What is the initial approach to managing a patient with encephalopathy?

Initial Management of Encephalopathy

The first critical step is to distinguish true encephalitis (inflammatory brain process) from encephalopathy (brain dysfunction from systemic causes), as this fundamentally changes management—encephalitis requires urgent empiric acyclovir and lumbar puncture, while encephalopathy demands identification and correction of precipitating factors. 1

Immediate Assessment and Stabilization

Airway Protection

• Patients with altered consciousness who cannot protect their airway require immediate intubation, particularly if there is risk of aspiration or Glasgow Coma Scale deterioration 1, 2
• Higher grades of encephalopathy necessitate intensive care monitoring 1
• Use short-acting sedatives (propofol, dexmedetomidine) rather than benzodiazepines if intubation is required, as benzodiazepines worsen hepatic encephalopathy 2, 3

Distinguish Encephalitis from Encephalopathy

Key features suggesting encephalitis (requiring urgent antimicrobial therapy): 1

• Fever with altered consciousness
• New focal neurological signs
• New seizures
• Headache, nausea, vomiting
• Speech disturbances or behavioral changes

Key features suggesting encephalopathy (requiring identification of systemic cause): 1

• Past history of similar episodes
• Symmetrical neurological findings
• Myoclonus or asterixis
• Lack of fever
• Metabolic acidosis or unexplained base deficit

Management Algorithm for Suspected Encephalitis

If clinical features suggest encephalitis, implement a four-pronged approach simultaneously: 1

1. Empiric Treatment (Do Not Delay)

• Start IV acyclovir immediately before diagnostic results return, as HSV encephalitis has high mortality without treatment 1
• Continue acyclovir for 14 days if HSV confirmed 1

2. Urgent Diagnostic Workup

• CT brain before lumbar puncture in most patients to exclude contraindications, though radiological contraindications should be considered case-by-case 1
• Lumbar puncture with: opening pressure, CSF glucose (with paired serum glucose), CSF protein, microscopy/culture/sensitivity (×2), virology PCR (especially HSV), lactate, and consider oligoclonal bands 1
• If HSV PCR not sent on first LP, repeat CSF PCR on second LP at 24 hours 1
• Consider HSV CSF IgG at 10-14 days 1

3. Identify Alternative Causes

• Metabolic disturbances (glucose, electrolytes, renal/hepatic function) 1
• Toxic exposures 1
• Autoimmune causes (consider if subacute presentation over weeks-months, orofacial dyskinesia, choreoathetosis, intractable seizures, or hyponatremia) 1
• Systemic sepsis 1

4. Supportive Care

• Frequent neurological monitoring 1
• Seizure management if present 1
• Maintain adequate oxygenation and blood pressure 4

Management Algorithm for Encephalopathy (Non-Inflammatory)

If features suggest encephalopathy rather than encephalitis, follow this systematic approach:

1. Identify and Correct Precipitating Factors (Resolves 90% of Cases)

Common precipitants to systematically evaluate: 1, 5, 6

• Infections (pneumonia, UTI, spontaneous bacterial peritonitis)
• Gastrointestinal bleeding
• Constipation
• Dehydration and electrolyte disturbances
• Sedative medications (especially benzodiazepines)
• Renal dysfunction
• Hypoglycemia or hyperglycemia

2. Hepatic Encephalopathy Specific Management

If hepatic encephalopathy suspected (cirrhosis, asterixis, elevated ammonia):

First-line therapy: 1, 5, 6, 7

• Lactulose 30-45 mL (20-30 g) orally three to four times daily, titrated to produce 2-3 soft stools per day
• For rapid effect in acute setting: hourly doses of 30-45 mL until laxation achieved, then reduce to maintenance dosing
• Via nasogastric tube if patient cannot swallow safely
• As retention enema (300 mL lactulose mixed with 700 mL water/saline, retained 30-60 minutes, repeated every 4-6 hours) if oral route impossible

Second-line therapy (add if lactulose alone insufficient): 1, 5, 6

• Rifaximin 550 mg twice daily reduces recurrence risk by 58% when added to lactulose
• Continue indefinitely for secondary prophylaxis after first episode

Nutritional support: 1, 5

• Provide moderate hyperalimentation with small, frequent meals including late-night snack
• Protein intake 0.5 g/kg/day initially, advancing to 1-1.5 g/kg/day as tolerated
• Multivitamin supplementation

3. Monitor for Complications

• Frequent mental status checks with ICU transfer if consciousness declines 5
• Monitor glucose, potassium, magnesium, phosphate 5
• Avoid nephrotoxic, neurotoxic medications (aminoglycosides, cefepime in high doses) 4

Critical Pitfalls to Avoid

• Do not delay acyclovir while awaiting LP or imaging if encephalitis suspected—mortality is high without treatment 1
• Do not rely on ammonia levels alone for diagnosis or monitoring of hepatic encephalopathy; normal ammonia should prompt diagnostic reevaluation 1, 5
• Do not use rifaximin as monotherapy for acute hepatic encephalopathy—always combine with lactulose 5, 6
• Do not over-titrate lactulose causing severe diarrhea, dehydration, or aspiration risk 1, 6
• Do not prescribe benzodiazepines for sleep disturbances in patients with hepatic encephalopathy—they worsen encephalopathy 3
• Do not assume encephalopathy is hepatic without excluding other metabolic, toxic, and infectious causes 1

Long-Term Considerations

• Secondary prophylaxis with lactulose is mandatory after first episode of hepatic encephalopathy to prevent recurrence (50-70% recur within one year without prophylaxis) 1, 5, 6
• Liver transplantation evaluation should be initiated after first episode of hepatic encephalopathy or if recurrent/intractable despite therapy 1, 5
• Patients and families should be informed about support resources (e.g., Encephalitis Society for viral encephalitis cases) 1