What is the protocol to rapidly assess and intervene for reversible causes of refractory terminal delirium?

Protocol for Rapid Assessment and Intervention of Reversible Causes in Refractory Terminal Delirium

Perform delirium assessments both before and after stopping sedation to identify rapidly reversible sedation-associated delirium, as this subtype has outcomes similar to patients who never develop delirium. 1

Step 1: Immediate Sedation Assessment and Trial

• Stop all continuous sedatives and analgesics immediately and reassess delirium status within 2 hours using CAM-ICU or DSM criteria 1
• If delirium resolves within 2-4 hours of stopping sedation, this represents rapidly reversible sedation-associated delirium (occurs in only 12-20% of cases) with benign prognosis 1, 2
• If delirium persists beyond 4 hours after sedation cessation (occurs in 75-83% of cases), proceed with comprehensive reversible cause assessment as this persistent delirium is associated with worse outcomes including longer ICU stay 1, 2

Critical pitfall: Do not discount positive delirium assessments when patients are arousable on sedation, as the majority of patients will have persistent delirium even after discontinuation of sedatives 1

Step 2: Medication Review and Elimination

• Identify and discontinue all delirium-inducing medications immediately: 1, 3, 4, 5

  • Anticholinergic agents (antisecretory agents, antidepressants, antispasmodics) 4, 5
  • Benzodiazepines 4, 5
  • High-dose opioids 4, 5
  • Corticosteroids 1, 4
  • NSAIDs 4
  • Antipsychotics (can paradoxically cause delirium) 3, 6
  • Antiepileptics 4

• For opioid-induced neurotoxicity (OIN): Perform opioid rotation to fentanyl or methadone with 30-50% reduction in equianalgesic dose 1, 3, 6

Step 3: Metabolic and Physiologic Causes

Assess and correct the following in order of clinical urgency:

Hypercalcemia

• Administer IV pamidronate or zoledronic acid immediately for confirmed hypercalcemia, as bisphosphonates can reverse delirium in a substantial number of cases 1

Hypomagnesemia

• Replace magnesium immediately for documented hypomagnesemia 1

SIADH

• Discontinue implicated medications, implement fluid restriction, and ensure adequate oral salt intake for confirmed SIADH 1

Infection

• Treat infection with appropriate antimicrobials if infection is identified as a precipitating factor and treatment aligns with goals of care 1

Hypoxia and Metabolic Derangements

• Correct hypoxia, hypercarbia, hypoglycemia, uremia, and hepatic encephalopathy 7, 5

Step 4: Non-Pharmacological Interventions (Concurrent with Above Steps)

• Implement reorientation strategies: Provide orientation cues, cognitive stimulation, and maintain day-night cycles 3
• Optimize sleep hygiene: Reduce nighttime noise and light, cluster care activities 3
• Create calm environment: Minimize unnecessary stimulation, ensure familiar objects are present 3
• Remove unnecessary tubes, catheters, and physical restraints 3
• Engage family members in monitoring and delivering non-pharmacological interventions 3

Step 5: Pharmacological Management (Only After Above Steps)

Do NOT use haloperidol, atypical antipsychotics, dexmedetomidine, statins, or ketamine to prevent or treat delirium in critically ill adults as guideline evidence shows conditional recommendation against their use 1

However, for moderate delirium symptoms with distressing agitation after addressing reversible causes:

• Consider oral quetiapine, olanzapine, or aripiprazole at lowest effective doses for shortest duration 3
• Avoid haloperidol and risperidone as they have not demonstrated benefit in mild-to-moderate delirium and may worsen symptoms 3
• Do not use benzodiazepines as initial treatment unless patient has pre-existing benzodiazepine or alcohol dependence 3, 6

Critical caveat: Antipsychotics and benzodiazepines can themselves cause agitation and delirium, so use with extreme caution and only for persistent distressing symptoms 6

Step 6: Refractory Terminal Delirium Management

For delirium that remains refractory despite addressing all reversible causes in actively dying patients:

• Consult palliative care specialist for consideration of palliative sedation 1, 3
• Focus on family support and education about delirium to reduce distress 1, 3
• Provide debriefing opportunities for patients who recover from delirium episodes 3

Important distinction: Delirium is reversible in up to 50% of cases when appropriate interventions are implemented, making this systematic approach to reversible causes essential even in terminal illness 7, 4