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From the Department of Anesthesiology, The University of Tokyo, Faculty of Medicine, Tokyo, Japan.
Address correspondence to: Dr. Tomoki Nishiyama, 3-2-6-603, Kawaguchi, Kawaguchi-shi, Saitama, 332-0015, Japan. Phone: 81-3-5800-8668; Fax: 81-3-5800-9655; E-mail: nishit-tky{at}umin.ac.jp
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Abstract |
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Methods: Eighty female patients undergoing partial mastectomy were randomly allocated to AAI or BIS (40 per group). Anesthesia was induced with propofol 2 mg·kg–1 and fentanyl 3 µg·kg–1 during the inhalation of oxygen. A laryngeal mask airway (LMA) #3 was inserted. Anesthesia was maintained with propofol 4 mg·kg–1·hr–1, fentanyl 1 µg·kg–1 given at the start of surgery, and nitrous oxide 4 L·min–1 in oxygen 2 L·min–1. Blood pressure, heart rate, and AAI or BIS were monitored, including recovery time of the index after disturbance by electrocautery.
Results: The AAI but not the BIS increased significantly with LMA insertion and skin incision, while blood pressure and heart rate did not change. The BIS decreased from 87 ± 7 to 30–60 while the AAI decreased from 75 ± 8 to 10–25 during anesthesia. The increase of the AAI was larger than that of the BIS at recovery from anesthesia. The variation of the index was smaller in the AAI than in the BIS. Recovery time of the index after electrocautery was significantly longer in the BIS group (21 ± 9 sec) than that in the AAI group (5 ± 3 sec).
Conclusions: During propofol-fentanyl-nitrous oxide anesthesia, the AAI responded to LMA insertion or surgical incision, but not the BIS, and the AAI had smaller variations. The AAI recovered faster from the disturbance by electrocautery than the BIS. Thus, the AAI may be a more sensitive and useful detector of arousal than the BIS.
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Introduction |
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Methods |
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Midazolam 5 mg and atropine 0.5 mg were administered intramuscularly 30 min before anesthesia. Anesthesia was induced with propofol 2 mg·kg–1 and fentanyl 3 µg·kg–1 while patients breathed oxygen. After loss of response to verbal command and eyelash reflex, a laryngeal mask airway (LMA) #3 was inserted. Anesthesia was maintained with propofol 4 mg·kg–1·hr–1, fentanyl 1 µg·kg–1 given at the start of surgery (total 4 µg·kg–1), and nitrous oxide 4 L·min–1 in oxygen 2 L·min–1. Ventilation was adjusted to keep the end-tidal carbon dioxide tension between 30 and 35 mmHg during surgery. No muscle relaxants were used. The propofol infusion was stopped when skin suture started. Inhalation of nitrous oxide was stopped at the end of skin suture. After stopping nitrous oxide, awakening was evaluated every minute. When patients responded to verbal command "open your eyes" and "grip my hand" and breathed spontaneously, the LMA was removed. All patients were anesthetized by a single senior anesthesiologist and operated by the same surgeons.
Non-invasive blood pressure, heart rate, AAI or BIS, and the recovery time of the index after each signal disturbance by electrocautery (measured from the end of electrocautery to the recovery of good signals shown by the disappearance of alarm at each randomly selected five cauteries, mean recovery time calculated) were measured to observe the differences between the two devices. The AAI was measured by the Alaris AEP monitorTM (A-AEPTM, version 1.5, Alaris Medical Systems, Hampshire, UK) and the BIS was measured by the A-2000 BISTM monitor (BISTM, version 3.1, Aspect Medical Systems, Newtown, MA, USA). The BISTM uses special electrodes, is calculated on the basis of two second epochs and its mean value is updated every second. The A-AEPTM uses a headphone and three separate electrodes, is elicited with a binaural click stimulus of 65-dB intensity, 2 msec duration, and repetition rate of 9 Hz (one click each 110 msec). The AEP is extracted over 15 sweeps, producing an update delay of six seconds. The AAI is calculated every two seconds.
Data are expressed as mean ± standard deviation. Statistical analysis was performed with Student’s t test for demographic data and the recovery time of the index after electrocautery, and repeated measures analysis of variance followed by the Student-Newman-Keuls method as a post-hoc test for blood pressure, heart rate, and both indexes. A P < 0.05 was considered statistically significant. Sample size was analyzed by post hoc power analysis (G PowerTM, v 2.1.2, Trieter University, Trieter, Germany).
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). No patient moved during induction and maintenance of anesthesia. Blood pressure and heart rate decreased significantly with anesthesia induction, did not change significantly after LMA insertion and surgical incision, and returned to baseline at the end of surgery in both groups. Blood pressure and heart rate were not different between groups (Figure 1).
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). The AAI, but not the BIS, increased significantly with LMA insertion and skin incision. When patients responded to verbal command at recovery from anesthesia, both BIS and AAI were still lower than control values (P = 0.04 and 0.014 in BIS and AAI groups, respectively), while the increase of the index during recovery from anesthesia was larger with the AAI than with the BIS. Both returned to control values at extubation. The BIS showed larger variations than the AAI. The BIS at the end of propofol infusion was significantly larger than that before LMA insertion but the AAI was not.
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Discussion |
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We tested each monitor on different patients. To compare these two monitors more precisely, both should have been tested simultaneously in the same patients. However, the effects of auditory stimuli on the BIS remain unclear. Therefore, only one monitor was used in each patient.
During propofol anesthesia, the BIS at which 50 and 95% of the population lose consciousness is reported to be 63 (62–65) and 51 (48–55), respectively.6 In the study by Litvan et al.,7 the AAI is 30.7 ± 9.5 when patients respond only after mild prodding or shaking (modified observer’s assessment of alertness/sedation scale (MOAAS 2), and 21.1 ± 9.5 when patients respond only after painful trapezius squeeze (MOAAS 1) during propofol induction. In the present study, BIS and AAI in awake patients were 87 ± 7 and 75 ± 8 and decreased to 38 ± 9 and 15 ± 3, respectively, before LMA insertion when patients ceased to respond to verbal command and lost their eyelash reflex. These variations of the indexes are almost identical to those reported in other studies.6,7 We did not measure the depth of sedation precisely during anesthesia, but the absence of movements during surgery without any muscle relaxants suggests patients were adequately anesthetized. The preoperative values were slightly lower than the usual awake values, which might reflect the effects of premedication.
During recovery from an induction dose of propofol, concentration related effects on the AEP were found.8 Doi et al.9 reported no difference between the awake index and the index when patients open their eyes on command. However, in our study, when patients responded to verbal command during the recovery phase, both BIS (67 ± 8) and AAI (46 ± 11) were still significantly lower than before anesthesia (BIS; 87 ± 7, P = 0.04, AAI; 75 ± 8, P = 0.014). The difference between our results and the report by Doi et al.9 might be due to the difference in time when the response was examined and the different monitors used.
BIS is reported to respond to laryngoscopy and intubation,10 to movement with LMA insertion,11 to intubation,12 or to skin incision.13 However, in this study, the AAI increased significantly in response to LMA insertion and skin incision, while the BIS did not. Blood pressure and heart rate increased after these stimuli in both groups but not significantly. Even when blood pressure does not change significantly or no movements occur, intubation or skin incision can still be stressful to the patient, send an impulse to the spinal cord and then to the brain to induce changes in the EEG. Therefore, the AAI might be more sensitive to fine changes than the BIS, while further studies are necessary to confirm this.
The AAI was reported to be able to follow rapid changes from wakefulness to sleep and detect short-term periods of consciousness.14 The more rapid response of the AAI to LMA insertion or skin incision, and faster recovery from signal disturbance by electrocautery compared to BIS might be simply due to the faster response time of the A-AEP. Extraction of the MLAEP is usually done by moving time averaging over many sweeps (usually 250 to 1,000), which can produce a delay of more than one minute.15 However, this problem was addressed by applying autoregressive modelling with exogenous input that enables extraction of the AEP within 15 sweeps by the A-AEP.16 The BIS value represents the mean of at least 15 but sometimes 60 sec of data, and a delay of one minute can be expected. However, in Nieuwenhuijs’s study,17 the delay was two minutes or longer with the BIS.
Surgical stimulation is reported to increase the amplitude of MLAEP, which indicates that the amplitude does not simply reflect graded concentrations of the anesthetic agent but, more importantly, depicts the balance between surgical stimulation and anesthetic depression.14 Therefore, the AAI would indicate both sedation and response to stimuli, i.e., level of anesthesia. The evoked response is an indication of the responsiveness of the central nervous system whereas the EEG reflects the resting level. This difference might be the reason for the different response to stimuli between the AAI and the BIS. However, the BIS at the end of propofol infusion was significantly larger than that before LMA insertion but the AAI was not and the BIS had larger variations than the AAI. These might suggest again that the AAI was more sensitive to the changes of stimulation with smaller variations between subjects. In the study by Kreuer et al.,18 the AAI had larger variations than the BIS, which is inconsistent with our results. However, their study controlled the BIS to achieve target values, therefore there is no doubt that the BIS had to be in a more narrow range than the AAI.
Further studies are necessary to elucidate whether the different response between BIS and AAI is due only to different response times or not.
In the present study, we administered midazolam 5 mg with atropine 0.5 mg as a premedication in all patients. In the study using volunteers, im atropine dose dependently increased delta power, decreased alpha power, and tended to increase theta power and reduce beta and theta frequency in EEG.19 No data are available for the effects of atropine on the BIS and AAI. In the study by Liu et al.,20 the BIS exhibited a good correlation with sedation levels during midazolam induced sedation, while Barr et al.21 reported a large variation of BIS during clinically adequate anesthesia with midazolam and fentanyl. Our anesthesia protocol included fentanyl and nitrous oxide. The MLAEP has been reported to be an insensitive marker of opioid and nitrous oxide effect.22,23 BIS was reported to decrease from 47.7 to 39.8 by increasing nitrous oxide concentration from 0 to 60% during sevoflurane anesthesia,24 while it did not change with the addition of nitrous oxide to isoflurane anesthesia.25 The addition or withdrawal of nitrous oxide during constant sevoflurane anesthesia was found to cause only minor changes in the AAI.23 With fentanyl or nitrous oxide, MLAEP have been reported to remain nearly unchanged.26 In the present study, we could not differentiate the effects of each anesthetic on the BIS and the AAI.
In conclusion, during propofol-fentanyl-nitrous oxide anesthesia, the AAI responded to the stimuli of LMA insertion and skin incision but the BIS did not. The AAI recovered faster from the disturbance by electric cautery than the BIS. The variation of the index was smaller in the AAI than in the BIS. Thus, the AAI might be a more useful monitor than the BIS during propofol-fentanyl-nitrous oxide anesthesia.
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Footnotes |
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Accepted for publication October 28, 2003. Revision accepted February 18, 2004.
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2 Glass PS, Bloom M, Kearse L, Rosow C, Sebel P, Manberg P. Bispectral analysis measures sedation and memory effects of propofol, midazolam, isoflurane, and alfentanil in healthy volunteers. Anesthesiology 1997; 86: 836–47.[Medline]
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P < 0.05 vs the AAI group.