Narcolepsy or Gélineau syndrome is a chronic sleep disorder of unknown etiology characterized by uncontrollable attacks of deep sleep and is typically associated with cataplexy (sudden complete loss of muscle tone).1 Due to the rarity of the syndrome, guidelines for the anesthetic management and/or monitoring of patients with narcolepsy during surgery have not been established. Postoperative complications after inhaled anesthesia have been reported in a narcoleptic patient who had increased sensitivity to general anesthetics. The interactions of inhaled anesthetics with drugs used to treat narcolepsy2 have also been studied. However, regional anesthesia also seems to entail considerable risks to narcoleptic patients as two narcoleptic/ cataplectic spells were reported in a patient who underwent surgery under spinal anesthesia.3
Numerous electroencephalographic (EEG)-derived cerebral monitors are used in clinical practice for monitoring the effects of anesthetic/hypnotic drugs. Among the currently available monitors, the Bispectral Index (BIS) was shown to correlate to various conditions that could influence the EEG.4 We chose the BIS to monitor a patient with a long history of narcolepsy-cataplexy undergoing surgery under regional anesthesia because his EEG-derived BIS could possibly reflect the EEG changes of a potential narcolepsy episode, whereas monitoring of electromyographic (EMG) activity in decibel (dB) could offer an additional advantage of possibly predicting an ensuing cataplectic spell with its associated hazards of complete loss of muscle tone. We assessed the utility of using BIS for monitoring a possible narcolepsy-cataplexy episode and whether a distinctive BIS profile could offer an early warning of an impending narcoleptic/ cataplectic spell.
A 57-yr-old male patient with a long history of recurrent daytime 2–3 h sleep attacks with sudden complete loss of muscle power was scheduled to undergo lower limb surgery under femoral nerve block. For his narcolepsy-cataplexy condition, our patient was not receiving any amphetamine-like medications or other central nervous system stimulants that might alter the BIS monitoring. The patient gave a written informed consent to publish any collected data. He did not receive any premedication before the operation. Soon after the patient was admitted to the operating room we recorded both hemispheres using two synchronized BIS-XP monitors (algorithm version 3.4, Aspect Medical Systems, Newton, MA) connected to two BIS Quatro sensors. Real-time EEG, BIS data, and EMG power displayed in dB units were continuously collected and stored on two laptop computers. Heart rate, mean arterial blood pressure, and respiratory rate were continuously recorded. Paired comparisons using paired t-test were used to compare parameter changes at different stages. The patient's vigilance was assessed by a simple stimulus-response test (response to calling the patient's name). The vigilance state was graded as “high,” if our patient promptly responded; “low,” if he was drowsy, lethargic, dazed and his responses were slow or staccato speech; and “nonresponsive,” if he was in a stupor. The patient received a femoral nerve block (ropivacaine 0.5% 30 mL, using a 0.1 ms nerve stimulator with 0.4 mA stimulations to identify the femoral nerve). After testing for successful nerve block, surgery was commenced, with no sedation given during the surgical procedure.
Twenty minutes from the start of BIS recording, the patient started experiencing a narcolepsy-cataplexy episode as he went through three stages (Fig. 1): the first phase of prodromal intermittent low-vigilance in which he would repeatedly drift from low-vigilance to high muscular activity. Mean ± sd BIS alternated from 55.5 ± 5.8 to 93.8 ± 2.3 (P < 0.00001), which was associated with alternating EMG activity from 32.9 ± 2.0 to 50.1 ± 3.8 dB (P < 0.00001). This was followed by a second phase of continuous low-vigilance in which he was calm (left BIS 76.3 ± 6.6, right BIS 72.7 ± 5.9) with no muscular activity (left EMG 31.6 ± 1.3, right EMG 31.9 ± 1.1 dB). Raw EEG tracings revealed slow Δ and θ waves with a decrease in the fast α and β waves. This was followed by a third phase of full-blown narcolepsy-cataplexy episode of complete nonresponsive vigilance as both sides (left BIS 44.1 ± 2.5, right BIS 44.5 ± 3.3) significantly declined (P < 0.00001) with complete cataplectic loss of muscle power (left 31.1 ± 0.9, right 32.0 ± 0.6 dB). However, there was no statistically significant difference between the EMG of the second and third phases (P = 0.5396). Although our patient's mean arterial blood pressure, heart rate, and respiratory rate declined in the second and third phases compared with the first phase, the differences still did not reach statistical significance. Other than careful surveillance of his vital signs, no interventions were taken during the narcoleptic episode. Eventually the BIS increased as the patient emerged from his narcolepsy-cataplexy episode with the termination of his surgery. His BIS showed a similar pattern when derived from left and right hemispheres (Fig. 1). The patient fully recovered and postoperatively there seemed to be no change in the frequency or duration of his narcolepsy-cataplexy episodes.
To the best of our knowledge, this is the first report of BIS monitoring of an active 2 h narcolepsy-cataplexy episode under regional anesthesia. During the initial prodromal intermittent low-vigilance phase, BIS showed what could be considered a distinctive profile of rapidly alternating high/low BIS associated with alternating high/low EMG values, which might offer an early warning of an impending potentially hazardous narcoleptic/cataplectic spell with total loss of muscle power. This was followed by a relatively stable phase of BIS around 75 during the continuous low-vigilance phase, before ending with the potentially hazardous phase of a full-blown narcoleptic episode with atonia, sudden total loss of muscle power, in which BIS readings were down to around 45 for about half an hour.
During the first phase, the initial BIS decline described a prodromal low-vigilance state interrupted by BIS being spuriously increased by high EMG activity.5 The high muscular activity at the initial phase strongly suggests that our narcoleptic patient was making several attempts to counteract his impending low vigilance state. EMG activities are artifact signals that occur within the “range of interest” frequency of the bispectrum. Since the EMG frequency band could simulate the BetaRatio, one of the BIS component descriptors, the intermittent increase in EMG activity in the first prodromal phase would be construed by the BIS algorithm as EEG activity and assigned an increased BIS value.5
This was followed by a second phase of typical narcoleptic diurnal low vigilance state with enhanced sleep drive. This diurnal state was reported, in a previous EEG mapping study, to manifest in narcoleptic patients as an increase in θ power with slowing of the α, β, and total power spectrum.6 This was detected by the BIS algorithm and displayed as low BIS of around 75. Finally, a drastic BIS decline to around 45 in a full-blown narcoleptic episode, similar to when our patient was in stupor, was investigated in a study of the pathophysiology of narcoleptic patients' sleep episodes. It showed a significant EEG suppression manifesting as slow waves predominance and a decrease in β EEG power density with decreased central arousal activity,7 that was again reflected in our patient's BIS drastic decline to around 45. In the second phase, our patient was calm as he showed no muscular activity but was not atonic, which would explain the absence of a statistically significant difference between EMG of the second phase and the EMG of the third phase of a full blown cataleptic loss of muscle power.
In that regard, two previous reports demonstrated that BIS was a consistent marker of depth of sleep, as BIS progressively declined with the conventional stages of natural physiological sleep, in which light sleep occurred at BIS 75–90, slow-wave sleep at BIS 20–70, and rapid eye movement sleep at BIS 75–92.8 Whereas in another study BIS values for arousal, light, slow wave, and rapid eye movement sleep were 67 ± 20.2, 50 ± 16.5, 42 ± 11.2, and 48 ± 7.1, respectively.9 However, our narcoleptic patient experienced a totally different BIS profile than that of normal physiological sleep, as the distinctive prodromal first phase of rapid BIS/EMG changes might offer an early warning of an impending narcoleptic/cataplectic spell with its associated hazards.
Narcolepsy is an under-diagnosed neurological disorder as the incidence of the syndrome is estimated to be 0.025%. Once established, the condition becomes chronic, without remission.10 Narcolepsy seems to have a genetic basis and has been linked to human leukocyte antigens DR2 and DQwl.11 Narcolepsy is an extremely incapacitating disorder that currently has no cure, as treatment focuses on the control of symptoms using amphetamine-like central nervous system stimulants for excessive day sleepiness and antidepressants for cataplexy.1 Hence, prolonged emergence, postoperative apnea, cataplectic spells or an increase in frequency/duration of narcoleptic episodes after general anesthesia are serious concerns.3 However, regional anesthesia seems to be an attractive option aiming at avoiding any interaction between general anesthetics and patient's disease or medications. Unfortunately, our patient still suffered a narcoleptic-cataplectic episode while undergoing surgery under femoral nerve block.
The purpose of presenting this report is to emphasize the fact that narcoleptic patients can still run the risk of loss of consciousness with atonia under regional anesthesia, and such an undesirable complication cannot be under-estimated. BIS monitoring is a simple method that could offer an early warning of an imminent episode, with its associated hazards, in patients with narcolepsy-cataplexy undergoing surgery under regional anesthesia.
The authors would like to thank Mr. Charles Zhou and Ms. Yu Cai, BTTCO, People's Republic of China for their great efforts and meticulous work in data preparation and collection.
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