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

Abstract

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

Spontaneous recovery from neuromuscular block after a single dose of a muscle relaxant in pediatric patients: A systematic review using a network meta‐analytic and meta‐regression approach

“…The decline of the clearance is probably related to the decreasing body surface area/body weight ratio 126 This is demonstrated by the similar values for rocuronium clearance that can be obtained in children and adults when normalized for body surface area (ml∙min −1 ∙m −2 ) 121,126 . Isometric/allometric 118,119,127 scaling has been used to adjust PK parameters from adults to children in population PKPD modeling of rocuronium 128,129 …”

“…121,126 Isometric/allometric 118,119,127 scaling has been used to adjust PK parameters from adults to children in population PKPD modeling of rocuronium. 128,129 Contrary to aminosteroid NMBAs, the benzylisoquinolonium compounds atracurium, cisatracurium, and mivacurium have only limited organ-dependence or maturational sensitivity for elimination. 106,[130][131][132] Developmental changes in the neuromuscular junction between 2 and 11 years are likely to increase the margin of safety for the relay of motor nerve signals to the muscle, 133,134 explaining lower sensitivity and faster recovery from the neuromuscular block in children.…”

Sugammadex dose in infants

“…9,10 There are a few dose studies that explore greater depth in those2-17 years. 11 We do have systematic reviews of available literature that are confounded by study inadequacies. There are no PKPD studies in neonates and infants that explore the complex interaction between rocuronium, sugammadex and neuromuscular blockade and that review covariates such as size, age, and drug EDITO RIA L interactions between those commonly used during anesthesia.…”

“…Sugammadex dose estimation in children 2–17 years is improving, mostly through observational data or extrapolation from adult data 9,10 . There are a few dose studies that explore greater depth in those 2–17 years 11 . We do have systematic reviews of available literature that are confounded by study inadequacies.…”