Delirium Management Guide

🔬 Specific Medical Causes of Delirium

Antibiotics (Most Common Drug-Induced Cause)

Cardiac Medications

Anticholinergic Medications

Opioids and Analgesics

Corticosteroids

Electrolyte and Metabolic Disturbances

Sodium Disorders

• Hyponatremia (<135 mEq/L):
  • Rapid correction can cause osmotic demyelination
  • Symptoms worsen with rapid onset or severe hyponatremia
  • Correction rate: <12 mEq/L per 24 hours (slower if chronic)
  • Common causes: SIADH, diuretics, SSRIs, carbamazepine
• Hypernatremia (>145 mEq/L):
  • More common in elderly, often from dehydration
  • Correction rate: 0.5 mEq/L per hour maximum
  • Associated with higher mortality than hyponatremia

Glucose Abnormalities

• Hypoglycemia (<70 mg/dL):
  • Rapid onset, often first sign is behavioral change
  • Risk factors: Insulin, sulfonylureas, reduced oral intake
  • Can mimic psychiatric symptoms (agitation, confusion)
  • Always check glucose in altered mental status
• Severe Hyperglycemia (>400 mg/dL):
  • Diabetic ketoacidosis, hyperosmolar hyperglycemic state
  • Dehydration and electrolyte abnormalities compound effects
  • Gradual correction prevents cerebral edema

Other Critical Electrolytes

• Hypocalcemia (<8.5 mg/dL):
  • Check ionized calcium if albumin low
  • Can cause seizures, laryngospasm, tetany
  • Common in critically ill patients
• Severe Hypomagnesemia (<1.2 mg/dL):
  • Often concurrent with hypocalcemia and hypokalemia
  • Difficult to correct other electrolytes without fixing magnesium
  • Associated with proton pump inhibitor use

Organ System Failures

Hepatic Encephalopathy

• Pathophysiology: Ammonia accumulation, GABA-ergic dysfunction
• Grading: West Haven Criteria (Grade 1-4)
• Precipitants: GI bleeding, infection, constipation, high protein load
• Treatment: Lactulose, rifaximin, identify precipitants
• Monitoring: Ammonia levels may not correlate with severity

Uremic Encephalopathy

• Threshold: Usually BUN >100 mg/dL, but varies by individual
• Pathophysiology: Uremic toxins, electrolyte imbalances
• Clinical Features: Asterixis, myoclonus, seizures
• Treatment: Urgent dialysis consultation

Hypoxemia and Hypercapnia

• Hypoxemia (<90% SpO2):
  • Acute: Agitation, confusion, combativeness
  • Chronic: Gradual cognitive decline, depression
  • Elderly may not show typical signs of hypoxia
• Hypercapnia (CO2 >50 mmHg):
  • CO2 narcosis: Somnolence, confusion
  • Risk with excessive oxygen in COPD patients
  • Can be subtle in chronic retention

Infectious Causes

Urinary Tract Infections (UTIs)

• Elderly Presentation: Often no fever, dysuria, or urinary symptoms
• Delirium may be only sign in elderly patients
• Diagnosis: Urinalysis, culture (avoid treating asymptomatic bacteriuria)
• Complications: Urosepsis, especially in immunocompromised

Pneumonia

• Atypical Presentation: Elderly may lack fever, cough, or chest pain
• Silent Pneumonia: Mental status changes may precede respiratory symptoms
• Diagnosis: CXR, inflammatory markers, blood cultures

Central Nervous System Infections

• Meningitis/Encephalitis:
  • Classic triad (fever, neck stiffness, altered mental status) in <50%
  • High index of suspicion needed in elderly
  • Lumbar puncture often required for diagnosis

Endocrine Disorders

Thyroid Disorders

• Hyperthyroidism:
  • Thyroid storm: Hyperthermia, tachycardia, altered mental status
  • Apathetic hyperthyroidism in elderly
  • Can precipitate atrial fibrillation
• Severe Hypothyroidism:
  • Myxedema coma: Hypothermia, bradycardia, altered consciousness
  • Gradual onset, often missed in elderly
  • Can cause "myxedema madness" with psychotic features

Adrenal Disorders

• Adrenal Insufficiency:
  • Addisonian crisis: Hypotension, hyponatremia, hyperkalemia
  • Often precipitated by stress, illness, steroid withdrawal
  • Can be life-threatening if unrecognized

Nutritional Deficiencies

B-Vitamin Deficiencies

• Thiamine (B1) Deficiency:
  • Wernicke encephalopathy: Confusion, ataxia, ophthalmoplegia
  • High risk: Alcoholism, malnutrition, hyperemesis
  • Give thiamine BEFORE glucose to prevent worsening
• Vitamin B12 Deficiency:
  • Can cause reversible dementia and psychosis
  • May occur without anemia or macrocytosis
  • Check B12, folate, methylmalonic acid
• Niacin (B3) Deficiency:
  • Pellagra: 4 D's - diarrhea, dermatitis, dementia, death
  • Rare but can occur with severe malnutrition

Drug Withdrawal Syndromes

Alcohol Withdrawal

• Timeline: 6-24 hours after last drink
• Stages: Tremor → hallucinations → seizures → delirium tremens
• Delirium Tremens: 5-15% mortality if untreated
• Treatment: Benzodiazepines, thiamine, supportive care

Benzodiazepine Withdrawal

• Timeline: Variable based on half-life (hours to weeks)
• Features: Anxiety, insomnia, seizures, hyperthermia
• Risk Factors: High doses, long-term use, abrupt discontinuation
• Treatment: Gradual taper, avoid abrupt cessation

Opioid Withdrawal

• Timeline: 6-12 hours (short-acting), 24-48 hours (long-acting)
• Features: Agitation, insomnia, GI symptoms, mydriasis
• Not life-threatening but can precipitate delirium in vulnerable patients

🌳 Medical Workup Decision Tree

Initial Laboratory Screen (All Patients)

• Basic Metabolic Panel: Glucose, sodium, creatinine, BUN
• Complete Blood Count: Look for infection, anemia
• Liver Function Tests: AST, ALT, bilirubin, ammonia if indicated
• Urinalysis: Infection, protein, specific gravity
• Arterial Blood Gas: If hypoxia or acidosis suspected

Targeted Testing Based on Clinical Suspicion

• If Infection Suspected:
  • Blood cultures, urine culture
  • Chest X-ray
  • Procalcitonin, CRP, ESR
  • Lumbar puncture if CNS infection suspected
• If Metabolic Cause Suspected:
  • Thyroid function tests (TSH, free T4)
  • Cortisol level, ACTH stimulation test
  • Vitamin B12, folate, thiamine
  • Magnesium, phosphorus, ionized calcium
• If Neurological Cause Suspected:
  • CT head (rule out stroke, hemorrhage)
  • EEG if seizure activity suspected
  • MRI if encephalitis or structural lesion suspected

Medication Review Checklist

• Recently Started Medications (within 7 days)
• Recently Stopped Medications (withdrawal syndromes)
• Dose Changes in past 2 weeks
• Drug Interactions (new combinations)
• Over-the-Counter Medications (often overlooked)
• Anticholinergic Burden Scale calculation

🎭 Delirium Subtypes: Clinical Presentation & Management

Feature	Hyperactive (25%)	Hypoactive (50%)	Mixed (25%)
Presentation	Agitated, restless, hypervigilant	Withdrawn, lethargic, apathetic	Alternating between both
Recognition Rate	High (obvious symptoms)	Low (often missed)	Moderate
Mortality Risk	Moderate	Highest	High
Length of Stay	Moderate increase	Longest	Moderate-High
Common Causes	Substance withdrawal, infections	Medications, metabolic disorders	Multi-factorial

Hyperactive Delirium

• Clinical Features: Agitation, restlessness, hypervigilance, combativeness, pulling at tubes/lines
• Immediate Priorities: Safety assessment, fall risk, harm to self/others
• Management Focus: Environmental calming, verbal de-escalation, avoid restraints
• Medication Indications: Only when verbal de-escalation fails and safety risk present

Hypoactive Delirium

• Clinical Features: Lethargy, psychomotor retardation, reduced speech, withdrawal from social interaction
• Recognition Challenges: Often mistaken for depression, fatigue, or "good patient behavior"
• Screening Tools: 4AT and 3D-CAM perform better than CAM-ICU for detection
• Outcome Impact: Associated with longer ICU stays, higher mortality, worse cognitive outcomes
• Management Priority: Early recognition and non-pharmacological activation

💊 Pharmacological Treatments: Evidence-Based Approach

First-Line Antipsychotics

• Quetiapine (Preferred Choice):
  • Dosing: 25-50mg Q12H, titrate to 50-200mg BID
  • Advantages: Lowest EPS risk (<5%), safe in Parkinson's disease
  • Best evidence for delirium management
  • Can be used as "non-deliriogenic sedative" at low doses
• Olanzapine (QTc-Safe Option):
  • Dosing: 2.5-5mg daily, max 20mg/day
  • Advantages: No QTc prolongation, multiple routes (PO/IM/IV/ODT)
  • Best for patients with cardiac concerns
  • Rapid onset with IM/IV administration
• Haloperidol (Rapid Control):
  • Dosing: 2.5-5mg (elderly), up to 10mg (younger patients)
  • Routes: PO/IM/IV available
  • Caution: QTc prolongation risk with IV use
  • Requires cardiac monitoring if IV administration

Preventive Medications

• Melatonin (Prevention):
  • Dosing: 0.5-5mg nightly × 5-14 days
  • Evidence: 49% risk reduction in surgical patients
  • Mechanism: Circadian rhythm regulation
  • Excellent safety profile
• Suvorexant (Novel Breakthrough):
  • Dosing: 10-20mg nightly
  • Evidence: 16.8% vs 26.5% delirium incidence
  • Mechanism: Orexin pathway modulation
  • Particularly effective in mild dementia
• Dexmedetomidine (ICU Setting):
  • Dosing: 0.2-1.5 mcg/kg/hr IV infusion
  • Evidence: 63% delirium risk reduction
  • Advantages: Respiratory-sparing sedation
  • Indication: ICU sedation and delirium prevention

Medication Selection Algorithm

• QTc Normal (<450ms): Quetiapine first-line
• QTc Prolonged (>450ms): Olanzapine preferred
• Immediate Danger: Haloperidol IM/IV (with cardiac monitoring)
• Parkinson's Disease: Quetiapine only safe option
• Prevention Focus: Melatonin + non-pharmacological interventions

🌟 Non-Pharmacological Interventions: First-Line Treatment

Environmental Modifications

• Lighting Management:
  • Bright light (>2500 lux) during day
  • Dim lighting at night
  • Avoid bright lights during nighttime care
  • Natural light exposure when possible
• Noise Control:
  • Limit noise to <45 decibels at night
  • Use sound-absorbing materials
  • Cluster care activities to minimize disruption
  • Quiet zones during sleep hours
• Orientation Tools:
  • Large clocks and calendars
  • Photos of family members
  • Familiar objects from home
  • Clear room signage

Sleep Hygiene Protocol

• Circadian Rhythm Support:
  • Consistent sleep-wake schedule
  • Avoid daytime napping >30 minutes
  • Light therapy in morning
  • Melatonin supplementation
• Sleep Promotion:
  • Cluster nighttime care
  • Avoid caffeine after 2 PM
  • Comfortable room temperature
  • Noise-canceling headphones

Cognitive Stimulation

• Daily Activities:
  • Reality orientation exercises
  • Cognitive games and puzzles
  • Reading newspapers/magazines
  • Listening to familiar music
• Social Engagement:
  • Family presence encouraged
  • Familiar caregiver assignment
  • Pet therapy when available
  • Chaplain/spiritual support

Early Mobility Program

• Progressive Mobilization:
  • Sitting at bedside within 24 hours
  • Standing/walking as tolerated
  • Physical therapy consultation
  • Range of motion exercises
• Safety Measures:
  • Fall risk assessment
  • Assistive devices as needed
  • 1:1 supervision if high risk
  • Remove restraints whenever possible

📋 Assessment Tools: Evidence-Based Screening

Rapid Screening Tools (2-5 minutes)

• 4AT (4 A's Test):
  • Sensitivity: 76-89%, Specificity: 84-95%
  • Administration: <2 minutes, minimal training
  • Scoring: 0 = unlikely, 1-3 = possible, 4+ = likely delirium
  • Best for: Nursing staff, routine screening
• 3D-CAM (3-Minute CAM):
  • Sensitivity: 93-96%, Specificity: 89-95%
  • Administration: 3 minutes, moderate training
  • Excellent for hypoactive delirium detection
  • Best for: General medical patients

Comprehensive Assessment Tools

• CAM-ICU (ICU Gold Standard):
  • Sensitivity: 80%, Specificity: 96%
  • Requires RASS ≥ -3 for administration
  • Validated for mechanically ventilated patients
  • Best for: ICU settings
• DRS-R-98 (Psychiatric Gold Standard):
  • Sensitivity: 92%, Specificity: 95%
  • 16-item scale, requires 15-30 minutes
  • Provides severity scoring (0-39 points)
  • Best for: Psychiatric consultation, research

Supportive Assessment Tools

• Richmond Agitation-Sedation Scale (RASS):
  • Assesses level of consciousness (-5 to +4)
  • Required before delirium screening
  • Patient must be RASS ≥ -3 for testing
• Confusion Assessment Method (CAM):
  • Four features: acute onset, inattention, disorganized thinking, altered consciousness
  • Requires features 1+2 + either 3 or 4
  • Classic diagnostic algorithm

👥 Special Populations: Tailored Approaches

Elderly Patients (≥65 years)

• Medication Dosing:
  • Start with 25% of standard adult dose
  • Titrate slowly with frequent reassessment
  • Monitor for anticholinergic burden
  • Consider drug-drug interactions
• Risk Factors:
  • Baseline cognitive impairment
  • Polypharmacy (≥5 medications)
  • Sensory impairments
  • Functional dependence
• FDA Black Box Warning:
  • 1.6-1.7x mortality risk in dementia
  • Informed consent required
  • Document risk-benefit assessment
  • Regular reassessment mandatory

ICU Patients

• ABCDEF Bundle Integration:
  • A: Assess, prevent, manage pain
  • B: Both SAT and SBT (spontaneous breathing trials)
  • C: Choice of analgesia and sedation
  • D: Delirium assess, prevent, manage
  • E: Early mobility and exercise
  • F: Family engagement and empowerment
• Sedation Strategy:
  • Dexmedetomidine preferred over benzodiazepines
  • Light sedation targets (RASS -1 to 0)
  • Daily sedation interruption
  • Avoid propofol infusion syndrome

Palliative Care Patients

• Goals of Care Integration:
  • Distinguish reversible vs irreversible delirium
  • Family communication about prognosis
  • Comfort-focused interventions
  • Symptom management over cognitive recovery
• Medication Considerations:
  • Lower threshold for pharmacological intervention
  • Focus on distress reduction
  • Consider subcutaneous routes
  • Midazolam for refractory agitation

🎯 Clinical Decision Support Summary

Emergency Red Flags

• Immediate Action Required:
  • Acute agitation with risk of self-harm
  • Pulling at life-support equipment
  • Combative behavior toward staff
  • Severe psychomotor agitation

Treatment Algorithm Summary

• Step 1: Identify and treat underlying causes
• Step 2: Implement non-pharmacological interventions
• Step 3: Verbal de-escalation and environmental modification
• Step 4: Consider medication only if safety risk persists
• Step 5: Regular reassessment and dose reduction

Medication Quick Guide

• Normal QTc: Quetiapine 25-50mg Q12H
• Prolonged QTc: Olanzapine 2.5-5mg daily
• Emergency: Haloperidol 2.5-10mg IM/IV
• Prevention: Melatonin 0.5-5mg nightly

Monitoring Requirements

• Daily: Mental status, safety assessment, medication review
• q8-12h: Delirium screening (4AT or CAM-ICU)
• Weekly: Medication necessity review, dose optimization
• Discharge: Cognitive assessment, family education