Population Pharmacokinetic-Pharmacodynamic Modeling and Probability of Target Attainment Analysis of Rocuronium and Sugammadex in Children Undergoing Surgery.

Background And Objectives: Probability of target attainment (PTA) curves are commonly used to support dose recommendations of antibiotics for different patient groups. In this study we propose PTA analysis to optimize sugammadex dosing in children.

Methods: This study involved data from an observational cohort study of 30 American Society of Anesthesiologists (ASA) Physical Status I and II children undergoing surgery requiring muscle relaxation. All patients received 0.6 mg/kg rocuronium, with sugammadex administered at the end of surgery in three different doses (0.5, 1.0, and 2.0 mg/kg) to reverse the neuromuscular blockade.

Results: The data were analyzed using a population Bayesian-based approach. The developed model was used to simulate pharmacokinetic-pharmacodynamic profiles for different patient groups and dosing regimens before the PTA analysis was performed to translate these simulations into a clinically useful measure. The target was defined as neuromuscular blockade reversal measured by Train-of-Four (TOF ratio > 90%) at 1.5, 3, and 5 min post sugammadex dose. The sugammadex doses leading to 90% PTA were determined for different patients' body weights, rocuronium doses, and time gaps between rocuronium and sugammadex administration assuming the model, priors, and gathered data. For comparison, PTA curves for a range of clinical scenarios are provided to illustrate the usefulness of PTA analysis in selecting the appropriate dose for a given patient.

Conclusions: The proposed PTA analysis is useful to support the sugammadex dose selection in different clinical scenarios.

Trial Registration: The study was registered by ClinicalTrials.gov under number NCT04851574 on 21 April 2021.