How to manage acute confusion/delirium in an elderly patient with normal laboratory workup and normal head computed tomography (CT) scan?

Differential Diagnosis for Elderly Patient with Acute Confusion/Delirium and Normal Laboratory/Head CT

When laboratory workup and head CT are normal in an elderly patient with acute delirium, immediately pursue a systematic evaluation for occult infection (particularly urinary tract infection without pyuria, aspiration pneumonia, and bacteremia), medication-related causes (especially anticholinergics, benzodiazepines, and opioids), pain, constipation/urinary retention, and sensory deprivation as the most common reversible contributors. 1

Priority Differential Diagnoses to Pursue

Occult Infections Without Laboratory Abnormalities

• Bacteremia without clear source: Over 80% of patients with bacteremia have neurological symptoms ranging from lethargy to coma, yet may not show obvious laboratory abnormalities initially 2
• Aspiration pneumonia: May not be evident on initial chest imaging or laboratory studies but should be suspected with any history of dysphagia or witnessed aspiration 1
• Urinary tract infection: However, avoid treating asymptomatic bacteriuria with antibiotics, as this worsens functional recovery and increases Clostridium difficile infections in elderly patients with delirium 2

Medication-Related Delirium (Most Common Reversible Cause)

• Anticholinergics: Including antihistamines like cyclizine, which should be avoided 2
• Benzodiazepines: Strong precipitant that must be discontinued unless treating alcohol/benzodiazepine withdrawal 2, 1
• Opioids: Particularly in patients with renal impairment where metabolites accumulate 2
• Atropine and sedative hypnotics: Both are common culprits 2
• Corticosteroids: Often overlooked as delirium precipitants 2

Metabolic Causes Not Detected by Routine Labs

• Hypercalcemia: Should be suspected even with indolent symptoms of confusion, asthenia, or drowsiness; hypercalcemia-induced delirium is reversible in 40% of cases 2
• Hyponatremia due to SIADH: May require specific testing beyond basic metabolic panel 2
• Hypoglycemia: Requires point-of-care glucose testing, not just laboratory glucose 1

Pain and Physical Discomfort

• Unrecognized pain: Elderly patients, particularly those with cognitive impairment, are reluctant to report pain and it is systematically undertreated 2
• Constipation and urinary retention: Common precipitants that require physical examination, not laboratory testing 1
• Pressure injuries: May cause pain-related delirium without obvious laboratory changes 2

Sensory and Environmental Factors

• Visual and hearing impairment: Lack of glasses or hearing aids contributes significantly to delirium 2
• Sleep deprivation: Disrupted sleep-wake cycle is both a symptom and perpetuating factor 2
• Dehydration: Common precipitating factor that may not be evident on initial laboratory studies 2

Systematic Evaluation Algorithm

Immediate Assessment (Within Hours of Diagnosis)

1. Comprehensive medication review: Discontinue all anticholinergics, benzodiazepines (except for alcohol withdrawal), and reduce opioids to minimum necessary doses 2, 1
2. Targeted physical examination: Check for urinary retention (bladder scan), constipation (rectal examination), pressure injuries, and signs of pain 1
3. Sensory optimization: Ensure patient has glasses and hearing aids in place 2
4. Vital signs review: Look for subtle hypoxia, fever, or hypotension not initially recognized 1

Extended Workup (Within 24-48 Hours)

1. Repeat calcium and sodium levels: Specifically looking for hypercalcemia and hyponatremia 2
2. Blood cultures: Even without fever or leukocytosis, given high prevalence of bacteremia causing delirium 2
3. Chest X-ray: If not already obtained, to exclude aspiration pneumonia 1
4. Urinalysis with culture: Only treat if patient has systemic signs of infection (fever, leukocytosis, hemodynamic instability); do not treat asymptomatic bacteriuria 2
5. Electroencephalogram: Consider if seizure activity is suspected, as >80% of patients with bacteremia have EEG abnormalities 2

Critical Management Pitfalls to Avoid

Do Not Empirically Treat Asymptomatic Bacteriuria

• Time-limited antibiotic trials in elderly patients with delirium and asymptomatic bacteriuria result in worse functional recovery and higher C. difficile infection rates 2
• Only treat urinary tract infections when patient meets systemic sepsis criteria 2

Do Not Overuse Neuroimaging

• Avoid repeat CT/MRI scans unless new focal neurological findings develop, as sedation or restraints required for imaging can worsen delirium 2, 1

Do Not Use Physical Restraints

• Physical restraints exacerbate delirium and should be avoided for managing behavioral symptoms 2, 1

Do Not Delay Treatment While Awaiting Workup

• Delays in identifying and treating underlying causes prolong delirium duration and increase morbidity and mortality 2, 1

Multicomponent Non-Pharmacological Intervention (Implement Immediately)

All elderly patients with delirium should receive multicomponent interventions by an interdisciplinary team, as this is the only evidence-based treatment approach. 2, 1

Core Intervention Components

• Reorientation: Frequent verbal reorientation, visible clocks and calendars 2, 1
• Early mobilization: Physical therapy consultation within 24 hours 2, 1
• Sleep hygiene: Non-pharmacologic sleep protocol, minimize nighttime disruptions 2, 1
• Nutrition and hydration: Feeding assistance, encourage oral intake, avoid unnecessary NPO status 2, 1
• Pain management: Use multimodal analgesia starting with paracetamol, cautious opioid use 2, 1
• Adequate oxygenation: Maintain SpO2 >90% 1

Pharmacological Management (Reserved for Severe Agitation Only)

• Antipsychotics: Use only for severe agitation, extreme distress, or substantial threat to self/others; use lowest effective dose for shortest time 1
• Quetiapine: For elderly patients, start at 25-50 mg/day and increase by 25-50 mg increments every 2 days as needed 3
• Avoid benzodiazepines: Except for alcohol or benzodiazepine withdrawal 1
• Discontinue immediately: Once acute distressing symptoms resolve 1