• Matthew Luchette, Kerri LaRovere, Cheuk C Au, Robert C Tasker, and Alireza Akhondi-Asl.
• Department of Anesthesiology, Critical and Pain Medicine, Boston Children's Hospital and Department of Anaesthesia, Harvard Medical School, Boston, MA.
• Pediatr Crit Care Me. 2023 Jan 1; 24 (1): 515551-55.

ObjectivesTo model bolus dosing, infusion rate, and weaning rate on theoretical serum concentration of midazolam and pentobarbital used in the treatment of refractory status epilepticus (RSE).DesignOne- and two-compartment in silico pharmacokinetic models of midazolam and pentobarbital.SettingNot applicable.SubjectsNot applicable.InterventionsWe compared the model variables used in midazolam and pentobarbital protocols for standard RSE.Measurements And Main ResultsStandard RSE treatment protocols result in steady-state serum concentrations that are 6.2-9.0-fold higher for the one-compartment model and 2.3-4.7-fold higher for the two-compartment model. In the model, not including bolus doses delays the achievement of serum steady-state concentration by 0.5 and 2.7 hours for midazolam and pentobarbital, respectively. Abrupt discontinuation of these medications reduces modeled medication exposure by 1.1 and 6.4 hours, respectively.ConclusionsOur in silico pharmacokinetic modeling of standard midazolam and pentobarbital dosing protocols for RSE suggests potential variables to optimize in future clinical studies.Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

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