Delirium and agitation

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Delirium changes over hours. Core features are impaired attention and altered awareness, with disorganised thinking, perceptual disturbance, sleep reversal and variable arousal. Hyperactive delirium is visible, but hypoactive delirium is more common and easily missed. Ask family what the person was like days ago and whether alertness, conversation and recognition vary across the day.

Assessment starts at the bedside. Check observations, oxygenation, capillary glucose, hydration, pain behaviour, mouth, chest, abdomen, bladder, bowel, skin, neurology and medicines. The 4AT supports rapid recognition and does not require special training, but a score is not the end of diagnosis. Identify whether dementia or communication disability affects the baseline and use an interpreter or aids.

Common palliative contributors cluster. Opioid metabolites accumulate during renal failure and cause hallucinations or myoclonus. Corticosteroids disturb sleep and can provoke mood or psychotic symptoms. Anticholinergics cause retention and cognitive change. Infection, hypercalcaemia, hepatic failure, hypoxia, constipation and unfamiliar environments interact. More than one cause is the rule, so correcting one abnormal result may not resolve the syndrome.

Non-drug care reduces threat and sensory error. Use a quiet well-lit room, visible clock and familiar objects, glasses and hearing aids. Reintroduce yourself, give one-step explanations and avoid repeated staff changes. Encourage daytime movement and light, protect night sleep, treat thirst and pain and invite a familiar person when calming. Do not argue with hallucinations; acknowledge fear and orient gently.

Medicine is reserved for severe distress or risk when de-escalation is insufficient. NICE advises short-term haloperidol at the lowest clinically appropriate dose after risk assessment. Older or frail people are particularly vulnerable to QT and extrapyramidal effects. Avoid haloperidol in Parkinson's disease or Lewy-body dementia unless specialist advice identifies an exceptional justified use. Review ECG and interactions where feasible and proportionate.

Terminal agitation is not automatically irreversible. Check pain, retention, impaction, pump delivery, medication withdrawal and family concern. When dying is recognised and causes cannot be reversed without disproportionate burden, the goal may become relief of distress. Specialist protocols may use levomepromazine for severe delirium and midazolam for anxiety or refractory agitation, titrated proportionately rather than aiming for unconsciousness by default.

Capacity must be assessed for the actual decision during the best achievable lucid period. A delirium diagnosis does not prove inability for every choice. If capacity is absent, follow a valid advance decision or authorised representative and otherwise make a best-interests decision. Any restraint or covert administration must be necessary, proportionate, least restrictive and reviewed under applicable law.

Key points

Delirium is an acute or subacute fluctuating disturbance of attention, awareness and cognition caused by one or more physical or medication factors.
Look actively for hypoactive delirium: drowsiness, reduced speech, poor intake, withdrawal and slowed movement are easily mistaken for fatigue or depression.
First-line screening uses the 4AT or another locally validated tool, followed by clinical diagnosis, collateral baseline and focused examination.
Check pain, oxygenation, glucose, infection, bladder, bowel, hydration, renal and hepatic function, calcium, medicines and withdrawal according to the clinical context.
Use glasses, hearing aids, daylight, orientation, sleep protection, familiar people, mobility, hydration and calm repeated explanation before medicine when safe.
Treat a reversible cause when likely benefit matches goals; near death, use only investigations and interventions that can improve comfort or an agreed outcome.
If severe distress or risk persists despite de-escalation, use short-term low-dose haloperidol only after Parkinson, Lewy-body, cardiac and interaction review.
For refractory terminal agitation, specialist palliative care may use levomepromazine, midazolam or both with explicit proportional-sedation goals and frequent review.
The gold-standard record describes attention and fluctuation, precipitant assessment, capacity, non-drug measures, target behaviour, medicine response and stop or review point.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Systemic illness

Infection, hypoxia, shock, organ failure, anaemia and inflammatory cancer states disrupt brain function and often coexist.

Metabolic disturbance

Hypercalcaemia, hyponatraemia, hypoglycaemia, dehydration, uraemia, hepatic encephalopathy and carbon-dioxide retention alter neuronal activity, attention and arousal.

Medication and withdrawal

Opioids, anticholinergics, corticosteroids, sedatives, dopamine agents and abrupt alcohol or benzodiazepine withdrawal can precipitate distinct delirium patterns.

Brain vulnerability and environment

Dementia, metastases, sensory loss, sleep disruption, unfamiliar settings, immobility and social isolation reduce cognitive reserve and increase susceptibility.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Network dysfunction
Diffuse disturbance of attention and arousal networks prevents sustained focus, coherent integration of information and stable sleep-wake regulation.
2
Neurotransmitter imbalance
Reduced cholinergic activity, excess dopaminergic signalling and altered GABA, glutamate and serotonin contribute cognitive, perceptual and motor features.
3
Inflammatory signalling
Systemic cytokines, endothelial dysfunction and blood-brain barrier change disrupt vulnerable neural circuits during infection and advanced disease.
4
Metabolic energy failure
Hypoxia, hypoglycaemia, impaired clearance and electrolyte disturbance reduce neuronal energy or membrane stability and alter consciousness.
5
Circadian disorganisation
Illness, nocturnal disturbance, absent daylight and sedatives fragment sleep and worsen evening confusion, attention and behavioural control.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Hyperactive delirium

Restlessness, pulling lines, wandering, fear, irritability, hallucinations and sleep reversal occur with fluctuating attention and awareness.

Hypoactive delirium

Drowsiness, slowed responses, quiet withdrawal, reduced intake and poor engagement conceal serious organic dysfunction and often go unrecognised.

Mixed pattern

The patient alternates between agitation and reduced arousal over hours, making a single calm observation falsely reassuring.

Opioid neurotoxicity

Myoclonus, allodynia, vivid hallucinations and sedation after dose or renal change suggests metabolite accumulation.

Withdrawal delirium

Autonomic overactivity, tremor, agitation, hallucinations or seizures after stopping alcohol or benzodiazepine requires a specific withdrawal pathway.

Immediate safety riskRed flag

Violence, falls, airway compromise, line removal or inability to deliver essential care requires urgent least-restrictive safety intervention.

Red flags requiring action

New inattention, altered arousal or fluctuating cognition is delirium until assessed, including quiet withdrawal and reduced intake.
Focal neurology, severe headache, seizure, meningism, trauma or anticoagulation raises intracranial emergency and imaging need.
Hypoxia, hypotension, fever, hypoglycaemia, retention, impaction or uncontrolled pain requires prompt treatment rather than sedation alone.
Myoclonus, hallucinations, allodynia and drowsiness during opioid therapy suggests neurotoxicity, particularly after renal decline.
Haloperidol can cause serious extrapyramidal and cardiac harm and is especially hazardous in Parkinson's disease and dementia with Lewy bodies.
Benzodiazepines can worsen ordinary delirium but may be required for alcohol or benzodiazepine withdrawal, seizure, or refractory terminal agitation under a defined plan.
Covert medicine, restraint or deprivation of liberty requires necessity, proportionality, best-interests reasoning and the relevant legal safeguards.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
First-line 4AT and clinical assessmentFirst stepFirst line
Why
Screen alertness, orientation, attention and acute fluctuation and establish a bedside delirium diagnosis.
Interpretation and limitations
A score of 4 or more suggests delirium or cognitive impairment, but clinical context, baseline and communication support determine interpretation.
02
Collateral baseline and timeline
Why
Ask family and staff about usual cognition, function, sleep, personality, onset, fluctuation and recent medicines or events.
Interpretation and limitations
Acute change from baseline distinguishes delirium from stable dementia and may reveal a temporal drug, infection or environment trigger.
03
ABCDE, pain, bladder and bowel review
Why
Identify hypoxia, shock, hypoglycaemia, pain, retention, impaction, dehydration and other immediately reversible distress.
Interpretation and limitations
Treat bedside contributors before sedating; response can confirm an important mechanism and restore capacity.
04
Targeted blood and infection tests
Why
Assess full blood count, renal and liver function, glucose, calcium, electrolytes, inflammation and cultures when results can alter care.
Interpretation and limitations
Choose tests by goals and trajectory; in the last hours, burdensome testing without a comfort-changing treatment may be inappropriate.
05
Medication, patch and pump reconciliation
Why
Identify opioids, anticholinergics, steroids, sedatives, dopaminergic drugs, withdrawal, infusion error and renal dose mismatch.
Interpretation and limitations
Hold or change plausible offending treatment carefully and avoid abrupt withdrawal from dependence-forming medicines.
06
Neurological testing or imaging
Why
Investigate focal deficit, trauma, seizure, severe headache, anticoagulation or suspected intracranial tumour, bleed or infection.
Interpretation and limitations
CT, MRI, EEG or lumbar puncture follows the suspected pathology and safety; do not perform lumbar puncture when raised intracranial pressure is possible.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Dementia

Chronic progressive cognitive decline without prominent daily fluctuation differs from delirium, although both commonly coexist and collateral history is essential.

Depression

Persistent low mood, anhedonia and slowed responses can resemble hypoactive delirium but usually preserve attention and stable consciousness.

Psychosis or mania

Organised delusions, sustained elevated mood and relatively preserved attention suggest psychiatric illness, while late-life first presentation still demands medical assessment.

Seizure and postictal state

Automatisms, unresponsiveness, focal signs and stereotyped episodes may represent non-convulsive seizure or postictal confusion and require neurological review.

Expected dying

Reduced consciousness can accompany the final hours, but acute pain, retention, medicine toxicity and family-distressing agitation remain assessable and treatable.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01Initial deliriumRecognise, protect and find contributorsFirst stepA person develops acute or fluctuating inattention, altered arousal, cognition or behaviour.

1Use 4AT and clinical assessment, obtain collateral baseline and perform ABCDE, glucose, pain, bladder, bowel, neurological and medication review.
2Treat urgent hypoxia, infection, metabolic change, retention, impaction or toxicity and institute orientation, sensory, sleep and mobility measures.
3Assess capacity and risk, explain the syndrome to family and review repeatedly because cause, arousal and decision ability fluctuate.

02Distress or dangerUse the least restrictive effective responseEscalationSevere agitation, hallucination or behaviour threatens the patient or others after initial de-escalation.

1Reduce noise and people, use one calm communicator and familiar support, meet pain and basic needs and remove avoidable lines or environmental hazards.
2AlternativeIf risk persists, use the lowest short-term local haloperidol regimen only after Parkinson, Lewy-body, QT and interaction assessment, or seek specialist alternative.
3Observe effect and adverse events closely, stop as soon as no longer needed and document capacity, proportionality and any restraint safeguards.

03Terminal agitationRelieve refractory distress proportionatelyThe person is dying and agitation remains severe after comfort-relevant contributors and non-drug measures are addressed.

1Confirm the symptom and goal with patient or lawful process, check pain, retention, impaction, opioid toxicity and pump delivery and explain uncertainty to family.
2Obtain specialist palliative advice and use patient-specific levomepromazine, midazolam or other local treatment with rescue and continuous-infusion plan only as needed.
3Review comfort, arousal, breathing, adverse effects and family understanding frequently and titrate to relief rather than automatic deep sedation.

04Capacity and restraintProtect rights during fluctuating cognitionThe patient resists treatment, tries to leave or cannot participate safely in a significant decision.

1Support communication and reassess decision-specific capacity at an optimal time, treating reversible delirium and seeking the person's current view.
2If capacity is absent, identify advance decision or authorised proxy and make a documented best-interests choice using the least restrictive viable option.
3Apply legal safeguards for restraint, covert administration or liberty restriction, seek senior or legal review for material dispute and review necessity frequently.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Treats severe distressing hallucinations or agitation when de-escalation is ineffective and medicine is necessary for safety or comfort.

Haloperidol for severe distress or risk

In a frail palliative adult, start 500 micrograms to 1 mg orally or subcutaneously as a patient-specific dose under the local delirium protocol, repeat only after reviewed response and keep the total and duration as low and short as possible.

Avoid in Parkinson's disease and Lewy-body dementia without specialist advice; review QT, electrolytes, interacting medicines, akathisia, rigidity, swallowing and hepatic impairment.

Provides broader antipsychotic and sedative effect for severe terminal agitation that has not responded to safer initial treatment.

Levomepromazine for refractory terminal delirium

Specialist palliative protocols may use 6.25 to 12.5 mg subcutaneously as rescue and a patient-specific 24-hour infusion, often beginning around 25 mg, with cautious titration to relief.

Marked sedation, hypotension, anticholinergic effects, QT prolongation and lowered seizure threshold occur; use lower exposure in frailty and hepatic dysfunction and seek specialist oversight.

Reduces severe anxiety and motor agitation and supports proportional sedation when refractory distress persists in the last days.

Midazolam for refractory terminal agitation

Use 2.5 mg subcutaneously as a patient-specific rescue and, when repeated benefit establishes need, commonly 5 to 10 mg over 24 hours by continuous subcutaneous infusion under the local specialist protocol.

Can worsen ordinary delirium and depress breathing with opioids; check pain and reversible causes, use lower doses in frailty or hepatic impairment and review arousal and goal.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Injury and treatment disruption

Falls, line removal, aspiration, pressure damage and refusal or inability to take essential treatment cause avoidable clinical deterioration.

Loss of decision capacity

Fluctuating inability to understand or weigh information complicates urgent treatment, discharge and advance-care decisions and requires repeated assessment.

Prolonged cognitive decline

Delirium can persist after the precipitant improves and is associated with greater dependence, institutionalisation and mortality.

Medication harm

Antipsychotics and sedatives can cause extrapyramidal effects, QT prolongation, hypotension, aspiration, falls and clinically important respiratory depression.

Family and staff trauma

Unexplained personality change, accusations and uncontrolled agitation can create fear, guilt, conflict, exhaustion and complicated bereavement.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Repeat 4AT components, arousal and observed attention at different times and after treatment rather than declaring delirium resolved from one calm review.
Track pain, oxygenation, hydration, bowel, bladder, sleep and infection or metabolic markers relevant to the identified cause.
Review renal and hepatic function and all opioid, anticholinergic, steroid and sedative changes during ongoing symptoms.
During haloperidol monitor rigidity, tremor, akathisia, swallowing, hypotension and cardiac symptoms and stop promptly when no longer necessary.
During sedative treatment review respiratory rate and effort, arousability, distress behaviour and whether the agreed goal is being exceeded.
Reassess capacity for each significant decision when attention improves or the decision changes.
Ask family about recognition, fear, sleep and the effect of explanations and include them in non-drug orientation when desired.
Document and review every restraint or covert-medicine episode with its legal authority, proportionality and least-restrictive alternatives.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Quiet delirium is dangerous

Hypoactive patients fall, aspirate and miss treatment while appearing less disruptive than those who are agitated.

One cause is uncommon

Advanced illness often combines infection, organ failure, medicines, pain and environmental disruption, requiring a layered response.

Lucidity creates opportunity

A calm interval may permit communication or a specific decision and should not be missed because capacity was absent overnight.

Akathisia mimics agitation

Antipsychotic-induced inner restlessness can appear as worsening delirium and provoke a harmful cycle of further dosing.

Family orientation can soothe

A familiar voice and simple repeated explanation may reduce threat without arguing about inaccurate perceptions.

Proportional sedation has a target

The aim is relief of otherwise refractory distress with the minimum impairment needed, not unconsciousness as a default outcome.

11Common pitfallsFrequent interpretation and management errors.

01
Missing hypoactive delirium because the patient is quiet.
02
Calling confusion dementia without establishing acute fluctuation.
03
Sedating before checking glucose, oxygen, pain, bladder and bowel.
04
Using haloperidol in Parkinson's disease or Lewy-body dementia without specialist input.
05
Treating akathisia from haloperidol as worsening agitation.
06
Using benzodiazepine as routine monotherapy for non-withdrawal delirium.
07
Ordering exhaustive tests in the last hours without a comfort-changing treatment option.
08
Assuming delirium removes capacity for every decision permanently.
09
Using restraint or covert medicine without legal and proportionality review.
10
Titrating terminal sedation without explaining and recording the symptom goal.