How should severe hyperammonemia (ammonia ~170 µmol/L) be treated in hepatic encephalopathy?

Treatment of Ammonia Level 170 µmol/L

For an ammonia level of 170 µmol/L in the context of hepatic encephalopathy, initiate immediate lactulose therapy (30-45 mL orally or via nasogastric tube every 1-2 hours until bowel movement, then titrate to 2-3 soft stools daily) and consider escalation to continuous kidney replacement therapy if neurological status is rapidly deteriorating or if moderate-to-severe encephalopathy is present. 1, 2

Immediate Medical Management

First-Line Pharmacological Therapy

• Start lactulose immediately at 30-45 mL orally or via nasogastric tube every 1-2 hours until bowel movement occurs, then titrate to achieve 2-3 soft stools daily 1
• Lactulose achieves recovery in 70-90% of hepatic encephalopathy patients and should be initiated based on clinical symptoms, not ammonia levels alone 1
• Rifaximin can be added as adjunctive therapy to lactulose for enhanced ammonia reduction 3, 4

Nutritional Modifications

• Temporarily discontinue all oral protein intake to reduce nitrogen load while providing adequate calories (≥100 kcal/kg daily) as intravenous glucose and lipids 2
• Maintain glucose infusion rate of 8-10 mg/kg/min and provide lipids (0.5 g/kg daily, up to 3 g/kg daily) to prevent protein catabolism that drives further ammonia production 2
• Gradually reintroduce protein within 48 hours by 0.25 g/kg daily increments, targeting 1.5 g/kg daily, as prolonged protein restriction causes catabolism and worsens ammonia levels 2

Indications for Escalation to Kidney Replacement Therapy

Critical Decision Points at Ammonia 170 µmol/L

At this ammonia level (170 µmol/L), the decision to escalate to kidney replacement therapy depends primarily on neurological status rather than the ammonia number itself 1, 2:

• Initiate CKRT if rapidly deteriorating neurological status, coma, or cerebral edema is present with ammonia >150 µmol/L 5, 2
• Initiate CKRT if moderate or severe encephalopathy is present at any ammonia level 5, 2
  • Moderate encephalopathy: lethargy, distal flexion, decreased activity, hypotonia, weak suck, constricted pupils, or bradycardia 5
  • Severe encephalopathy: stupor or coma, no activity, decerebrate posture, flaccid tone, absent reflexes, pupils non-reactive to light 5

Dialysis Modality Selection

• High-dose continuous venovenous hemodialysis (CVVHD) is the preferred first-line modality when kidney replacement therapy is indicated, with blood flow rate 30-50 mL/min and dialysate flow rate to blood flow rate ratio >1.5 5, 2
• CVVHD provides superior ammonia clearance compared to CVVH while maintaining hemodynamic stability and avoiding rebound hyperammonemia 5
• Use warmed dialysate to maintain hemodynamic stability during CVVHD 5, 2
• Continue CVVHD until ammonia levels are <200 µmol/L on two consecutive hourly measurements 5, 2

Alternative: Intermittent Hemodialysis

• Intermittent HD achieves 50% reduction in ammonia within 1-2 hours and is more effective for rapid clearance than CKRT 2
• Hybrid therapy (HD followed by CKRT) can be used to rapidly reduce ammonia while controlling rebound effect 5

Nitrogen-Scavenging Agents

When to Consider

• Administer nitrogen-scavenging agents if ammonia remains elevated despite lactulose or while preparing for dialysis in severe cases 2
• Intravenous sodium benzoate: 250 mg/kg for body weight <20 kg; 5.5 g/m² for body weight >20 kg 2
• Intravenous sodium phenylacetate: 250 mg/kg for body weight <20 kg; 5.5 g/m² for body weight >20 kg 2

Monitoring Strategy

Serial Assessments

• Check plasma ammonia levels every 3-4 hours initially until normalized, but only in severe hyperammonemia requiring dialysis 1, 2
• Monitor neurological status continuously using Glasgow Coma Scale or West Haven criteria 1, 2
• Focus on clinical improvement (mental status, asterixis resolution) rather than ammonia normalization as the primary endpoint 1
• Monitor electrolytes, especially during CKRT, to prevent complications 2

Critical Pitfalls to Avoid

Common Errors

• Do not delay treatment waiting for ammonia results—treat based on clinical suspicion of hepatic encephalopathy 1
• Do not use ammonia levels to assess encephalopathy severity or guide treatment adjustments—ammonia levels do not correlate with encephalopathy severity in cirrhotic patients 1, 6
• Do not prolong protein restriction beyond 48 hours—this causes catabolism and paradoxically worsens ammonia levels 2
• Ensure proper ammonia sample collection (free-flowing venous or arterial blood, transported on ice, processed within 15 minutes) to avoid false elevations 2

Prognostic Considerations

• The duration of hyperammonemic coma prior to dialysis initiation is the most important prognostic factor, not the rate of ammonia clearance 5, 2
• Ammonia levels >200 µmol/L are associated with cerebral herniation risk and poor neurological outcomes 7
• Early recognition and treatment are essential to prevent irreversible neurological damage 2

Alternative Diagnoses to Exclude

When Ammonia is Elevated but Context is Unclear

• A normal ammonia level has high negative predictive value and should prompt immediate investigation for alternative diagnoses (intracranial hemorrhage, septic encephalopathy, hyponatremia, Wernicke's encephalopathy, medication effects) 1
• Consider adult-onset urea cycle defects (ornithine transcarbamylase deficiency) if encephalopathy occurs at modest ammonia elevations 7
• Valproic acid can cause hyperammonemia even without liver dysfunction—discontinue if present 7