Towards an Algorithm-Based Tailored Treatment of Acute Neonatal Hyperammonemia

Acute neonatal hyperammonemia is associated with poor neurological outcomes and high mortality. We developed, based on kinetic modeling, a user-friendly and widely applicable algorithm 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 Q(B)). By a single measurement of ammonia concentration at the dialyzer inlet and outlet, dialyzer clearance (K) can be calculated as K = Q(B)∙[(C(inlet) − C(outlet))/C(inlet)]. The time (T) needed to decrease the ammonia concentration from a predialysis start concentration C(start) to a desired target concentration C(target) is then equal to T = (−V/K)∙LN(C(target)/C(start)). By implementing these formulae in a simple spreadsheet, medical staff can draw an institution-specific flowchart for patient-tailored treatment of hyperammonemia.