eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Metabolic Diseases

Hyperammonemia: Treatment & Medication

Author: Karl S Roth, MD, Professor and Chair, Department of Pediatrics, Creighton University School of Medicine
Contributor Information and Disclosures

Updated: Jun 3, 2009

Treatment

Medical Care

  • Hyperammonemia is a medical emergency because of the neurotoxicity, which is a direct effect of ammonia on the CNS.
  • Initial management should consist of protein intake cessation with the provision of as many nonprotein calories as is practical via intravenous routes, oral routes, or both (if possible). More specific therapy depends on the etiology of the hyperammonemia. Hemodialysis, intravenous sodium phenylacetate/benzoate (Ammonul), or both may be needed.

Consultations

  • Geneticist
    • The role of the biochemical geneticist is to assist in interpretation of available laboratory tests toward a diagnosis of a specific genetic entity. Treatment must be guided by a professional experienced in the treatment of urea cycle disorders. This professional may be a biochemical geneticist, clinical geneticist, endocrinologist, or pediatrician, depending on the expertise available at a specific institution.
    • If such a diagnosis is confirmed, the patient requires long-term follow-up with a geneticist.
    • Guidelines for clinical genetic evaluation of children with mental retardation or developmental delays have been established.2
  • Neurologist
    • The role of the neurologist is to provide a basic status evaluation for later reference during follow-up care.
    • This evaluation is especially useful in the primary genetic entities, in which recurrence is a virtual certainty and the risk of additional nervous system compromise exists.
  • Gastroenterologist: A gastroenterologist may be of assistance in evaluation of liver disease or when hepatic transplant is considered as therapy for a urea cycle defect. A study of four children with neonatal urea cycle defects concluded that, given the poor prognosis of urea cycle defects with conservative therapy, liver cell transplantation had considerable beneficial effects.3

Diet

  • Dietary therapy greatly depends on the etiologic diagnosis.
  • Protein restriction is helpful in most cases, and restriction of specific amino acids may be imperative in treatment of particular entities.
  • Dietary treatment of urea cycle disorders is highly specialized and usually requires consultation with a registered dietitian who works in a metabolic disease clinic.

Medication

Treatment of hyperammonemia is somewhat dependent on cause. Emergency treatment of life-threatening severe hyperammonemia is hemodialysis. Recommendations for treatment of urea cycle disorders may be found in the specific articles (ie, Ornithine Transcarbamylase Deficiency). (See Differentials and Other Problems to be Considered.)

Metabolic agents

The use of benzoate and phenylacetate is based on the need to provide alternate routes for disposition of waste nitrogen. Benzoate is transaminated to form hippuric acid, which is rapidly cleared by the kidney. Phenylacetate is converted to phenylacetyl CoA and then conjugated with glutamine to form phenylacetylglutamine. Each of these 2 pathways results in disposition of 1 and 2 molecules of ammonia, respectively. Phenylbutyrate is more acceptable as a form of oral therapy because of a diminished odor but is not available for intravenous use.


Sodium phenylacetate and sodium benzoate (Ammonul)

Benzoate combines with glycine to form hippurate, which is excreted in urine. One mole of benzoate removes 1 mole of nitrogen. Phenylacetate conjugates (via acetylation) glutamine in the liver and kidneys to form phenylacetylglutamine, which is excreted by the kidneys. The nitrogen content of phenylacetylglutamine per mole is identical to that of urea (2 mol of nitrogen). Ammonul must be administered with arginine for CPS, OTC, ASA synthetase, or ASA lyase deficiencies. Indicated as adjunctive treatment of acute hyperammonemia associated with encephalopathy caused by urea cycle enzyme deficiencies. Serves as an alternative to urea to reduce waste nitrogen levels.

Adult

Ammonul 10% injection (100 mg/mL):
Loading: 55 mL (5.5 g)/m2 IV over 90-120 min via central line
Maintenance: 55 mL (5.5 g)/m2/d IV over 24 h via central line
Dilute IV dose in at least 25 mL/kg of dextrose 10% before administration

Pediatric

Ammonul 10% injection (100 mg/mL):
Loading: 2.5 mL (250 mg)/kg IV over 90-120 min via central line
Maintenance: 2.5 mL (250 mg)/kg/d IV over 24 h via central line
Dilute IV dose in at least 25 mL/kg of dextrose 10% before administration
>20 kg: Administer as in adults

Penicillin may decrease effects of sodium benzoate/sodium phenylacetate; probenecid may inhibit renal excretion of products of sodium benzoate and sodium phenylacetate; valproate may antagonize efficacy of sodium benzoate and sodium phenylacetate; corticosteroids may increase body protein metabolism, thereby increasing plasma ammonia levels; do not use concomitantly with oral sodium phenylbutyrate (Buphenyl) due to additive effects

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution when administering to patients with neonatal hyperbilirubinemia (competes for bilirubin binding sites on albumin); due to sodium content exercise caution when giving to patients with congestive heart failure, severe renal dysfunction, and sodium retention with edema; common side effects include nausea, vomiting, tinnitus, and visual disturbance; IV must be diluted with dextrose 10% and administered via central line; phenylacetate may cause neurotoxicity; typically administered with antiemetic to prevent common occurrence of nausea and vomiting; caution in severe congestive heart failure or severe renal insufficiency since it contains large amount of sodium (30.5 mg/mL in undiluted IV product)

More on Hyperammonemia

Overview: Hyperammonemia
Differential Diagnoses & Workup: Hyperammonemia
Treatment & Medication: Hyperammonemia
Follow-up: Hyperammonemia
Multimedia: Hyperammonemia
References
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References

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Further Reading

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Keywords

hyperammonemia, elevated serum ammonia level, ammoniemia, elevated ammonia levels, urea, adult-onset genetic disorders of the urea cycle, alpha-amino group, a-amino group, hepatic urea cycle, waste nitrogen, extrahepatic tissues, mitochondrial dysfunction, N -acetylglutamate, NAG, adenosine diphosphate, ADP, adenosine triphosphate, ATP, total free ammonia, glutamine, N -methyl D-aspartate, NMDA, gamma-aminobutyric acid, GABA, astroglial glutamate transporter molecules, astrocytes, membrane permeability transition phenomenon, hepatic encephalopathy, ornithine transcarbamylase deficiency, OTC, hepatic necrosis, N -acetylglutamate synthetase, arginase deficiency, carbamyl phosphate synthetase, CPS, citrullinemia, argininosuccinic acid synthase deficiency, citrullinuria, argininosuccinate lyase deficiency, ASA, argininosuccinic aciduria, argininosuccinase deficiency, hyperargininemia, familial argininemia

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Contributor Information and Disclosures

Author

Karl S Roth, MD, Professor and Chair, Department of Pediatrics, Creighton University School of Medicine
Karl S Roth, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American College of Nutrition, American Pediatric Society, American Society for Clinical Nutrition, American Society of Nephrology, Association of American Medical Colleges, Medical Society of Virginia, New York Academy of Sciences, Sigma Xi, Society for Pediatric Research, and Southern Society for Pediatric Research
Disclosure: MDS Pharma Salary Employment

Medical Editor

Robert D Steiner, MD, Professor, Departments of Pediatrics and Molecular and Medical Genetics, Vice Chair for Research, Department of Pediatrics, Oregon Health & Science University; Director and Consulting Staff, Metabolic Bone Disease Clinic, Shriner's Hospital and Doernbecher Children's Hospital; Co-Director: Pediatric and Child Health Research, Oregon Clinical and Translational Research Institute (CTSA).
Robert D Steiner, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American College of Medical Genetics, American Society of Human Genetics, Oregon Medical Association, Society for Inherited Metabolic Disorders, Society for Pediatric Research, Society for the Study of Inborn Errors of Metabolism, and Western Society for Pediatric Research
Disclosure: Genzyme Honoraria Speaking and teaching; Genzyme Grant/research funds Other; Shire Honoraria Speaking and teaching; Actelion Honoraria Speaking and teaching; Biomarin Honoraria Speaking and teaching; Biomarin Consulting fee Consulting

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Leonard G Feld, MD, PhD, MMM, FAAP, Sara H Bissell and Howard C Bissell Endowed Chair in Pediatrics, Chief Medical Officer, Levine Children's Hospital, Carolinas Medical Center
Leonard G Feld, MD, PhD, MMM, FAAP is a member of the following medical societies: American Academy of Pediatrics, American College of Physician Executives, American Society of Nephrology, American Society of Pediatric Nephrology, International Society of Nephrology, and Juvenile Diabetes Foundation International
Disclosure: Nothing to disclose.

CME Editor

Paul D Petry, DO, FACOP, FAAP, Consulting Staff, Freeman Pediatric Care, Freeman Health System
Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD, Professor, Department of Pediatrics, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics and Rehabilitation, University of Nebraska Medical Center
Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association
Disclosure: Nothing to disclose.

 
 
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