Neonatal Hyperammonemia
INTRODUCTION
Neonatal hyperammonemia is a feature of many different inborn errors of metabolism that may be individually rare but have about a 1:5000 cumulative incidence.1,2 It can also be a feature of fulminant liver failure of any cause and of structural anomalies leading to portosystemic shunting. Neonatal hyperammonemia represents a true metabolic emergency as rapid identification and intervention are critical to a positive neurologic outcome. It is essential that neonatal centers have a protocol and plan in place to address these patients. A representative protocol is provided in this chapter (Table 106-1) and details are provided.
Table 106-1 Timeline for Management of Hyperammonemia
Hour 0–1
Arrange transfer to tertiary care center with appropriate facilities and specialists
Establish central vascular access
Avoid compromise of potential dialysis sites
Intubation and airway stabilization
Sedate aggressively to reduce metabolic demand
Collect specimens for necessary diagnostic laboratory tests
Plasma ammonia
Plasma amino acids
Urine organic acids
Plasma acylcarnitine profile
Assemble multidisciplinary team
Neonatology
Metabolic genetics
Nutrition
Nephrology
Surgery
Nursing
Alert laboratory team about need for rapid results and frequent assessments
Alert pharmacy team about need for specialized medications and nutrition
Intravenous fluids/nutrition
Stop enteral feeding
Intravenous fluids
Maximize glucose infusion rate (10% dextrose in water [D10W] or higher)
Intralipids (2–3 g/kg/d)
Goal of 80–120 kcal/kg/d
Medications
Urea cycle disorders
Sodium phenylacetate/sodium benzoate infusion (250 mg/kg of each as initial bolus then as a continuous daily infusion)
Intravenous arginine (200 mg/kg unless AS or AL deficiency suspected, then 400–700 mg/kg) as initial bolus then as a continuous daily infusion
Carbamylglutamate 25 mg/kg/dose every 6 hours (if available)
Organic acidemias
Intravenous carnitine (100 mg/kg/dose every 4–6 hours)
Carbamylglutamate 25 mg/kg/dose every 6 hours (if available)
Hours 1–12
Begin hemodialysis at maximal flow rates
Review diagnostic lab results as available
If essential amino acid deficiency is present, consider reintroducing protein sooner to reverse catabolic state
Monitor for hypotension
Common with hemodialysis
May be exacerbated by arginine infusion (nitric oxide donor)
May reduce arginine rate if vasodilation/hypotension present
Monitor for seizures
Intermittent or continuous EEG; treat if present
Hours 12–48
Transition from hemodialysis to hemofiltration
Monitor for rebound hyperammonemia
Laboratory monitoring
Electrolytes and ammonia every 6 hours
Reintroduce protein
Start with 0.5 g protein/kg/d and titrate upward
50% of protein goals from essential amino acids
50% of protein goals from whole protein
Enteral route preferred
Hours 48 and beyond
Nutrition tailored to specific cause of hyperammonemia
∼ 1.5 g protein/kg/d in neonates
Tailor nutrition to specific inborn error of metabolism
50% of protein from disease-specific formula
50% of protein from breast milk or whole-protein formula
Assess nutritional parameters (growth, plasma amino acids) frequently
Transition intravenous nutrition and medication to enteral
Urea cycle disorders: sodium phenylbutyrate 450–600 mg/kg/d
Organic acidemias: carnitine 100–200 mg/kg/d
Other medications depending on specific cause
Assess for neurologic sequelae
Brain MRI
EEG
Developmental assessment
Consider gastrostomy
Genetic counseling for family
Discharge planning
Emergency protocol given to family
Ensure home access for medications and nutrition
Follow up in metabolic clinic
Abbreviations: AS, argininosuccinate synthetase; AL, argininosuccinate lyase; EEG, electroencephalography; MRI, magnetic resonance imaging.
TREATMENT PROTOCOL
Hours 0–1: Initial Assessment and Activation of Metabolic Team
Once hyperammonemia is recognized in the neonate, the treating clinician must assess the duration of symptoms; hours 0–1 should involve the initial assessment and activation of the metabolic team. Studies of patients with urea cycle disorders have shown that neurologic and cognitive outcomes are tightly correlated with duration of hyperammonemic coma in the neonate. Diagnosis of hyperammonemia is sometimes delayed; neonates may be initially suspected to have sepsis and are treated with antibiotics for a number of days before metabolic disorders are considered. In such a patient who has been comatose for greater than 72 hours, consideration should be given to the appropriateness of heroic interventions, as with prolonged hyperammonemia the chances of significant neurologic recovery are small. Withdrawal of care is reasonable in these cases.3–6
If the patient has only been symptomatic for a short time, intervention must proceed quickly. Central venous access is critical; this allows frequent laboratory monitoring as well as delivery of medications and dialysis. Antibiotic therapy and evaluation for sepsis are recommended because sepsis is an important consideration in the primary presentation and, if present, may lead to further catabolism. Care should be given to the preservation of potential dialysis access sites. Once critical hyperammonemia is identified, intubation and aggressive sedation are indicated to reduce metabolic activity and catabolism. Initial laboratory assessment may help narrow the differential diagnosis and permit tailoring of specific therapy (Table 106-2). Collected specimens for initial laboratory studies include arterial blood gas, comprehensive metabolic panel, and urinalysis. In addition, specimens for plasma amino acid analysis, urine organic acid analysis, and acylcarnitine profile should all be collected and sent to a regional metabolic center for rapid evaluation.
Table 106-2 Initial Laboratory Evaluation of Hyperammonemia
