I: Metabolic-Genetic

Neonatal Hyperammonemia

               Brendan Lanpher, Marshall Summar, and Mark L. Batshaw

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.36

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

Dec 28, 2016 | Posted by in PEDIATRICS | Comments Off on I: Metabolic-Genetic

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