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)center dot[(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)center dot 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.

Automated summary

This study developed a user-friendly algorithm based on kinetic modeling for the treatment of acute neonatal hyperammonemia, allowing for personalized treatment based on measured changes in ammonia concentration during dialysis sessions.