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Anaesthesia, 2001, 56, pages 202±207 ................................................................................................................................................................................................................................................

The effect of nitrous oxide on the inhibition of somatosensory evoked potentials by sevoflurane in children V. Vieira da Costa,1 R. A. Saraiva,2 A. Cardozo de Almeida,3 M. R. Rodrigues,1 L. G. N. Nunes4 and J. C. D. Ferreira5 1 Staff Anaesthetist, 2 Chairman of Department of Anaesthesia, 3 Staff Clinical Neurophysiologist, 4 Statistician, and 5 Chairman of Department of Clinical Neurophysiology, SARAH Hospital of Brasilia, SMHS Quadra 501 Conjunto: A, 70330±150 Brasilia DF, Brazil Summary

Inhalational anaesthetics inhibit somatosensory evoked potentials. The present study examined the effect of nitrous oxide in anaesthetic mixture with sevoflurane on the somatosensory evoked potential in children. Forty-five patients aged between 6 months and 6 years undergoing club foot surgery were studied to verify the influence of sevoflurane alone (21 patients) and sevoflurane with nitrous oxide (24 patients) on the somatosensory evoked potential. Fractional inspired concentration of nitrous oxide and fractional end-tidal (alveolar) sevoflurane were measured to estimate the multiples and submultiples of the minimal alveolar concentration (age corrected). The somatosensory evoked potential signals were obtained by stimulation of the median nerve. Nitrous oxide (FI 0.63 ^ 2.5) with sevoflurane caused more reduction in the amplitude of somatosensory evoked potential waves and a greater increase in the latency of somatosensory evoked potential waves in comparison with sevoflurane alone. The results show that it is possible to obtain the inhibition of somatosensory evoked potential with smaller concentrations of sevoflurane, when it is used with nitrous oxide. Keywords

potentials.

Anaesthesia, general: nitrous oxide; sevoflurane. Monitoring: somatosensory evoked

................................................................................................. Correspondence to: Dr R. A. Saraiva Accepted: 26 February 2000

Although clinically possible, the action of anaesthetic agents on the central nervous system (CNS) is not directly monitored. Techniques and instruments exist for this purpose, but their use is neither frequent nor routine. Effective monitoring of the anaesthetic is important for the clinical management of the patient, as well as for an understanding of the mechanisms of anaesthesia. The electroencephalogram (EEG) registers waves that represent the cerebral activity obtained with spontaneous stimuli. The EEG can be used to evaluate cerebral cortex function and depth of anaesthesia, as well as measuring cerebral blood flow and the brain's oxygen demands. However, the EEG does not indicate the subcortical organic functions, nor the anaesthetic's action on these organs. Since anaesthetic agents act mainly on the synapses of the CNS, the somatosensory evoked potential can 202

monitor their action. The somatosensory evoked potential is obtained by a peripheral stimulus evoked by the CNS [1]. Anaesthetic agents inhibit the somatosensory evoked potential at the thalamus and brain levels, reducing the amplitude and increasing the latency [2, 3]. The somatosensory evoked potential is a simple technique to use. The somatosensory evoked potential of upper limbs is obtained by electrical stimulation of the median nerve at the wrist, and measurement at the supraclavicular region (N9), cervical region (P/N13), and the contralateral central parietal region of the skull (N19 and P22) according to system 10/20 of the International Federation of Clinical Neurophysiology. The somatosensory evoked potential of the legs is obtained by electrical stimulation of the tibial nerve at the ankle with the sensing electrodes positioned at the medial thoracolombar region (N19) and medial parietal region of the scalp (N/P37). q 2001 Blackwell Science Ltd

Anaesthesia, 2001, 56, pages 202±207 V. Vieira da Costa et al Inhibition of somatosensory evoked potentials ................................................................................................................................................................................................................................................

The minimal alveolar concentration (MAC) is described as Anaesthetic Dose50 (AD50) and the MACExpanded (AD95). Both block the pain stimulus in the anterior region of the leg [4, 5]. It is likely that when the patient has an alveolar concentration equivalent to a MAC, there is inhibition of stimulus transmission which may be dose dependent. At AD50, the inhibition is partial and at AD95, the inhibition should be complete. Following this line of reasoning, it seems logical that some drugs which reduce the MAC values can also reduce the alveolar concentration of inhaled anaesthetic which would consequently inhibit the somatosensory evoked potential. Thus, nitrous oxide should reduce the inhaled anaesthetic requirements necessary to inhibit the somatosensory evoked potential, in the same way that it theoretically reduces the MAC values. The present study will: 1 examine the influence of inhalational anaesthetic sevoflurane on the somatosensory evoked potential of children; 2 establish a correlation between the grade of inhibition of somatosensory evoked potential amplitude and latency and MAC values; 3 examine the effect of nitrous oxide on the inhibition of somatosensory evoked potential by sevoflurane; 4 examine the inhibition of somatosensory evoked potential in monitoring inhaled anaesthetic action.

Methods

After obtaining Hospital Ethics Committee approval and parental consent, 45 children aged between 6 months and 6 years, classified as ASA 1 or 2 and who were scheduled for surgical correction of congenital club feet were studied. Surgery was undertaken under general anaesthesia and epidural block (lumbar or caudal) with 0.25% bupivacaine to avoid interference of surgical stimulus on somatosensory evoked potential. All patients received 0.7 mg.kg21 midazolam orally 30 min before induction of anaesthesia. In the anaesthetic room, the patients were randomly allocated to one of two groups. One group was given only sevoflurane; the other group was given both sevoflurane and nitrous oxide. In both groups, the induction of anaesthesia was with increasing concentrations of sevoflurane. Following the loss of the eyelid reflex, an intravenous cannula was inserted and an infusion of compound sodium lactate solution started. Monitoring consisted of continous noninvasive arterial blood pressure, ECG, pulse oximetry, capnometry, oesophageal temperature and precordial stethoscope. Measurements of inspired and end-expired concentrations q 2001 Blackwell Science Ltd

Fig. 1. The site of peripheral electrical stimulus of the median

nerve at the wrist and sites of evoked potentials measured in the central nervous system.

of inhaled anaesthetics were performed by the respiratory gas monitor of the Ohmeda 7850 anaesthetic machine. The patients had tracheal intubation under deep general anaesthesia, followed by administration of 60% nitrous oxide in association with 40% oxygen. Sevoflurane was still used with an inspired concentration (FI) sufficient to provide an end-tidal concentration (FE 0 ) similar to alveolar concentration (FA), close to MAC, according to age [6], and corrected by barometric pressure to keep the same partial pressure of anaesthetic vapour. The alveolar concentration during anaesthesia increased (MAC multiples) at induction to permit tracheal intubation, and decreased (MAC submultiples) in the recovery period. Considering the difficulties in obtaining somatosensory evoked potential signs in conscious, small children, the measurements of anaesthetic concentrations and records of somatosensory evoked potential waves were monitored during anaesthesia until the moment of awakening. The somatosensory evoked potential was obtained by electrical stimulus of the median nerve (Fig. 1). A Dantec ± Keypoint monitor was used; values of amplitude were expressed in microvolts and latency in milliseconds. Statistical analysis was performed using the anova test and linear regression. A value of p , 0.05 was taken to represent a significant difference. Results

Twelve males and nine females aged between 1 and 203

V. Vieira da Costa et al Inhibition of somatosensory evoked potentials Anaesthesia, 2001, 56, pages 202±207 ................................................................................................................................................................................................................................................

Table 1. Patient characteristics

Age; years Weight; kg Male/female ASA class; I/II

Sevoflurane 1 O2

Sevoflurane 1 O2/N2O (60%)

p

2.6 (0.6±7.0 13.9 (6.8±25.0) 9/12 18/3

1.9 (0.1±8.0) 12.4 (7.8±28.0) 16/8 18/6

0.35* 0.41* 0.11² 0.37²

*Analyses of variance; ²chi-squared.

6 years received sevoflurane alone. Eight males and 16 females, predominantly aged 1±6 years, received sevoflurane and nitrous oxide. There were no statistically significant differences between age, sex, weight and physical state in the two groups (Table 1). In both groups, the physiological variables remained stable (Tables 2 and 3). Only the end-tidal carbon dioxide partial pressure in the sevoflurane and nitrous oxide group was a little high at the beginning of anaesthesia, when the alveolar concentration was higher. When the alveolar concentration was lower, the end-tidal carbon dioxide returned to normal values. Table 2. Mean minimum alveolar concentration (MAC), heart

rate and arterial pressure during anaesthesia and awakening in sevoflurane alone and sevoflurane and nitrous oxide groups Anaesthesia

Sleeping

Awake

0.98 51 100

0.60 57 99

0.20 63 92

Sevoflurane and nitrous oxide MAC 0.85 52 Heart rate; beat.min21 Arterial pressure; mmHg 130

0.51 55 124

0.17 61 112

Sevoflurane alone MAC Heart rate; beat.min21 Arterial pressure; mmHg

Table 3. Mean end-tidal carbon dioxide, respiratory rate and

peripheral oxygen saturation of haemoglobin during anaesthesia and awakening in sevoflurane alone and sevoflurane and nitrous oxide groups Anaesthesia

Sleeping

Awake

Sevoflurane alone End-tidal CO2 Respiratory rate; breath.min21 Oxygen saturation; %

36 37 98

34 32 99

33 25 99

Sevoflurane and nitrous oxide End-tidal CO2 Respiratory rate; breath.min21 Oxygen saturation; %

37 45 100

38 36 99

35 27 100

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The inhaled anaesthetics were somatosensory evoked potential inhibitors at the thalamus (wave N19) and cortical (wave P22) levels. During anaesthesia, the waves had a tendency to be isoelectrical; however, the peripheral (N9) and spinal (P/N13) waves remained unchanged (Figs 2 and 3). There was amplitude reduction and increase in latency in the somatosensory evoked potential waves when sevoflurane was used alone and when it was administered together with nitrous oxide. It was observed that these changes were more frequent with higher alveolar concentrations of anaesthetics. At the end of anaesthesia, when the alveolar concentration of sevoflurane was reduced to values lower than 1.0 MAC, the first signs of somatosensory evoked potential waves were recorded. Progressively, the waves increased in amplitude and reduced in latency according to the reduction in alveolar concentration. With an alveolar concentration of 0.2 MAC or less, the patients showed signs of awakening and the somatosensory evoked potential waves exhibited a normal shape, amplitude and latency. With the alveolar concentration corresponding to 1.0 MAC of sevoflurane, the use of nitrous oxide was associated with a reduction in amplitude of 0.2 mV, about 48.8% less than the amplitude of 1.0 MAC with sevoflurane alone. The addition of nitrous oxide resulted in a latency increase of 1.76 ms, i.e. 7.5% slower than when sevoflurane alone was used. Most patients who received sevoflurane and nitrous oxide woke with alveolar concentrations about of 0.15 MAC, and a delay to return of the somatosensory evoked potential waves to normal compared with the patients who received sevoflurane alone (Figs 4 and 5). Discussion

The results show the importance of somatosensory evoked potential in monitoring the action of inhaled anaesthetic agents. It was verified that sevoflurane alone exerts a significant influence, more intense when associated with nitrous oxide, on the latency and amplitude of the somatosensory evoked potential waves as in other agents previously studied [7±10]. Sevoflurane is known as an anaesthetic agent which maintains good cardiovascular stability [11] as confirmed in the study. Despite the statistically significant difference between the heart rates in the groups, no clinically untoward events occurred. The increase in cardiac frequency from 15% to 20% of baseline value was related with the use of both sevoflurane alone and in association with nitrous oxide 66% [12]. As with other inhaled anaesthetics, sevoflurane causes dose-dependent respiratory depression [13]. The tidal volume is reduced according to the depth of anaesthesia. The respiratory q 2001 Blackwell Science Ltd


Fig. 2. SEP waves with the patient

awake. N9, brachial plexus; N13, cervical spine; N19 and P22 thalamus and somatosensory cortex.

frequency usually increases; however, it is not sufficient to maintain the respiratory minute volume [13]. Consequently, the end-tidal carbon dioxide is elevated. This occurred in patients who were administered sevoflurane and nitrous oxide as these cases have an even more

rapid deep anaesthesia. No clinical consequences were found. The inhibition of somatosensory evoked potential at the thalamus and cerebral cortex, exhibited in waves N19 and P22, support the studies which reported that these are

Fig. 3. SEP waves with the patient

anaesthetised. N19 and P22 have disappeared.

q 2001 Blackwell Science Ltd

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V. Vieira da Costa et al Inhibition of somatosensory evoked potentials Anaesthesia, 2001, 56, pages 202±207 ................................................................................................................................................................................................................................................

Fig. 4. Comparison between the regression of amplitude of SEP waves at CNS level with MAC of sevoflurane alone and sevoflurane

MAC with nitrous oxide, when the patients were at the end of anaesthesia and awake.

the main sites of anaesthetic action by synaptic blockade. It should be noted that the somatosensory evoked potential waves at peripheral levels N9 and P/N13 showed no inhibition (Figs 2 and 3). In this study, it was verified that alveolar concentration of sevoflurane equivalent to MAC submultiples, 0.2 MAC with sevoflurane alone, and 0.1 MAC with sevoflurane and nitrous oxide, resulted in the patient waking immediately. In addition, somatosensory evoked potential waves became natural in amplitude and latency, very similar to before induction and during recovery of anaesthesia in adult patients given isoflurane in other studies [7, 9]. The results found in this study suggest a clinical application of somatosensory evoked potentials enabling a satisfactory anaesthetic level with lower alveolar concentrations of sevoflurane, when combined with nitrous oxide than with sevoflurane alone. It is possible to have an anaesthetic effect with an alveolar concentration equivalent

to anaesthetic dose AD95 (1.3 MAC) using the alveolar concentration equivalent to AD50 (1.0 MAC). According to previous studies, when the alveolar concentration is closer to AD95, the inhibition effects of inhaled anaesthetic on somatosensory evoked potential are greater, and the addition of nitrous oxide to volatile anaesthetics permits the total inhibition of somatosensory evoked potential with an alveolar concentration equivalent to AD50. These findings were clinically observed; however, since the patients have no movement reactions during surgery, they present cardiovascular signs such as tachychardia, arterial hypertension, lacrimation and sweating, thus indicating `light' anaesthesia. The somatosensory evoked potential waves showed reduction in amplitude and small increases in latency, but no complete inhibition [10]. However, when the alveolar concentration was equal to AD95, or AD50 with nitrous oxide, there was total inhibition of somatosensory evoked potential and the clinical signs of `light' anaesthesia disappeared.

Fig. 5. Comparison between the regression of latency of SEP waves at CNS level with MAC of sevoflurane alone and sevoflurane

MAC with nitrous oxide, when the patients were at the end of anaesthesia and awake.

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These data support the use of somatosensory evoked potential in the clinical management of patients, and the monitoring of anaesthetic action during induction, maintenance and recovery. It is possible to conclude that sevoflurane alone does show dose-dependent inhibition of somatosensory evoked potential on the central nervous system of children. With sevoflurane and nitrous oxide, this inhibition is more accentuated. References 1 Mahla ME. Electro physiologic monitoring of the brain and spinal cord. ASA Refresher Courses in Anesthesiology. 1991; 87±99. 2 Chiappa KH. Evoked Potential in Clinical Medicine, 2nd edn. New York: Raven Press, 1990; 307±70. 3 Schindler E et al. Changes in somatosensory evoked potentials after sevoflurane and isoflurane. A randomizes phase ill study. Anaesthesist 1999; 45 (Suppl. 1): S52±6. 4 Eger EI, Saidman LJ, Brandstater B. Minimum alveolar concentration. A standard of anesthetic potency. Anesthesiology 1965; 26: 756±63. 5 Jong R, Eger EI. MAC expanded. Anesthesiology 1975; 42: 382.


6 Mapleson WW. Effect of age on MAC of humans: a metaanalysis. British Journal of Anaesthesia 1996; 76: 179±85. 7 Guimaraes LF, Silva MD, Goncalves MHL, Saraiva RA. Monitorizacao da Anestesia pelo Potencial Evocado Somatosensitivo. Rev. Bras. Anestesiologia 1995; 56 (Suppl. 21): CBA004. 8 Peterson D, Drummond JC, Todd MM. Effects of hatothane, enflurane, isoflurane and N2O on somatosensory evoked potentials in humans. Anesthesiology 1986; 65: 35±40. 9 Goncalves MHL, Silva MD, Guimares LF, Saraiva RA. Comportamento do Potencial Evocado Somatossensitivo na lnducao, Manutencao e Regressao da Anestesia. Rev. Bras. Anestesiologia 1996; 46 (Suppl 21): CBA003. 10 Paes WML, Saraiva RA. Anestesia pelo Desflurano: Relacao entre CAM e inibicao do Potential Evocado Somatosensorial. Rev. Bras. Anestesiologia 1997; 47 (Suppl 22): CBA156. 11 Ebert TJ, Harkin CP, Muzi M. Cardiovascular responses to sevoflurane. A review. Anesthesia and Analgesia 1995; 81: S11±22. 12 Lerman J, Sikich N, Kleinman S, Yentis S. The pharmacology of sevoflurane in infants and children. Anesthesiology 1994; 80: 814±24. 13 Green WB Jr. The ventilatory effects of sevoflurane. Anesthesia and Analgesia 1995; 81: S23±6.

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