Consciousness and General Anesthesia: Challenges for Measuring the Depth of Anesthesia.

The optimal consciousness level required for general anesthesia with surgery is unclear, but in existing practice, anesthetic oblivion, may be incomplete. This article discusses the concept of consciousness, how it is altered by anesthetics, the challenges for assessing consciousness, currently used technologies for assessing anesthesia levels, and future research directions. Wakefulness is marked by a subjective experience of existence (consciousness), perception of input from the body or the environment (connectedness), the ability for volitional responsiveness, and a sense of continuity in time. Anesthetic drugs may selectively impair some of these components without complete extinction of the subjective experience of existence. In agreement with Sanders et al. (2012), the authors propose that a state of disconnected consciousness is the optimal level of anesthesia, as it likely avoids both awareness and the possible dangers of oversedation. However, at present, there are no reliably tested indices that can discriminate between connected consciousness, disconnected consciousness, and complete unconsciousness.

Support-vector classification of low-dose nitrous oxide administration with multi-channel EEG power spectra.

Support-vector machines (SVMs) can potentially improve patient monitoring during nitrous oxide anaesthesia. By elucidating the effects of low-dose nitrous oxide on the power spectra of multi-channel EEG recordings, we quantified the degree to which these effects generalise across participants. In this single-blind, cross-over study, 32-channel EEG was recorded from 12 healthy participants exposed to 0, 20, 30 and 40% end-tidal nitrous oxide. Features of the delta-, theta-, alpha- and beta-band power were used within a 12-fold, participant-wise cross-validation framework to train and test two SVMs: (1) binary SVM classifying EEG during 0 or 40% exposure (chance = 50%); (2) multi-class SVM classifying EEG during 0, 20, 30 or 40% exposure (chance = 25%). Both the binary (accuracy 92%) and the multi-class (accuracy 52%) SVMs classified EEG recordings at rates significantly better than chance (p < 0.001 and p = 0.01, respectively). To determine the relative importance of frequency band features for classification accuracy, we systematically removed features before re-training and re-testing the SVMs. This showed the relative importance of decreased delta power and the frontal region. SVM classification identified that the most important effects of nitrous oxide were found in the delta band in the frontal electrodes that was consistent between participants. Furthermore, support-vector classification of nitrous oxide dosage is a promising method that might be used to improve patient monitoring during nitrous oxide anaesthesia.

Preliminary pharmacokinetics and patient experience of jet-injected dexmedetomidine in healthy adults.

Jet injection is a drug delivery system without a needle. A compressed liquid drug formulation pierces the skin, depositing the drug into the subcutaneous or intramuscular tissues. We investigated the pharmacokinetics and patient experience of dexmedetomidine administered using jet injection in six healthy adult study participants. This needleless jet injection device was used to administer dexmedetomidine 0.5 µg/kg to the subcutaneous tissues overlying the deltoid muscle. Serum concentrations of dexmedetomidine were assayed at approximately 5 minutes, 15 minutes, 30 minutes, 1 hour and 4 hours after administration. Pharmacokinetic interrogation of concentration time profiles estimated an absorption half time for jet-injected dexmedetomidine of 21 minutes (coefficient of variation 69.4%) with a relative bioavailability assumed unity. In our samples the measured median peak (range) concentration was 0.164 µg/l (0.011-0.325 µg/l), observed in the sample taken at a median (range) of 13.5 minutes (11-30 minutes). The Richmond agitation sedation scale was used to assess the sedative effect, and scored 0 (alert and calm) or -1 (drowsy) in all participants. Five of the six participants stated they would prefer jet injection to needle injection in the future and one had no preference. The findings suggest that the use of a larger dose (>2 µg/kg) would be required to achieve the clinically relevant target concentration of 1 µg/l necessary to achieve deeper sedation (Richmond agitation sedation scale ≤3).

Airway management of lingual tonsillar hypertrophy: A narrative review.

Lingual tonsillar hypertrophy is rarely identified on routine airway assessment but may cause difficulties in airway management. We conducted a narrative review of case reports of lingual tonsillar hypertrophy to examine associated patient factors, success rates of airway management techniques and complications. We searched the literature for anaesthetic management of cases with lingual tonsillar hypertrophy. We found 89 patients in various case reports, from which we derived 92 cases to analyse. 64% of cases were assessed as having a normal airway. Difficult and impossible face mask ventilation occurred in 29.6% and 1.4% of cases, respectively. Difficult intubation and failed intubation occurred in 89.1% and 21.7% of cases, respectively. Multiple attempts (up to six) at intubation were performed, with no successful intubation after the third attempt with direct laryngoscopy. Some 16.5% of patients were woken up and 4.3% required emergency front of neck access. Complications included oesophageal intubation (10.9%), bleeding (9.8%) and severe hypoxia (3.2%). Our findings show that severe cases of lingual hypertrophy may cause an unanticipated difficult airway and serious complications, including hypoxic brain damage and death. A robust airway strategy is required which includes limiting the number of attempts at laryngoscopy, and early priming and performance of emergency front of neck access if required. In patients with known severe lingual tonsillar hypertrophy, awake intubation should be considered.

Development of Postanesthesia Care Unit Delirium Is Associated with Differences in Aperiodic and Periodic Alpha Parameters of the Electroencephalogram during Emergence from General Anesthesia: Results from a Prospective Observational Cohort Study.

BACKGROUND: Intraoperative alpha-band power in frontal electrodes may provide helpful information about the balance of hypnosis and analgesia and has been associated with reduced occurrence of delirium in the postanesthesia care unit. Recent studies suggest that narrow-band power computations from neural power spectra can benefit from separating periodic and aperiodic components of the electroencephalogram. This study investigates whether such techniques are more useful in separating patients with and without delirium in the postanesthesia care unit at the group level as opposed to conventional power spectra. METHODS: Intraoperative electroencephalography recordings of 32 patients who developed perioperative neurocognitive disorders and 137 patients who did not were considered in this post hoc secondary analysis. The power spectra were calculated using conventional methods and the "fitting oscillations and one over f" algorithm was applied to separate aperiodic and periodic components to see whether the electroencephalography signature is different between groups. RESULTS: At the group level, patients who did not develop perioperative neurocognitive disorders presented with significantly higher alpha-band power and a broadband increase in power, allowing a "fair" separation based on conventional power spectra. Within the first third of emergence, the difference in median absolute alpha-band power amounted to 8.53 decibels (area under the receiver operator characteristics curve, 0.74 [0.65; 0.82]), reaching its highest value. In relative terms, the best separation was achieved in the second third of emergence, with a difference in medians of 7.71% (area under the receiver operator characteristics curve, 0.70 [0.61; 0.79]). The area under the receiver operator characteristics curve values were generally lower toward the end of emergence with increasing arousal. CONCLUSIONS: Increased alpha-band power during emergence in patients who did not develop perioperative neurocognitive disorders can be traced back to an increase in oscillatory alpha activity and an overall increase in aperiodic broadband power. Although the differences between patients with and without perioperative neurocognitive disorders can be detected relying on traditional methods, the separation of the signal allows a more detailed analysis. This may enable clinicians to detect patients at risk for developing perioperative neurocognitive disorders in the postanesthesia care unit early in the emergence phase.

Effect of Propofol on Heart Rate and Its Coupling to Cortical Slow Waves in Humans.

BACKGROUND: Propofol causes significant cardiovascular depression and a slowing of neurophysiological activity. However, literature on its effect on the heart rate remains mixed, and it is not known whether cortical slow waves are related to cardiac activity in propofol anesthesia. METHODS: The authors performed a secondary analysis of electrocardiographic and electroencephalographic data collected as part of a previously published study where n = 16 healthy volunteers underwent a slow infusion of propofol up to an estimated effect-site concentration of 4 µg/ml. Heart rate, heart rate variability, and individual slow electroencephalographic waves were extracted for each subject. Timing between slow-wave start and the preceding R-wave was tested against a uniform random surrogate. Heart rate data were further examined as a post hoc analysis in n = 96 members of an American Society of Anesthesiologists Physical Status II/III older clinical population collected as part of the AlphaMax trial. RESULTS: The slow propofol infusion increased the heart rate in a dose-dependent manner (mean ± SD, increase of +4.2 ± 1.5 beats/min/[µg ml-1]; P < 0.001). The effect was smaller but still significant in the older clinical population. In healthy volunteers, propofol decreased the electrocardiogram R-wave amplitude (median [25th to 75th percentile], decrease of -83 [-245 to -28] µV; P < 0.001). Heart rate variability showed a loss of high-frequency parasympathetic activity. Individual cortical slow waves were coupled to the heartbeat. Heartbeat incidence peaked about 450 ms before slow-wave onset, and mean slow-wave frequency correlated with mean heart rate. CONCLUSIONS: The authors observed a robust increase in heart rate with increasing propofol concentrations in healthy volunteers and patients. This was likely due to decreased parasympathetic cardioinhibition. Similar to non-rapid eye movement sleep, cortical slow waves are coupled to the cardiac rhythm, perhaps due to a common brainstem generator.

Electroencephalographic signatures of consciousness: uncovering the fake news.

Amongst electroencephalographic markers of anaesthetic-induced unresponsiveness, those that estimate loss of frontoparietal functional connectivity detect loss of sensory perceptual connection with the outside world, rather than full phenomenological unconsciousness. This transition to unconsciousness is manifest as further incremental changes in indices of electroencephalographic complexity.

Comparing the EMMA capnograph with sidestream capnography and arterial carbon dioxide pressure at 284 kPa.

Introduction: Capnography aids assessment of the adequacy of mechanical patient ventilation. Physical and physiological changes in hyperbaric environments create ventilation challenges which make end-tidal carbon dioxide (ETCO2) measurement particularly important. However, obtaining accurate capnography in hyperbaric environments is widely considered difficult. This study investigated the EMMA capnograph for hyperbaric use. Methods: We compared the EMMA capnograph to sidestream capnography and the gold standard arterial carbon dioxide blood gas analysis in a hyperbaric chamber. In 12 resting subjects breathing air at 284 kPa, we recorded ETCO2 readings simultaneously derived from the EMMA and sidestream capnographs during two series of five breaths (total 24 measurements). An arterial blood gas sample was also taken simultaneously in five participants. Results: Across all measurements there was a difference of about 0.1 kPa between the EMMA and sidestream capnographs indicating a very slight over-estimation of ETCO2 by the EMMA capnograph, but fundamentally good agreement between the two end-tidal measurement methods. Compared to arterial blood gas pressure the non-significant difference was about 0.3 and 0.4 kPa for the EMMA and sidestream capnographs respectively. Conclusions: In this study, the EMMA capnograph performed equally to the sidestream capnograph when compared directly, and both capnography measures gave clinically acceptable estimates of arterial PCO2.

The art of chasing numbers in titration of anaesthetic dose.

There is no difference in between-patient variability of concentrations when comparing propofol and sevoflurane titrated to a bispectral index of 40-60. There is about a 300% variation in hypnotic concentration between the bottom 5% and top 5% of the population. Anaesthesia titration cannot be based solely on measured or estimated drug concentrations.

A systematic review of electroencephalography in acute cerebral hypoxia: clinical and diving implications.

Introduction: Hypoxia can cause central nervous system dysfunction and injury. Hypoxia is a particular risk during rebreather diving. Given its subtle symptom profile and its catastrophic consequences there is a need for reliable hypoxia monitoring. Electroencephalography (EEG) is being investigated as a real time monitor for multiple diving problems related to inspired gas, including hypoxia. Methods: A systematic literature search identified articles investigating the relationship between EEG changes and acute cerebral hypoxia in healthy adults. Quality of clinical evidence was assessed using the Newcastle-Ottawa scale. Results: Eighty-one studies were included for analysis. Only one study investigated divers. Twelve studies described quantitative EEG spectral power differences. Moderate hypoxia tended to result in increased alpha activity. With severe hypoxia, alpha activity decreased whilst delta and theta activities increased. However, since studies that utilised cognitive testing during the hypoxic exposure more frequently reported opposite results it appears cognitive processing might mask hypoxic EEG changes. Other analysis techniques (evoked potentials and electrical equivalents of dipole signals), demonstrated sustained regulation of autonomic responses despite worsening hypoxia. Other studies utilised quantitative EEG analysis techniques, (Bispectral index [BISTM], approximate entropy and Lempel-Ziv complexity). No change was reported in BISTM value, whilst an increase in approximate entropy and Lempel-Ziv complexity occurred with worsening hypoxia. Conclusions: Electroencephalographic frequency patterns change in response to acute cerebral hypoxia. There is paucity of literature on the relationship between quantitative EEG analysis techniques and cerebral hypoxia. Because of the conflicting results in EEG power frequency analysis, future research needs to quantitatively define a hypoxia-EEG response curve, and how it is altered by concurrent cognitive task loading.

Predictors of Low Risk for Delirium during Anesthesia Emergence.

BACKGROUND: Processed electroencephalography (EEG) is used to monitor the level of anesthesia, and it has shown the potential to predict the occurrence of delirium. While emergence trajectories of relative EEG band power identified post hoc show promising results in predicting a risk for a delirium, they are not easily transferable into an online predictive application. This article describes a low-resource and easily applicable method to differentiate between patients at high risk and low risk for delirium, with patients at low risk expected to show decreasing EEG power during emergence. METHODS: This study includes data from 169 patients (median age, 61 yr [49, 73]) who underwent surgery with general anesthesia maintained with propofol, sevoflurane, or desflurane. The data were derived from a previously published study. The investigators chose a single frontal channel, calculated the total and spectral band power from the EEG and calculated a linear regression model to observe the parameters' change during anesthesia emergence, described as slope. The slope of total power and single band power was correlated with the occurrence of delirium. RESULTS: Of 169 patients, 32 (19%) showed delirium. Patients whose total EEG power diminished the most during emergence were less likely to screen positive for delirium in the postanesthesia care unit. A positive slope in total power and band power evaluated by using a regression model was associated with a higher risk ratio (total, 2.83 [95% CI, 1.46 to 5.51]; alpha/beta band, 7.79 [95% CI, 2.24 to 27.09]) for delirium. Furthermore, a negative slope in multiple bands during emergence was specific for patients without delirium and allowed definition of a test for patients at low risk. CONCLUSIONS: This study developed an easily applicable exploratory method to analyze a single frontal EEG channel and to identify patterns specific for patients at low risk for delirium.

Permutation entropy is not an age-independent parameter for EEG-based anesthesia monitoring.

Background: An optimized anesthesia monitoring using electroencephalographic (EEG) information in the elderly could help to reduce the incidence of postoperative complications. Processed EEG information that is available to the anesthesiologist is affected by the age-induced changes of the raw EEG. While most of these methods indicate a "more awake" patient with age, the permutation entropy (PeEn) has been proposed as an age-independent measure. In this article, we show that PeEn is also influenced by age, independent of parameter settings. Methods: We retrospectively analyzed the EEG of more than 300 patients, recorded during steady state anesthesia without stimulation, and calculated the PeEn for different embedding dimensions m that was applied to the EEG filtered to a wide variety of frequency ranges. We constructed linear models to evaluate the relationship between age and PeEn. To compare our results to published studies, we also performed a stepwise dichotomization and used non-parametric tests and effect sizes for pairwise comparisons. Results: We found a significant influence of age on PeEn for all settings except for narrow band EEG activity. The analysis of the dichotomized data also revealed significant differences between old and young patients for the PeEn settings used in published studies. Conclusion: Based on our findings, we could show the influence of age on PeEn. This result was independent of parameter, sample rate, and filter settings. Hence, age should be taken into consideration when using PeEn to monitor patient EEG.

The Characteristics of Electroencephalogram Signatures in Minimally Conscious State Patients Induced by General Anesthesia.

OBJECTIVE: General anesthesia (GA) is necessary for surgery, even for patients in a minimally conscious state (MCS). The characteristics of the electroencephalogram (EEG) signatures of the MCS patients under GA are still unclear. METHODS: The EEG during GA were recorded from 10 MCS patients undergoing spinal cord stimulation surgery. The power spectrum, phase-amplitude coupling (PAC), the diversity of connectivity, and the functional network were investigated. Long term recovery was assessed by the Coma Recovery Scale-Revised at one year after the surgery, and the characteristics of the patients with good or bad prognosis status were compared. RESULTS: For the four MCS patients with good prognostic recovery, slow oscillation (0.1-1 Hz) and the alpha band (8-12 Hz) in the frontal areas increased during the maintenance of a surgical state of anesthesia (MOSSA), and "peak-max" and "trough-max" patterns emerged in frontal and parietal areas. During MOSSA, the six MCS patients with bad prognosis demonstrated: increased modulation index, reduced diversity of connectivity (from mean±SD of 0.877 ± 0.003 to 0.776 ± 0.003, p < 0.001), reduced function connectivity significantly in theta band (from mean±SD of 1.032 ± 0.043 to 0.589 ± 0.036, p < 0.001, in prefrontal-frontal; and from mean±SD of 0.989 ± 0.043 to 0.684 ± 0.036, p < 0.001, in frontal-parietal) and reduced local and global efficiency of the network in delta band. CONCLUSIONS: A bad prognosis in MCS patients is associated with signs of impaired thalamocortical and cortico-cortical connectivity - as indicated by inability to produce inter-frequency coupling and phase synchronization. These indices may have a role in predicting the long-term recovery of MCS patients.

Outcomes of Postoperative Overnight High-Acuity Care in Medium-Risk Patients Undergoing Elective and Unplanned Noncardiac Surgery.

Importance: Postoperative complications are increasing, risking patients' health and health care sustainability. High-acuity postoperative units may benefit outcomes, but existing data are very limited. Objective: To evaluate whether a new high-acuity postoperative unit, advanced recovery room care (ARRC), reduces complications and health care utilization compared with usual ward care (UC). Design, Setting, and Participants: In this observational cohort study, adults who were undergoing noncardiac surgery at a single-center tertiary adult hospital, anticipated to stay in hospital for 2 or more nights, were scheduled for postoperative ward care, and at medium risk (defined as predicted 30-day mortality of 0.7% to 5% by the National Safety Quality Improvement Program risk calculator) were included. Allocation to ARRC was based on bed availability. From 2405 patients assessed for eligibility with National Safety Quality Improvement Program risk scoring, 452 went to ARRC and 419 to UC, with 8 lost to 30-day follow-up. Propensity scoring identified 696 patients with matched pairs. Patients were treated between March and November 2021, and data were analyzed from January to September 2022. Interventions: ARRC is an extended postanesthesia care unit (PACU), staffed by anesthesiologists and nurses (1 nurse to 2 patients) collaboratively with surgeons, with capacity for invasive monitoring and vasoactive infusions. ARRC patients were treated until the morning after surgery, then transferred to surgical wards. UC patients were transferred to surgical wards after usual PACU care. Main Outcome and Measures: The primary end point was days at home at 30 days. Secondary end points were health facility utilization, medical emergency response (MER)-level complications, and mortality. Analyses compared groups before and after propensity scoring matching. Results: Of 854 included patients, 457 (53.5%) were male, and the mean (SD) age was 70.0 (14.4) years. Days at home at 30 days was greater with ARRC compared with UC (mean [SD] time, 17 [11] vs 15 [11] days; P = .04). During the first 24 hours, more patients were identified with MER-level complications in ARRC (43 [12.4%] vs 13 [3.7%]; P < .001), but after return to the ward, these were less frequent from days 2 to 9 (9 [2.6%] vs 22 [6.3%]; P = .03). Length of hospital stay, hospital readmissions, emergency department visits, and mortality were similar. Conclusions and Relevance: For medium-risk patients, brief high-acuity care with ARRC allowed enhanced detection and management of early MER-level complications, which was followed by a decreased incidence of subsequent MER-level complications after discharge to the ward and by increased days at home at 30 days.

Determination of Krogh Coefficient for Oxygen Consumption Measurement from Thin Slices of Rodent Cortical Tissue Using a Fick's Law Model of Diffusion.

To investigate the impact of experimental interventions on living biological tissue, ex vivo rodent brain slices are often used as a more controllable alternative to a live animal model. However, for meaningful results, the biological sample must be known to be healthy and viable. One of the gold-standard approaches to identifying tissue viability status is to measure the rate of tissue oxygen consumption under specific controlled conditions. Here, we work with thin (400 µm) slices of mouse cortical brain tissue which are sustained by a steady flow of oxygenated artificial cerebralspinal fluid (aCSF) at room temperature. To quantify tissue oxygen consumption (Q), we measure oxygen partial pressure (pO2) as a function of probe depth. The curvature of the obtained parabolic (or parabola-like) pO2 profiles can be used to extract Q, providing one knows the Krogh coefficient Kt, for the tissue. The oxygen trends are well described by a Fick's law diffusion-consumption model developed by Ivanova and Simeonov, and expressed in terms of ratio (Q/K), being the rate of oxygen consumption in tissue divided by the Krogh coefficient (oxygen diffusivity × oxygen solubility) for tissue. If the fluid immediately adjacent to the tissue can be assumed to be stationary (i.e., nonflowing), one may invoke conservation of oxygen flux K·(∂P/∂x) across the interface to deduce (Kt/Kf), the ratio of Krogh coefficients for tissue and fluid. Using published interpolation formulas for the effect of salt content and temperature on oxygen diffusivity and solubility for pure water, we estimate Kf, the Krogh coefficient for aCSF, and hence deduce the Kt coefficient for tissue. We distinguish experimental uncertainty from natural biological variability by using pairs of repeated profiles at the same tissue location. We report a dimensionless Krogh ratio (Kt/Kf)=0.562±0.088 (mean ± SD), corresponding to a Krogh coefficient Kt=(1.29±0.21)×10-14 mol/(m·s·Pa) for mouse cortical tissue at room temperature, but acknowledge the experimental limitation of being unable to verify that the fluid boundary layer is truly stationary. We compare our results with those reported in the literature, and comment on the challenges and ambiguities caused by the extensive use of 'biologically convenient' non-SI units for tissue Krogh coefficient.