply. Note that both drugs have the potential to cause extrapyramidal side-effects and should be used in caution or avoided altogether in some patients (eg, people with Lewy-body Parkinson's disease).

• 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. See also the separate Acute Alcohol Withdrawal and Delirium Tremens article.

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.

Drug-induced delirium

Drug-induced delirium is very common amongst the elderly. Drugs can be the sole cause of delirium in some. Common drug causes of delirium include:

• Benzodiazepines.

• Narcotic analgesics.

• First-generation antihistamines.

• Antispasmodics.

• Flouroquinolones.

• Warfarin.

• Captopril.

• Theophylline.

• Isosorbide dinitrate.

• Dipyridamole.

• Furosemide.

• Lithium.

• Tricyclic antidepressants.

• Cimetidine.

• Anti-arrhythmics.

• Statins.⁸

• Digoxin.

• Steroids.

• Beta-blockers.

• Over-the-counter medications - eg, liquid medications containing alcohol or chlorphenamine.

The role of medications may be suggested by a temporal relationship between onset of delirium and start of new medication. However, this is not always the case and practitioners need to be aware of this. Medication lists should be thoroughly reviewed in delirium. The exact mechanism of delirium is unclear but it is postulated that central cholinergic pathway blockade is a major factor. This may explain why anticholinergic medications readily lead to delirious states. It may be that this factor along with the pharmacokinetic changes that occur later in life and comorbidities increase the susceptibility of elderly patients to drug-induced delirium.

Management involves stopping the offending drug; however, the actual causal medication is often unknown. In this case, all unnecessary medications should be stopped or doses reduced. These medications can be increased or re-introduced when the patient has improved. Furthermore, it may be prudent to prescribe alternatives to medications with high anticholinergic activity - eg, use of proton pump inhibitors rather than cimetidine.

Complications

• Hospital-acquired infections - eg, Clostridium difficile and meticillin-resistant Staphylococcus aureus (MRSA).

• Pressure sores.

• Fractures - eg, femoral or hip fractures from falls.

• Residual psychiatric and cognitive impairment.

• Some progress to stupor, coma and eventual death.

Prognosis¹

• Delirium has a fluctuating course and recovery can be rapid or take weeks to months.
  Persistent delirium occurs more often in older hospitalized patients, and is associated with adverse outcomes.

• Physical function can be impaired for 30 days or more after discharge in people who have developed delirium in hospital.

• ‘Subsyndromal’ delirium (symptoms of disorientation, inattention, and memory impairment that do not fulfil the diagnostic criteria for delirium) may persist for up to 12 months.

• Cognitive impairment is common in surgical patients who develop delirium and can persist for up to a year.

• Factors associated with a poorer prognosis include:

  • Pre-existing dementia or cognitive impairment.

  • Older age and frailty.

  • Hypoxic illness such as severe pneumonia.

  • Visual impairment.

  • Hypoactive subtype of delirium.

  • Longer duration and increased severity of delirium.

Delirium prevention^{3 4}

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

The National Institute for Health and Care Excellence (NICE) recommends a 'tailored multicomponent intervention package' which consists of the following:³

• Multidisciplinary team approach to the prevention of delirium.

• Patients should be assessed within 24 hours of admission, making note of factors that may precipitate and worsen delirium.

• There are various interventions listed in the NICE guidance, based on the identified clinical factors - for example:
  

  • Cognitive impairment or disorientation - provide appropriate lighting and regularly orientate the person. Promote cognitively stimulating activities and regular visits from people well known to the patient.

  • Hypoxia - identify and correct with the appropriate amount of oxygen.

  • Pain - assess verbally and non-verbally and treat.

  • Medications - should be reviewed on a daily basis and non-essential medication stopped.

  • Other factors include dehydration, constipation, reduced mobility, infection, poor nutrition, sensory impairment and sleep disturbance.

Routine use of antipsychotic medications - eg, haloperidol for prevention of delirium - is not supported by research data.⁹