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*Department of Anesthesia and Intensive Care, Helsinki University Hospital, Helsinki, Finland; Department of Clinical Neurophysiology, Tampere University Hospital, Tampere, Finland; GE Healthcare Finland, Helsinki, Finland; and Department of Anesthesia, Medical School, University of Tampere, and Department of Anesthesia and Intensive Care, Tampere University Hospital, Tampere, Finland
Address correspondence and reprint requests to Anne Vakkuri, MD, PhD, Surgical Hospital, P.O. Box 263, 00029 HUS, Helsinki, Finland. Address e-mail to anne.vakkuri{at}hus.fi.
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Abstract |
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Introduction |
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Tachycardia has also been observed during rapid increase in the inhaled concentration of desflurane (D) (5). Airway irritation may be the cause (6), but other mechanisms must also be involved, as hemodynamic changes of similar type also occur during the rapid increase in D concentration when direct airway contact is completely avoided by administering D during cardiopulmonary bypass (7).
Electroencephalogram (EEG) has not been studied during a rapidly increasing concentration of D. Therefore, the role of EEG activity, especially the possible appearance of epileptiform EEG during hyperdynamic circulatory response during D anesthesia, is unknown. We tested the hypothesis that tachycardia during a rapidly increasing concentration of D is associated with epileptiform EEG, similar to S. Mask induction of anesthesia with a large dose of S is most often associated with epileptiform EEG (2,4,8). Because D is unsuitable for mask induction as a result of its airway-irritating properties (9), a method was developed that enabled a similar abrupt increase in concentration with both S and D. Our hypothesis was that D-induced tachycardia is associated with epileptiform EEG activity.
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Methods |
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Patients were randomized to the D or S group by sealed envelopes. Diazepam 5 mg orally 1 h before anesthetic induction was used as premedication. Noninvasive arterial blood pressure and heart rate (HR) were recorded at 1-min intervals. Other routine monitoring consisted of pulse oximetry, end-tidal (ET) carbon dioxide (ETco2), ET anesthetic concentration, and electrocardiogram (ECG). EEG was recorded with a 4-channel EEG-monitor (BIS A-1000, Aspect Medical Systems, Natick, MA) using self-adhesive ZipPrepTM electrodes (Aspect Medical Systems) and recorded with 3 channels. The montage used was F7: left mastoid, F8: right mastoid, Fpz: left temporal, and ground electrode on the upper right side of the forehead. EEG was band-pass filtered (1–50 Hz), amplified, and digitized (sampling rate, 128 Hz). Impedances below 5 k
were considered acceptable. Recorded EEG tracings were collected on a laptop computer with the Datalogger program (Aspect Medical Systems) and evaluated off-line. Spectral analysis of selected EEG epochs was made using MatLab 7 (MathWorks, Inc., Natick, MA).
ECG lead II was recorded with the fourth channel of the Bispectral Index (BIS) A-1000 monitor (128 Hz) and stored on a personal computer with the Datalogger program.
After an initial IV dose of Ringer’s acetate solution 10 mL/kg, anesthesia was induced with propofol 1.5–2.0 mg/kg, remifentanil 1.0 µg/kg, and rocuronium 30 mg. Endotracheal intubation was performed and the patients’ lungs were ventilated mechanically with a Sulla 808VTM Dräger ventilator (Drägerwerk AG, Lübeck, Germany). After intubation, the patients first received small dose inhaled anesthesia with either D (1.2% ET) or S (0.45% ET) in 50% N2O/O2 for 10 min. The purpose of this 10-min waiting period was to allow the anesthetic effect of propofol and remifentanil to fade to achieve circumstances similar to the rapid increase in the concentration of volatile anesthetic agent during mask induction of anesthesia. After 10 min, the vaporizer setting of the ventilator was adjusted to the highest reading of the vaporizer, 7% for S, 18% for D, for 5 min. Normoventilation (ETco2 5.0%) was maintained throughout the study.
To create an abrupt increase in inhaled anesthetic concentration while avoiding hyperventilation, we placed a Bain breathing circuit between the intubation tube connector and the Y-piece of the anesthesia system for the 5-min study period. Fresh gas flow with the desired anesthetic gas concentrations was adjusted to maintain the ETco2 at more than the 5% level so as to avoid diluting the anesthetic gas concentration of fresh gas flow in the rebreathing circuit of the ventilator and ensure instant tracheal administration of the anesthetic. After 5 min, the anesthetic concentration was decreased, the Bain circuit was removed, and the study period was finished. Surgery was then allowed to start and anesthesia was continued according to clinical needs.
The study design was double-blind concerning EEG effects: The patients were not aware of their group assignment and the EEGs were classified by a clinical neurophysiologist (VJ) familiar with anesthesia EEGs but unaware of the anesthetic used. EEG tracings were classified as recordings containing epileptiform activity and those not containing such activity. The main criteria for epileptiform EEG were occurrence of spikes (pointed waveforms standing out from the background and a duration of 20–70 ms), polyspikes (a spike with more than 2 negative and positive deflections), rhythmic polyspikes (polyspikes occurring at nearly regular intervals), and periodic epileptiform discharges (repetitive sharp waves, spikes, or sharply contoured waves occurring at regular intervals and without clear evolution in frequency or location).
Sample size was not based on power analysis, as there was no prior information regarding the potential of D to induce epileptiform EEG in this type of setting. Instead, we decided to first study 30 patients and, if D also had epileptiform EEG provoking potential, calculate the necessary sample size if there was no statistical difference in the incidence of epileptiform EEG at that point between groups. In statistical analysis, analysis of variance for repeated measures was used for comparing HRs, with unpaired t-tests as post hoc testing. Age, height, and weight were analyzed with unpaired t-tests. For the incidence of epileptiform EEG, 
2 test was used. Statistical analysis was performed using SPSS 12.01 for Windows; (SPSS Inc., Chicago, IL). P < 0.05 was considered statistically significant. Values are mean ± sd unless otherwise noted.
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Results |
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No significant differences were found in age, height, or weight between groups. Epileptiform activity (periodic spikes, polyspikes, or rhythmic bursts) was seen in EEG recordings of eight of 15 S patients (Fig. 1). In group D, no epileptiform activity occurred (P < 0.05 versus S). In all subjects, the epileptiform EEG activity disappeared after decreasing the S concentration. Motor manifestations of epileptiform EEG were not seen in any of the patients. All patients had an uncomplicated recovery.
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Spectral analysis of EEG was made from both groups during 3 10-s periods: 1) immediately before the rapid increase in anesthetic concentration (ETdes 1.5% ± 0.4%, ETsevo 0.6% ± 0.3%), 2) after 2 min (ETdes 12.6% ± 1.4%, ETsevo 5.0% ± 0.3%), and 3) at the end of the 5-min study period with the large anesthetic concentration (ETdes 14.5% ± 1.6%, ETsevo 5.6% ± 0.4%) (Fig. 2). Spectral edge frequencies 95% were 17.3 ± 3.2 Hz, 4.4 ± 1.4 Hz, and 10.0 ± 6.2 Hz for D and 16.9 ± 3.4 Hz, 10.0 ± 5.8 Hz, and 10.4 ± 3.8 Hz for S during periods 1, 2, and 3, respectively.
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ET concentrations of anesthetics increased rapidly (Fig. 3). HR increased with both anesthetics (not significant between groups) (Fig. 3). The largest single increase in group D was 57% at 2 min after advancing the inhaled concentration. The single most rapid recorded HR in group D was 123 bpm. In group D, the increase in HR was sharp, causing a transient tachycardia, which typically lasted for 3 min. In group S, the increase in HR was more gradual, reaching its maximum value at 5 min. The single most rapid recorded HR among patients with epileptiform activity was 122 bpm versus 103 bpm in a patient without epileptiform EEG in group S. In group S, there were higher HR values among patients with epileptiform EEG, when compared with those patients without epileptiform EEG, but the differences were not statistically significant.
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Discussion |
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The initiating mechanisms of tachycardia during D anesthesia are unclear but reactivity of lung tissue has been suggested (6). However, differences in hemodynamics in comparison to S were also detected when direct airway contact was avoided by administering D during cardiopulmonary bypass (7), thus suggesting other possible mechanisms besides airway irritation. In our study, the patient population was not sufficiently large enough to show a statistical difference in HR. With power analysis and data from the 2-minute time point after the increase in anesthetic concentration, we conclude that with a study population of 72 patients the difference in HRs would have been statistically significant. This might be considered when planning for follow-up studies.
The EEG effects of D have been studied during steady-state conditions in various doses, both in animals (10) and in humans (11), without evidence of epileptiform EEG. Additionally, at the human study, a situation predisposing to epileptiform EEG was created (11). At 1.24 MAC, subjects’ lungs were hyperventilated and the subjects were exposed to rhythmic, loud clapping in an attempt to provoke excitatory phenomena. No epileptiform activity was seen. The EEG effects of a rapid increase in D concentration have not been studied. D has been considered very safe for patients with epilepsy, and inhaled anesthesia with D has been recommended as a suitable therapy for patients with refractory status epilepticus (12). Based on this study, we conclude that D is a suitable and very safe anesthetic for patients with epilepsy.
S consistently produces epileptiform discharges during mask induction of anesthesia with a large inspired concentration (2,4,8) and is dose-dependently epileptogenic at steady-state, surgical levels of anesthesia (3,13). Many reports have appeared regarding seizures during S anesthesia, some with EEG verification (13–15) and some without (16–18). In the current study, a rapidly increased concentration of S in normoventilated patients was associated with transient epileptiform EEG activity in eight of 15 patients. HR increased gradually. The different profile in the development of tachycardia during rapidly increasing D or S concentrations may reflect different underlying mechanisms of action between these two anesthetics. Although not reaching statistical significance in this experiment, those S patients with epileptiform phenomena in EEG tended to have more rapid HR readings during the study period. Therefore, tachycardia during S anesthesia might be explained, at least partly, by transient epileptiform activity in the central nervous system, as suggested earlier (2,4).
Detecting pathological EEG has become easier with the widespread use of EEG monitoring for adequacy of anesthesia, e.g., BIS, Entropy, auditory evoked potentials, and Narcotrend. Most of these devices show good quality raw EEG along with the index calculated from it. It is important to look at the raw EEG tracing at a clinical situation, when unexpected hemodynamic acceleration occurs, to detect possible epileptiform phenomena. In our study, these EEG transients during large concentrations of S disappeared rapidly after readjusting the level of anesthetic to meet clinical needs. Furthermore, our patients made uneventful postanesthetic recovery, and we did not detect any long-lasting consequences of intraoperative epileptiform EEG.
Motor manifestations were not seen during epileptiform EEG. The muscle relaxant administered during the anesthetic induction of this study may have prevented these. However, clinical convulsions were not seen more than a couple of times in earlier studies, even though these previous studies had a frequent incidence of epileptiform EEG and no neuromuscular blocking drug was used (2,4).
The incidence of epileptiform EEG may have been affected by diazepam premedication, and the residual effect of propofol. However, as the groups received similar treatment, except the randomly selected anesthetic, the observed differences in the incidence of epileptiform EEG between groups were likely drug-related. We used premedication in our study to have similar conditions to our everyday practice.
The effect of a single, small bolus dose of remifentanil had ceased during the 10-minute waiting time before the test period (19). Propofol 1.5 -2 mg/kg bolus dose may still have had a small residual effect after 10 minutes, but this is not likely to have a proconvulsant effect (3). Thus, anesthetic induction with propofol and remifentanil may have had a reducing impact on the incidence of epileptiform EEG in both groups.
Hyperventilation with hypocapnia increases the incidence of epileptiform EEG when using enflurane (20) and may increase the incidence of epileptiform EEG during S inhaled anesthetic induction (8). To avoid the effect of hyperventilation with hypocapnia, we strictly maintained normoventilation at all times during this study. This may have influenced the smaller incidence of epileptiform EEG in the S group compared with the S inhalation induction studies.
In conclusion, in contrast to S, rapidly increasing concentrations of D were not associated with epileptiform EEG in normoventilated patients.
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Footnotes |
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Accepted for publication January 4, 2005.
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