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document
Pharmacokinetic-pharmacodynamic relationship of rocuronium under stable nitrous oxide-fentanyl or nitrous oxide-sevoflurane anesthesia in children . BACKGROUND 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 . METHODS 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 . RESULTS 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 . CONCLUSIONS 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 .
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Intervention_Pharmacological
rocuronium
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Intervention_Pharmacological
nitrous oxide-fentanyl
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Intervention_Pharmacological
nitrous oxide-sevoflurane
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Intervention_Pharmacological
rocuronium
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Intervention_Pharmacological
nitrous oxide ( N2O ) and fentanyl
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Intervention_Pharmacological
N2O and sevoflurane
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Intervention_Pharmacological
N2O/O2-fentanyl or N2O/O2-sevoflurane
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Intervention_Physical
electromyographically
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Intervention_Pharmacological
rocuronium
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Outcome_Other
rocuronium PK parameters
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Outcome_Other
Clearance
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Outcome_Other
Effect compartment concentrations corresponding to 50 % inhibition of T1
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Outcome_Other
rate constants for equilibration between plasma and effect compartment ( k ( e0 ) )
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Outcome_Other
Disposition of rocuronium
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Outcome_Other
rocuronium transfer
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Participant_Condition
anesthesia
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Participant_Age
children
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Participant_Age
children
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Participant_Sample-size
Twenty-four
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Participant_Age
children
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Participant_Age
3-11 years old
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Participant_Condition
ASA PS I or II