A Forensic Disassembly of the BIS Monitor.

BACKGROUND: The bispectral index (BIS) monitor has been available for clinical use for >20 years and has had an immense impact on academic activity in Anesthesiology, with >3000 articles referencing the bispectral index. Despite attempts to infer its algorithms by external observation, its operation has nevertheless remained undescribed, in contrast to the algorithms of other less commercially successful monitors of electroencephalogram (EEG) activity under anesthesia. With the expiration of certain key patents, the time is therefore ripe to examine the operation of the monitor on its own terms through careful dismantling, followed by extraction and examination of its internal software. METHODS: An A-2000 BIS Monitor (gunmetal blue case, amber monochrome display) was purchased on the secondary market. After identifying the major data processing and storage components, a set of free or inexpensive tools was used to retrieve and disassemble the monitor's onboard software. The software executes primarily on an ARMv7 microprocessor (Sharp/NXP LH77790B) and a digital signal processor (Texas Instruments TMS320C32). The device software can be retrieved directly from the monitor's hardware by using debugging interfaces that have remained in place from its original development. RESULTS: Critical numerical parameters such as the spectral edge frequency (SEF), total power, and BIS values were retraced from external delivery at the device's serial port back to the point of their calculation in the extracted software. In doing so, the locations of the critical algorithms were determined. To demonstrate the validity of the technique, the algorithms for SEF and total power were disassembled, comprehensively annotated and compared to their theoretically ideal behaviors. A bug was identified in the device's implementation of the SEF algorithm, which can be provoked by a perfectly isoelectric EEG. CONCLUSIONS: This article demonstrates that the electronic design of the A-2000 BIS Monitor does not pose any insuperable obstacles to retrieving its device software in hexadecimal machine code form directly from the motherboard. This software can be reverse engineered through disassembly and decompilation to reveal the methods by which the BIS monitor implements its algorithms, which ultimately must form the definitive statement of its function. Without further revealing any algorithms that might be considered trade secrets, the manufacturer of the BIS monitor should be encouraged to release the device software in its original format to place BIS-related academic literature on a firm theoretical foundation and to promote further academic development of EEG monitoring algorithms.

The cumulative duration of bispectral index less than 40 concurrent with hypotension is associated with 90-day postoperative mortality: a retrospective study.

BACKGROUND: The relationship between intraoperative low bispectral index (BIS) values and poor clinical outcomes has been controversial. Intraoperative hypotension is associated with postoperative complication. The purpose of this study was to investigate the influence of intraoperative low BIS values and hypotension on postoperative mortality in patients undergoing major abdominal surgery. METHODS: This retrospective study analyzed 1862 cases of general anesthesia. We collected the cumulative time of BIS values below 20 and 40 as well as electroencephalographic suppression and documented the incidences in which these states were maintained for at least 5 min. Durations of intraoperative mean arterial pressures (MAP) less than 50 mmHg were also recorded. Multivariable logistic regression was used to evaluate the association between suspected risk factors and postoperative mortality. RESULTS: Ninety-day mortality and 180-day mortality were 1.5 and 3.2% respectively. The cumulative time in minutes for BIS values falling below 40 coupled with MAP falling below 50 mmHg was associated with 90-day mortality (odds ratio, 1.26; 95% confidence interval, 1.04-1.53; P = .019). We found no association between BIS related values and 180-day mortality. CONCLUSIONS: The cumulative duration of BIS values less than 40 concurrent with MAP less than 50 mmHg was associated with 90-day postoperative mortality, not 180-day postoperative mortality.

Anesthetic Management Using Multiple Closed-loop Systems and Delayed Neurocognitive Recovery: A Randomized Controlled Trial.

BACKGROUND: Cognitive changes after anesthesia and surgery represent a significant public health concern. We tested the hypothesis that, in patients 60 yr or older scheduled for noncardiac surgery, automated management of anesthetic depth, cardiac blood flow, and protective lung ventilation using three independent controllers would outperform manual control of these variables. Additionally, as a result of the improved management, patients in the automated group would experience less postoperative neurocognitive impairment compared to patients having standard, manually adjusted anesthesia. METHODS: In this single-center, patient-and-evaluator-blinded, two-arm, parallel, randomized controlled, superiority study, 90 patients having noncardiac surgery under general anesthesia were randomly assigned to one of two groups. In the control group, anesthesia management was performed manually while in the closed-loop group, the titration of anesthesia, analgesia, fluids, and ventilation was performed by three independent controllers. The primary outcome was a change in a cognition score (the 30-item Montreal Cognitive Assessment) from preoperative values to those measures 1 week postsurgery. Secondary outcomes included a battery of neurocognitive tests completed at both 1 week and 3 months postsurgery as well as 30-day postsurgical outcomes. RESULTS: Forty-three controls and 44 closed-loop patients were assessed for the primary outcome. There was a difference in the cognition score compared to baseline in the control group versus the closed-loop group 1 week postsurgery (-1 [-2 to 0] vs. 0 [-1 to 1]; difference 1 [95% CI, 0 to 3], P = 0.033). Patients in the closed-loop group spent less time during surgery with a Bispectral Index less than 40, had less end-tidal hypocapnia, and had a lower fluid balance compared to the control group. CONCLUSIONS: Automated anesthetic management using the combination of three controllers outperforms manual control and may have an impact on delayed neurocognitive recovery. However, given the study design, it is not possible to determine the relative contribution of each controller on the cognition score.

Analyzing Electroencephalography (EEG) Waves Provides a Reliable Tool to Assess the Depth of Sevoflurane Anesthesia in Pediatric Patients.

BACKGROUND Studies have reported that BIS is unreliable in children because its algorithm provides misleading information about the actual depth of anesthesia. Raw EEG analysis provides direct neurophysiologic measurement of cerebral activity. The relationship between age and EEG has rarely been reported, thus the aim of the present study was to compare raw electroencephalography (EEG) among different age groups of surgical patients under general anesthesia with 1.0 MAC sevoflurane. MATERIAL AND METHODS We enrolled 135 patients aged 0-80 years old (ASA physical status I or II) undergoing surgery, who were divided into 6 groups: 1-12 months old (group 1), 1-3 years old (group 2), 3-6 years old (group 3), 6-18 years old (group 4), 18-65 years old (group 5), and 65-80 years old (group 6). Different raw EEG waves (alpha, delta, and theta) were compared for all subjects. RESULTS The BIS values in groups 1 to 6 were 52.2±12.7, 55.0±8.0, 44.5±7.3, 43.8±7.3, 44.2±6.2, and 49.1±6.2 respectively. Compared with groups 1 and 2 (52.2±12.7, 55.0±8.0), BIS values of groups 3, 4, and 5 (44.5±7.3, 43.8±7.3, 44.2±6.2, respectively) were lower (P<0.05). Theta frequency was observed in the 6 groups. The EEG frequencies in groups 1 to 6 were 6.0 (5.5-6.0), 6.0 (5.5-6.0), 6.0 (5.5-6.0), 6.0 (6.0-7.0), 6.3 (6.0-7.0), and 6.0 (5.1-6.0), respectively. Compared with group 6, EEG frequencies in groups 4 and 5 were higher (P<0.05). BIS value was significantly correlated with EEG frequency (R²=0.063, P<0.01). CONCLUSIONS Analyzing raw EEG waves provides more accurate judgement of depth of anesthesia, especially in pediatric cases in which monitors often provide misleading values.

Brain monitoring with electroencephalography and the electroencephalogram-derived bispectral index during cardiac surgery.

Cardiac surgery presents particular challenges for the anesthesiologist. In addition to standard and advanced monitors typically used during cardiac surgery, anesthesiologists may consider monitoring the brain with raw or processed electroencephalography (EEG). There is strong evidence that a protocol incorporating the processed EEG bispectral index (BIS) decreases the incidence intraoperative awareness in comparison with standard practice. However, there is conflicting evidence that incorporating the BIS into cardiac anesthesia practice improves "fast-tracking," decreases anesthetic drug use, or detects cerebral ischemia. Recent research, including many cardiac surgical patients, shows that a protocol based on BIS monitoring is not superior to a protocol based on end-tidal anesthetic concentration monitoring in preventing awareness. There has been a resurgence of interest in the anesthesia literature in limited montage EEG monitoring, including nonproprietary processed indices. This has been accompanied by research showing that with structured training, anesthesiologists can glean useful information from the raw EEG trace. In this review, we discuss both the hypothesized benefits and limitations of BIS and frontal channel EEG monitoring in the cardiac surgical population.

Association of perioperative risk factors and cumulative duration of low bispectral index with intermediate-term mortality after cardiac surgery in the B-Unaware Trial.

BACKGROUND: Current data suggest that mortality after noncardiac surgery may be associated with persistent hypotension and the cumulative duration of low processed electroencephalogram-based bispectral index (BIS). This study assessed the relationships among cumulative duration of low BIS (BIS < 45), intermediate-term mortality, and anesthetic dose after cardiac surgery. METHODS: The authors studied 460 patients (mean age, 63.0 +/- 13.1 yr; 287 men) who underwent cardiac surgery between September 2005 and October 2006 at Washington University Medical Center, St Louis, Missouri. By using multivariable Cox regression analysis, perioperative factors were evaluated for their potential association with intermediate-term all-cause mortality. RESULTS: A total of 82 patients (17.8%) died during a median follow-up of 3 yr (interquartile range, 2.7-3.3 yr). Comparing patients who died with those who survived, there was no statistically significant difference in the relationship between end-tidal anesthetic gas concentrations during the anesthetic maintenance phase and the BIS. Cumulative duration of low BIS was independently associated with intermediate-term mortality. The 1.29 adjusted hazard ratio (95% CI, 1.12-1.49) for intermediate-term mortality with cumulative duration of low BIS translated into a 29% increased risk of death for every cumulative hour spent with a BIS less than 45. The final multivariable Cox regression model showed a good discriminative ability (c-index of 0.78). CONCLUSIONS: This study found an association between cumulative duration of low BIS and mortality in the setting of cardiac surgery. Notably, this association was independent of both volatile anesthetic concentration and duration of anesthesia, suggesting that intermediate-term mortality after cardiac surgery was not causally related to excessive anesthetic dose.