Delirium

Delirium, also known as an acute confusional state, is an acute neuropsychiatric syndrome characterized by an altered level of consciousness, reduced awareness of the environment, impaired attention, disorientation to time, place, and sometimes person, and disturbances in cognition. The condition develops over a short period (hours to days), fluctuates throughout the day, and is usually secondary to an underlying medical, neurological, toxicological, or substance-related disorder. Delirium is a medical emergency requiring prompt recognition, identification of the underlying cause, and appropriate management to reduce morbidity and mortality.

Epidemiology

Delirium occurs in:

• Approximately 10–30% of hospitalized patients.

• Up to 50% of elderly hospitalized patients.

• A high proportion of patients admitted to intensive care units (ICUs).

• Patients with severe acute medical illness, where it is associated with increased morbidity, mortality, prolonged hospitalization, and long-term cognitive impairment.

Risk factors

Patient-related factors

• Advanced age (>65 years)

• Dementia or pre-existing cognitive impairment

• Previous episodes of delirium

• Severe medical illness

• Visual or hearing impairment

• Malnutrition

• Dehydration

Medical factors

• Infection (e.g., urinary tract infection, pneumonia, sepsis)

• Metabolic disturbances

• Hypoxia

• Renal failure

• Hepatic failure

• Stroke

• Head injury

Drug-related factors

• Polypharmacy

• Sedatives and hypnotics

• Anticholinergic medications

• Opioids

• Alcohol withdrawal

• Substance withdrawal

Environmental factors

• Sleep deprivation

• Intensive care unit admission

• Immobilization

• Social isolation

• Sensory deprivation

Pathophysiology

Delirium results from acute cerebral dysfunction caused by multiple interacting mechanisms, including:

• Neurotransmitter imbalance characterized by decreased acetylcholine and increased dopamine activity.

• Neuroinflammation.

• Oxidative stress.

• Impaired cerebral metabolism.

• Disturbance of the sleep–wake cycle.

• Systemic inflammatory responses affecting cerebral function.

Clinical presentation

Delirium presents with an acute onset of fluctuating disturbances in attention, awareness, cognition, behaviour, and consciousness. Patients may exhibit hyperactive, hypoactive, or mixed forms of delirium.

Clinical subtypes

Hyperactive delirium

• Agitation

• Restlessness

• Hallucinations

• Aggressive behaviour

Hypoactive delirium

• Lethargy

• Reduced responsiveness

• Withdrawal

• Slowed movements

Mixed delirium

• Alternating episodes of hyperactivity and hypoactivity.

Symptoms

Reduced awareness of the environment

• Inability to maintain attention.

• Difficulty shifting attention between topics.

• Becoming fixed on one idea.

• Easily distracted.

• Withdrawal with little interaction.

• Reduced response to the surrounding environment.

Cognitive impairment

• Poor recent memory.

• Disorientation to time, place, and sometimes person.

• Difficulty speaking or recalling words.

• Rambling or incoherent speech.

• Difficulty understanding speech.

• Difficulty reading or writing.

Behavioural symptoms

• Visual hallucinations.

• Restlessness.

• Agitation.

• Combative behaviour.

• Calling out or moaning.

• Quiet and withdrawn behaviour, especially in older adults.

• Slowed movement.

• Lethargy.

• Disturbed sleep pattern.

• Reversal of the normal sleep–wake cycle.

Emotional disturbances

• Anxiety

• Fear

• Paranoia

• Depression

• Irritability

• Anger

• Euphoria

• Apathy

• Rapid and unpredictable mood changes

• Personality changes

Clinical signs

• Altered level of consciousness.

• Reduced attention.

• Fluctuating mental status.

• Disorientation.

• Poor concentration.

• Memory impairment.

• Impaired cognition.

• Psychomotor agitation or retardation.

• Hallucinations.

• Delusions.

• Behavioural disturbance.

• Evidence of the underlying medical illness.

Differential diagnosis

• Dementia

• Acute psychotic disorder

• Schizophrenia

• Major depressive disorder with psychotic features

• Substance intoxication

• Substance withdrawal

• Non-convulsive status epilepticus

• Encephalitis

• Metabolic encephalopathy

Diagnostic criteria

Diagnosis is primarily clinical and is based on:

• Acute onset with a fluctuating course.

• Altered level of consciousness.

• Reduced awareness and impaired attention.

• Disorientation.

• Cognitive impairment.

• Behavioural disturbance.

• Hallucinations or paranoia where present.

• Evidence of an underlying medical, neurological, toxicological, or substance-related cause.

Primary psychiatric disorders should be excluded before diagnosing delirium.

Investigations

Initial assessment

• Comprehensive physical examination.

• Neurological examination.

• Medication review.

Laboratory investigations

• Full blood picture (FBP)

• Blood glucose

• Serum electrolytes

• Renal function tests (RFT)

• Liver function tests (LFT)

• Thyroid function tests

• Infection screening

• Blood cultures where indicated

• Urinalysis

Additional investigations

• Arterial blood gas

• Toxicology screen

• Electrocardiogram (ECG)

• Chest X-ray

• CT or MRI of the brain when neurological signs or structural brain disease are suspected

Management

Management focuses on rapid stabilization, ensuring patient safety, identifying and treating the underlying cause, controlling severe agitation when necessary, and preventing complications.

Initial management should include:

• Assess airway, breathing, and circulation.

• Ensure the safety of the patient and healthcare staff.

• Identify and treat the underlying medical condition.

• Assess for reversible causes such as infection, hypoxia, metabolic disturbances, medication toxicity, or substance withdrawal.

• Monitor vital signs and neurological status regularly.

Non-pharmacological treatment

Non-pharmacological interventions are the first-line management for all patients and should include:

• Control the acute disturbance safely.

• Perform a thorough physical assessment and appropriate investigations to identify and treat the underlying medical condition.

• Provide a calm, well-lit, low-stimulation environment.

• Frequently reorient the patient to time, place, and person.

• Encourage the presence of family members or caregivers where appropriate.

• Maintain adequate hydration and nutrition.

• Correct sensory deficits using hearing aids or glasses where required.

• Promote normal sleep–wake cycles.

• Encourage early mobilization when clinically appropriate.

• Avoid physical restraints whenever possible.

Pharmacological treatment

Pharmacological treatment should be reserved for patients with severe agitation, behaviour that poses a risk to themselves or others, or when agitation interferes with essential medical treatment.

Treat the underlying medical condition whenever present. Other symptoms should be managed symptomatically.

Acute management

• Haloperidol – 5 mg – IM – stat; repeat after 30–60 minutes if required (maximum dose: 20 mg within 24 hours).

AND/OR

• Diazepam – 10 mg – IV – stat.

OR

• Lorazepam – 1–4 mg – IM – stat.

Switch to the oral route once adequate behavioural control has been achieved.

Management according to underlying cause

Infection

• Initiate appropriate antimicrobial therapy based on the suspected source of infection.

Metabolic disturbances

• Correct electrolyte abnormalities, hypoglycaemia, dehydration, or acid-base disorders.

Hypoxia

• Administer oxygen therapy and treat the underlying respiratory or cardiovascular condition.

Drug-induced delirium

• Review and discontinue or adjust offending medications where appropriate.

Alcohol or sedative withdrawal

• Manage according to established withdrawal protocols.

Neurological disorders

• Investigate and treat stroke, seizures, or other neurological conditions as indicated.

Referral

Urgently refer patients with delirium to the appropriate medical specialty.

Immediate referral is indicated for patients with:

• Persistent or worsening altered consciousness.

• Severe agitation requiring repeated sedation.

• Respiratory compromise.

• Suspected neurological emergency.

• Severe sepsis.

• Hemodynamic instability.

• Failure to identify the underlying cause.

• Requirement for intensive care.

Complications

• Falls and traumatic injury.

• Aspiration pneumonia.

• Pressure ulcers.

• Functional decline.

• Prolonged hospitalization.

• Long-term cognitive impairment.

• Respiratory depression related to sedative medications.

• Neuroleptic malignant syndrome.

• Increased mortality.

Prognosis

The prognosis depends on the underlying cause, the patient's age, baseline cognitive status, and the speed of diagnosis and treatment. Delirium is often reversible with prompt management of the precipitating cause; however, older adults and patients with severe underlying illness may experience prolonged recovery, persistent cognitive impairment, or increased mortality.

Prevention

Prevention focuses on identifying high-risk patients and implementing multicomponent preventive strategies, including maintaining hydration, optimizing nutrition, avoiding unnecessary sedative medications, preserving normal sleep patterns, treating pain adequately, preventing infection, correcting sensory impairment, promoting early mobilization, and minimizing environmental stressors.