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. 2021 Jul 13;13(7):484.
doi: 10.3390/toxins13070484.

Towards an Algorithm-Based Tailored Treatment of Acute Neonatal Hyperammonemia

Sunny Eloot  1 , Jonathan De Rudder  1 , Patrick Verloo  2 , Evelyn Dhont  3 , Ann Raes  4 , Wim Van Biesen  1 , Evelien Snauwaert  4
Affiliations

Towards an Algorithm-Based Tailored Treatment of Acute Neonatal Hyperammonemia

Sunny Eloot et al. Toxins (Basel). .

Abstract

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 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.

Keywords: hemodialysis; hyperammonemia; inborn errors of metabolism; infant.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Ammonia concentration curve in patient 1: dialysis with 4008/FXPaed on day 1 and with CarpeDiem/0.15m2 on day 2.
Figure 2
Figure 2
Time–ammonia concentration curves of the simulations in a 3 kg male infant, for different start concentrations and using different dialysis setups with a blood flow of 30 (left panels) and 50 mL/min (right panels). Dialysis setup 4008/FXPaed (full line), CarpeDiem/0.15 m2 (dotted line) and CarpeDiem/0.25 m2 (dashed line). QB50 can only be executed with the 4008/FXPaed setup.
Figure 3
Figure 3
Algorithm to predict ammonia concentration decline.
Figure 4
Figure 4
Flow chart of the proposed protocol.
Figure 5
Figure 5
One-compartmental kinetic model.
See this image and copyright information in PMC

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