# Delirium: Prevention, Recognition, and Management

## Introduction

Delirium is an acute, fluctuating disturbance in attention and awareness that is common among hospitalized patients, particularly the elderly. It is associated with increased mortality, prolonged hospital stays, long-term cognitive decline, and higher rates of institutionalization. Despite its clinical significance, delirium remains under-recognized by medical teams. Prevention is the most effective strategy, and every internist must be skilled in identifying and managing this condition.

## Epidemiology

- Affects **20-30% of hospitalized medical patients** and up to 80% of ICU patients
- Prevalence increases with age, surgical interventions, and critical illness
- Associated with **increased in-hospital mortality** (up to 3-fold)
- Independently predicts prolonged hospitalization, functional decline, and nursing home placement
- Estimated to contribute to over $150 billion in annual healthcare costs in the United States

## Pathophysiology

- Multifactorial: interaction between **predisposing** (baseline vulnerability) and **precipitating** factors
- Neurotransmitter imbalance: **acetylcholine deficiency** and **dopamine excess**
- Neuroinflammation, blood-brain barrier disruption, oxidative stress
- Medications with anticholinergic properties are the most common iatrogenic cause

## Risk Factors

### Predisposing Factors (Baseline Vulnerability)

- **Age >= 65 years**
- Pre-existing dementia or cognitive impairment (single strongest predisposing factor)
- Functional impairment, immobility
- Sensory impairment (vision, hearing)
- History of alcohol use disorder
- Multiple comorbidities, frailty

### Precipitating Factors (Acute Triggers)

- **Medications**: benzodiazepines, opioids, anticholinergics, corticosteroids, fluoroquinolones
- **Infections**: urinary tract infection, pneumonia, sepsis
- **Metabolic derangements**: electrolyte abnormalities, hypoglycemia, uremia, hepatic encephalopathy
- **Pain**: both undertreated and overtreated
- **Sleep deprivation** and ICU environment
- Urinary retention, fecal impaction, dehydration
- Surgery, anesthesia, restraint use, indwelling catheters

![Diagram illustrating the interaction between predisposing and precipitating factors in delirium development](/images/residency/delirium-risk-factors.jpg)

## Clinical Subtypes

| Subtype | Frequency | Features | Prognosis |
|---------|-----------|----------|-----------|
| Hyperactive | ~25% | Agitation, hallucinations, psychomotor activation | Easily recognized; better outcomes |
| Hypoactive | ~50% | Lethargy, withdrawal, reduced alertness | Most frequently missed; worst prognosis |
| Mixed | ~25% | Fluctuates between hyperactive and hypoactive | Intermediate |

- **Hyperactive delirium**: agitation, psychomotor activation, hallucinations; easy to recognize but accounts for only ~25%
- **Hypoactive delirium**: lethargy, reduced alertness, withdrawal; most common (~50%) and most frequently missed
- **Mixed delirium**: fluctuates between hyperactive and hypoactive features (~25%)
- Hypoactive delirium carries the worst prognosis because it is often undetected

## Diagnosis

### Confusion Assessment Method (CAM)

The most widely validated bedside screening tool. Requires both **1 and 2**, plus either **3 or 4**:

1. **Acute onset and fluctuating course**: is there an acute change from baseline that waxes and wanes?
2. **Inattention**: does the patient have difficulty focusing? (spell WORLD backward, months of the year backward)
3. **Disorganized thinking**: incoherent or illogical thought process
4. **Altered level of consciousness**: anything other than fully alert

### CAM-ICU

- Adapted for intubated and critically ill patients
- Uses the Richmond Agitation-Sedation Scale (RASS) to assess level of consciousness
- Validated and widely used in ICU settings

### Workup for Underlying Cause

- **Always search for reversible causes**: medication review (the most important step), infection screen, metabolic panel, urinalysis
- CBC, BMP, calcium, magnesium, liver function tests, TSH
- Blood cultures, chest X-ray, urinalysis if infection suspected
- Consider head CT only if focal neurologic findings, head trauma, or anticoagulation
- EEG if seizures suspected (nonconvulsive status epilepticus)

![CAM screening tool with step-by-step assessment instructions for bedside use](/images/residency/cam-screening-tool.jpg)

## Prevention

### HELP (Hospital Elder Life Program)

The most evidence-based multicomponent delirium prevention program. Reduces delirium incidence by approximately **30-40%**. Components include:

- **Orientation**: reorientation protocols, clocks, calendars, familiar objects
- **Sleep promotion**: noise reduction, nighttime medication bundling, warm beverages, avoid nighttime vitals if stable
- **Early mobilization**: get patients out of bed and ambulating as early as possible
- **Sensory optimization**: ensure glasses and hearing aids are available and in use
- **Hydration and nutrition**: encourage oral intake, avoid unnecessary NPO status
- **Cognitive stimulation**: conversation, word games, reminiscence activities

### Medication-Based Prevention

- **Avoid deliriogenic medications**: benzodiazepines, anticholinergics, meperidine, diphenhydramine
- Review the **Beers Criteria** for potentially inappropriate medications in older adults
- Use the lowest effective dose of necessary medications
- No pharmacologic agent has been proven to prevent delirium (including antipsychotics and melatonin)

## Management

### Non-Pharmacologic Interventions (First-Line)

- Identify and treat the underlying cause (this is the definitive treatment)
- Reorientation and reassurance; consistent caregivers
- Family presence at bedside
- Minimize tethers: remove unnecessary lines, catheters, and restraints
- Normalize sleep-wake cycle; daytime light exposure, minimize nighttime disruptions
- Early mobilization and physical therapy
- Optimize pain management (prefer acetaminophen, avoid opioids when possible)

### Pharmacologic Management

- **Reserved for patients who are a danger to themselves or others** despite non-pharmacologic measures
- **Haloperidol**: most studied agent; start 0.5-1 mg PO/IV; titrate cautiously
- **Atypical antipsychotics**: quetiapine (12.5-25 mg), olanzapine (2.5-5 mg); may be better tolerated
- Monitor QTc before and during antipsychotic use
- **Avoid benzodiazepines** except in alcohol/benzodiazepine withdrawal or Parkinson disease-related psychosis (use quetiapine instead)
- **No evidence** that antipsychotics shorten delirium duration or reduce mortality
- Discontinue antipsychotics as soon as delirium resolves; do not discharge patients on new antipsychotics started for delirium

![Algorithm for stepwise management of delirium from non-pharmacologic to pharmacologic interventions](/images/residency/delirium-management-algorithm.jpg)

## Key Clinical Pearls

- Delirium is a medical emergency; always search for and treat the underlying cause
- Hypoactive delirium is the most common subtype and the most frequently missed
- Prevention with multicomponent interventions (HELP program) is more effective than any pharmacologic treatment
- The single most important step in delirium workup is a thorough medication review
- Antipsychotics are symptom management only; use the lowest dose for the shortest time and always discontinue before discharge

## References

1. Inouye SK, Westendorp RG, Saczynski JS. Delirium in elderly people. *Lancet*. 2014;383(9920):911-922.
2. Hshieh TT, Yue J, Oh E, et al. Effectiveness of multicomponent nonpharmacological delirium interventions: a meta-analysis. *JAMA Intern Med*. 2015;175(4):512-520.
3. Ely EW, Shintani A, Truman B, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. *JAMA*. 2004;291(14):1753-1762.
4. American Geriatrics Society Expert Panel on Postoperative Delirium in Older Adults. Postoperative delirium in older adults: best practice statement. *J Am Coll Surg*. 2015;220(2):136-148.