Burst Suppression Ratio Research Articles

Telemetric electroencephalography recording in anesthetized mice—A novel system using minimally-invasive needle electrodes with a wireless OpenBCI™ Cyton Biosensing Board

Telemetric electroencephalography (EEG) recording, using subdermal needle electrodes, is a minimally-invasive method to investigate mammalian neurophysiology during anesthesia. These inexpensive systems may streamline experiments examining global brain phenomena during surgical anesthesia or disease. We utilized the OpenBCI™ Cyton board with subdermal needle electrodes to extract EEG features in six C57BL/6J mice undergoing isoflurane anesthesia. Burst suppression ratio (BSR) and spectral features were compared for a verification of our method. Following an increase from 1.5% to 2.0% isoflurane, the BSR increased (Wilcoxon-signed-rank statistic; p = 0.0313). Furthermore, although the absolute EEG spectral power decreased, the relative spectral power remained comparable (Wilcoxon-Mann-Whitney U-Statistic; 95% CI exclusive AUC=0.5; p < 0.05). Compared to tethered systems, this method confers several improvements for anesthesia specific protocols: 1-Avoiding electrode implant surgical procedures, 2-Anatomical non-specificity for needle electrode placement to monitor global cortical activity representative of anesthetic state, 3-Facility to repeat recordings in the same animal, 4-User-friendly for non-experts, 5-Rapid set-up time, and 6-Lower costs.•Minimally-invasive telemetric EEG recording systems ergonomically improve tethered systems for anesthesia protocols.•Using this method, we verified that higher isoflurane concentrations resulted in an increased EEG burst suppression ratio and decreased EEG absolute spectral power, with no change in frequency distribution.

Perioperative Brain Function Monitoring with Electroencephalography in Horses Anesthetized with Multimodal Balanced Anesthetic Protocol Subjected to Surgeries.

Simple SummaryThis study aimed to investigate the use of electroencephalography (EEG) and EEG-derived (processed) indices for detecting brain activity changes perioperatively in 12 anesthetized adult horses subjected to various surgery. Frontal electrodes together with Sedline/Root monitor were used on these horses from soon after anesthesia induction and continued until the horse first attempted to stand in recovery. The EEG waves were characterized by low-frequency high amplitude alpha, theta, and alpha waves during the isoflurane maintenance and surgery, which is commonly observed in profound anesthesia. The processed EEG indices including Patient State Index, Burst Suppression Ratio, and 95% Spectral Edge Frequency changed significantly between the stages (induction, surgery, and recovery) of anesthesia. Collectively, the presence of the slow EEG wave activities and the presence of burst suppression implies that these horses were profoundly unconscious during the anesthesia. We concluded that the use of EEG in conjunction with traditional cardiorespiratory monitoring provides clinically relevant information about perioperative brain state changes in the anesthetized horses.This study aimed to investigate the use of electroencephalography (EEG) for detecting brain activity changes perioperatively in anesthetized horses subjected to surgery. Twelve adult horses undergoing various surgeries were evaluated after premedication with xylazine and butorphanol, induction with ketamine, midazolam, and guaifenesin, and maintenance with isoflurane. The frontal EEG electrodes were placed after the horse was intubated and mechanically ventilated. The EEG data were collected continuously from Stage (S)1—transition from induction to isoflurane maintenance, S2—during surgery, S3—early recovery before xylazine sedation (0.2 mg kg IV), and S4—recovery after xylazine sedation. The Patient State Index (PSI), (Burst) Suppression Ratio (SR), and 95% Spectral Edge Frequency (SEF95) were compared across the stages. The PSI was lowest in S2 (20.8 ± 2.6) and increased to 30.0 ± 27.7 (p = 0.005) in S3. The SR increased from S1 (5.5 ± 10.7%) to S3 (32.7 ± 33.8%, p = 0.0001). The spectral power analysis showed that S3 had a significantly higher content of delta wave activity (0.1–4 Hz) in the EEG and lower relative power in the 3 Hz to 15 Hz range when compared to S1 and S2. A similar result was observed in S4, but the lower power was in a narrower range, from 3 Hz to 7 Hz, which indicate profound central nervous system depression potentiated by xylazine, despite the cessation of isoflurane anesthesia. We concluded that the use of EEG provides clinically relevant information about perioperative brain state changes of the isoflurane-anesthetized horse.

Always Assess the Raw Electroencephalogram: Why Automated Burst Suppression Detection May Not Detect All Episodes.

Electroencephalogram (EEG)-based monitors of anesthesia are used to assess patients' level of sedation and hypnosis as well as to detect burst suppression during surgery. One of these monitors, the Entropy module, uses an algorithm to calculate the burst suppression ratio (BSR) that reflects the percentage of suppressed EEG. Automated burst suppression detection monitors may not reliably detect this EEG pattern. Hence, we evaluated the detection accuracy of BSR and investigated the EEG features leading to errors in the identification of burst suppression. With our study, we were able to compare the performance of the BSR to the visual burst suppression detection in the raw EEG and obtain insights on the architecture of the unrecognized burst suppression phases. We showed that the BSR did not detect burst suppression in 13 of 90 (14%) patients. Furthermore, the time comparison between the visually identified burst suppression duration and elevated BSR values strongly depended on the BSR value being used as a cutoff. A possible factor for unrecognized burst suppression by the BSR may be a significantly higher suppression amplitude ( P = .002). Six of the 13 patients with undetected burst suppression by BSR showed intraoperative state entropy values >80, indicating a risk of awareness while being in burst suppression. Our results complement previous results regarding the underestimation of burst suppression by other automated detection modules and highlight the importance of not relying solely on the processed index, but to assess the native EEG during anesthesia.

Robust Control of a Biophysical Model of Burst Suppression

Abstract Burst suppression is a phenomenon in which the electroencephalogram (EEG) of a pharmacologically sedated patient alternates between higher frequency and amplitude bursting to lower frequency and amplitude suppression. The level of sedation can be quantified by the burst suppression ratio (BSR), which is defined as the amount of time that an EEG is suppressed over the amount of time measured. Maintaining a stable BSR in patients is an important clinical problem, which has led to an interest in the development of BSR-based closed-loop pharmacological control systems. Methods to address the problem typically involve pharmacokinetic (PK) modeling that describes the dynamics of drug infusion in the body as well as signal processing methods for estimating burst suppression from EEG measurements. In this regard, simulations, physiological modeling, and control design can play a key role in producing a solution. This paper seeks to add to prior work by incorporating a Schnider PK model with the Wilson–Cowan neural mass model to use as a basis for robust control design of biophysical burst suppression dynamics. We add to this framework actuator modeling, real-time burst suppression estimation, and uncertainty modeling in both the patient's physical characteristics and neurological phenomena to form a closed-loop system. Using the Ziegler–Nichols tuning method for proportional-integral-derivative (PID) control, we were able to control this system at multiple BSR set points over a simulation time of 18 h in both nominal, patient varied with noise added and with reduced performance due to BSR bounding when including patient variation and noise as well as neurological uncertainty.

Targeted Interventions to Increase Blood Pressure and Decrease Anaesthetic Concentrations Reduce Intraoperative Burst Suppression: A Randomised, Interventional Clinical Trial.

BackgroundIt has been suggested that intraoperative electroencephalographic (EEG) burst suppression (BSupp) may be associated with post-operative neurocognitive disorders in the elderly, and EEG-guided anaesthesia may help to reduce BSupp. Despite of this suggestion, a standard treatment does not exist, as we have yet to fully understand the phenomenon and its underlying pathomechanism. This study was designed to address two underlying phenomena—cerebral hypoperfusion and individual anaesthetic overdose.ObjectivesWe aimed to demonstrate that targeted anaesthetic interventions—treating intraoperative hypotension and/or reducing the anaesthetic concentration—reduce BSupp.MethodsWe randomly assigned patients to receive EEG-based interventions during anaesthesia or EEG-blinded standard anaesthesia. If BSupp was detected, defined as burst suppression ratio (BSR) > 0, the primary intervention aimed to adjust the mean arterial blood pressure to patient baseline (MAP intervention) followed by reduction of anaesthetic concentration (MAC intervention).ResultsEEG-based intervention significantly reduced total cumulative BSR, BSR duration, and maximum BSR. MAP intervention caused a significant MAP increase at the end of a BSR > 0 episode compared to the control group. Coincidentally, the maximum BSR decreased significantly; in 55% of all MAP interventions, the BSR decreased to 0% without any further action. In the remaining events, additional MAC intervention was required.ConclusionOur results show that targeted interventions (MAC/MAP) reduce total cumulative amount, duration, and maximum BSR > 0 in the elderly undergoing general anaesthesia. Haemodynamic intervention already interrupted or reduced BSupp, strengthening the current reflections that hypotension-induced cerebral hypoperfusion may be seen as potential pathomechanism of intraoperative BSupp.Clinical Trial RegistrationNCT03775356 [ClinicalTrials.gov], DRKS00015839 [German Clinical Trials Register (Deutsches Register klinischer Studien, DRKS)].

Quantifying seizure termination patterns reveals limited pathways to seizure end

ObjectiveDespite their possible importance in the design of novel neuromodulatory approaches and in understanding status epilepticus, the dynamics and mechanisms of seizure termination are not well studied. We examined intracranial recordings from patients with epilepsy to differentiate seizure termination patterns and investigated whether these patterns are indicative of different underlying mechanisms. MethodsSeizures were classified into one of two termination patterns: (a) those that end simultaneously across the brain (synchronous), and (b) those whose termination is piecemeal across the cortex (asynchronous). Both types ended with either a burst suppression pattern, or continuous seizure activity. These patterns were quantified and compared using burst suppression ratio, absolute energy, and network connectivity. ResultsSeizures with electrographic generalization showed burst suppression patterns in 90% of cases, compared with only 60% of seizures which remained focal. Interestingly, we found similar absolute energy and burst suppression ratios in seizures with synchronous and asynchronous termination, while seizures with continuous seizure activity were found to be different from seizures with burst suppression, showing lower energy during seizure and lower burst suppression ratio at the start and end of seizure. Finally, network density was observed to increase with seizure progression, with significantly lower densities in seizures with continuous seizure activity compared to seizures with burst suppression. SignificanceBased on this spatiotemporal classification scheme, we suggest that there are a limited number of seizure termination patterns and dynamics. If this bears out, it would imply that the number of mechanisms underlying seizure termination is also constrained. Seizures with different termination patterns exhibit different dynamics even before their start. This may provide useful clues about how seizures may be managed, which in turn may lead to more targeted modes of therapy for seizure control.

Sedation-Induced Burst Suppression Predicts Positive Outcome Following Traumatic Brain Injury.

While electroencephalogram (EEG) burst-suppression is often induced therapeutically using sedatives in the intensive care unit (ICU), there is hitherto no evidence with respect to its association to outcome in moderate-to-severe neurological patients. We examined the relationship between sedation-induced burst-suppression (SIBS) and outcome at hospital discharge and at 6-month follow up in patients surviving moderate-to-severe traumatic brain injury (TBI). For each of 32 patients recovering from coma after moderate-to-severe TBI, we measured the EEG burst suppression ratio (BSR) during periods of low responsiveness as assessed with the Glasgow Coma Scale (GCS). The maximum BSR was then used to predict the Glasgow Outcome Scale extended (GOSe) at discharge and at 6 months post-injury. A multi-model inference approach was used to assess the combination of predictors that best fit the outcome data. We found that BSR was positively associated with outcomes at 6 months (P = 0.022) but did not predict outcomes at discharge. A mediation analysis found no evidence that BSR mediates the effects of barbiturates or propofol on outcomes. Our results provide initial observational evidence that burst suppression may be neuroprotective in acute patients with TBI etiologies. SIBS may thus be useful in the ICU as a prognostic biomarker.

Processed intraoperative burst suppression and postoperative cognitive dysfunction in a cohort of older noncardiac surgery patients.

Postoperative cognitive dysfunction (POCD) is a decline in cognitive test performance which persists months after surgery. There has been great interest in the anesthesia community regarding whether variables generated by commercially available processed EEG monitors originally marketed to prevent awareness under anesthesia can be used to guide intraoperative anesthetic management to prevent POCD. Processed EEG monitors represent an opportunity for anesthesiologists to directly monitor the brain even if they have not been trained to interpret EEG waveforms. There is continued equipoise regarding whether any of the variables generated by the machines' interpretation of raw data are associated with POCD. Most literature has focused on the depth of anesthesia number, however recent studies have shown that processed depth may not be accurate in older age groups due to reduced alpha band power. Burst suppression is an encephalographic pattern of high voltage activity alternating with periods of electrical silence and is another marker of depth which can be obtained from commercial processed EEG monitors. We performed a prospective cohort study to determine whether burst suppression and burst suppression ratio as measured by the BIS Monitor (Bispectral Index, BIS Medtronic, Boulder CO), is associated with cognitive dysfunction 3months after surgery. We recruited 167 elective surgery patients, 65years of age and older, anticipated to require at least 2day inpatient admission. Our main outcome measure was cognitive decline in composite z-score on the Alzheimer's Disease Research Center UDS Battery of at least 1 standard deviation 3months after surgery relative to preoperative baseline. 14% experienced POCD, this group was older (72 [70, 74] versus 70 [67, 75] years), and had frailty scores as measured by the FRAIL Scale (2 [0, 3] versus 1 [0, 2]) and lower baseline z-scores (-0.2 [-0.6, 0.5] versus 0.1 [-0.3, 0.5]). There was a univariable association between suppression ratio > 10 (SR > 10) and POCD (4.8 [0, 37.3] versus 15.4 [4.0-142.4] min), p = .038. However, after adjustment this relationship did not persist, only anesthetic technique, age, and pain remained in the model. In our cohort of older elective noncardiac surgery patients we found a marginal association between processed burst suppression (total burst suppression p = .067, SR > 5 p = .052, SR > 10.038) which did not persist in a multivariable model. Patients with POCD had almost twice the number of minutes of burst suppression, and three times the amount of time for SR > 5 and > 10. Our finding may be a limitation of the monitor's ability to detect burst suppression. The consistent trend towards more intraoperative burst suppression in patients who developed POCD suggests that future studies are needed to investigate the relationship of raw intraoperative burst suppression and POCD.Trial registry Clinical trial number and registry URL: Optimizing Postoperative Cognitive Dysfunction in the Elderly-PRESERVE, Clinical Trials Gov# NCT02650687; https://clinicaltrials.gov/ct2/show/NCT02650687 .

P.019 A machine learning approach to asymmetric burst suppression and refractory status epilepticus outcome

Background: Treatment of refractory status epilepticus (RSE) is often titrated to achieve EEG burst suppression. However, optimal burst suppression characteristics are largely unknown. We used an unsupervised machine learning algorithm to predict RSE outcome based on the quantitative burst suppression ratio (QBSR). Methods: We conducted principal component analysis (PCA) as a linear combination of 22 QBSR features from non-anoxic adult RSE patients at the Winnipeg Health Sciences Centre. We also determined the most predictive components that significantly differed between survivors and non-survivors. Results: Using 135,765 QBSRs from 7 survivors and 10 non-survivors, PCA identified a predominantly non-survivor cluster of 8 patients (75% non-survivors). The first 2 PCA components comprised 75% data variance. The most important first component feature was skewness of QBSR distribution in the right or left hemisphere (0.52 each). The most important second component feature was third QBSR quantile of the left hemisphere (0.49). Only right hemispheric QBSR features significantly differed between groups: QBSR skewness for the first component (Benjamini-Hochberg adjusted p=0.038) and average QBSR for the second component (0.32, Benjamini-Hochberg adjusted p=0.046). Conclusions: Our pilot study shows that RSE patient survival may be impacted by QBSR, with differential hemispheric EEG burst suppression characteristics predicting poor RSE outcome.

Instantaneous EEG Signal Analysis Based on Empirical Mode Decomposition Applied to Burst-Suppression in Propofol Anaesthesia

The human electroencephalogram (EEG) constitutes a nonstationary, nonlinear electrophysiological signal resulting from synchronous firing of neurons in thalamocortical structures of the brain. Due to the complexity of the brain's physiological structures and its rhythmic oscillations, analysis of EEG often utilises spectral analysis methods.Aim: to improve clinical monitoring of neurophysiological signals and to further explain basic principles of functional mechanisms in the brain during anaesthesia.Material and methods. In this paper we used Empirical Mode decomposition (EMD), a novel spectral analysis method especially suited for nonstationary and nonlinear signals. EMD and the related Hilbert-Huang Transform (HHT) decompose signal into constituent Intrinsic Mode Functions (IMFs). In this study we applied EMD to analyse burst-suppression (BS) in the human EEG during induction of general anaesthesia (GA) with propofol. BS is a state characterised by cyclic changes between significant depression of brain activity and hyper-active bursts with variable duration, amplitude, and waveform shape. BS arises after induction into deep general anaesthesia after an intravenous bolus of general anaesthetics. Here we studied the behaviour of BS using the burst-suppression ratio (BSR).Results. Comparing correlations between EEG and IMF BSRs, we determined BSR was driven mainly by alpha activity. BSRs for different spectral components (IMFs 1-4) showed differing rates of return to baseline after the end of BS in EEG, indicating BS might differentially impair neural generators of low-frequency EEG oscillations and thalamocortical functional connectivity.Conclusion. Studying BS using EMD represents a novel form of analysis with the potential to elucidate neurophysiological mechanisms of this state and its impact on post-operative patient prognosis.

Association Between Burst-Suppression Latency and Burst-Suppression Ratio Under Isoflurane or Adjuvant Drugs With Isoflurane Anesthesia in Mice.

The same doses of anesthesia may yield varying depths of anesthesia in different patients. Clinical studies have revealed a possible causal relationship between deep anesthesia and negative short- and long-term patient outcomes. However, a reliable index and method of the clinical monitoring of deep anesthesia and detecting latency remain lacking. As burst-suppression is a characteristic phenomenon of deep anesthesia, the present study investigated the relationship between burst-suppression latency (BSL) and the subsequent burst-suppression ratio (BSR) to find an improved detection for the onset of intraoperative deep anesthesia. The mice were divided young, adult and old group treated with 1.0% or 1.5% isoflurane anesthesia alone for 2 h. In addition, the adult mice were pretreated with intraperitoneal injection of ketamine, dexmedetomidine, midazolam or propofol before they were anesthetized by 1.0% isoflurane for 2 h. Continuous frontal, parietal and occipital electroencephalogram (EEG) were acquired during anesthesia. The time from the onset of anesthesia to the first occurrence of burst-suppression was defined as BSL, while BSR was calculated as percentage of burst-suppression time that was spent in suppression periods. Under 1.0% isoflurane anesthesia, we found a negative correlation between BSL and BSR for EEG recordings obtained from the parietal lobes of young mice, from the parietal and occipital lobes of adult mice, and the occipital lobes of old mice. Under 1.5% isoflurane anesthesia, only the BSL calculated from EEG data obtained from the occipital lobe was negatively correlated with BSR in all mice. Furthermore, in adult mice receiving 1.0% isoflurane anesthesia, the co-administration of ketamine and midazolam, but not dexmedetomidine and propofol, significantly decreased BSL and increased BSR. Together, these data suggest that BSL can detect burst-suppression and predict the subsequent BSR under isoflurane anesthesia used alone or in combination with anesthetics or adjuvant drugs. Furthermore, the consistent negative correlation between BSL and BSR calculated from occipital EEG recordings recommends it as the optimal position for monitoring burst-suppression.

Effect of electroencephalography-guided anesthesia on neurocognitive disorders in elderly patients undergoing major non-cardiac surgery: A trial protocol The POEGEA trial (POncd Elderly GEneral Anesthesia)

IntroductionThe number of elderly patients undergoing major surgery is rapidly increasing. They are particularly at risk of developing postoperative neurocognitive disorders (NCD). Earlier studies suggested that processed electroencephalographic (EEG) monitors may reduce the incidence of postoperative NCD. However, none of these studies controlled for intraoperative nociception levels or personalized blood pressure targets. Their results remain unclear if the reduction in the incidence of postoperative NCD relates to avoidance of any electroencephalographic pattern suggesting excessive anesthesia depth.ObjectiveThe objective of this trial is to investigate–in patients ≥ 70 years old undergoing major non-cardiac surgery–the effect of EEG-guided anesthesia on postoperative NCD while controlling for intraoperative nociception, personalized blood pressure targets, and using detailed information provided by the EEG monitor (including burst suppression ratio, density spectral array, and raw EEG waveform).Material and methodsThis prospective, randomized, controlled trial will be conducted in a single Canadian university hospital. Patients ≥ 70 years old undergoing elective major non-cardiac surgery will be included in the trial. The administration of sevoflurane will be adjusted to maintain a BIS index value between 40 and 60, to keep a Suppression Ratio (SR) at 0%, to keep a direct EEG display without any suppression time and a spectrogram with most of the EEG wave frequency within the alpha, theta, and delta frequencies in the EEG-guided group. In the control group, sevoflurane will be administered to achieve an age-adjusted minimum alveolar concentration of [0.8–1.2]. In both groups, a nociception monitor will guide intraoperative opioid administration, individual blood pressure targets will be used, and cerebral oximetry used to tailor intraoperative hemodynamic management. The primary endpoint will be the incidence of NCD at postoperative day 1, as evaluated by the Montreal Cognitive Assessment (MoCA). Secondary endpoints will include the incidence of postoperative NCD at different time points and the evaluation of cognitive trajectories up to 90 days after surgery among EEG-guided and control groups.Study registrationNCT04825847 on ClinicalTrials.gov.

Impact of Propofol Bolus Administration on the Nociceptive Flexion Reflex Threshold and Bispectral Index in Children—A Case Series

We analyzed the impact of propofol administration during continuous sedation and analgesia on the nociceptive flexion reflex threshold (NFRT) and Bispectral Index (BIS) in ventilated children. We examined patients who received propofol before planned endotracheal suctioning. Patients were clinically assessed using the modified Face, Legs, Activity, Cry, Consolability (mFLACC) scale and COMFORT-B (Comfort Behavior) scale. We continuously recorded the NFRT and BIS. We recorded 23 propofol administrations in eight patients with an average age of 8.6 ± 3.5 years. The median (minimum-maximum) scores for the mFLACC scale and COMFORT-B scale were 0 (0–5) and 6 (6–17), respectively, before the bolus. The administration of a weight-adjusted propofol bolus of 1.03 ± 0.31 mg/kg resulted in an increase in NFRT and burst-suppression ratio; BIS and electromyogram values decreased. Changes from baseline (95% CI) after propofol bolus administration were BIS −23.9 (−30.8 to −17.1), EMG -10.5 dB (−13.3 to −7.7), SR 14.8 % (5.6 to 24.0) and NFRT 13.6 mA (5.5 to 21.7). Further studies are needed to determine whether sedated children may benefit from objective pain and sedation monitoring with BIS and NFRT.

Oral Abstracts Electroencephalogram (EEG) O-EG001. Stratified outcome analyses of the quantitative burst suppression ratio in refractory status epilepticus

Introduction . In refractory status epilepticus (RSE), seizures are generally managed by anaesthetic sedation. Although sedation depth correlates with EEG suppression level, the optimal degree of suppression is unknown. We sought to assess the relationship between the ‘quantitative burst suppression ratio’ (QBSR) as a marker of EEG suppression, and RSE patient outcomes. Methods . We used Persyst software to calculate QBSR/10-second EEG epoch from non- anoxic adult RSE intensive care unit (ICU) patients over 15 months. QBSR was the percentage of each epoch with EEG amplitude under 3 microvolts/millimetre. Between unfavourable and favourable (defined as surviving to discharge from ICU) groups, we compared median QBSR per-patient (multivariate regression), per-daily EEG recording session (generalized estimating equation), and per-EEG epoch (quasi-least squared model) using Stata 14 or MATLAB software to control for aSTESS (adjusted status epilepticus severity score), sedative number, and gender. Results . 135,765 QBSRs were calculated from 158 EEGs derived from 17 patients. There were 7 favourable group patients who all survived 3 months post-discharge from ICU. Stratifying analyses per-patient, per-session, and per-epoch, high aSTESS is consistently associated with unfavourable outcome (per-patient OR 0.59–0.97, p = 0.033; per-session OR 0.06–0.94, p = 0.041; per-epoch OR 0.67–0.71, p < 0.001). On per-epoch analysis, greater sedative use is associated with favourable outcome (OR 1.45–1.54, p < 0.001) while gender does not associate with outcome (OR 1–1, p < 0.001). On all analyses, there was no significant association between QBSR and outcome. Conclusion . Our findings validate the prognostic value of aSTESS, but do not support an association between RSE outcomes and EEG suppression depth measured by QBSR. However, an association between more sedative use and better outcome on per-epoch analysis may suggest that more aggressive treatment targeted against foreground transients such as seizures may be more beneficial in RSE than quantitative background suppression.

Processed electroencephalography: impact of patient age and surgical position on intraoperative processed electroencephalogram monitoring of burst-suppression.

We previously reported that processed EEG underestimated the amount of burst suppression compared to off-line visual analysis. We performed a follow-up study to evaluate the reasons for the discordance. Forty-five patients were monitored intraoperatively with processed EEG. A computer algorithm was used to convert the SedLine® (machine)-generated burst suppression ratio into a raw duration of burst suppression. The reference standard was a precise off-line measurement by two neurologists. We measured other potential variables that may affect machine accuracy such as age, surgery position, and EEG artifacts. Overall, the median duration of bust suppression for all study subjects was 15.4min (Inter-quartile Range [IQR] = 1.0-20.1) for the machine vs. 16.1min (IQR = 0.3-19.7) for the neurologists' assessment; the 95% limits of agreement fall within -4.86 to 5.04s for individual 30-s epochs. EEG artifacts did not affect the concordance between the two methods. For patients in prone surgical position, the machine estimates had significantly lower overall sensitivity (0.86 vs. 0.97; p = 0.038) and significantly wider limits of agreement ([-4.24, 3.82] seconds vs. [-1.36, 1.13] seconds, p = 0.001) than patients in supine position. Machine readings for younger patients (age < 65years) had higher sensitivity (0.96 vs 0.92; p = 0.021) and specificity (0.99 vs 0.88; p = 0.007) for older patients. The duration of burst suppression estimated by the machine generally had good agreement compared with neurologists' estimation using a more precise off-line measurement. Factors that affected the concordance included patient age and position during surgery, but not EEG artifacts.

Inactivation of Prefrontal Cortex Delays Emergence From Sevoflurane Anesthesia.

Studies aimed at investigating brain regions involved in arousal state control have been traditionally limited to subcortical structures. In the current study, we tested the hypothesis that inactivation of prefrontal cortex, but not two subregions within parietal cortex—somatosensory barrel field and medial/lateral parietal association cortex—would suppress arousal, as measured by an increase in anesthetic sensitivity. Male and female Sprague Dawley rats were surgically prepared for recording electroencephalogram and bilateral infusion into prefrontal cortex (N = 13), somatosensory barrel field (N = 10), or medial/lateral parietal association cortex (N = 9). After at least 10 days of post-surgical recovery, 156 μM tetrodotoxin or saline was microinjected into one of the cortical sites. Ninety minutes after injection, rats were anesthetized with 2.5% sevoflurane and the time to loss of righting reflex, a surrogate for loss of consciousness, was measured. Sevoflurane was stopped after 45 min and the time to return of righting reflex, a surrogate for return of consciousness, was measured. Tetrodotoxin-mediated inactivation of all three cortical sites decreased (p < 0.05) the time to loss of righting reflex. By contrast, only inactivation of prefrontal cortex, but not somatosensory barrel field or medial/lateral parietal association cortex, increased (p < 0.001) the time to return of righting reflex. Burst suppression ratio was not altered following inactivation of any of the cortical sites, suggesting that there was no global effect due to pharmacologic lesion. These findings demonstrate that prefrontal cortex plays a causal role in emergence from anesthesia and behavioral arousal.

Revealing the Cortical Glutamatergic Neural Activity During Burst Suppression by Simultaneous wide Field Calcium Imaging and Electroencephalography in Mice

Burst suppression (BS) is an electroencephalogram (EEG) pattern in which signals alternates between high-amplitude slow waves (burst waves) and nearly flat low-amplitude waves (suppression waves). In this study, we used wide-field (8.32 mm × 8.32 mm) fluorescent calcium imaging to record the activity of glutamatergic neurons in the parietal and occipital cortex, in conjunction with EEG recordings under BS induced by different anesthetics (sevoflurane, isoflurane, and propofol), to investigate the spatiotemporal pattern of neural activity under BS. The calcium signal of all observed cortices was decreased during the phase of EEG suppression. However, during the phase of EEG burst, the calcium signal in areas of the medial cortex, such as the secondary motor and retrosplenial area, was excited, whereas the signal in areas of the lateral cortex, such as the hindlimb cortex, forelimb cortex, barrel field, and primary visual area, was still suppressed or only weakly excited. Correlation analysis showed a strong correlation between the EEG signal and the calcium signal in the medial cortex under BS (except for propofol induced signals). As the burst-suppression ratio (BSR) increased, the regions with strong correlation coefficients became smaller, but strong correlation coefficients were still noted in the medial cortex. Taken together, our results reveal the landscape of cortical activity underlying BS.

Dorsal raphe serotonergic neurons promote arousal from isoflurane anesthesia.

AimsGeneral anesthesia has been widely applied in surgical or nonsurgical medical procedures, but the mechanism behind remains elusive. Because of shared neural circuits of sleep and anesthesia, whether serotonergic system, which is highly implicated in modulation of sleep and wakefulness, regulates general anesthesia as well is worth investigating.MethodsImmunostaining and fiber photometry were used to assess the neuronal activities. Electroencephalography spectra and burst‐suppression ratio (BSR) were used to measure anesthetic depth and loss or recovery of righting reflex to indicate the induction or emergence time of general anesthesia. Regulation of serotonergic system was achieved through optogenetic, chemogenetic, or pharmacological methods.ResultsWe found that both Fos expression and calcium activity were significantly decreased during general anesthesia. Activation of 5‐HT neurons in the dorsal raphe nucleus (DRN) decreased the depth of anesthesia and facilitated the emergence from anesthesia, and inhibition deepened the anesthesia and prolonged the emergence time. Furthermore, agonism or antagonism of 5‐HT 1A or 2C receptors mimicked the effect of manipulating DRN serotonergic neurons.ConclusionOur results demonstrate that 5‐HT neurons in the DRN play a regulative role of general anesthesia, and activation of serotonergic neurons could facilitate emergence from general anesthesia partly through 5‐HT 1A and 2C receptors.

Inadvertent Burst Suppression During Total Intravenous Anesthesia in 112 Consecutive Patients Undergoing Spinal Instrumentation Surgery: A Retrospective Observational Quality Improvement Project.

The incidence and quantification of inadvertent electroencephalographic burst suppression during total intravenous anesthesia (TIVA) for spine instrumentation surgery has not previously been reported. The primary aim of this retrospective observational quality improvement project was to establish the prevalence of burst suppression during spine instrumentation surgery with TIVA. The secondary outcome was the incidence of postoperative delirium. One hundred twelve consecutive patients, aged between 20 and 88 years, underwent spinal instrumentation surgery. Seventy-eight (69.6%) patients experienced inadvertent burst suppression; the maximal degree of burst suppression ratio was 20% to 100%. Median (interquartile range [IQR]) time spent in burst suppression was 44 (77) minutes, and burst suppression was present for 22% (range: 2% to 93%) of the monitoring period. Average (±SD) propofol dose was lower in patients with burst suppression (87±19 vs. 93±15 µg/kg/min, P=0.04). Ten (8.9%) patients experienced postoperative delirium. Intraoperative burst suppression was more prevalent in those that experienced delirium (100% vs. 66.7%, P=0.03, relative risk: 1.5, 95% confidence interval: 1.3-1.7). The proportion of the monitoring period spent in maximal burst suppression (15.3 [25.9]% vs.11.7 [21.7]%) was similar between those that did, and did not, experience delirium. High rates and prolonged periods of inadvertent burst suppression may be prevalent during spine instrumentation surgery with TIVA. Our findings suggest that usage of electroencephalography alone is incomplete without prompt interpretation and intervention, mandating close communication between neuromonitoring and anesthesia teams. The dose-response relationship between burst suppression, total time spent in maximal burst suppression, and their association with delirium warrants further evaluation.

Overnight Caloric Restriction Prior to Cardiac Arrest and Resuscitation Leads to Improved Survival and Neurological Outcome in a Rodent Model.

While interest toward caloric restriction (CR) in various models of brain injury has increased in recent decades, studies have predominantly focused on the benefits of chronic or intermittent CR. The effects of ultra-short, including overnight, CR on acute ischemic brain injury are not well studied. Here, we show that overnight caloric restriction (75% over 14 h) prior to asphyxial cardiac arrest and resuscitation (CA) improves survival and neurological recovery as measured by, behavioral testing on neurological deficit scores, faster recovery of quantitative electroencephalography (EEG) burst suppression ratio, and complete prevention of neurodegeneration in multiple regions of the brain. We also show that overnight CR normalizes stress-induced hyperglycemia, while significantly decreasing insulin and glucagon production and increasing corticosterone and ketone body production. The benefits seen with ultra-short CR appear independent of Sirtuin 1 (SIRT-1) and brain-derived neurotrophic factor (BDNF) expression, which have been strongly linked to neuroprotective benefits seen in chronic CR. Mechanisms underlying neuroprotective effects remain to be defined, and may reveal targets for providing protection pre-CA or therapeutic interventions post-CA. These findings are also of high importance to basic sciences research as we demonstrate that minor, often-overlooked alterations to pre-experimental dietary procedures can significantly affect results, and by extension, research homogeneity and reproducibility, especially in acute ischemic brain injury models.