What are the methods for correcting elevated ammonia levels (hyperammonemia)?

Methods for Correcting Elevated Ammonia Levels (Hyperammonemia)

Continuous kidney replacement therapy (CKRT), specifically high-dose continuous venovenous hemodialysis (CVVHD), is the recommended first-line treatment for severe hyperammonemia when available. 1

Initial Non-Kidney Replacement Therapy (NKRT) Management

• Immediately conduct further investigations without delaying treatment when elevated ammonia levels are detected 2
• Discontinue all oral feeds to reduce nitrogen load and provide adequate calories (≥100 kcal/kg daily) as intravenous glucose and lipids 1, 2
• Maintain a glucose infusion rate of 8-10 mg/kg/min and provide lipids (0.5 g/kg daily, up to 3 g/kg daily) 1, 2
• Gradually reintroduce protein (by 0.25 g/kg daily, up to 1.5 g/kg daily) within 48 hours to prevent protein catabolism driving further ammonia production 1, 2

Pharmacological Therapy

Nitrogen Scavengers

• Use nitrogen-scavenging agents such as sodium benzoate and sodium phenylacetate at recommended dosages 1, 2:
  • Intravenous sodium benzoate: body weight <20 kg, 250 mg/kg; body weight >20 kg, 5.5 g/m² 1, 2
  • Intravenous sodium phenylacetate: body weight <20 kg, 250 mg/kg; body weight >20 kg, 5.5 g/m² 1, 2

Urea Cycle Intermediates

• Administer intravenous L-arginine hydrochloride based on specific urea cycle disorder 1, 2:
  • For OTC and CPS deficiencies: body weight <20 kg, 200 mg/kg; weight >20 kg, 4 g/m² 1
  • For ASS and ASL deficiencies: body weight <20 kg, 600 mg/kg; weight >20 kg, 12 g/m² 1

For Hepatic Encephalopathy

• Lactulose reduces blood ammonia levels by 25-50% by acidifying the gastrointestinal tract and inhibiting ammonia production by coliform bacteria 3, 4
• Rifaximin decreases intestinal production and absorption of ammonia by altering gastrointestinal flora 4
• L-ornithine L-aspartate (LOLA) lowers ammonia levels by stimulating the urea cycle 5

Kidney Replacement Therapy (KRT)

Indications for KRT

• Rapidly deteriorating neurological status, coma, or cerebral edema with blood ammonia level >150 μmol/l 1
• Moderate or severe encephalopathy 1
• Persistently high blood ammonia levels >400 μmol/l refractory to NKRT medical measures 1
• Rapid rise in blood ammonia levels to >300 μmol/l within a few hours that cannot be controlled via NKRT 1

Continuous Kidney Replacement Therapy (CKRT)

• High-dose CVVHD is the recommended first-line treatment for hyperammonemia when possible 1
• For initial treatment of patients with blood ammonia level >1,000 μmol/l, use high-dose CKRT with blood flow rate (Qb) 30-50 ml/min, aiming at dialysis fluid flow rate (Qd)/Qb >1.5 1
• Warming the dialysate helps maintain hemodynamic stability 1
• A Qd >1,000 ml/h is required to exploit the maximum potential of CKRT in neonates 1

Hemodialysis (HD)

• Intermittent HD is recommended for patients requiring rapid ammonia clearance 1
• HD is more effective than CKRT for rapidly reducing blood ammonia levels, with patients treated with HD showing a 50% reduction in ammonia levels within 3 hours 1
• Consider HD as initial therapy in patients with blood ammonia levels >1,000 μmol/l 1

Hybrid Therapy

• Combination of HD and CKRT (hybrid or sequential therapy) can gradually reduce ammonia levels while controlling rebound effect 1
• HD or CKRT combined with ECMO is recommended for neonates who are hemodynamically unstable 1
• Step-down CKRT can follow HD or high-dose CKRT when the blood ammonia level is <200 μmol/l on at least two consecutive hourly measurements 1

Peritoneal Dialysis (PD)

• PD is less efficient than HD or CKRT in reducing ammonia levels 1
• Consider PD only in situations where extracorporeal therapies are not available or unsafe 1

Monitoring During Treatment

• Check plasma ammonia levels every 3-4 hours until normalized 2
• Assess neurological status regularly for signs of encephalopathy 2
• Monitor electrolytes, especially during CKRT 2

Common Pitfalls and Caveats

• Delayed recognition and treatment can lead to irreversible neurological damage 2
• Ammonia samples must be collected from free-flowing venous or arterial blood, transported on ice, and processed within 15 minutes to avoid false elevations 2
• Protein restriction should not be prolonged beyond 48 hours to avoid catabolism 2
• Nitrogen scavengers will be dialyzed during CKRT but can still be effective when used concurrently 2
• The duration of hyperammonemic coma prior to the start of dialysis is the most important prognostic factor, not the rate of ammonia clearance 1