Sevoflurane increases fade of neuromuscular response to TOF stimulation following rocuronium administration in children. A PK/PD analysis.
BACKGROUND
Sevoflurane enhances neuromuscular block produced by rocuronium, affecting not only single twitch response but also the response to high-frequency stimulation, increasing tetanic [or train-of-four (TOF)] fade.


METHODS
We compared the degree of fade during spontaneous recovery from rocuronium-induced neuromuscular block in 24 children (3-11 years old, ASA groups I and II), anesthetized with nitrous oxide-sevoflurane (one MAC, endtidal concentration) or nitrous oxide-fentanyl. Neuromuscular transmission was monitored electromyographically (EMG), stimulating the ulnar nerve at the wrist with TOF, 2 Hz for 2 s, repeated at 20-s intervals and recording EMG potential from adductor pollicis brevis. Depression of the fourth twitch, T4, was used as a measure of fade. Following an intubating dose of rocuronium, 0.6 mgxkg(-1), continuous infusion of rocuronium was given to maintain stable 90-99% T1 depression. Plasma concentration of rocuronium was determined with high performance liquid chromatography with electrochemical detection (HPLC-EC) method at the moment of discontinuation of rocuronium infusion and 10, 20, 30, 40, 50, 60, and 75 min afterwards. A two compartment model was used for pharmacokinetic (PK) calculations. PK parameters were fixed and pharmacodynamic data were fitted to effect compartment model proposed by Sheiner.


RESULTS
Sevoflurane reduced rocuronium concentration in effect compartment producing 50% inhibition of both T1 and T4 response and significantly delayed not only T1, but also T4 recovery.


CONCLUSIONS
Potentiating effect of sevoflurane on rocuronium-induced neuromuscular block influences not only postsynaptic, but also the presynaptic part of the neuromuscular junction, enhancing fade of neuromuscular response to high-frequency stimulation. The intensity of this latter effect is clinically relevant.
Woloszczuk-Gebicka
Bogumila
B
Department of Pediatric Anesthesiology and Intensive Therapy, Medical University of Warsaw, Warsaw, Poland. Bogumila.Gebicka@acn.waw.pl
Wyska
Elzbieta
E
Grabowski
Tomasz
T
D000732:Androstanols / Q000493:pharmacokinetics / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000493:pharmacokinetics / Q000494:pharmacology; D018686:Anesthetics, Intravenous; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002648:Child; D002851:Chromatography, High Pressure Liquid; D004558:Electric Stimulation; D004576:Electromyography; D005283:Fentanyl; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008738:Methyl Ethers / Q000493:pharmacokinetics / Q000494:pharmacology; D016343:Monitoring, Intraoperative; D009126:Muscle Relaxation / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000294:innervation; D003473:Neuromuscular Nondepolarizing Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D009609:Nitrous Oxide; D000077123:Rocuronium; D000077149:Sevoflurane; D009435:Synaptic Transmission / Q000187:drug effects*
D000732:Androstanols; D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D008738:Methyl Ethers; D003473:Neuromuscular Nondepolarizing Agents; D000077149:Sevoflurane; D009609:Nitrous Oxide; D005283:Fentanyl; D000077123:Rocuronium