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Confusion and Delirium¶

Chapter 29 | Part 2: Cardinal Manifestations and Presentation of Diseases · Part 2 – Cardinal Manifestations & Presentation · Chapter 29

Key Clinical Points¶

Delirium is a clinical diagnosis made at the bedside, characterized by an acute decline in cognition fluctuating over hours or days.
The hallmark of delirium is a deficit of attention; other features include altered sleep-wake cycles, hallucinations, and autonomic instability.
Two subtypes exist: hyperactive (agitation, hallucinations) and hypoactive (withdrawn, quiet). Hypoactive cases are frequently underdiagnosed.
Mortality rates for hospitalized patients range from 25% to 33%, comparable to sepsis; it is a high-morbidity condition with significant economic costs.
Delirium serves as a 'stress test' that can unmask underlying neurodegenerative diseases (e.g., Alzheimer's, Parkinson's, DLB).
Pathophysiology involves cholinergic deficiency and potentially dopamine excess; it is often caused by infections, metabolic disturbances, or medications.
Diagnosis requires identifying the underlying cause through a systematic evaluation of toxins, metabolic conditions, infections, and other systemic issues.
Management focuses on treating the primary insult (e.g., infection, electrolyte imbalance) and providing supportive care (reorientation, sensory aids).
EEG is essential if seizures are suspected or if the etiology remains unclear after initial workup.

DEFINITION & OVERVIEW¶

• Clinical Definition: A relatively acute decline in cognition that fluctuates over hours or days. • Harrison's Definition: "Delirium is a clinical diagnosis that is made only at the bedside." • Synonyms: Encephalopathy, acute brain failure, acute altered mental status, acute confusional state, and postoperative/ICU psychosis. • Hallmark: A deficit of attention (the primary neuropsychological hallmark). • Clinical Manifestations: ◦ Cognitive Domains: Memory, executive function, visuospatial tasks, and language are variably involved. ◦ Associated Symptoms: Altered sleep-wake cycles, perceptual disturbances (hallucinations/delusions), affect changes, and autonomic instability (heart rate/blood pressure). ◦ Level of Consciousness: Ranges from hyperarousal to lethargy to coma. ◦ Course: Fluctuates over hours or days; may worsen at night (sundowning). • Subtypes of Delirium: ◦ Hyperactive: Characterized by agitation, hallucinations, and hyperarousal (e.g., delirium tremens). Often accompanied by life-threatening autonomic instability. ◦ Hypoactive: Characterized by being withdrawn, quiet, with prominent apathy and psychomotor slowing (e.g., benzodiazepine intoxication). ◦ Clinical Note: Patients often fall on a spectrum between these extremes; hypoactive patients are more frequently overlooked and underdiagnosed.

EPIDEMIOLOGY¶

• Prevalence: ◦ Hospitalized patients: 10% to >50% (higher in elderly and those undergoing hip surgery). ◦ ICU patients (elderly): Up to 75%. ◦ Nursing homes: Nearly one-quarter. ◦ End-of-life: 50–80%. • Clinical Impact: ◦ Mortality: 25% to 33% in-hospital (similar to sepsis). ◦ Long-term: 5x higher mortality rate in the months following illness compared to age-matched non-delirious patients. ◦ Economic/Clinical Burden: Longer length of stay, higher readmission rates, and increased risk of permanent cognitive decline. • Risk Factors: ◦ Age (>65). ◦ Baseline cognitive dysfunction (e.g., Alzheimer's, Parkinson's, DLB). ◦ In-hospital risks: Restraints, catheters, and new medications.

ETIOLOGY & PATHOPHYSIOLOGY¶

• Neuroanatomy: The attentional deficit has a diffuse localization in the brainstem, thalamus, prefrontal cortex, and parietal lobes. • Pathogenesis: ◦ Cholinergic Deficiency: Key role; medications with anticholinergic properties frequently cause delirium. Patients with preexisting dementia are particularly susceptible due to basal forebrain neuron loss. ◦ Dopamine Excess: Can lead to delirium (e.g., in Parkinson's patients on dopaminergic meds). ◦ Neuroimaging/EEG: EEG often shows symmetric slowing (non-specific). Focal lesions causing delirium are rare but typically involve the nondominant parietal or medial dorsal thalamic regions. • The 'Stress Test' Concept: Delirium can unmask a decreased cerebral reserve. If a previously healthy individual develops delirium from a minor insult (e.g., UTI, surgery), it may herald an underlying neurodegenerative disease.

CLINICAL FEATURES¶

• Core Symptoms: ◦ Altered level of consciousness (hyperarousal to lethargy to coma). ◦ Fluctuating course (often worse at night, known as 'sundowning'). ◦ Associated features: Altered sleep-wake cycles, hallucinations/delusions, and autonomic instability. • Assessment of Attention: ◦ Clinical signs: Tangential speech, fragmented flow of ideas, inability to follow complex commands. ◦ Digit Span Test: → Task: Patient repeats random strings of digits at 1 per second. → Result: Healthy adults ≥ 5–7; ≤ 4 indicates an attentional deficit. Many delirious patients have a span of ≤ 3.

DIFFERENTIAL DIAGNOSIS¶

• Table 29-1: Differential Diagnosis of Delirium • Toxins: ◦ Prescription medications: Especially those with anticholinergic properties, narcotics, and benzodiazepines. ◦ Drugs of abuse: Alcohol (intoxication/withdrawal), opiates, ecstasy, LSD, GHB, PCP, ketamine, cocaine, "bath salts," marijuana and its synthetic forms. ◦ Poisons: Inhalants, carbon monoxide, ethylene glycol, pesticides. • Metabolic Conditions: ◦ Electrolyte disturbances: Hypoglycemia, hyperglycemia, hyponatremia, hypernatremia, hypercalcemia, hypocalcemia, hypomagnesemia. ◦ Organ Failure: Liver failure (hepatic encephalopathy), renal failure (uremia), cardiac failure. ◦ Other: Hypothermia/hyperthermia, pulmonary failure (hypoxemia/hypercarbia), vitamin deficiencies (B12, thiamine, folate, niacin), dehydration, malnutrition, anemia. • Infections: ◦ Systemic: UTI, pneumonia, skin and soft tissue infections, sepsis. ◦ CNS: Meningitis, encephalitis, brain abscess. • Endocrine Conditions: ◦ Hyper/hypothyroidism, hyperparathyroidism, adrenal insufficiency. • Cerebrovascular Disorders: ◦ Global hypoperfusion states, hypertensive encephalopathy, focal ischemic strokes and hemorrhages (rare; especially nondominant parietal and thalamic lesions). • Autoimmune Disorders: ◦ CNS vasculitis, cerebral lupus, paraneoplastic/autoimmune encephalitis. • Seizure-Related Disorders: ◦ Nonconvulsive status epilepticus, intermittent seizures with prolonged postictal states. • Neoplastic Disorders: ◦ Diffuse metastases to the brain, diffuse glioma, carcinomatous meningitis, CNS lymphoma. • Other: Terminal end-of-life delirium.

DIAGNOSTIC APPROACH¶

Initial Evaluation • History: Focus on medications (including over-the-counter and herbals). • Physical Examination: General physical examination and neurologic examination. • Laboratory Work: ◦ Complete blood count (CBC). ◦ Electrolyte panel (including calcium, magnesium, phosphorus). ◦ Liver function tests (including albumin). ◦ Renal function tests.
First-Tier Further Evaluation (Guided by Initial Results) • Infection Screen: Urinalysis and culture; Chest radiograph and tests for respiratory pathogens; Blood cultures. • Monitoring: Electrocardiogram (ECG); Arterial blood gas (ABG). • Toxicology: Serum and/or urine toxicology screen (perform earlier in young persons). • Imaging: Brain imaging with MRI (with diffusion and gadolinium preferred) or CT. • Specialized Tests: ◦ Lumbar puncture (if CNS infection or other inflammatory disorder is suspected; perform after brain imaging). ◦ Electroencephalogram (EEG) (if seizure-related etiology is suspected; perform immediately if high suspicion).
Second-Tier Further Evaluation • Vitamin levels: B12, folate, thiamine. • Endocrinologic laboratories: Thyroid-stimulating hormone (TSH), free T4, cortisol. • Metabolic/Inflammatory: Serum ammonia, Sedimentation rate (ESR). • Serologies: ◦ Autoimmune: Antinuclear antibodies (ANA), complement levels, p-ANCA, c-ANCA; consider paraneoplastic/autoimmune encephalitis testing in serum and CSF. ◦ Infectious: Rapid plasmin reagin (RPR); fungal and viral serologies if high suspicion; HIV antibody. • Repeat Imaging/Lumbar puncture (if not performed in first tier).

MANAGEMENT & TREATMENT¶

Identify and Treat Underlying Cause • Infections: Treat UTI, pneumonia, or sepsis. • Metabolic: Correct electrolyte disturbances (sodium, calcium, magnesium), dehydration, or organ failure. • Toxins: Address drug toxicity or withdrawal (e.g., benzodiazepines for alcohol withdrawal).
Supportive Care Interventions • Reorientation: Provide orientation to person, place, and time. • Sensory Aids: Provide glasses and hearing aids to reduce sensory deprivation. • Environment: Maintain sleep hygiene and mimic the home environment.
Monitoring & Escalation • Monitor for seizures (EEG if etiology remains unclear). • Assess for progression of underlying illness (e.g., sepsis, heart failure).

PROGNOSIS & COMPLICATIONS¶

• Prognosis: ◦ Often reversible if the underlying cause is treated. ◦ Potential for permanent neuronal damage and long-term cognitive decline. • Complications: ◦ Risk of recurring episodes due to untreated neurodegenerative disease. ◦ Post-delirium state: May include varying degrees of amnesia or re-experiencing of confusion (similar to PTSD).

KEY PEARLS & CLINICAL TRAPS¶

• Attention is Key: If a patient has a normal level of consciousness but appears confused, specifically test for an attentional deficit (e.g., digit span). • Don't Miss Hypoactive: These patients are often quiet and may be overlooked; they are just as likely to have serious underlying illness. • The 'Stress Test': Use the onset of delirium in a stable patient as a prompt to screen for undiagnosed dementia or other neurological disorders. • Medication Review: Always correlate the timing of new medications (especially those with anticholinergic properties) with the onset of confusion.

Reference Tables¶

TABLE 29-1 Differential Diagnosis of Delirium Toxins Prescription medications: especially those with anticholinergic…¶

Harrison's 22e, p.184

Toxins
Prescription medications: especially those with anticholinergic properties,
narcotics, and benzodiazepines
Drugs of abuse: alcohol intoxication and alcohol withdrawal, opiates, ecstasy,
LSD, GHB, PCP, ketamine, cocaine, “bath salts,” marijuana and its synthetic
forms
Poisons: inhalants, carbon monoxide, ethylene glycol, pesticides
Metabolic Conditions
Electrolyte disturbances: hypoglycemia, hyperglycemia, hyponatremia,
hypernatremia, hypercalcemia, hypocalcemia, hypomagnesemia
Hypothermia and hyperthermia
Pulmonary failure: hypoxemia and hypercarbia
Liver failure/hepatic encephalopathy
Renal failure/uremia
Cardiac failure
Vitamin deficiencies: B , thiamine, folate, niacin
12
Dehydration and malnutrition
Anemia
Infections
Systemic infections: urinary tract infections, pneumonia and other respiratory
infections, skin and soft tissue infections, sepsis
CNS infections: meningitis, encephalitis, brain abscess
Endocrine Conditions
Hyperthyroidism, hypothyroidism
Hyperparathyroidism
Adrenal insufficiency
Cerebrovascular Disorders
Global hypoperfusion states
Hypertensive encephalopathy
Focal ischemic strokes and hemorrhages (rare): especially nondominant parietal
and thalamic lesions
Autoimmune Disorders
CNS vasculitis
Cerebral lupus
Neurologic paraneoplastic and autoimmune encephalitis
Seizure-Related Disorders
Nonconvulsive status epilepticus
Intermittent seizures with prolonged postictal states
Neoplastic Disorders
Diffuse metastases to the brain
Diffuse glioma
Carcinomatous meningitis
CNS lymphoma
Hospitalization
Terminal end-of-life delirium

TABLE 29-2 Stepwise Evaluation of a Patient with Delirium Initial Evaluation History with special attention to…¶

Harrison's 22e, p.185

Initial Evaluation
History with special attention to medications (including over-the-counter and
herbals)
General physical examination and neurologic examination
Complete blood count
Electrolyte panel including calcium, magnesium, phosphorus
Liver function tests, including albumin
Renal function tests
First-Tier Further Evaluation Guided by Initial Evaluation
Systemic infection screen
Urinalysis and culture
Chest radiograph and tests for respiratory pathogens
Blood cultures
Electrocardiogram
Arterial blood gas
Serum and/or urine toxicology screen (perform earlier in young persons)
Brain imaging with MRI with diffusion and gadolinium (preferred) or CT
Suspected CNS infection or other inflammatory disorder: lumbar puncture after
brain imaging
Suspected seizure-related etiology: electroencephalogram (EEG) (if high
suspicion, should be performed immediately)
Second-Tier Further Evaluation
Vitamin levels: B , folate, thiamine
12
Endocrinologic laboratories: thyroid-stimulating hormone (TSH) and free T; cortisol
4
Serum ammonia
Sedimentation rate
Autoimmune serologies: antinuclear antibodies (ANA), complement levels;
p-ANCA, c-ANCA, consider paraneoplastic/autoimmune encephalitis testing in
the serum and CSF
Infectious serologies: rapid plasmin reagin (RPR); fungal and viral serologies if
high suspicion; HIV antibody
Lumbar puncture (if not already performed)
Brain MRI with and without gadolinium (if not already performed)