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Department of Anesthesiology, University Hospital of the RWTH Aachen, Aachen, Germany
Address correspondence and reprint requests to Kunitz Oliver, MD, Department of Anesthesiology, University Hospital of the RWTH Aachen, Pauwelsstr. 30, D-52074 Aachen, Germany. Address e-mail to okunitz{at}ukaachen.de
| Abstract |
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IMPLICATIONS: Except for xenon, the interactions of inhaled anesthetics with neuromuscular blocking drugs are known. Therefore, the influence of xenon on the onset time, duration, recovery index, and recovery time of rocuronium during propofol and xenon anesthesia was compared. No differences were found.
| Introduction |
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Xenon, an inhaled anesthetic with an extreme low blood-gas partition coefficient of 0.1150.14 (3) and a minimum alveolar anesthetic concentration (MAC) of 63%71% (4), has proven its clinical safety and efficacy (5). Xenon has shown its cardio- and neuroprotective effects in many studies (59). With its ecological and pharmacological qualities, xenon is an interesting alternative to other inhaled anesthetics. Our aim was to measure the influence of xenon on the neuromuscular blocking effects of rocuronium, because there are no studies on the effect of xenon on rocuronium. Our hypothesis was that xenon had no influence on onset time, duration, recovery index, and clinical recovery after a single dose (2 x 95% effective dose) of rocuronium compared with a total IV anesthesia (TIVA) with propofol.
| Methods |
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Standard monitoring was used including xenon concentrations. The IV line and arterial blood pressure monitoring were placed on the contralateral arm of the neuromuscular monitoring.
According to GCRP guidelines, neuromuscular monitoring was performed using an acceleromyograph (TOF-Watch SX®; Organon Teknika, Boxtel, the Netherlands) for neuromuscular monitoring (10). The arm was fixed to a special board (arm board TOF-Guard®; Organon Teknika). Skin was cleaned with alcohol and hairs were removed if necessary. The electrodes for neuromuscular monitoring were placed at the ulnar nerve on the volar side of the wrist. The piezoelectric wafer was placed at the distal interphalangeal joint of the thumb, ensuring free movement of the thumb. The temperature sensor was fixed at the distal end of the forearm. The temperature was maintained at >32°C. Train-of-four (TOF) stimulation was used (supramaximal square wave impulse at 2 Hz every 15 s, 200-µs duration). The onset time is defined as time of injection of rocuronium until a 95% depression of the first twitch (T1) is reached. Duration T25 of neuromuscular recovery is defined as beginning of injection of rocuronium to a 25% recovery of the first twitch. The recovery index T2575 is defined as the time between 25% T1 and 75% T1 response of the TOF and clinical recovery T250.8 as the time interval between T25 and a TOF ratio (T1/T4) of 0.8. Data were collected using the specific software (TOF-Watch SX®, version 1.1).
Bispectral index (BIS, model A-2000®; Aspect Medical Systems, Newton, MA) was monitored aiming for BIS values of <50, being in the suggested tolerance between 4060 (11). However BIS monitoring was measured as a surrogate variable to have some extra information about depth of anesthesia knowing that it is not validated for use in xenon anesthesia. The BIS electrodes® (Aspect Medical Systems) were applied after the skin of the forehead and temple was cleaned and dried. BIS monitoring was registered at a fixed interval of every 5 min.
Premedication was performed with midazolam 7.5 mg orally, 45 min before induction. Anesthesia was induced IV with a single dose of propofol 2 mg/kg and remifentanil with 0.5 µg/kg in an infusion pump within 60 s in both groups. Variations to clinical needs (changes in arterial blood pressure and heart rate more than ±20%) were allowed. Xenon administration was started via a face mask (xenon group) or propofol was injected via infusion pump and ventilation was performed with oxygen/air (propofol group). Xenon was applied using a closed circuit anesthesia machine (PhysioFlex®; Draeger, Lübeck, Germany) with a modified software to reduce xenon consumption under minimal flow conditions (12).
Maintenance of anesthesia was achieved either by xenon (60% in O2 reflecting a MAC value of approximately 0.85, referring to a MAC of 71% xenon) or propofol (0.060.12 mg · kg1 · min1, propofol group) and remifentanil adapted to clinical needs in both groups. After an end-expiratory concentration of 60% xenon was maintained for at least 1 min, the automatic set-up procedure of the TOF-Watch was performed to determine the supramaximal stimulus. TOF monitoring was started and, after stabilization of the signal for 5 min, rocuronium 0.6 mg/kg (2 x 95% effective dose) was injected within 5 s. Intubation of the trachea was performed after the first twitch of the TOF reached 5% of the preinjection value of rocuronium. In the xenon group, the PhysioFlex® system was flushed in case xenon decreased to <55% until 60% was reached again. Ventilation was adjusted to maintain an end-expiratory carbon dioxide concentration at 4.96.1 kPa. Normothermia (35.5°37.0°C) was achieved by using warming blankets. Complete recovery of neuromuscular block was reached at the end of operation in each patient. None of the patients required redosing of neuromuscular block and none of the patients required pharmacological antagonism. The depth of anesthesia was continuous during full recovery from neuromuscular block. At the end of operation, administration of the anesthetics was stopped immediately.
The sample size was calculated with a power of ß = 0.8 and a significance level of
= 5%, the clinically important difference
= 30 s, and a standard deviation (SD) of 30 s for the onset time with 17 patients. The clinically important difference and SD were taken from a previous study by Lowry et al. (13). The sample size was determined at 20 patients in each group, including some reserve.
Demographic data were analyzed for homogeneity. Onset time, duration T25, recovery index T2575, and clinical recovery T250.8 were presented as mean ± SD. They were analyzed using a 2-sided rank sum test of Wilcoxon. Statistical analysis was performed using SAS software version 8.0® (SAS Institute Inc., Cary, NC).
| Results |
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| Discussion |
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Mechanomyography, electromyography, and acceleromyography have been used for neuromuscular monitoring for scientific purposes. Engbaek et al. (14) showed that electromyography, often used for neuromuscular monitoring, could not reach full recovery to initial values after a long period of constant stimulation. Acceleromyography, validated for clinical use by Viby-Mogensen et al. (10,15) and accepted for neuromuscular monitoring in the GCRP guidelines for phase III studies, was used for neuromuscular monitoring in this study. It is important that the results of different methods should not be compared. Nakata et al. (16) confirmed that acceleromyography and electromyography cannot be used interchangeably with either xenon or sevoflurane anesthesia.
The short equilibration time of six minutes may be a possible disadvantage of the study design. Some authors demand a 30- to 40-minute period of equilibration of the muscular compartment when using inhaled anesthetics with a high blood-gas solubility (1). Xenon has the lowest blood-gas solubility of all inhaled anesthetics by a wide margin. The solubility of volatile anesthetics in muscle is influenced by body temperature and patients age. Solubility of xenon in muscle is 0.082 and thus extremely low compared with values for middle-aged adults for halothane (1.44 ± 0.17), enflurane (1.09 ± 0.10), isoflurane (1.52 ± 0.11), sevoflurane (1.08 ± 0.20), desflurane (0.62 ± 0.06), or even nitrous oxide (0.54) (1719). Based on these data, it can be assumed that the equilibration of xenon in the muscle compartment is finished when a steady-state end-expiratory concentration has been achieved.
To verify the hypothesis of this study, we used a TIVA with propofol at values of 0.09 ± 0.03 mg · kg1 · min1 corresponding to the lower limits from the literature to have the smallest possible effect of propofol on neuromuscular transmission. We accepted the disadvantage of the comparability of xenon as an inhaled and propofol as an IV anesthetic. It is important to note that most studies that have examined the neuromuscular effects of inhaled anesthetics used MAC concentrations of 1.52.0. These concentrations are not achievable because of the large MAC of xenon. In this study, xenon was given at a MAC of 0.85 referring to the validated value of 71%. This limits the comparability to previous studies with other inhaled anesthetics.
The results by Kunitz et al. (20) and Nakata et al. (21) support the hypothesis of this study. Nakata et al. (21) measured vecuronium-induced neuromuscular block during xenon or sevoflurane anesthesia in humans. Anesthesia was maintained using 57% xenon and 1.6% sevoflurane equal to 0.8 MAC. The end-tidal anesthetic concentration and twitch response were stable for 45 minutes before 0.05 mg/kg vecuronium was injected. Neuromuscular block was monitored with an accelerometer. The study demonstrated that xenon had a lesser effect on recovery from vecuronium-induced neuromuscular block than sevoflurane. Kunitz et al. (20) measured onset time, duration, and recovery after a single bolus of 0.16 mg/kg mivacurium using an identical protocol as the present study. There were no significant differences between the groups concerning the onset time, duration, recovery index, and clinical recovery.
The use of xenon with its extreme low blood-gas solubility allows rapid emergence and recovery from anesthesia. In contrast to other inhaled anesthetics, it does not prolong the neuromuscular block. Xenon does not influence onset time, duration, and recovery any differently than TIVA with propofol after a single dose of 0.6 mg/kg rocuronium.
| Acknowledgments |
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| Footnotes |
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This article has been cited by other articles:
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O. Kunitz, J.-H. Baumert, K. Hecker, M. Coburn, T. Beeker, A. Zuhlsdorff, J. Fassl, and R. Rossaint Xenon does not modify mivacurium induced neuromuscular block: [Le xenon ne modifie pas le bloc neuromusculaire induit par le mivacurium] Can J Anesth, November 1, 2005; 52(9): 940 - 943. [Abstract] [Full Text] [PDF] |
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