Rapid lowering of plasma ammonia. Level should be ≤200 μmol/L (even if diagnosis is not yet established) due to severely toxic effect of ↑ ammonia level on the brain.

• In the pediatric population CKRT (specifically CVVHD) is recommended for hyperammonemia.
  High-dose CKRT w/blood flow rate of 30-50 mL/min recommended for initial treatment of those w/ammonia level >1,000 μmol/L
  Intermittent HD recommended in those who require rapid ammonia clearance due to fast deterioration & signs of cerebral edema
  Regular CKRT can follow hemodialysis or high-dose CKRT for stabilization when blood ammonia level is <200 μmol/L [Raina et al 2020].
• An older patient can receive intermittent HD or high-dose CKRT & can also be switched to a CKRT for stabilization.

• Treatment utilizes an alternative pathway for excretion of excess nitrogen (see Table 4).
• Nitrogen scavenger therapy is available as an IV infusion of a mixture of sodium phenylacetate & sodium benzoate for acute mgmt & as an oral preparation of phenylbutyrate or sodium benzoate for long-term maintenance therapy.
• Citrulline is supplemented at 170 mg/kg/day or 3.8 g/m²/day (enterally).

• Total energy provided should be 100%-120% estimated needs to ensure catabolism reversal.
• Provide calories from glucose & fat; resume protein intake (in the form of natural protein & an essential amino acid mix) ≤24 hrs after protein intake was discontinued.
• Use of a high glucose infusion rate supported by continuous insulin infusion to maintain high set point normoglycemia (140-180 mg/dL) as needed. Goal for a newborn in crisis: to deliver ≥100 kcal/kg/day, mostly from glucose & fat.

• Persons on hemodialysis or hemofiltration need adequate nutrition to overcome catabolism, as nutrients are removed by these procedures.
• Restart protein intake after 24 hrs, as deficiency of essential amino acids → protein breakdown & uncontrolled nitrogen release.
• Daily to 2x-wkly quantitative plasma amino acid analysis should guide nutritional therapy. Goal: to keep essential amino acid levels in normal range.

• Intubated & sedated persons may not show clinical signs of seizures, which are prevalent in acute hyperammonemia. EEG surveillance is thus highly recommended to allow EEG detection & subsequent treatment of seizures.
  Note: Phenobarbital is removed by dialysis & valproic acid is contraindicated in urea cycle disorders.
• No other interventions (besides ↓ ammonia level) have proven efficacy for neuroprotection in hyperammonemic coma due to a urea cycle disorder or other conditions.