How should delirium be managed, including non‑pharmacologic measures and pharmacologic treatment?

Management of Delirium

The cornerstone of delirium management is identifying and treating reversible causes through comprehensive assessment, followed by non-pharmacologic interventions as first-line therapy; pharmacologic treatment should be reserved for severe agitation or when non-pharmacologic measures fail, with haloperidol and risperidone showing NO benefit for mild-to-moderate delirium. 1

Initial Assessment and Diagnosis

• Diagnose delirium using DSM or ICD criteria through clinical assessment by a trained healthcare professional, not screening tools alone 1
• Obtain detailed collateral history from family or caregivers to establish baseline cognitive function and exact timeline of symptom onset 2
• Recognize that delirium presents as either hyperactive (agitation, hypervigilance) or hypoactive (sedation, withdrawal) subtypes, with hypoactive being most common and frequently underdiagnosed 1
• Perform repeated evaluations throughout the day, as symptoms fluctuate markedly 3

Identify and Treat Reversible Causes (Priority)

Conduct a comprehensive initial assessment to identify predisposing and precipitating factors 1:

Metabolic and Electrolyte Abnormalities

• Treat hypercalcemia with IV bisphosphonates (pamidronate or zoledronic acid), which can reverse delirium in substantial cases 1
• Correct hypomagnesemia with magnesium replacement 1
• Manage SIADH by discontinuing implicated medications, fluid restriction, and adequate oral salt intake 1

Medication Review

• Discontinue or reduce delirium-inducing medications (steroids, anticholinergics) 1
• Consider deprescribing in older patients to reduce anticholinergic burden 1, 2
• For opioid-induced delirium, rotate to fentanyl or methadone 1

Infection and Other Causes

• Treat infections if consistent with patient's goals of care 1
• Withdraw anticancer treatments (chemotherapy, immunotherapies) if implicated 1

Non-Pharmacologic Interventions (First-Line)

Maximize non-pharmacologic interventions before using medications 1:

• Implement reorientation strategies, cognitive stimulation, and sleep hygiene 1
• Provide frequent reorientation by nursing staff 4
• Ensure adequate lighting, minimize noise, and maintain day-night orientation 5
• Encourage early mobility when possible 6
• Incorporate family into care for comfort and familiarity 6
• Remove unnecessary tubes and medical equipment 1

Note: Clinically assisted hydration is NOT more effective than placebo for preventing or treating delirium 1

Pharmacologic Management

Mild-to-Moderate Delirium

DO NOT use haloperidol or risperidone for mild-to-moderate delirium, as they show no demonstrable benefit 1

Consider these alternatives:

• Olanzapine may offer benefit 1
• Quetiapine may offer benefit 1
• Aripiprazole may offer benefit 1

Severe Delirium with Agitation

For severe delirium with significant agitation, use antipsychotic neuroleptics 1:

• Haloperidol (oral or parenteral) 1, 7
• Olanzapine 1
• Chlorpromazine (IV only in bed-bound patients due to hypotensive effects) 1

Titrate doses to optimal symptom relief 1

Refractory Agitation

• Add a benzodiazepine (lorazepam) only for agitation refractory to high-dose neuroleptics 1
• Therapeutic levels of neuroleptics prevent paradoxical excitation from benzodiazepines 1
• DO NOT use benzodiazepines as initial treatment except for alcohol or sedative-hypnotic withdrawal 1, 4

Special Considerations

Hypoactive Delirium:

• Methylphenidate may improve cognition when delusions and perceptual disturbances are absent and no cause identified 1

Opioid-Related Delirium:

• Consider opioid dose reduction or rotation 1

Critical Pitfalls to Avoid

• Never use benzodiazepines as first-line treatment (except for alcohol/sedative withdrawal), as they can worsen delirium 1, 4
• Avoid prolonged antipsychotic use due to risks of extrapyramidal symptoms, metabolic syndrome, and increased mortality in elderly patients with dementia 2
• Do not combine opioids with other sedating medications (benzodiazepines) without extreme caution due to FDA black box warning 1
• Recognize that sedation often precedes respiratory depression when using opioids 1

Refractory Delirium in Dying Patients

• In the final hours to days, delirium is usually refractory 1
• Increase doses and/or change routes of administration for neuroleptics and benzodiazepines 1
• Consider palliative sedation after consultation with palliative care specialists 1
• Remove unnecessary medications and tubes 1

Family Support and Education

• Provide information about delirium pre-emptively and at repeated intervals, especially if patient's condition is declining 1
• Supplement written information with educational and psychological support for families 1
• Support caregivers in coping with this distressing condition 1