Ashraf A. Dahaba

Different Conditions That Could Result in the Bispectral Index Indicating an Incorrect Hypnotic State

Since its introduction in 1996, the Bispectral Index (BIS) has gained increasing popularity in daily anesthesia practice. However, numerous reports have been appearing in the literature of paradoxical BIS changes and inaccurate readings. The purpose of this review is to assess the utility of BIS monitoring through examining the various published reports of all BIS values not coinciding with a clinically judged sedative-hypnotic state, whether arising from an underlying pathophysiology of electroencephalographic (EEG) cerebral function or because of shortcomings in the performance and design of the BIS monitor. High electromyographic activity and electric device interference could create subtle artifact signal pollution without their necessarily being displayed as artifacts. This would be misinterpreted by the BIS algorithm as EEG activity and assigned a spuriously increased BIS value. Numerous clinical conditions that have a direct effect on EEG cerebral function could also directly influence the BIS value.

Remifentanil versus morphine analgesia and sedation for mechanically ventilated critically ill patients: A randomized double blind study

Background: The rapid onset and offset of action of remifentanil could make it quickly adjustable to the required level of sedation in critically ill patients. The authors hypothesized that the efficacy of a remifentanil-based regimen was greater than that of a morphine-based regimen. Methods: Forty intent-to-treat patients were randomly allocated to receive a blinded infusion of either remifentanil 0.15 &mgr;g·kg−1·min−1 or morphine 0.75 &mgr;g·kg−1·min−1. The opioid infusion was titrated, in the first intent, to achieve optimal sedation defined as Sedation Agitation scale of 4. A midazolam open-label infusion was started if additional sedation was required. Results: The mean percentage hours of optimal sedation was significantly longer in the remifentanil group (78.3 ± 6.2) than in the morphine group (66.5 ± 8.5). This was achieved with less frequent infusion rate adjustments (0.34 ± 0.25 changes/h) than in the morphine group (0.42 ± 0.22 changes/h). The mean duration of mechanical ventilation and extubation time were significantly longer in the morphine group (18.1 ± 3.4 h, 73 ± 7 min) than in the remifentanil group (14.1 ± 2.8 h, 17 ± 6 min), respectively. Remifentanil mean infusion rate was 0.13 ± 0.03 &mgr;g·kg−1·min−1, whereas morphine mean infusion rate was 0.68 ± 0.28 &mgr;g·kg−1·min−1. More subjects in the morphine group (9 of 20) than in the remifentanil group (6 of 20) required midazolam. The incidence of adverse events was low and comparable across the two treatment groups. Conclusions: A remifentanil-based regimen was more effective in the provision of optimal analgesia-sedation than a standard morphine-based regimen. The remifentanil-based regimen allowed a more rapid emergence from sedation and facilitated earlier extubation.

The effect of different stages of neuromuscular block on the bispectral index and the bispectral index-XP under remifentanil/propofol anesthesia.

Facial electromyographic activity and neuromuscular block could influence bispectral index (BIS) depth of anesthesia monitoring. In this study we examined, in 30 patients undergoing general surgical procedures, the effect of different stages of neuromuscular block on BIS monitoring and compared the conventional A-2000 BIS™ (BIS3.4) with the new BIS-XP™ (BISXP). At deep surgical anesthesia BIS3.4 of approximately 40, under a propofol 3.61 μg/mL target-controlled infusion and a 0.15–0.3 μg·kg−1·min−1 remifentanil infusion, mivacurium 0.15 mg/kg was administered. The onset of neuromuscular block triggered a brief transient odd divergence in response that manifested as a BIS3.4 increase from 43 ±4 to 49±7 (P = 0.007) and a BISXP decline from 41 ±3 to 35 ±3 (P = 0.003) at 1 ±0.2 min. Then, 2.5 ±1 min after mivacurium administration, both monitors returned to baseline values of 43 ±5 and 40 ± 4, respectively. After that, BIS3.4 and BISXP did not significantly change during complete neuromuscular block or during various levels of neuromuscular recovery. At all phases, BISXP was significantly lower than BIS3.4. Our study indicated that the BIS3.4/BISXP bias and the wide limits of agreement do not allow values given by the two monitors to be used interchangeably.

The Neuromuscular Transmission Module Versus the Relaxometer Mechanomyograph for Neuromuscular Block Monitoring

The neuromuscular transmission module (M-NMT) is an integrated piezoelectric motion sensor module incorporated in the AS/3™ anesthesia monitor. We compared the neuromuscular block of 0.6 mg/kg rocuronium (twice the 95% effective dose) monitored by the M-NMT with that monitored by the Relaxometer® mechanomyograph (MMG). The two monitors were alternately allocated to the left or right hands of 20 patients. T1%, the first twitch of the train-of-four (TOF), and the TOF ratio (T4/T1) were used for evaluating the neuromuscular block. There was no significant difference in the mean (min) ± sd onset time or time to 0.8 TOF ratio recovery measured by the M-NMT (1.5 ± 0.3, 49.4 ± 8.1) compared with MMG (1.8 ± 0.6, 50.9 ± 9.9), respectively. However, the time (min) to 25% T1 recovery was significantly longer when monitored by the M-NMT (25.6 ± 8) than by the MMG (20.2 ± 6.3). During recovery from neuromuscular block, the difference between the TOF ratios measured by the two monitors showed a bias of −0.031, and the limits of agreement (bias ±1.96 sd) were −0.281 and +0.22. The M-NMT monitor could determine the time to tracheal intubation as well as full recovery from neuromuscular block, but it lagged behind the MMG in determining the time to rocuronium repeat dose administration.

Bispectral-index-guided versus clinically guided remifentanil/propofol analgesia/sedation for interventional radiological procedures: an observer-blinded randomized study.

Patients undergoing potentially painful interventional radiological procedures generally require a combination of analgesia and sedation. This sedation/analgesia should allow the patient to communicate while also remaining calm. Bispectral index (BIS) monitoring could be useful in achieving this. The primary end-point of our study was to compare the percentage time with optimal sedation, defined as Sedation Agitation Scale (SAS) grade 4, between a BIS-guided remifentanil/propofol regimen and a clinically guided regimen in 54 randomly allocated patients. The mean ± sd percentage time with optimal sedation was significantly longer (P = 0.004) in the BIS group (76.6% ± 14.7%) than in the SAS group (63.8% ± 16.4%). There was a significant difference in the weighted mean infusion rates of remifentanil (P = 0.0067) and propofol (P = 0.0075) in the BIS group (0.066 ± 0.027 &mgr;g · kg−1 · min−1 1.59 ± 0.44 mg · kg−1 · h−1) compared with the SAS group (0.091 ± 0.036 &mgr;g · kg−1 · min−1 1.92 ± 0.43 mg · kg−1 · h−1), respectively. BIS values exhibited a temporal correlation to SAS scores (r2 = 0.72). In conclusion, a BIS-guided regimen was more effective than a SAS-guided regimen. The use of BIS resulted in fewer remifentanil and propofol doses. The targeted BIS range of 80–85 provided a sufficient functional level of sedation.

Sensitivity and specificity of bispectral index for classification of overt hepatic encephalopathy.A multicentre, observer-blinded, validation study

Background: The severity of hepatic encephalopathy is currently graded clinically using West Haven criteria and psychometric tests. Objective: To assess the discriminative power of the bispectral index (BIS) monitor to classify the degree and progression of hepatic encephalopathy. Design: A consecutive, multicentre, observer blinded validation study. Setting: Medical University of Graz (Graz, Austria), Zhejiang University First Affiliated Hospital (Hang Zhou, China), and Cairo University (Cairo, Egypt). Patients: 28 consecutive patients with hepatic encephalopathy were first enrolled at Medical University of Graz as a test set. The estimated BIS cut off values were subsequently tested in a validation set of 31 patients at Zhejiang University First Affiliated Hospital and 26 patients at Cairo University; 18 patients were reassessed later in a longitudinal study. Fifteen of 85 patients (18%) were excluded from the final analysis (11 became too agitated with high electromyographic activity; four fell asleep during the recording). Results: Applying the Austrian BIS cut off values of 85, 70, and 55 for discriminating West Haven grades 1 to 4 yielded agreement between BIS classification and West Haven grades in 40 of the 46 validation patients (87%), and in 16 of the 18 follow up patients (89%). Mean (SD) BIS values differed significantly between patients with West Haven grade 1 (90.2 (2.5)), grade 2 (78.4 (6.6)), grade 3 (63.2 (4.8)), and grade 4 (45.4 (5.0)). Conclusions: BIS is a useful measure for grading and monitoring the degree of involvement of the central nervous system in patients with chronic liver disease.

Geographic Regional Differences in Rocuronium Bromide Dose-Response Relation and Time Course of Action An Overlooked Factor in Determining Recommended Dosage

Background:Geographic location is not acknowledged as a stratifying factor that can directly affect drug potency, because drugs are still licensed with the same recommended dose for different geographic regions. The aim of the current study was to compare the potency and duration of action of rocuronium bromide in 54 patients in three countries with different life habits, diet, and ambient conditions, namely white Austrians, white North Americans, and Han Chinese in China. Methods:Neuromuscular block of six consecutive 50-&mgr;g/kg rocuronium incremental doses followed by 300 &mgr;g/kg was evaluated using the Relaxometer mechanomyograph (Groningen University, Groningen, Holland). Dose–response curves were created using log-dose-probit transformation. The authors compared rocuronium bromide ED50, ED90, and ED95 (effective doses required for 50%, 90%, and 95% first twitch depression, respectively) as well as Dur25 and Dur0.8 (times from last incremental dose administration until 25% first twitch and 0.8 train-of-four ratio recovery, respectively) in patients of the three countries. Results:Rocuronium ED50, ED90, and ED95 were significantly higher in Austrian patients (258 ± 68, 530 ± 159, and 598 ± 189 &mgr;g/kg) and Chinese patients (201 ± 59, 413 ± 107, and 475 ± 155 &mgr;g/kg) compared with American patients (148 ± 48, 316 ± 116, and 362 ± 149 &mgr;g/kg, respectively). Dur25 and Dur0.8 were significantly shorter in Austrian patients (22.3 ± 5.5 and 36.9 ± 12.8 min) and Chinese patients (30.4 ± 7.5 and 45.7 ± 15.9 min) compared with American patients (36.7 ± 8.5 and 56.2 ± 16.7 min, respectively). Conclusions:The authors demonstrated a significant difference in rocuronium potency and duration of action among patients in the three countries. Larger studies are required for determining dosage recommendations for different geographic regions.

Effect of sugammadex or neostigmine neuromuscular block reversal on bispectral index monitoring of propofol/remifentanil anaesthesia

BACKGROUND Sugammadex is a modified γ-cyclodextrin with a novel mechanism of action for reversing the steroidal neuromuscular blocking agent rocuronium. Bispectral index (BIS) is an EEG-derived measure which can be sensitive to frontal electromyographic (EMG) artifacts. We compared BIS values before and after sugammadex or neostigmine neuromuscular block (NMB) reversal in patients with or without high EMG activity. METHODS During stable propofol/remifentanil anaesthesia and rocuronium-induced block, 48 patients were randomly allocated to receive sugammadex 4 mg kg(-1) or neostigmine 50 μg kg(-1)/glycopyrrolate 10 μg kg(-1), 10 min after the end of surgery. RESULTS Five minutes after sugammadex administration, mean BIS 50.1 (10.3) increased (P=0.018) to 61.7 (7.9) in 11 patients with high EMG activity. In contrast, BIS 49.3 (4.9) remained at 51.9 (5.4) in 13 patients who had no EMG activity. Fifteen minutes after neostigmine administration, mean BIS 51.9 (8.1) increased (P=0.007) to 63.9 (8.1) in 13 patients who had reappearance of muscle activity. However, in 11 patients who had no EMG activity, BIS 52.3 (7.4) remained at 53.3 (6.8). There was no significant difference between the sugammadex and neostigmine groups over time. CONCLUSIONS We have shown that reversal of NMB with sugammadex or neostigmine increased BIS values dependent on the presence of EMG activity. Thus, the effect of muscle activity reappearance during rocuronium NMB reversal spuriously increasing the BIS value should be taken into consideration when relying on BIS monitoring for evaluating propofol/remifentanil recovery.

BIS-vista occipital montage in patients undergoing neurosurgical procedures during propofol-remifentanil anesthesia.

Background:Neurosurgical procedures that require a frontal approach could be an impediment for a successful Bispectral Index® (BIS®) frontal sensor placement. The aim of this study was to explore the utility of using the new BIS-Vista™ monitor (Aspect Medical Systems, Newton, MA) for occipital sensor placement in the patients undergoing brain neurosurgical procedures during propofol–remifentanil anesthesia. Methods:Two BIS® Quatro sensors (Aspect Medical Systems, Newton, MA) mounted on the occipital and frontal regions were connected to two BIS-Vista™ monitors at three anesthesia states: before induction, during anesthesia maintenance, and recovery. Results:There were significant differences before induction (P = 0.0002) and at anesthesia maintenance (P = 0.0014) between mean ± SD occipital (83.4 ± 4.8, 66.7 ± 7.2) and frontal (93.1 ± 3.4, 56.9 ± 9.1) BIS-Vista™ values. During anesthesia recovery, there was no difference (P = 0.7421) between occipital (54.6 ± 9.3) and frontal (53.1 ± 7.3) BIS-Vista™ values. Bland and Altman analysis revealed a BIS-Vista negative-bias (limits of agreement) of −9.7 (+1.1, −20.5) before anesthesia induction, +9.8 positive-bias (+22.8, −1.7) during anesthesia maintenance, and −0.9 bias (+10.9, −12.8) during anesthesia recovery. Conclusion:We demonstrated that not only the regional limits of agreement are too wide to allow data of the two montages to be used interchangeably but also the variation is a function of anesthetic depth. However, keeping in mind a relatively consistent BIS-Vista™ −10 bias before induction and +10 bias during anesthesia maintenance with limits of agreement of approximately ±11 BIS units, approximately double the clinically acceptable less than 10 BIS units level of agreement, BIS-Vista™ off-label occipital montage might be helpful in following a trend of propofol–remifentanil anesthesia in individual cases where frontal access is particularly difficult.

Effect of Flumazenil on Bispectral Index Monitoring in Unpremedicated Patients

Background:Flumazenil is an imidazobenzodiazepine that promptly reverses via competitive inhibition the hypnotic/sedative effects of benzodiazepines on γ-aminobutyric acid receptors. Endogenous benzodiazepine ligands (endozepines) were isolated in urine, cerebrospinal fluid, and breast milk of women who had not received benzodiazepines. The bispectral index (BIS), an electroencephalographically derived parameter widely used for monitoring the effects of anesthetic/hypnotic drugs, was shown to correlate to various conditions that could influence electroencephalography. The authors examined the hypothesis that 0.5 mg of flumazenil administered to healthy unpremedicated patients during deep surgical remifentanil/propofol anesthesia would increase the BIS value and might expedite recovery from anesthesia. Methods:Sixty healthy unpremedicated patients were randomly allocated to the flumazenil or control groups. After study drug administration, the authors compared BIS values and various recovery parameters in the flumazenil and control groups. Results:BIS baseline values in the flumazenil group (38.7 ± 3.8) increased 15 min after flumazenil administration (53.2 ± 4.7), with a significant difference over time (P < 0.0001) between the two groups. Mean recovery parameters time, comprising time to spontaneous breathing, eye opening/hand squeezing on verbal command, extubation, and date of birth recollection, was significantly shorter (P = 0.0002) in the flumazenil group (6.9 ± 2.6 min) compared with the control group (9.8 ± 2.9 min). Conclusions:This study demonstrates that flumazenil given to healthy unpremedicated patients during propofol/remifentanil anesthesia significantly increased the BIS value and allowed earlier emergence from anesthesia. This may indicate that flumazenil could be used on a case-by-case basis to reverse endogenous or exogenous endozepines that might play a role during anesthesia.