In 1993, Petersen-Felix and colleagues  first reported an almost 20% decrease in the minimum alveolar concentration for tetanus stimuli (MACtetanus) of isoflurane after removal of a herniated intervertebral disc in surgery, although it had generally been assumed that the potency of inhalational anaesthetics remained unchanged during the course of administration [2,3]. The decrease in the MACtetanus of isoflurane was confirmed by the same authors in 1994 . However, to our knowledge, there is no information about a change in the MACtetanus during anaesthesia and surgery for different inhalational anaesthetics. The purpose of the present study was to quantify a change of MACtetanus in the MACtetanus sevoflurane after shoulder arthroscopy in healthy patients.
The study was approved by the hospital Ethics Committee and written informed consent was obtained from each patient before participation in the study. Eleven patients (five female), ASA I, undergoing general anaesthesia for arthroscopy of the shoulder participated in the study. Female patients had a negative result to pregnancy testing, and reported menstruation in the previous 4 weeks. Exclusion criteria were: age >40 or <20 yr; history of coronary heart disease, neuroendocrine disease, hypo- or hypertension, diabetes mellitus, drug or alcohol abuse, and use of drugs known to affect the anaesthetic requirement.
No premedication was given. Each patient was monitored in the anaesthetic room using an electrocardiograph, an automated pressure cuff and an oxygen saturation (SpO2) probe. Induction of anaesthesia was performed using the vital capacity breath technique . Sevoflurane was delivered, via a sevoflurane vaporizer (Penlon® PPV Σ; Penlon, Abingdon, UK), in 50% oxygen and air via a facemask using a semiclosed breathing system with a fresh gas flow rate of 6 L min−1. After the patient became unresponsive to verbal commands, succinylcholine 1 mg kg−1 intravenously was given and the trachea intubated with an endotracheal tube. After intubation, the end-tidal concentration of sevoflurane was maintained at 2.2%. The carbon dioxide, oxygen and sevoflurane concentrations were monitored continuously through a 19-G catheter inserted through the breathing system to reach the distal end of the tracheal tube. Gas concentrations were analysed using a Capnomac Ultima® gas analyser (Datex, Helsinki, Finland) with a nominal sample flow rate of 200 mL min−1. The analyser was calibrated immediately before each study using a cylinder containing a mixture of gases of known concentrations.
When the function of the neuromuscular junction had returned to normal, the MAC was determined by observing successive responses to tetanic electric stimuli to the ulnar nerve at varying concentrations of sevoflurane. After cleaning the skin, a silver-silver chloride electrode was placed over the ulnar nerve at the proximal skin crease of the wrist and the other electrode was placed 5 cm proximally. A 10 s, 50 Hz, 80 mA transcutaneous tetanic stimulus was delivered in 200 μs pulses by a constant-current peripheral nerve stimulator (NS252®; Fisher & Paykel Healthcare, Auckland, New Zealand). A positive response was recorded if there was movement in one of the non-stimulated limbs during the tetanus. Swallowing, coughing and slight movement of the shoulder or arm of the stimulated side were not classified as positive responses.
The end-tidal concentration of sevoflurane was held constant at each desired value for a 15 min equilibration. At an initial end-tidal sevoflurane concentration of 2.2%, the tetanic stimulus was applied. If a positive reaction was observed, the end-tidal sevoflurane concentration was increased by 0.1%; if no reaction was observed, the concentration was decreased by 0.1%. The MAC for each patient was taken as the mean of the two concentrations just permitting and just preventing movement. No muscle relaxants were given during operation and the sevoflurane concentration was kept sufficiently high to avoid movement. After shoulder arthroscopy had been completed, individual MACtetanus were measured as described above, starting at a sevoflurane concentration 0.1% below the last concentration at which a positive response had been recorded. Rectal temperature was monitored continuously during the study. Body temperature was maintained at 36-37°C using a forced-air warming blanket (Snuggle Warm®; Smiths Industries, Irvine, CA, USA) throughout measurement of the MACtetanus and for the duration of the operation.
Data are presented as mean ± SD. A Wilcoxon signed rank sum test tested the statistical difference between the MACtetanus taken before and after arthroscopy. P < 0.05 was considered as significant. Table 1 summarizes patients' characteristics. The individual MACtetanus before and after arthroscopy are shown in Figure 1 and Table 1. The mean MACtetanus decreased from 2.22 ± 0.29% before arthroscopy to 1.82 ± 0.26% after arthroscopy (P < 0.01). A decrease in individual MACtetanus was observed in all patients. No patient had an increase in MACtetanus. There was no significant change in mean temperature between the two MACtetanus measurements, 36.6 ± 0.2°C before arthroscopy to 36.5 ± 0.1°C after arthroscopy (P = 0.87). There was an increase in temperature in three patients, and a decrease in temperature in eight patients (Table 1). Before surgery, MACtetanus was determined as 69 min (range 37-91 min) after induction (time from the vital capacity induction until the middle of the bracketing procedure); after surgery it was determined at 221 (128-318) min after induction, giving an elapsed time of 152 (91-247) min between the two MACtetanus determinations. The mean duration of arthroscopy was 50 (25-115) min. Blood loss during the operation was minimal in all patients, and between the two MAC determinations, no patient received >1000 mL acetate Ringer's solution.
The results indicated a significant decrease in the MACtetanus of sevoflurane during anaesthesia and arthroscopy, confirming Petersen-Felix and colleagues' findings  of a significant decrease in the MACtetanus of isoflurane during anaesthesia and surgery to remove a herniated intervertebral disc. The extent of the MACtetanus reduction of sevoflurane in the present study was approximately 20%, which was consistent with that in Petersen-Felix and colleagues' study.
Hypothermia decreases the requirement for volatile anaesthetics in animals and children [6-8]. The MAC of isoflurane decreased approximately 5% for each 1°C in reduction in body temperature in animals and children [6-8]. Therefore, we made an effort to prevent hypothermia in the present study. As a result, the difference in the mean temperatures between the two MACtetanus determinations was only 0.1°C in the present study. Assuming that the effects of temperature on the MAC of sevoflurane are similar to those of isoflurane, the decrease of 0.1°C in the temperature in the present study would account for only a 0.01% reduction in difference in the MACtetanus of sevoflurane. Furthermore, a change in solubility with time might explain the decrease in the MAC over time. Lerman and colleagues  observed a decrease in solubility over time with a concomitant decrease in the haematocrit and the three serum components (albumin, globulin, cholesterol). However, in the present study, blood loss was negligible and the amount of fluid infused between the two MACtetanus determinations was small. Therefore, the resulting changes in temperature and haematocrit (the change in solubility) should be negligible.
The mechanism underlying the decrease in the MAC is unclear. Although repeated electrical stimulation might progressively desensitize the underling skin , Petersen-Felix and colleagues  ruled out desensitization of the underling skin by electrical tetanic stimuli because there were no differences in the haemodynamics when stimulations at the beginning of a bracketing sequence were compared with those performed at the same isoflurane concentrations at the end of the bracketing . Zbinden and colleagues  also reported that a change in MAC with time could be explained by a changing sensitivity of neurons to inhaled anaesthetics.
Recent studies suggest that volatile anaesthetics produce immobility by acting on the spinal cord [11-13]. Depression of spinal cord motor neuron excitability has been proposed to contribute to the lack of movement response to noxious stimuli [11-13]. King and Rampil [11,12] studied the effects of volatile anaesthetics on spinal motor neurons using electromyograms following stimulation of a peripheral motor nerve. They reported a 50% depression of F-wave amplitude, which represents spinal-mediated, recurrent motor activity, between 0.8 and 1.2 MAC of isoflurane in rats. They concluded that the F-wave depression was a spinal rather than a peripheral (axonal, neuromuscular junctional or muscle) phenomenon because there was no effect of isoflurane on the orthodromically conducted M-wave amplitude [11,12]. In addition, they investigated the effect of time on M- and F-waves and found that M-wave amplitude decreased over time whereas F-wave amplitude did not change [11,12]. The mechanism and significance of these changes is unclear. Whether changes in the M- and F-waves are observed in human beings during anaesthesia and surgery remains to be clarified in a further study.
The study was supported by funding from institutional and department resources only.
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