Optimalisation of the Treatment of Acute Neonatal Hyperammonaemia

Study Overview
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Brief Summary
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Acute neonatal hyperammonemia is associated with poor neurological outcomes and high mortality. A user-friendly and widely applicable algorithm - based on kinetics - to tailor the treatment of acute neonatal hyperammonemia. A single compartmental model was calibrated assuming a distribution volume equal to the patient's total body water (V), as calculated using Wells' formula, and dialyzer clearance as derived from the measured ammonia time-concentration curves during 11 dialysis sessions in four patients (3.2 +/- 0.4 kg). Based on these kinetic simulations, dialysis protocols could be derived for clinical use with different body weights, start concentrations, dialysis machines/dialyzers and dialysis settings (e.g., blood flow QB). By a single measurement of ammonia concentration at the dialyzer inlet and outlet, dialyzer clearance (K) can be calculated as K = QB[(Cinlet - Coutlet)/Cinlet]. The time (T) needed to decrease the ammonia concentration from a predialysis start concentration Cstart to a desired target concentration Ctarget is then equal to T = (-V/K)LN(Ctarget/Cstart). By implementing these formulae in a simple spreadsheet, medical staff can draw an institution-specific flowchart for patient-tailored treatment of hyperammonemia. The aim of this study is to validate these formula with a prospective study.

Official Title
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Optimalisation of the Treatment of Acute Neonatal Hyperammonaemia

Conditions
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Hyperammonemic Encephalopathy

Intervention / Treatment
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* Diagnostic Test: user-friendly and widely applicable algorithm to tailor the treatment of acute neonatal hyperammonemia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: severe acute neonatal hyperammonaemia for which acute hemodialysis is indicated inborn error of metabolism below 1 year of age Exclusion Criteria: older than 1 year

Ages Eligible for Study
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Maximum Age: 1 Year

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Hyperammonaemia<br> | Diagnostic Test: user-friendly and widely applicable algorithm to tailor the treatment of acute neonatal hyperammonemia<br>* user-friendly and widely applicable algorithm to tailor the treatment of acute neonatal hyperammonemia, based on kinetic modelling<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum ammonium levels | serum ammonium levels | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Removal of treatment sodium benzoate, L-arginine | serum and dialysate concentration (mg/dL) of sodium benzoate and L-arginine | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hemodialysis, neonate, Hyperammonemic Encephalopathy, inborn error of metbolism