Pharmacokinetic–pharmacodynamic relationship of rocuronium under stable nitrous oxide–fentanyl or nitrous oxide–sevoflurane anesthesia in children

Abstract

The aim of this study was to compare pharmacokinetics and pharmacokinetic-pharmacodynamic (PK-PD) relationship of rocuronium in children anesthetized with nitrous oxide (N2O) and fentanyl or with N2O and sevoflurane. Twenty-four children (3-11 years old, ASA PS I or II) were randomized to receive N2O/O2-fentanyl or N2O/O2-sevoflurane (one MAC) anesthesia. Neuromuscular transmission was monitored electromyographically. Initial bolus dose of rocuronium, 0.6 mg x kg(-1) was followed by continuous infusion, targeting at steady-state 95% T1 depression. Neuromuscular transmission was allowed to recover spontaneously. Plasma samples were collected at the moment of discontinuation of infusion, and 10, 20, 30, 50, 60 and 75 min afterwards. Concentrations of rocuronium were measured using high-performance liquid chromatography with electrochemical detection (HPLC-EC). Rocuronium PK was described by a two-compartment model and PD parameters were estimated using effect compartment and sigmoidal E(max) models. No differences in rocuronium PK parameters were observed between study groups. Clearance was 3.91 +/- 2.07 and 3.62 +/- 0.80 ml x min(-1) x kg(-1) in sevoflurane and fentanyl groups, respectively (P < 0.65). Effect compartment concentrations corresponding to 50% inhibition of T1 (EC50) were 1.41 +/- 0.45 and 2.32 +/- 1.00 microg x ml(-1) (P < 0.02), and rate constants for equilibration between plasma and effect compartment (k(e0)) values were 0.10 +/- 0.04 and 0.24 +/- 0.14 min(-1) (P < 0.009) in sevoflurane and fentanyl groups, respectively. Disposition of rocuronium was similar under stable N2O-fentanyl and N2O-sevoflurane anesthesia. Sevoflurane reduced rocuronium requirements as well as decreased EC50 relevant to inhibition of T1 and rocuronium transfer to effect compartment. Therefore, the potentiating effect of sevoflurane seems to be mainly of PD origin, probably due to an increased sensitivity of the neuromuscular junction.