Emergence Electroencephalography in an Unresponsiveness Geriatric Patient in the Postanesthesia Care Unit: A Case Report.

Incomplete neurological awakening manifested as aberrant patterns of electroencephalography (EEG) at emergence may be responsible for an unresponsive patient in the postanesthesia care unit (PACU). We describe a case of an individual who remained unresponsive but awake in the PACU. Retrospective, intraoperative EEG analysis showed low alpha power and a sudden shift from deep delta to arousal preextubation. We explored parallels with diminished motivation disorders and anesthesia-induced sleep paralysis due to imbalances in anesthetic drug sensitivity between brain regions. Our findings highlight the relevance of end-anesthesia EEG patterns in diagnosing delayed awakening.

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.

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.

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.

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.

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.

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.

Encapsulation Dynamics of Neuromuscular Blocking Drugs by Sugammadex.

BACKGROUND: The clinical actions of sugammadex have been well studied, but the detailed molecular mechanism of the drug encapsulation process has not been systematically documented. The hypothesis was that sugammadex would attract rocuronium and vecuronium via interaction with the sugammadex side-chain "tentacles," as previously suggested. METHODS: Computational molecular dynamics simulations were done to investigate docking of sugammadex with rocuronium and vecuronium. To validate these methods, strength of binding was assessed between sugammadex and a heterogeneous group of nine other drugs, the binding affinities of which have been experimentally determined. These observations hinted that high concentrations of unbound sugammadex could bind to propofol, potentially altering its pharmacokinetic profile. This was tested experimentally in in vitro cortical slices. RESULTS: Sugammadex encapsulation of rocuronium involved a sequential progression down a series of metastable states. After initially binding beside the sugammadex molecule (mean ± SD center-of-mass distance = 1.17 ± 0.13 nm), rocuronium then moved to the opposite side to that hypothesized, where it optimally aligned with the 16 hydroxyl groups (distance, 0.82 ± 0.04 nm) before entering the sugammadex cavity to achieve energetically stable encapsulation by approximately 120 ns (distance, 0.35 ± 0.12 nm). Vecuronium formed fewer hydrogen bonds with sugammadex than did rocuronium; hence, it was less avidly bound. For the other molecules, the computational results showed good agreement with the available experimental data, showing a clear bilogarithmic relation between the relative binding free energy and the association constant (R2 = 0.98). Weaker binding was manifest by periodic unbinding. The brain slice results confirmed the presence of a weak propofol-sugammadex interaction. CONCLUSIONS: Computational simulations demonstrate the dynamics of neuromuscular blocking drug encapsulation by sugammadex occurring from the opposite direction to that hypothesized and also how high concentrations of unbound sugammadex can potentially weakly bind to other drugs given during general anesthesia.

Deconstructing delirium in the post anaesthesia care unit.

The course of neuro-cognitive recovery following anaesthesia and surgery is distinctive and poorly understood. Our objective was to identify patterns of neuro-cognitive recovery of the domains routinely assessed for delirium diagnosis in the post anaesthesia care unit (PACU) and to compare them to the cognitive recovery patterns observed in other studies; thereby aiding in the identification of pathological (high risk) patterns of recovery in the PACU. We also compared which of the currently available tests (3D-CAM, CAM-ICU, and NuDESC) is the best to use in PACU. This was a post hoc secondary analysis of data from the Alpha Max study which involved 200 patients aged over 60 years, scheduled for elective surgery under general anaesthesia lasting more than 2 h. These patients were assessed for delirium at 30 min following arrival in the PACU, if they were adequately arousable (Richmond Agitation Sedation Score ≥ -2). All tests for delirium diagnosis (3D-CAM, CAM-ICU, and NuDESC) and the sub-domains assessed were compared to understand temporal recovery of neurocognitive domains. These data were also analysed to determine the best predictor of PACU delirium. We found the incidence of PACU delirium was 35% (3D-CAM). Individual cognitive domains were affected differently. Few individuals had vigilance deficits (6.5%, n = 10 CAM-ICU) or disorganized thinking (19% CAM-ICU, 27.5% 3D-CAM), in contrast attention deficits were common (72%, n = 144) and most of these patients (89.5%, n = 129) were not sedated (RASS ≥ -2). CAM-ICU (27%) and NuDESC (52.8%) detected fewer cases of PACU delirium compared to 3D-CAM. In conclusion, return of neurocognitive function is a stepwise process; Vigilance and Disorganized Thinking are the earliest cognitive functions to return to baseline and lingering deficits in these domains could indicate an abnormal cognitive recovery. Attention deficits are relatively common at 30 min in the PACU even in individuals who appear to be awake. The 3D CAM is a robust test to check for delirium in the PACU.

Brain Complexities and Anesthesia: Their Meaning and Measurement.

SUMMARY: A complex system is often associated with emergence of new phenomena from the interactions between the system's components. General anesthesia reduces brain complexity and so inhibits the emergence of consciousness. An understanding of complexity is necessary for the interpretation of brain monitoring algorithms. Complexity indices capture the "difficulty" of understanding brain activity over time and/or space. Complexity-entropy plots reveal the types of complexity indices and their balance of randomness and structure. Lempel-Ziv complexity is a common index of temporal complexity for single-channel electroencephalogram containing both power spectral and nonlinear effects, revealed by phase-randomized surrogate data. Computing spatial complexities involves forming a connectivity matrix and calculating the complexity of connectivity patterns. Spatiotemporal complexity can be estimated in multiple ways including temporal or spatial concatenation, estimation of state switching, or integrated information. This article illustrates the concept and application of various complexities by providing working examples; a website with interactive demonstrations has also been created.

Does hyperbaric oxygen cause narcosis or hyperexcitability? A quantitative EEG analysis.

Divers breathe higher partial pressures of oxygen at depth than at the surface. The literature and diving community are divided on whether or not oxygen is narcotic. Conversely, hyperbaric oxygen may induce dose-dependent cerebral hyperexcitability. This study evaluated whether hyperbaric oxygen causes similar narcotic effects to nitrogen, and investigated oxygen's hyperexcitability effect. Twelve human participants breathed "normobaric" air and 100% oxygen, and "hyperbaric" 100% oxygen at 142 and 284 kPa, while psychometric performance, electroencephalography (EEG), and task load perception were measured. EEG was analyzed with functional connectivity and temporal complexity algorithms. The spatial functional connectivity, estimated using mutual information, was summarized with the global efficiency network measure. Temporal complexity was calculated with a "default-mode-network (DMN) complexity" algorithm. Hyperbaric oxygen-breathing caused no change in EEG global efficiency or in the psychometric test. However, oxygen caused a significant reduction of DMN complexity and a reduction in task load perception. Hyperbaric oxygen did not cause the same changes in EEG global efficiency seen with hyperbaric air, which likely related to a narcotic effect of nitrogen. Hyperbaric oxygen seemed to disturb the time evolution of EEG patterns that could be taken as evidence of early oxygen-induced cortical hyperexcitability. These findings suggest that hyperbaric oxygen is not narcotic and will help inform divers' decisions on suitable gas mixtures.

Comment on Mankowska et al. Critical Flicker Fusion Frequency: A Narrative Review. Medicina 2021, 57, 1096.

We have read with great interest the review by Mankowska et al. [...].