Chen, Xiaoguang MD*,; Tang, Jun MD*,; White, Paul F. PhD, MD, FANZCA*,; Wender, Ronald H. MD†,; Ma, Hong MD†,; Sloninsky, Alexander MD†, and; Kariger, Robert MD†
The quantitative assessment of consciousness during surgery has been a long-standing challenge for anesthesiologists (1). Although clinical signs are often used to monitor patients’ physiologic status during surgery, hemodynamic responses have a low predictive value in assessing the adequacy of anesthesia because of the complex array of factors that contribute to individual patients’ cardiovascular responses to surgical stimulation (2–4). In addition, the use of neuromuscular blocking drugs minimizes the value of patient movement as an indicator of an inadequate anesthetic state.
A wide variety of electroencephalographic (EEG) variables have been evaluated as possible indicators of anesthetic depth (2–9). However, many of these investigations have found that EEG-derived variables were drug specific and could not be monotonically related to either anesthetic effect or clinical response (5–8). The EEG bispectral index (BIS) monitor has a high probability of correctly predicting both the loss and recovery of consciousness and has been reported to be more reliable for assessing the level of sedation and hypnosis during surgery than other available processed EEG algorithms (9–11). Nevertheless, the BIS response is associated with both interpatient and anesthetic-related variability and is susceptible to interference during use of the electrocautery (11,12). The patient state index (PSI) has been introduced as a novel quantitative EEG index for assessing the level of consciousness during sedation and general anesthesia (13). In a recent multicenter study (14), Pierce et al. reported that use of the PSI to titrate propofol administration significantly decreased drug usage and improved the early recovery profile.
Therefore, we hypothesized that changes in the PSI after the administration of IV (e.g., propofol) and inhaled (e.g., desflurane) anesthetics would parallel perioperative changes in BIS values. In addition, this study was designed to compare the sensitivity and specificity of the BIS and PSI values with respect to predicting loss of consciousness and emergence from a standardized general anesthetic technique.
After approval was obtained from the local IRB, 20 ASA physical status I–II patients scheduled for laparoscopic surgery under general anesthesia were enrolled in this monitoring-only study. Patients with known neurological or psychiatric disorders; current use of anticonvulsant or other centrally active medications; clinically significant cardiovascular, respiratory, hepatic, renal, or metabolic disease; long-term drug or alcohol abuse; or a body weight >50% above the ideal body weight were excluded from participating in this study.
All patients received midazolam 2 mg IV for premedication. A BIS monitoring strip (A-2000; Aspect Medical Systems, Natick, MA) and a patient state analyzer array (PSA 4000; Physiometrix Inc., Billerica, MA) were applied simultaneously in the preoperative holding area. On arrival in the operating room, routine monitoring devices were placed, baseline (awake) BIS and PSI values were recorded with the patients’ eyes closed for 1–2 min before the induction of anesthesia, and these variables were subsequently recorded at 1- to 5-min intervals until patients were awake and oriented after anesthesia. Anesthesia was induced with propofol 2.0 mg/kg IV and fentanyl 1 μg/kg IV, injected over 15–30 s. Cisatracurium 0.3 mg/kg IV was administered to facilitate tracheal intubation, followed by desflurane 4% (initial inspired concentration) in combination with nitrous oxide (N2O) 60% in oxygen for the maintenance of anesthesia.
If the patient displayed autonomic signs consistent with inadequate anesthesia (e.g., increased heart rate [HR], diaphoresis, or lacrimation), then supplemental doses of propofol 20 mg IV were administered during the maintenance period. The inspired desflurane concentration was increased by 2% when the patient manifested a sustained (≥5-min) increase in mean arterial blood pressure (MAP) ≥20% of the preincision baseline value. In response to clinical signs of “excessive” anesthetic effect (e.g., a decrease in MAP ≥20% of the preincision value), the inspired concentration of desflurane was decreased by 2%. At the end of surgery, the inhaled anesthetics were discontinued, and residual neuromuscular blockade was reversed with glycopyrrolate 0.01 mg/kg IV and neostigmine 0.05 mg/kg IV.
The MAP, HR, BIS, and PSI values were measured at 1-min intervals during the induction and emergence periods, as well as immediately before and up to 5 min after a bolus of propofol or a change in the inspired concentration of desflurane. The end-tidal concentrations of desflurane and N2O, oxygen saturation, as well as the BIS and PSI values, were recorded at 5-min intervals during the maintenance period. Three investigators were simultaneously involved in the conduct of the study. The staff anesthesiologists (RHW, AS, and RK) were responsible for administering the anesthetics and for monitoring the depth of anesthesia using standard clinical signs. Both the BIS and PSA monitor screens were positioned out of their line of sight, and the second investigator (JT) ensured proper functioning of the BIS and PSA monitors during the operation. The third investigator (XC) recorded data at specific time intervals during the perioperative period. The incidence of electrocautery interference with the BIS and PSI values was determined by the presence or absence of a displayed BIS or PSI value each time the electrocautery unit was used during the operation.
The PSA 4000 monitor acquires the EEG signal and displays the PSI value by using a disposable EEG electrode appliance composed of a self-adjusting flexible head strap, which serves to position and hold the silver/silver chloride recording electrodes at the internationally defined EEG recording locations of Fp1, Fpz1, Cz, Pz with a linked ear reference, and ground (Fp2), and required 1–3 min to apply, depending on the amount of hair on the patient’s head. The frontopolar electrodes and mastoid pieces are self-adhesive and serve to additionally fix the appliance to the head, and the midline central and parietal electrodes use self-contained conductive gel for establishing contact with the underlying scalp. EEG data were collected at 2500 samples per second per channel and bandpass-filtered to 0.5–70 Hz, with 250 samples processed per second per channel. Recording electrode impedance was continuously monitored and alarmed when values were more than 15 KΩ. The BIS monitor used a conveniently applied self-adhesive EEG electrode strip (ZipPrep; Aspect Medical Systems), which was positioned on the forehead in <30 s. Electrode impedance was maintained at less than 2 KΩ. Both EEG monitoring systems use sophisticated artifact rejection algorithms, and the amplifiers had medical-grade isolation transformers. The two sets of EEG recording electrodes were applied in close proximity, consistent with the manufacturer’s recommendations, and there was no apparent interference between the two monitoring systems.
Data regarding the patient’s state of consciousness (e.g., ability to follow commands to open their eyes and squeeze the investigator’s hand and orientation to person, place, and time) were obtained at 15- to 30-s intervals from the start of the injection of the induction dose of propofol until loss of responsiveness to verbal commands and from discontinuing the inhaled anesthetics until the patient was awake and oriented. The PSI and BIS values were recorded at specific 1-min intervals, as defined previously.
Statistical analysis consisted of Student’s t-test and repeated-measures of analysis of variance with post hoc Bonferroni correction for continuous variables. Categorical data were analyzed with the χ2 test. The relationship between BIS and PSI values during the induction and emergence periods was analyzed with linear regression and correlation coefficients. Assessment of the nonlinear association between BIS and PSI values and of the probability of unconsciousness was accomplished by using the logistic regression procedure, which estimated the probability of a binary yes/no response. The area under the receiver operating characteristic (ROC) curve for each index was determined by plotting the sensitivity (fraction of unresponsive participants who were correctly predicted to be unconscious) against 1-specificity (fraction of responsive participants correctly identified), and it reflects the discriminating power of the indices. The area under the ROC curve summarizes the predictive power to achieve a high specificity at any given sensitivity (15). An area >0.5 indicates that the measurement is predictive, and a measurement with 100% accuracy would have an area of 1.0. All tests were two sided, and a P value <0.05 was considered statistically significant. Data are presented as mean values ± sd and as percentages.
Nine male and 11 female patients with a mean age of 48 ± 16 yr (range, 25–72 yr) and weight of 72 ± 21 kg (range, 58–94 kg) were enrolled in this monitoring study. The mean duration of surgery was 91 ± 38 min (range, 50–132 min). The dosages of propofol and fentanyl were 148 ± 42 mg and 99 ± 23 μg, respectively. In addition, the average end-tidal concentration of desflurane was 3.4% ± 0.6%. Emergence times to eye opening and orientation were 5.3 ± 2.9 min and 6.3 ± 2.9 min, respectively. No patient reported intraoperative recall on the 24-h follow-up interview.
The BIS and PSI values decreased progressively from preinduction values of 89 ± 12 and 92 ± 13 to preincision values of 52 ± 11 and 32 ± 18, respectively (Table 1). However, a greater degree of interpatient variability (±sd) was observed in the PSI (versus BIS) values. During the maintenance period, the pattern of changes in the PSI values was similar to that of the BIS values after bolus doses of propofol (Table 2) and increases or decreases in the desflurane concentration (Table 3). However, some of the PSI values were significantly lower than the BIS values when the patients manifested signs of an inadequate or excessive anesthetic state (Tables 2 and 3). Only relatively small changes were observed in MAP and HR values after propofol or desflurane supplementation (Table 4). Compared with the BIS monitor, the PSA monitor experienced significantly less interference (artifact) during use of the electrosurgical unit (16% versus 65%, respectively). During the interval from discontinuing the maintenance anesthetics until the patients were oriented, the BIS and PSI values increased from 55 ± 18 and 53 ± 21 to 93 ± 7 and 81 ± 10, respectively (Table 5). Although the indices were comparable during the induction period, the PSI values were significantly lower than the BIS values during the emergence period. Nevertheless, the PSI correlated well with the BIS during both the induction (r = 0.78) (Fig. 1) and emergence (r = 0.73) periods (Fig. 2). In contrast to the BIS, the mean PSI value failed to return to the preinduction value when the patient regained orientation after anesthesia (Table 5).
Logistic regression analysis demonstrated that the BIS and PSI were both significant predictors of unconsciousness (P < 0.01). Furthermore, the area under the ROC curve (Fig. 3) for the BIS and PSI was 0.79 ± 0.04 and 0.95 ± 0.04, respectively, confirming that both indices were predictive of the patient’s state of consciousness.
A reliable monitor of anesthetic depth should display a good correlation between the measured value and the physiologic response during surgery, independent of the anesthetic being administered, and its use would ideally be associated with minimal interpatient variability (16). The induction of general anesthesia is usually accompanied by an increase in high-frequency EEG activity, which spreads from the frontal region to more posterior regions of the brain, resulting in an increasing degree of sedation and, eventually, loss of consciousness (17). The pattern of changes in the PSI and BIS values was similar during the induction, maintenance, and emergence periods. However, the PSI values appeared to display a somewhat greater degree of interpatient variability than the BIS values. The possible explanation may include difficulties in obtaining a consistently acceptable EEG signal because of the cranial lead placements required for the PSA monitor.
The BIS has been found to be capable of monitoring the level of consciousness during sedation (10,11) and general anesthesia (9,12,16). The BIS has also been found to possess a reasonable combination of sensitivity and specificity for assessing the level of consciousness when different anesthetic regimens are used during surgery (9,12,16). Furthermore, use of the BIS monitor has been reported to improve the titration of both IV and inhaled anesthetics during general anesthesia (18,19). Analogous to the BIS, the PSI is a dimensionless number scaled from 100 to 0, with 100 representing an awake EEG and 0 representing complete electrical silence (13). Predictable changes in this quantitative EEG (PSI) value have been associated with loss of and return of consciousness in volunteers anesthetized with propofol and sevoflurane (20). The enhanced sensitivity of the PSI is in part due to the use of a self-norming technique in the development of the algorithm (13). This method takes into account differences in individual background EEG, as well as interindividual patient variability in the brain’s response to different anesthetics (21,22).
There have been no published reports in the peer-reviewed literature describing the behavior of the PSA monitor during routine anesthetic practice. However, Prichep et al. (13) used the PSA monitor on 176 surgical patients to evaluate the relationship between level of consciousness and the PSI value under different anesthetic conditions. In this preliminary study, the investigators demonstrated that the PSI was significantly related to the patient’s state of consciousness during total IV anesthesia with propofol and during inhaled anesthesia with isoflurane, sevoflurane, or desflurane and N2O. These investigators also reported excellent specificity and sensitivity of the PSI value with respect to both the loss and return of consciousness.
This comparative study demonstrated that both the PSA and BIS monitors were able to distinguish between awake and anesthetized states. Both monitoring devices displayed greater awake values before anesthesia and on recovery of consciousness compared with values during the maintenance period, when the patient was in an unconscious state. The PSI values were consistently lower than the BIS values at the times when supplemental propofol was administered or the desflurane concentration was changed, suggesting that at comparable depths of anesthesia, the PSI is lower than the BIS. Furthermore, the failure of the PSI to return to the preinduction baseline value with recovery of orientation suggests a potential difference between the two monitors with respect to their sensitivity to residual (subhypnotic) levels of anesthetic drugs and/or “drift” in the PSI values during the operation.
Analogous to earlier studies with the BIS monitor (18,19), these data also suggest that the PSI could be used to guide the administration of IV and inhaled anesthetics to optimize drug delivery to meet the needs of the individual patient, thereby facilitating a more rapid emergence from anesthesia. In their recent scientific abstract, Pierce et al. (14) suggested that using the PSI for guiding the administration of propofol significantly decreased the maintenance dosage requirement and improved early recovery times, without increasing unwanted events (e.g., intraoperative recall).
The ability of the PSA monitor to display PSI values during the operation of the electrocautery unit was superior to that of the BIS monitor. However, we did not use the recently Food and Drug Administration-approved BIS electrode (BIS Sensor XP), which is alleged to decrease electrical interference with the BIS readings during surgery. Compared with the BIS electrode system, application of the PSA electrode system is much more time consuming and less comfortable for the patient, making it less clinically acceptable in the current health care environment. Finally, the larger area under the ROC curve suggested that the PSI might possess a greater sensitivity and/or specificity and, possibly, better discriminatory performance than the BIS with respect to changes in the level of consciousness. However, both monitors demonstrated a good correlation during the induction of and emergence from anesthesia.
Our observational study can be criticized because only a small group of patients (n = 20) undergoing one type of surgical procedure were studied. In contrast to the extensive experience with the BIS monitor, there are only limited data for the PSI algorithm. Further studies with the PSA monitor are clearly needed in larger populations of surgical patients undergoing different types of surgical procedures (e.g., cardiothoracic, obstetrical, and trauma surgery). It would also be important to determine whether the use of the PSI for titrating volatile anesthetics during surgical procedures could facilitate the early recovery process while avoiding intraoperative recall.
In conclusion, the changes in PSI values followed a pattern similar to the BIS values during the perioperative period. Although there was less interference with the PSI readings during electrocautery use, application of the PSI electrodes was more time consuming compared with the BIS electrode system. Analogous to the BIS, the PSI appeared to possess a high degree of sensitivity and specificity in assessing consciousness during the induction of and emergence from general anesthesia. The PSI was also capable of detecting changes associated with the administration of propofol and desflurane during the maintenance period. However, further studies with the PSA monitor are needed to determine whether this monitor will become an acceptable alternative to the BIS monitor.
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