Depth of Anesthesia and Nociception Monitoring: Current State and Vision For 2050.
Anesthesia and analgesia
Anesthesia objectives have evolved into combining hypnosis, amnesia, analgesia, paralysis, and suppression of the sympathetic autonomic nervous system. Technological improvements have led to new monitoring strategies, aimed at translating a qualitative physiological state into quantitative metrics, but the optimal strategies for depth of anesthesia (DoA) and analgesia monitoring continue to stimulate debate. Historically, DoA monitoring used patient's movement as a surrogate of awareness. Pharmacokinetic models and metrics, including minimum alveolar concentration for inhaled anesthetics and target-controlled infusion models for intravenous anesthesia, provided further insights to clinicians, but electroencephalography and its derivatives (processed EEG; pEEG) offer the potential for personalization of anesthesia care. Current studies appear to affirm that pEEG monitoring decreases the quantity of anesthetics administered, diminishes postanesthesia care unit duration, and may reduce the occurrence of postoperative delirium (notwithstanding the difficulties of defining this condition). Major trials are underway to further elucidate the impact on postoperative cognitive dysfunction. In this manuscript, we discuss the Bispectral (BIS) index, Narcotrend monitor, Patient State Index, entropy-based monitoring, and Neurosense monitor, as well as middle latency evoked auditory potential, before exploring how these technologies could evolve in the upcoming years. In contrast to developments in pEEG monitors, nociception monitors remain by comparison underdeveloped and underutilized. Just as with anesthetic agents, excessive analgesia can lead to harmful side effects, whereas inadequate analgesia is associated with increased stress response, poorer hemodynamic conditions and coagulation, metabolic, and immune system dysregulation. Broadly, 3 distinct monitoring strategies have emerged: motor reflex, central nervous system, and autonomic nervous system monitoring. Generally, nociceptive monitors outperform basic clinical vital sign monitoring in reducing perioperative opioid use. This manuscript describes pupillometry, surgical pleth index, analgesia nociception index, and nociception level index, and suggest how future developments could impact their use. The final section of this review explores the profound implications of future monitoring technologies on anesthesiology practice and envisages 3 transformative scenarios: helping in creation of an optimal analgesic drug, the advent of bidirectional neuron-microelectronic interfaces, and the synergistic combination of hypnosis and virtual reality.
10.1213/ANE.0000000000006860
Effect of Continuous Infusion of Different Doses of Esketamine on the Bispectral Index During Sevoflurane Anesthesia: A Randomized Controlled Trial.
Drug design, development and therapy
Purpose:To investigate and quantify the effect of continuous esketamine infusion at different doses on the bispectral index (BIS) during sevoflurane anesthesia. Methods:A total of 120 patients scheduled for elective laparoscopic renal surgery were randomly divided into three groups. Under steady anesthesia and surgical situations, the patient was started on continuous infusion of the study drug: 0.125 mg/kg/h esketamine (group E1), 0.25 mg/kg/h esketamine (group E2), and the same volume of saline (group C). The primary outcome was changes in BIS value after 15 min (T), 30 min (T), 45 min (T), and 60 min (T) of drug infusion. The secondary outcomes were 95% spectral edge frequency (SEF95), electromyogram (EMG), heart rate (HR), and mean arterial pressure (MAP) from T to T. Furthermore, postoperative pain, postoperative recovery, and perioperative adverse events were evaluated. Results:Compared with group C, group E1 exhibited significant BIS elevation at T-T and group E2 at T-T ( < 0.001). Compared with group E1, group E2 showed a more significant BIS elevation at T-T ( < 0.001). The area under the curve (AUC) of BIS and SEF95 were significantly higher in group E2 than in groups C and E1 ( < 0.05). BIS value for any of the three groups was significantly correlated with SEF95 ( < 0.001). No significant differences were observed in the AUC of EMG, HR, and MAP among the three groups. Intraoperative remifentanil consumption and postoperative NRS of pain on movement were significantly reduced in group E2 compared with groups C and E1 ( < 0.05). Conclusion:Continuous infusion of both 0.125 and 0.25 mg/kg/h of esketamine increased the BIS value during sevoflurane anesthesia, and the BIS value gradually stabilized with the prolongation of the infusion time.
10.2147/DDDT.S457625
[Low doses of ketamine have no effect on bispectral index during stable propofol-remifentanil anesthesia].
Nonaka Akihiko,Makino Kenzo,Suzuki Satomi,Ikemoto Kodai,Furuya Atsushi,Tamaki Fumiaki,Asano Nobumasa
Masui. The Japanese journal of anesthesiology
BACKGROUND:Ketamine is associated with an increase in the bispectral index (BIS) values that can lead to an overdose of hypnotic agents. We investigated the effect of ketamine on BIS values during general anesthesia with a target-controlled infusion (TCI) of propofol and infusion of remifentanil. METHODS:Forty-five ASA I or II patients undergoing gynecological surgery were included in this study. After 5 min of steady-state anesthesia (BIS at 35-45) without surgical stimulation, patients received either a bolus administration of ketamine 0.2 mg x kg(-1) (LK group) or ketamine 0.5 mg x kg(-1) (HK group). Patients in the control group received no intervention. BIS values were recorded every minute until 15 min after ketamine administration. RESULTS:After ketamine administration, BIS value in HK group increased significantly compared with that at baseline. There were no significant changes for BIS values in LK group and control group over time. BIS values in HK group were significantly higher than those in the LK group and control group after ketamine injection. BIS values were not statistically different between LK group and control group. CONCLUSIONS:Under stable propofol and remifentanil anesthesia, a small dose of ketamine did not increase the BIS value over the next 15 min.
Effect of ketamine on bispectral index during propofol--fentanyl anesthesia: a randomized controlled study.
Sengupta Saikat,Ghosh Simantika,Rudra Amitava,Kumar Palash,Maitra Gaurab,Das Tanmoy
Middle East journal of anaesthesiology
BACKGROUND:The Bispectral Index (BIS) helps in the assessment of the depth of hypnosis. N-methyl-D-aspartic acid antagonist, ketamine, has been used in various doses to decrease postoperative morphine consumption. The purpose of our study was to compare the effects of two different doses (0.5 mg/kg and 0.2 mg/kg) of ketamine on BIS values. METHODS:Forty-five ASA I or II patients undergoing general anesthesia were included in this double-blind, prospective, control trial and randomly allocated into three groups. After induction of anesthesia and tracheal intubation, a propofol infusion was started and titrated to attain BIS values of around 40. After five minutes of stable BIS values and in the absence of any surgical stimulus, patients received either 0.5 mg/kg of ketamine (Group K1) or 0.2 mg/kg of ketamine (Group K2) or normal saline (Group N) as bolus intravenously. BIS values were recorded for the next 15 minutes, at five-minutes interval. RESULTS:Mean BIS values were significantly increased in Group K1 (63.5) while Group K2 (42.0) failed to show any significant rise. BIS values in Group K2 were comparable to those in Group N. CONCLUSION:Thus, under stable propofol anesthesia, a bolus ofketamine 0.5 mg/kg increases BIS values while ketamine 0.2 mg/kg does not.
Bispectral Index Changes Following Boluses of Commonly Used Intravenous Medications During Volatile Anesthesia Identified From Retrospective Data.
Anesthesia and analgesia
BACKGROUND:Although patients are commonly monitored for depth of anesthesia, it is unclear to what extent administration of intravenous anesthetic medications may affect calculated bispectral (BIS) index values under general anesthesia. METHODS:In a retrospective analysis of electronic anesthesia records from an academic medical center, we examined BIS index changes associated with 14 different intravenous medications, as administered in routine practice, during volatile-based anesthesia using a novel screening approach. Discrete-time windows were identified in which only a single drug bolus was administered, and subsequent changes in the BIS index, concentration of volatile anesthetic, and arterial pressure were analyzed. Our primary outcome was change in BIS index, following drug administration. Adjusted 95% confidence intervals were compared to predetermined thresholds for clinical significance. Secondary sensitivity analyses examined the same outcomes, with available data separated according to differences in baseline volatile anesthetic concentrations, doses of the administered medications, and length of time window. RESULTS:The study cohort was comprised of data from 20,170 distinct cases, 54.7% of patients were men, with a median age of 55. In the primary analysis, ketamine at a median dose of 20 mg was associated with a median (confidence limits) increase in BIS index of 3.8 (2.5-5.0). Midazolam (median dose 2 mg) was associated with a median decrease in BIS index of 3.0 (1.5-4.5). Neither of these drug administrations occurred during time periods associated with changes in volatile anesthetic concentration. Analysis for dexmedetomidine was confounded by concomitant decreases in volatile anesthetic concentration. No other medication analyzed, including propofol and common opioids, was associated with a significant change in BIS index. Secondary analyses revealed that similar BIS index changes occurred when midazolam and ketamine were administered at different volatile anesthetic concentrations and different doses, and these changes persisted 11 to 20 minutes postadministration. CONCLUSIONS:Modest, but persistent changes in BIS index occurred following doses of ketamine (increase) and midazolam (decrease) during periods of stable volatile anesthetic administration.
10.1213/ANE.0000000000006633
Effect of Ketamine on the Bispectral Index, Spectral Edge Frequency, and Surgical Pleth Index During Propofol-Remifentanil Anesthesia: An Observational Prospective Trial.
Anesthesia and analgesia
BACKGROUND:Ketamine administration during stable propofol anesthesia is known to be associated with an increase in bispectral index (BIS) but a "deepening" in the level of hypnosis. This study aimed to evaluate the association between the effect-site concentration of ketamine (CeK) and 2 electroencephalogram (EEG)-derived parameters, the BIS and spectral edge frequency (SEF95), after the administration of a ketamine bolus. Secondary aims included investigating the BIS and SEF95 variations with time and changes in the surgical pleth index (SPI). METHODS:We conducted an observational, prospective, single-center study analyzing intraoperative data from 14 adult female patients undergoing breast oncologic surgery. During stable propofol-remifentanil target-controlled infusion (TCI) anesthesia, a ketamine analgesic bolus was delivered with the target CeK set to 1 μg.mL-1 (Domino model) corresponding to a dose of 0.57 mg.kg-1 (interquartile range [IQR] 0.56-0.57 mg.kg-1). Once the CeK reached a value of 1 μg.mL-1, the target CeK was set to 0 μg.mL-1. We determined the median BIS, SEF95, and SPI trends with time and as a function of the modeled CeK. RESULTS:BIS and SEF95 showed no significant change from when ketamine was administered to when CeK=1 μg.mL-1, but a significant increase was observed at lower CeKs. The maximum BIS was reached at 16.0 minutes [10.2-22.7 minutes] after CeK=1 μg.mL-1, at CeK=0.22 μg.mL-1 [0.12-0.41 μg.mL-1]. The peak SEF95 value was observed at 10.0 minutes [8.62-14.1 minutes] after CeK=1 μg.mL-1, at CeK=0.43 μg.mL-1 [0.25-0.50 μg.mL-1]. No significant association was found between CeK and the registered SPI values. CONCLUSIONS:Our results show that BIS and SEF95, but not SPI, follow a CeK-dependent trend after administering a ketamine bolus. Interestingly, their peak values were not reached at CeK=1 μg.mL-1, but after several minutes after the drug infusion at CeKs in the 0.2 to 0.5 μg.mL-1 range. This may be explained by the specific pharmacodynamics of ketamine and its varying effects at different concentrations, as well as by the time delay associated with the calculation of the BIS.
10.1213/ANE.0000000000007255
The relationship of bispectral index values to conscious state: an analysis of two volunteer cohort studies.
British journal of anaesthesia
BACKGROUND:The ability of current depth-of-anaesthesia monitors to differentiate subtle changes in the conscious state has not been well characterised. We examine the variability in bispectral index (BIS) scores associated with disconnected conscious and unconscious states as confirmed by a novel serial awakening paradigm. METHODS:Seventy adult participants, given propofol or dexmedetomidine, had a cumulative 1381 electroencephalographic (EEG) recordings across two centres. Participants were awakened periodically, and their recent conscious experience interrogated by structured questioning. BIS were reconstructed from EEG using openibis, and the distribution of BIS scores were compared using linear mixed effects modelling. The predictive capacity of BIS across states of consciousness was also examined. RESULTS:Reconstructed BIS scores correlated significantly with blood concentrations of propofol and dexmedetomidine (all P<0.001). However, while the average BIS was different between baseline wakefulness (mean BIS=95.1 [standard deviation=3.5]); connected consciousness with drug present (84.0 [10.9]); disconnected consciousness (70.0 [16.9]); and unconsciousness (68.1 [16.1]), the interquartile range of these states (3.6, 15.1, 23.3 and 26.8, respectively) indicated high degrees of overlap and individual variability. Connected consciousness could be differentiated from either disconnected consciousness or unconsciousness with 86% accuracy (i.e. 14% error rate), and disconnected consciousness differentiated from unconsciousness with 74% accuracy. CONCLUSIONS:These results agree with previous studies that BIS scores fail to reliably differentiate between states of consciousness, exacerbated by segregating connected, disconnected, and unconscious states. To develop a method that reliably identifies the conscious state of an individual (not an average), work is needed to establish the causal mechanisms of disconnection and unconsciousness.
10.1016/j.bja.2024.09.032