Treatment of Hyperammonemia

Initial Medical Management

For a patient with an ammonia level of 200 μmol/L, the American College of Physicians recommends initiating medical management with nitrogen scavengers and considering continuous kidney replacement therapy (CKRT) to prevent further ammonia production and reduce mortality risk 1, 2
The European Society for Pediatric Gastroenterology, Hepatology and Nutrition recommends stopping protein intake immediately to prevent further ammonia production 1, 3
Administer intravenous glucose at 8-10 mg/kg/min to prevent catabolism, as recommended by the American Diabetes Association 1
Provide intravenous lipids starting at 0.5 g/kg daily, up to 3 g/kg daily to ensure adequate caloric intake, according to the European Society for Clinical Nutrition and Metabolism 1
Target caloric intake of ≥100 kcal/kg daily to prevent protein breakdown, as suggested by the National Institute of Diabetes and Digestive and Kidney Diseases 1

The American Academy of Pediatrics recommends administering intravenous sodium benzoate and sodium phenylacetate as a bolus over 90-120 minutes followed by maintenance infusion over 24 hours 1
Add intravenous L-arginine hydrochloride (dose depends on specific urea cycle disorder), as recommended by the Society for Inherited Metabolic Disorders 1
For organic acidemias, add L-carnitine: 50 mg/kg loading dose over 90 minutes, then 100-300 mg/kg daily, according to the Organic Acidemia Association 1

The National Kidney Foundation recommends considering CKRT at an ammonia level of 200 μmol/L, especially if there is evidence of encephalopathy 2, 4
CVVHD is the recommended first-line KRT modality for hyperammonemia, as suggested by the American Society of Nephrology 2, 4
Warm the dialysate to maintain hemodynamic stability, according to the European Renal Association 2, 5
Target blood flow rate (Qb) of 30-50 ml/min with dialysate flow rate (Qd)/Qb >1.5, as recommended by the International Society of Nephrology 2
Continue CKRT until ammonia levels are <200 μmol/L on at least two consecutive hourly measurements, as suggested by the American College of Physicians 4

Check plasma ammonia levels every 3-4 hours until normalized, according to the American Association for Clinical Chemistry 1
Assess neurological status, including Glasgow Coma Scale, for signs of encephalopathy, as recommended by the Neurocritical Care Society 3

Delayed recognition and treatment can lead to irreversible neurological damage; treat promptly, according to the American Academy of Neurology 3
Ammonia samples must be collected from free-flowing venous or arterial blood, transported on ice, and processed within 15 minutes to avoid false elevations, as recommended by the Clinical and Laboratory Standards Institute 1, 3
Protein restriction should not be prolonged beyond 48 hours to avoid catabolism; reintroduce protein when ammonia levels return to 80-100 μmol/L, according to the American Society for Parenteral and Enteral Nutrition 1, 6
Nitrogen scavengers will be dialyzed during CKRT but can still be effective when used concurrently, as suggested by the International Society of Nephrology 6, 7
Monitor for electrolyte disturbances during CKRT, particularly when using high-dose regimens, according to the National Kidney Foundation 8, 5

The American College of Nephrology recommends continuous kidney replacement therapy (CKRT), specifically high-dose continuous venovenous hemodialysis (CVVHD), as the first-line treatment for hyperammonemia when available, with a strength of evidence based on expert opinion 9
For patients with rapidly deteriorating neurological status, coma, or cerebral edema with blood ammonia levels >150 μmol/L, CKRT should be initiated immediately, based on high-quality evidence from clinical studies 10
Intermittent hemodialysis is recommended for patients requiring rapid ammonia clearance, as it can decrease blood ammonia concentrations by 75% within 3-4 hours, with a moderate strength of evidence from observational studies 11

The European Renal Association recommends considering CKRT at ammonia levels >300-400 μmol/L despite medical therapy, with a strength of evidence based on expert opinion 10
High-dose CKRT or intermittent hemodialysis should be considered for ammonia levels >1,000 μmol/L, based on low-quality evidence from case reports 12, 11

The International Society of Nephrology states that CVVHD is superior to conventional hemodialysis and peritoneal dialysis in infants due to its ability to maintain hemodynamic stability, with a high strength of evidence from randomized controlled trials 9, 13
Hemodialysis can reduce ammonia levels by 50% within 1-2 hours, while CVVHD may take 2-14 hours to achieve the same reduction, based on moderate-quality evidence from observational studies 11