How do you differentiate between Intensive Care Unit (ICU) psychosis and metabolic encephalopathy?

Differentiating ICU Delirium from Metabolic Encephalopathy

The key distinction is that ICU delirium and metabolic encephalopathy are overlapping syndromes rather than separate entities—metabolic encephalopathy is often the underlying cause of delirium in critically ill patients, making differentiation clinically challenging and often unnecessary for initial management. 1, 2

Understanding the Overlap

• Both conditions share core features: acute onset, fluctuating mental status, inattention, and altered consciousness, making them clinically indistinguishable in many cases 1, 3
• Metabolic encephalopathy frequently manifests as delirium in the ICU setting, with metabolic derangements (hypoxia, electrolyte disturbances, organ failure, sepsis) being the most common triggers 2, 4
• The term "ICU delirium" describes the clinical syndrome, while "metabolic encephalopathy" identifies the underlying pathophysiology—they represent different perspectives on the same patient 4, 3

Critical Distinguishing Features When They Differ

Level of Consciousness

• Metabolic encephalopathy typically causes progressive depression of consciousness ranging from mild confusion to stupor and coma, with a more predictable deterioration pattern 2, 5
• ICU delirium maintains relatively intact arousal with fluctuating attention and awareness, though hypoactive delirium can appear lethargic 1
• Patients with pure psychosis maintain completely intact consciousness and awareness, which is the clearest differentiator from both conditions 6, 7

Motor Findings

• Asterixis and myoclonus are hallmarks of metabolic encephalopathy and suggest specific metabolic derangements (hepatic, renal, or hypercapnic encephalopathy) 3, 5
• ICU delirium presents with abnormal psychomotor activity (hyperactive agitation or hypoactive lethargy) without the characteristic flapping tremor 1

EEG Patterns

• Metabolic encephalopathy shows progressive generalized slowing with triphasic waves (especially in hepatic encephalopathy), though triphasic waves are not specific and occur in other metabolic states 1, 5
• The severity of EEG slowing correlates with the depth of metabolic encephalopathy, progressing from frontal slowing to diffuse delta activity to eventual suppression 1
• EEG is particularly useful when the diagnosis is unclear, as it can identify subclinical seizures or focal abnormalities suggesting structural lesions 3, 5

Systematic Diagnostic Approach

Step 1: Assess Level of Consciousness and Attention

• Use validated screening tools (CAM-ICU or ICDSC) to identify delirium features: inattention, altered consciousness, disorganized thinking, and fluctuating course 1
• Document baseline neurological function before the acute change, especially in patients with pre-existing cognitive impairment or neurological injury 1

Step 2: Identify Metabolic Derangements

• Obtain comprehensive metabolic panel: glucose, electrolytes (sodium, calcium, magnesium), renal function (BUN, creatinine), hepatic function (ammonia, transaminases, bilirubin), and arterial blood gas 1, 8
• Arterial ammonia >200 μg/dL strongly predicts cerebral herniation in hepatic encephalopathy and requires urgent intervention 1
• Check thyroid function, complete blood count, and cardiac enzymes to identify hyperthyroidism, anemia, infection, or cardiac injury 8

Step 3: Evaluate for Specific Causes

• Septic encephalopathy is the most common metabolic cause in ICU patients, with mortality ranging 16-65% 9, 4
• Drug and alcohol withdrawal manifests as hyperactive delirium with specific autonomic signs: sweating, piloerection, mydriasis, tachycardia, and hypertension for opioid withdrawal; anxiety, tremors, and potential seizures for benzodiazepine withdrawal 1
• Wernicke encephalopathy requires high clinical suspicion in malnourished or alcoholic patients, as it represents a medical emergency requiring immediate thiamine replacement 2

Step 4: Rule Out Structural and Focal Lesions

• Obtain brain CT or MRI when focal neurological signs are present, mental status fails to improve with metabolic correction, or new-onset symptoms occur without clear metabolic cause 1, 6, 7
• Focal findings on examination suggest structural lesions (stroke, hemorrhage, abscess) or recrudescence of prior neurological injury rather than pure metabolic encephalopathy 3

Step 5: Consider EEG When Diagnosis Remains Unclear

• EEG helps differentiate metabolic encephalopathy (generalized slowing, triphasic waves) from nonconvulsive seizures (epileptiform discharges) and provides prognostic information 1, 5
• The degree of EEG slowing correlates with encephalopathy severity and can guide treatment intensity 1

Management Priorities

Treat Underlying Metabolic Causes First

• Address the primary metabolic derangement before attributing symptoms solely to "ICU psychosis"—up to 46% of psychiatric presentations have direct medical causes 8
• Correct hypoxia, hypoglycemia, electrolyte abnormalities, and organ dysfunction as these directly impair brain function 2, 4
• Manage sepsis aggressively, as septic encephalopathy carries high mortality and requires source control plus antimicrobial therapy 1, 9

Avoid Iatrogenic Worsening

• Benzodiazepines increase delirium risk and should be avoided for sedation unless treating alcohol or benzodiazepine withdrawal 1
• Dexmedetomidine reduces delirium incidence compared to benzodiazepines in mechanically ventilated patients, particularly those with sepsis 1
• Physical restraints paradoxically increase agitation, unplanned extubations, and delirium duration—use only as last resort for immediate safety 1

Symptomatic Management When Needed

• Reserve antipsychotics for severe agitation after medical causes are addressed, using low doses of atypical agents when possible 6, 8
• Avoid large initial antipsychotic doses, as they increase side effects without hastening recovery 6

Common Pitfalls to Avoid

• Don't dismiss altered mental status as "just ICU psychosis" without systematic evaluation for metabolic causes—this delays critical treatment 8, 4
• Don't assume delirium cannot be assessed in children, elderly with dementia, or patients with neurological injury—validated tools exist for all these populations 1
• Don't overlook hypoactive delirium, which is frequently missed but carries worse prognosis than hyperactive delirium 1
• Don't attribute fluctuating mental status to dementia alone—delirium superimposed on dementia is common and requires active treatment 1
• Don't delay thiamine administration in at-risk patients while awaiting laboratory confirmation of Wernicke encephalopathy 2

Prognostic Considerations

• Both delirium and metabolic encephalopathy predict worse outcomes: increased mortality, prolonged ICU and hospital stays, accelerated cognitive decline, and higher costs 1, 2, 9
• One-year survival with hepatic encephalopathy and cirrhosis is <50%, emphasizing the need for liver transplant evaluation in appropriate candidates 1, 9
• Episodes of metabolic encephalopathy accelerate cognitive decline in patients with diminished cognitive reserve, potentially converting reversible encephalopathy to permanent dementia if treatment is delayed 3, 5