Department of Anaesthesiology and Intensive Care, Department of Clinical Neurophysiology and Department of Otorhinolaryngology, Kuopio University Hospital, PO Box 1777, FIN-70211 Kuopio, Finland Hannu Kokki, Kuopio University Hospital, PO Box 1777, FIN-70211 Helsinki, Finland
Declaration of interest: Dr Kokki has been paid by Abbott for lecture fees.
Accepted for publication: July 7, 2002
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Abstract |
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Methods. EEG recordings were made before premedication with midazolam (0.1 mg kg1 i.v.), during induction of anaesthesia with thiopental (5 mg kg1), and during maintenance with sevoflurane (2% end-tidal concentration in air/oxygen without nitrous oxide) in 30 generally healthy, 3- to 8-year-old children having adenoids removed. Noise-free EEG data of good quality were successfully recorded from all 30 children.
Results. Two independent neurophysiologists did not detect epileptiform discharges in any of the recordings.
Conclusion. Premedication with midazolam, i.v. induction with thiopental and maintenance of anaesthesia with 2% sevoflurane in air does not cause epileptiform EEG patterns in children.
Br J Anaesth 2002; 89: 8536
Keywords: anaesthetics i.v., thiopental; anaesthetics volatile, sevoflurane; children; hypnotics benzodiazepine, midazolam; monitoring, electroencephalography
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Introduction |
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Although sevoflurane is generally well tolerated, adverse effects have been reported. For example, coughing, laryngospasm, agitation and excitement may occur during sevoflurane anaesthesia.1 In some reports of inhalation induction with high concentrations, seizure-like electrical activity or movement has been reported with an incidence of 2088%.25 However, agitation during sevoflurane anaesthesia is not usually associated with seizures6 and sevoflurane is not contraindicated in patients with epilepsy.7
Although induction of anaesthesia with sevoflurane has been investigated extensively, less is known about the electroencephalogram (EEG) during maintenance of anaesthesia with sevoflurane. In our hospital we induce anaesthesia with i.v. midazolam and thiopental, and then maintain anaesthesia with sevoflurane. Because both midazolam and thiopental may reduce the likelihood of seizures, we studied this anaesthesia regimen, looking for epileptiform changes in the EEG during anaesthesia induction and maintenance. We recorded EEG before premedication and continuously during anaesthesia induction and maintenance until electrocautery was used for the first time.
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Methods |
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All children received the same anaesthesia. EMLA cream (Astra, Södertelje, Sweden) was used for skin analgesia. After baseline measurements, midazolam (0.1 mg kg1 i.v.) was given. Five minutes later, anaesthesia was induced with thiopental (5 mg kg1 i.v.) and tracheal intubation was facilitated by cis-atracurium (0.1 mg kg1 i.v.). Patients were ventilated with oxygen in air to maintain an end-tidal carbon dioxide partial pressure of 4.85.5 kPa. Sevoflurane was started 3 min after the induction and adjusted to keep the end-tidal concentration at 2%. Fentanyl (1 µg kg1 i.v.) was given before surgery started. On completion of surgery, neuromuscular block was antagonized with neostigmine and glycopyrrolate. All children were given 5% glucose in 0.3% saline for intraoperative fluid maintenance. Intraoperative, non-invasive arterial pressure, electrocardiography, peripheral oxygen saturation, inspiratory and end-tidal oxygen, carbon dioxide and sevoflurane concentrations were monitored continuously by Cardiocap/5 (Datex-Ohmeda, Helsinki, Finland).
The EEG was recorded with a five-channel EEG measuring machine, EMMA (developed at the Department of Clinical Neurophysiology, Kuopio University Hospital, Kuopio, Finland). The EMMA EEG machine has been validated and there are no differences compared with a standard EEG machine that could affect the results.9 Ag/AgCl electrodes were placed on the scalp according to the international 1020 system. The EEG signal was recorded from the electrodes F4 and Fz which were referenced to C4' (2 cm behind C4). Additional M1 and O2 electrodes referenced to C4' were used for the first 11 patients. Electrodeskin impedances were <5 k. The signal was amplified, digitized at a rate of 279 Hz and stored on a PC for off-line analysis. Baseline EEG was recorded before premedication. EEG was then recorded continuously until electrocautery was used for the first time. Two children received midazolam (0.1 mg kg1 i.v.) and one child thiopental (1 mg kg1 i.v.) before baseline recordings to facilitate connection of electrodes. These three children were included in the EEG analysis as agreed in the trial protocol.
The EEG signal was inspected by two independent neurophysiologists (S W-P, J P) for detecting possible epileptiform discharges. They knew the purpose of the study, but the records were viewed with no patient details given. The EEG signal was classified as fast beta activity (>13 Hz), alpha activity (813 Hz), theta activity (58 Hz) and delta activity (4 Hz). Figure 1 shows the timing of the events during the EEG record.
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Statistical analysis
A sample size of 30 patients is commonly used in this kind of study,25 and was considered sufficient also for the present trial to detect a clinically important incidence of EEG abnormality. A sample size of 30 children has a 0.8 power to detect an incidence >27% at a significance level of 0.05.
Friedmans test was used for statistical comparison of repeated measures of arterial pressure and heart rate, followed by Wilcoxons signed-rank test with Bonferroni correction if indicated. Significance was set at P<0.05.
Data are presented as mean (SD) and range as appropriate.
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Results |
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After starting sevoflurane inhalation the EEG showed mainly mixed delta activity with various amounts of beta waves superimposed. Occasionally, this pattern resembled delta with spikes, but epileptiform spikes were not detected. No other epileptiform EEG pattern, such as suppression with spikes, rhythmic polyspikes or periodic epileptiform discharges, was seen. During anaesthesia with sevoflurane, the EEG showed mixed delta/theta/beta activity (Fig. 2).
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Discussion |
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Midazolam is frequently used in paediatric anaesthesia.10 In addition to anxiolysis and sedation, midazolam also has a significant anticonvulsant effect11 that makes it appropriate for co-induction with sevoflurane. Both midazolam and thiopental increase the threshold for convulsions and reduce the incidence of EEG abnormality. An increase in beta activity seen after midazolam injection was expected because benzodiazepines are known to enhance beta activity.12
Sevoflurane can cause epileptiform EEG signals when used for inhalation induction with hyperventilation. Vakkuri and co-workers4 used high sevoflurane concentrations (8% in nitrous oxide in oxygen) for anaesthesia induction and found several forms of abnormal EEG. Suppression with spikes, rhythmic polyspikes and periodic epileptiform discharges were found in most children; the incidence of these abnormalities was 88%. In contrast, Constant and co-workers6 did not find any seizures in children during inhalation induction with three different regimens. After midazolam premedication children were given either a rapid induction with 7% sevoflurane in oxygen; induction with incremental concentrations of sevoflurane of 2, 4, 6 and 7% in oxygen; or induction with halothane. They found a difference between sevoflurane and halothane. With sevoflurane, sharp slow waves with very fast rhythms were commonly seen, whereas slow waves and fast rhythms were observed with halothane.
Recently, an increase in the heart rate has been shown to develop during inhalation induction with various volatile anaesthetics, and higher heart rates are particularly common during concurrent epileptiform discharges.4 6 13 14 In the present study the heart rate did not increase with sevoflurane inhalation. However, a significant increase in the heart rate and mean arterial pressure was seen during intubation, application of a mouth gag and surgical incision. This indicates that the anaesthesia used in the present study was insufficient to completely abolish the haemodynamic responses to nociceptive stimuli.
In previous studies, epileptiform potentials were seen during induction of anaesthesia with high sevoflurane concentrations. In the present study the end-tidal sevoflurane concentration was set at 2% and no EEG problems occurred. It is not clear whether the lack of epileptiform potentials is because thiopental and midazolam were given or because a lower dose of sevoflurane was used.
We stopped recording when electrocautery was used for the first time and no EEG was recorded during emergence from anaesthesia. Because a high incidence of agitation during emergence from sevoflurane anaesthesia has been reported in previous trials,1 it would be interesting in future to record EEG during recovery from anaesthesia.
We conclude that anaesthesia maintenance with 2% sevoflurane in oxygen/air in children after i.v. induction with midazolam and thiopental does not elicit seizure-like changes in the EEG.
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References |
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