Neonatal Hyperammonemia Clinical Pathway – Emergency Department, N/IICU and PICU

Initial Evaluation
- History and Physical
- Differential Diagnosis
Review referring hospital records, labs, imaging
Resuscitation
- Airway support as indicated
- Establish IV access
- Initial Labs
- Initial Fluid Management
- Stop protein intake immediately
STAT Head US
- Should not delay initiation of Continuous Renal Replacement Therapy (CRRT)
Consults
- Metabolism
- Interventional Radiology
  - Central and hemodialysis access
- Nephrology

Neonates with hyperammonemia are at risk for severe neurologic impairment.
Rapid diagnosis and aggressive treatment by a coordinated multidisciplinary team are critical.

Priority Management Goals
Obtain adequate vascular access
Initiate amino acid and nitrogen-scavenger therapy
Continuous Renal Replacement Therapy if indicated

Admit to N/IICU: Hyperammonemia Therapy
Ammonia level, rate of rise, neurologic symptoms drive therapy escalation

Gather equipment for travel
Consider intubation especially if higher risk or to facilitate central catheter placement

Mild
Ammonia level < 200 umol/L
No encephalopathy

Moderate
Ammonia level 200–500 umol/L
Mild to moderate encephalopathy

Severe

Ammonia level ≥ 500 umol/L or
Tachypnea, respiratory alkalosis or
Severe encephalopathy

GIR goal: 10–15 mg/kg/min
Maintain normothermia

GIR goal: 10–15 mg/kg/min
Review with Metabolism
- IV Arginine therapy
- Sodium Phenylacetate + Sodium Benzoate (Ammonul)
Prepare for CRRT with Prismax machine
- Ammonia clearance may be inadequate with Aquadex or Carpediem
Access
- Central access
- Dialysis catheter as indicated
Maintain normothermia
- Use core temperature monitor
- Consider ArcticSun

GIR goal: 15–20 mg/kg/min
Initiate
- IV Arginine therapy
- Sodium Phenylacetate + Sodium Benzoate (Ammonul)
Prepare for CRRT with Prismax machine<
- Ammonia clearance may be inadequate with Aquadex or Carpediem
Access
- Obtain central access and dialysis catheter
Initiate CRRT for:
- Encephalopathy
- Ammonia > 1000 µmol/L
- Poor response to initial therapies
Maintain normothermia
- Use core temperature monitor
- Consider ArcticSun

Glucose Infusion Rate (GIR)

Glucose provokes a hyperinsulinemic response that inhibits protein and fat catabolism and decreases toxic intermediates

GIR

Infusion rate (mL/hr) × Dextrose concentration (g/dL) × 1000 (mg/g)
Wt (kg) × 60 (min/hr) × 100 (mL/dL)

Infusion Rate (mL/hr)

Glucose infusion rate goal × Wt (kg) × 6
Dextrose concentration in g/dL

Continued Medical Management
Initial Ammonia Monitoring	Mild q3–4hr Moderate q2hr Severe q1hr STAT Space lab frequency when neonate stable in consultation with Metabolism
Consults	Metabolism, IR, Nephrology Neurology—initiate EEG monitoring, should not delay CRRT Genetics
Imaging	MRI brain once stable Consider echocardiogram if hemodynamic instability, should not delay CRRT
Indications for CRRT	Ammonia > 1000 umol/L or not improving after 1–2 hrs of medical management Persistent encephalopathy Infant size and presence of coagulopathy may be contraindications
Glucose Management	Persistent hyperglycemia > 200 mg/dL, do not decrease GIR Goal: 100–200 mg/dL Start insulin infusion 0.01 units/kg/hr Titrate by 0.01 unit/kg/hr to maintain goal
Continued Care	Following stabilization with improving labs, physical exam Care plan coordinated by Neonatology in consultation with Metabolism and Nephrology

Posted: August 2020
Last Revised: July 2026
Authors:
- K. McKenna, MD
- B. Laskin, MD
- J. Fitzgerald, MD
- S. Vatsky, DO
- A. O’Brien, PharmD
- A. Lederman, RN
- K. Westgate, ACCNS-P
- D. Munson, MD
- E. Will, PA-C
- K. Ng, MD
- N. Abend, MD
- R. Kessler, MD
Editors: Clinical Pathways Team

Evidence

CHOP Program

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The clinical pathways are based upon publicly available medical evidence and/or a consensus of medical practitioners at The Children’s Hospital of Philadelphia (“CHOP”) and are current at the time of publication. These clinical pathways are intended to be a guide for practitioners and may need to be adapted for each specific patient based on the practitioner’s professional judgment, consideration of any unique circumstances, the needs of each patient and their family, and/or the availability of various resources at the health care institution where the patient is located.

Accordingly, these clinical pathways are not intended to constitute medical advice or treatment, or to create a doctor-patient relationship between/among The Children’s Hospital of Philadelphia (“CHOP”), its physicians and the individual patients in question. CHOP does not represent or warrant that the clinical pathways are in every respect accurate or complete, or that one or more of them apply to a particular patient or medical condition. CHOP is not responsible for any errors or omissions in the clinical pathways, or for any outcomes a patient might experience where a clinician consulted one or more such pathways in connection with providing care for that patient.

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Neonatal Hyperammonemia Clinical Pathway – Emergency Department, N/IICU and PICU

Emergency Department, N/IICU and PICU Clinical Pathwayfor Acute Hyperammonemia in Neonates

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Emergency Department, N/IICU and PICU Clinical Pathway
for Acute Hyperammonemia in Neonates