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insulin (starting at 0.01 units/kg/hr) should be used while carefully monitoring serum glucose instead of
decreasing or stopping dextrose-containing fluids. Hypotonic fluid overload should be avoided,
particularly in patients with hyperammonemia, because this could result in cerebral edema. Increased
intracranial pressure in patients with hyperammonemia should not be treated with steroids or mannitol.
Steroids increase catabolism and can therefore worsen hyperammonemia. Mannitol has not been shown
to be effective. Hypertonic saline can be used.


TABLE 95.7
EMERGENT TREATMENT
Access and establish airway, breathing, circulation
Fluid boluses normal saline, avoid lactated Ringer’s. Avoid hypotonic fluid load due to risk of
cerebral edema, particularly if hyperammonemia
Discontinue intake of offending agents, provide adequate glucose to prevent catabolism
NPO (especially no protein, galactose, or fructose)
Glucose for hypoglycemia, 0.25–1 g/kg (i.e., D10 neonates; D10 or D25 infant, child)
D10 to D15 with electrolytes: 8–12 mg/kg/min IV at 1–1.5 × maintenance to maintain serum glucose
level at 120–170 mg/dL
If necessary, treat hyperglycemia with insulin to further prevent hyperglycemia
Correct metabolic acidosis (pH <7.0–7.2) slowly, cautiously
Sodium bicarbonate and/or potassium acetate: 0.25–0.5 mEq/kg/hr (up to 1–2 mEq/kg/hr) IV; if
intractable acidosis, consider hemodialysis (peritoneal dialysis, hemofiltration, exchange
transfusion much less effective)
Eliminate toxic metabolites
Hyperammonemia therapy
For organic acidopathies, fatty acid oxidation defects, hyperammonemia is usually corrected by
treatment of dehydration, acidosis, and hypoglycemia . Hemodialysis should be considered for
persistent hyperammonemia for these conditions or suspected IEM
For urea cycle defects, recommendations of the New England Consortium are to perform dialysis
for ammonia >300 μg/dL if concentration is rising, prepare for possible dialysis for ammonia
>200–250 μg/dL, engaging receiving dialysis unit/facility as soon as possible. If dialysis not

immediately available or levels >100–125 μg/dL, use sodium phenylacetate, sodium benzoate as
Ammonul (Ucyclyd Pharma, 1-888-829-2593). If <20 kg load 250 mg/kg (2.5 mL/kg) in 10%
glucose via central line over 90–120 min, then 250 mg/kg/day (2.5 mL/kg/day) in 10% glucose via
central line continuous infusion, if ≥20 kg 5.5 g/m2 (55 mL/m2) over 90–120 min, then 5.5
g/m2/day (55 mL/m2/day) via central line; arginine HCl 600 mg/kg (6 mL/kg) IV in 10% glucose
over 90–120 min, then 600 mg/kg/day IV continuous infusion. Ammonul must be given by central
line. Arginine HCl can be mixed with Ammonul. Can decrease arginine HCl doses to 200 mg/kg if
carbamoyl phosphate deficiency, ornithine transcarbamylase deficiency. l-carnitine conjugates
with and inactivates sodium benzoate; therefore, it must not be given with Ammonul. Has also
been used for neonatal hyperammonemic coma of unknown etiology
Administer cofactors if indicated
Pyridoxine (B6 ) 100 mg IV for possible pyridoxine-responsive disorder (seizures unresponsive to
conventional anticonvulsants)
Folic acid as leucovorin; 2.5 mg IV for possible folate-responsive disorder (seizures unresponsive to
conventional anticonvulsants)
Biotin 10–40 mg NG tube for possible biotin-responsive disorder (seizures unresponsive to
conventional anticonvulsants)
L -carnitine 25–50 mg/kg over 2–3 min or as an infusion added to the maintenance fluid, followed
by 25–50 mg/kg over 24 hrs, max 100 mg/kg not to exceed 3 g/day for presumed carnitine
deficiency if life-threatening manifestations. Use is controversial, consultation with an IEM
specialist is recommended
Adapted from Weiner DL. Inborn errors of metabolism. In: Aghababian RV, ed. Emergency Medicine: The Core Curriculum . Philadelphia,
PA: Lippincott-Raven; 1999:707.


Hemodialysis is a rapid and effective method for removing ammonia. Extracorporeal membrane
oxygenation (ECMO) is the most effective method of ammonia removal but has higher risks than other
forms of dialysis, particularly in neonates. Exchange transfusion is not effective. There is no consensus
on what type of ammonia removal should be employed based on ammonia concentration. Dialysis is most
effective for ammonia concentrations higher than 300 μg/dL. Recommendations of the New England

Consortium are to perform dialysis for ammonia >300 μg/dL if concentration is rising, prepare for
possible dialysis for ammonia >200 to 250 μg/dL, engaging receiving dialysis unit/facility as soon as
possible. If dialysis is not immediately available or levels are higher than 100 to 125 μg/dL but lower
than 200 μg/dL, pharmacologic agents for ammonia removal should be administered to patients with
known or suspected urea cycle defect. Sodium phenylacetate and sodium benzoate, available in
combination as the preparation Ammonul, 100 mg each per mL (Ucyclyd Pharma, Inc., Scottsdale, AZ;
1-888-829-2593) eliminates nitrogen by an alternative pathway that does not rely on an intact urea cycle.
Ammonul does not remove ammonia rapidly enough to serve as primary therapy in patients with severe
hyperammonemia. Arginine, which enhances urea cycle activity in patients with most urea cycle defects,
should be administered in the face of hyperammonemia using arginine HCl 10% at a dose of 200 to 600
mg/kg IV over 90 to 120 minutes, followed by the same dose over 24 hours. Arginine HCl can be mixed
with Ammonul. If Ammonul/arginine HCl is being administered, the hourly infusion rate of maintenance
fluids should be reduced by the volume of Ammonul/arginine HCl being given. Given the high
concentration of sodium in Ammonul and chloride in arginine HCl, extreme caution must be taken if
administering other sodium chloride–containing fluids. Sodium phenylacetate may deplete potassium.
Potassium should be replaced as potassium acetate. Ondansetron (0.15 mg/kg up to every 8 hours) should
be administered for vomiting and/or prophylactically if treating with Ammonul. To assess patient
response to treatment, ammonia, electrolytes, and blood gas should be monitored every 4 hours. Usually,
2 to 3 days of therapy is necessary.
For seizures unresponsive to conventional anticonvulsants, empiric therapy with pyridoxine (B6 ; 100
mg IV), folic acid (leucovorin; 2.5 mg IV), and/or biotin (10 to 40 mg delivered by nasogastric tube)
should be considered in neonates and infants to treat a possible cofactor-responsive IEM. While there are
other disease-specific pharmacologic agents, their administration is rarely indicated in the ED. L carnitine may be administered in acutely life-threatening situations for suspicion of disorders associated
with carnitine deficiency, but its use is controversial and consultation with an IEM specialist is
recommended. L -carnitine is given at a dose of 25 to 50 mg/kg over 2 to 3 minutes or as an infusion
added to the maintenance fluid, followed by 25 to 50 mg/kg over 24 hours, maximum 3 g/day. Given that
some IEMs are associated with increased risk of infection and that serious bacterial infection can
precipitate metabolic crisis, antibiotics should be considered for any patient of concern for possible
serious bacterial infection. Fresh frozen plasma may be indicated for patients with coagulopathy.

KNOWN IEM
Goals of Treatment
For the child with known IEM and acute decompensation, goals of treatment are to expediently and
proactively evaluate for and manage cardiopulmonary decompensation and IEM-specific metabolic
derangements, and restore and maintain hydration. The child with an IEM in the ED for conditions that
could precipitate decompensation, such as acute infectious process, but presently without acute
manifestations of their IEM should receive aggressive therapy to prevent metabolic derangements and
decompensation. The family may have an emergency treatment plan with them developed by an IEM
specialist, specifically for their child. Use of clinical pathways for treatment of patients with an IEM in
the ED has been shown to improve timeliness and effectiveness of care. All patients with decompensation
should be admitted to the hospital, and there should be a low threshold for admitting any patient at risk
for acute decompensation.


CLINICAL PEARLS AND PITFALLS
Acute decompensations are most commonly seen with tyrosinemia, organic acidemias, urea
cycle defects, fatty acid oxidation defects, and galactosemia.
Early recognition of acute metabolic decompensation is critical for effective management of
patients with known IEM.
A history of physiologic stress, such as intercurrent illness or recent surgery, or
noncompliance with diet may precipitate symptoms and warrants preventative management.

Current Understanding
Manifestations of IEM are disease specific but also patient specific. Understanding of these specifics, as
well as advances in treatment, will most expeditiously and effectively guide evaluation and management.

Clinical Considerations
Triage
Patients with known IEM associated with potential for acute life-threatening decompensation should be
triaged expeditiously. Many families have treatment pathways in hand (or delineated in EMR) to

optimize care ( Table 95.8 ).

AMINO ACID DISORDERS
Goals of Treatment
Treatment of children with amino acid disorders includes avoiding dietary intake of the offending amino
acid(s), and correcting acute metabolic and physiologic derangements.

Current Understanding
Most amino acid disorders do not cause acute decompensation. A notable exception is tyrosinemia type I,
a disorder of phenylalanine and tyrosine metabolism that initially causes liver failure and later
hepatocellular carcinoma. It usually presents in early infancy but can present in the neonatal period.

Clinical Considerations
Assessment
Clinical features include lethargy, vomiting, diarrhea, failure to thrive, hypoglycemia, jaundice, ascites,
edema, bleeding, and renal tubular acidosis. Patients, particularly neonates, may have sepsis. Infants and
children, in addition to manifestations seen in the neonate, may have hepatosplenomegaly, rickets,
hypotonia, and neurologic deficit. CBC, electrolytes, glucose, phosphate, calcium, albumin, PT, PTT, and
blood gas should be obtained upon presentation for illness. As clinically indicated, cultures and lactate to
evaluate for sepsis should be sent.
Management
To treat dehydration, normal saline bolus(es), 10 mL/kg for neonates and 20 mL/kg for infants and
children should be administered. If the patient is hypoglycemic a bolus of 0.25 to 1 g/kg as D10 for
neonates and D10 or D25 for infants and children should be given. After administration of bolus fluid and
correction of any hypoglycemia, D10 in ½ normal saline should be continued at 1 to 1.5 times
maintenance to maintain serum glucose levels at 120 to 170/mg/dL. Insulin is sometimes required to
prevent catabolism in which case additional dextrose is often required. Stable patients without
decompensation and able to feed must avoid offending amino acids. Formula brought by the family may
need to be used until the appropriate formula can be obtained for the patient within the hospital.