Treatment of Hyperammonemia in the ICU
Prompt identification and treatment of hyperammonemia are imperative to optimize outcomes and avoid irreversible brain damage in ICU patients. 1 The management approach depends on ammonia levels, clinical presentation, and available resources.
Initial Medical Management
Immediate Stabilization
- Secure airway, breathing, and circulation
- Establish intravenous access
- Monitor vital signs
- Check blood glucose levels
- Provide adequate rehydration with dextrose-containing fluids at high infusion rates
- Obtain accurate ammonia measurement on free-flowing venous or arterial blood sample collected in lithium heparin or EDTA tube, transported on ice, processed within 15 minutes 1
Non-Kidney Replacement Therapy (NKRT)
For ammonia levels >150 μmol/L (255 μg/dL):
Stop protein intake temporarily
Provide caloric support:
- IV glucose: 8-10 mg/kg/min
- IV lipids: 0.5 g/kg daily, up to 3 g/kg daily
- Total caloric intake: ≥100 kcal/kg daily 1
Administer nitrogen-scavenging agents:
IV sodium benzoate and sodium phenylacetate:
IV L-arginine hydrochloride (dose depends on specific deficiency)
IV L-carnitine: 50 mg/kg loading dose over 90 minutes, then 100-300 mg/kg daily (for organic acidemias) 1
Monitor ammonia levels every 3 hours 1
Reintroduce protein within 48 hours after ammonia levels decrease to 80-100 μmol/L (136-170 μg/dL) to prevent catabolism 1
Kidney Replacement Therapy (KRT)
Indications for KRT
KRT should be initiated when:
- Rapidly deteriorating neurological status, coma, or cerebral edema with ammonia >150 μmol/L (256 μg/dL)
- Moderate or severe encephalopathy
- Persistently high ammonia levels >400 μmol/L (681 μg/dL) refractory to NKRT
- Rapid rise in ammonia to >300 μmol/L (511 μg/dL) within hours that cannot be controlled with NKRT 1
- Ammonia levels fail to fall below 150 μmol/L or by more than 40% within 4-8 hours of receiving nitrogen-scavenging therapy 2
Preferred KRT Modalities
Continuous Kidney Replacement Therapy (CKRT)
- First-line treatment: High-dose continuous venovenous hemodialysis (CVVHD) 1
- Blood flow rate (Qb): 30-50 ml/min
- Dialysis fluid flow rate (Qd)/Qb >1.5
- Warming the dialysate helps maintain hemodynamic stability
- For ammonia >1,000 μmol/L (1,703 μg/dL), use high-dose CKRT 1
- CVVHD provides greater ammonia clearance than CVVH 1, 3
Plasma Exchange
- For acute liver failure patients with hyperammonemia (ammonia >150 μmol/L) 1
Peritoneal Dialysis (PD)
- Only if CKRT and HD are unavailable
- Less efficient than other modalities
- Not recommended with rigid peritoneal catheters due to increased complications 1
Step-down approach:
- Transition to lower-intensity CKRT when ammonia <200 μmol/L (341 μg/dL) on at least two hourly measurements 1
Monitoring During Treatment
- Plasma ammonia levels (every 3 hours)
- Glutamine and quantitative plasma amino acids
- Blood glucose
- Electrolytes
- Venous or arterial blood gases
- AST and ALT
- Neurological status and Glasgow Coma Scale
- Signs of cerebral edema 2
Prognostic Factors
Poor prognostic factors include:
- Hyperammonemic coma lasting >3 days
- Increased intracranial pressure
- Plasma ammonia >1,000 μmol/L (1,703 μg/dL) 1
Common Pitfalls and Caveats
Delayed recognition and treatment can lead to irreversible neurological damage. Any unexplained change in consciousness should prompt ammonia level testing.
Inadequate caloric support can worsen hyperammonemia through catabolism.
Failure to reintroduce protein within 48 hours can lead to catabolism and worsen hyperammonemia.
Relying solely on NKRT when ammonia levels are very high (>400 μmol/L) or when there is neurological deterioration.
Inappropriate KRT modality selection - CVVHD provides better ammonia clearance than CVVH or peritoneal dialysis 1, 3.
Inaccurate ammonia measurement - samples must be properly collected, transported on ice, and processed within 15 minutes 1.
Failure to monitor for rebound hyperammonemia after discontinuation of KRT.