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Controversy surrounds regional cerebral oximetry (rSO2) because extracranial contamination and unmeasured changes in cerebral arterial:venous ratio confound readings. Correlation of rSO2 with brain tissue oxygen (PbrO2), a “gold standard” for cerebral oxygenation, could help resolve this controversy but PbrO2 measurement is highly invasive. This was a prospective cohort study. The primary aim was to evaluate correlation between PbrO2 and rSO2 and the secondary aim was to investigate the relationship between changing ventilation regimens and measurement of PbrO2 and rSO2. Patients scheduled for elective removal of cerebral metastases were anesthetized with propofol and remifentanil, targeted to a BIS range 40–60. rSO2 was measured using the INVOS 5100B monitor and PbrO2 using the Licox brain monitoring system. The Licox probe was placed into an area of normal brain within the tumor excision corridor. FiO2 and minute ventilation were sequentially adjusted to achieve two set points: (1) FiO2 0.3 and paCO2 30 mmHg, (2) FiO2 1.0 and paCO2 40 mmHg. PbrO2 and rSO2 were recorded at each. Nine participants were included in the final analysis, which showed a positive Spearman’s correlation (r = 0.50, p = 0.036) between PbrO2 and rSO2. From set point 1 to set point 2, PbrO2 increased from median 6.0, IQR 4.0–11.3 to median 22.5, IQR 9.8–43.6, p = 0.015; rSO2 increased from median 68.0, IQR 62.5–80.5 to median 83.0, IQR 74.0–90.0, p = 0.047. Correlation between PbrO2 and rSO2 is evident. Increasing FiO2 and PaCO2 results in significant increases in cerebral oxygenation measured by both monitors.

The neurobiology of the psychedelic experience is not fully elucidated. Identifying common brain network changes induced by both canonical (i.e., acting at the 5-HT2 receptor) and non-canonical psychedelics would provide mechanistic insight into state-specific characteristics. We analyzed whole-brain functional connectivity based on resting-state fMRI data in humans, acquired before and during the administration of nitrous oxide, ketamine, and lysergic acid diethylamide. We report that, despite distinct molecular mechanisms and modes of delivery, all three psychedelics reduced within-network functional connectivity and enhanced between-network functional connectivity. More specifically, all drugs tested increased connectivity between right temporoparietal junction and bilateral intraparietal sulcus as well as between precuneus and left intraparietal sulcus. These regions fall within the posterior cortical “hot zone,” posited to mediate the content of consciousness. Thus, both canonical and non-canonical psychedelics modulate networks within an area of known relevance for conscious experience, identifying a biologically plausible candidate for their subjective effects.

Cerebrovascular autoregulation (CA) is a protective mechanism that enables the cerebral vasculature to automodulate tone in response to changes in cerebral perfusion pressure to ensure constant levels of cerebral blood flow (CBF) and oxygen delivery. CA can be impaired after neurological injury and contributes to secondary brain injury. In this study, we report novel impedance indices using trans-ocular brain impedance (TOBI) during controlled systemic hemorrhage and hypotension to assess CA in comparison with pressure reactivity index (PRx). Yorkshire swine were instrumented to record intracranial pressure (ICP), mean arterial pressure (MAP), and CBF. TOBI was recorded using electrocardiographic electrodes placed on the closed eyelids. Impedance changes (dz) were recorded in response to introducing an alternating current (0.4 mA) through the electrodes. MAP, ICP, and CBF were also measured. Animals were subjected to a controlled hemorrhage to remove 30–40% of each animal’s total blood volume over 25–35 min. Hemorrhage was titrated to reach an MAP of approximately 35 mm Hg and end-tidal carbon dioxide above 28 mm Hg. PRx was calculated as a moving Pearson correlation between MAP and ICP. TOBI indices were calculated as the amplitude of the respiratory-induced changes in dz. DZx was calculated as a moving Pearson correlation between dz and MAP. TOBI indices (dz and DZx) were compared with hemodynamic indicators and PRx. dz was shown to be highly correlated with MAP, ICP, cerebral perfusion pressure, and CBF (r = − 0.823, − 0.723, − 0.813, and − 0.726), respectively (p

Cerebrovascular autoregulation (CA) is often impaired following traumatic brain injury. Established technologies and metrics used to assess CA are invasive and conducive for measurement, but not for continuous monitoring. We developed a trans-ocular brain impedance (TOBI) method that may provide non-invasive and continuous indices to assess CA. In this study, we monitored impedance metrics such as respiratory-induced impedance amplitude changes (dz) as well as a novel impedance index (DZx), which is a moving Pearson correlation between mean arterial pressure (MAP) and dz. Yorkshire swine were instrumented to continuously record ICP, MAP, and cerebral blood flow (CBF). TOBI was recorded by placement of standard ECG electrodes on closed eyelids and connected to a data acquisition system. MAP, ICP and CBF were manipulated utilizing an intravenous vasopressor challenge. TOBI indices (dz and DZx) were compared to the hemodynamic indicators as well as pressure reactivity index (PRx). During the vasopressor challenge, dz was highly correlated with ICP, CPP, and CBF (r =

Recent modeling and empirical studies support the hypothesis that large-scale brain networks function near a critical state. Similar functional connectivity patterns derived from resting state empirical data and brain network models at criticality provide further support. However, despite the strong implication of a relationship, there has been no principled explanation of how criticality shapes the characteristic functional connectivity in large-scale brain networks. Here, we hypothesized that the network science concept of partial phase locking is the underlying mechanism of optimal functional connectivity in the resting state. We further hypothesized that the characteristic connectivity of the critical state provides a theoretical boundary to quantify how far pharmacologically or pathologically perturbed brain connectivity deviates from its critical state, which could enable the differentiation of various states of consciousness with a theory-based metric. To test the hypothesis, we used a neuroanatomically informed brain network model with the resulting source signals projected to electroencephalogram (EEG)-like sensor signals with a forward model. Phase lag entropy (PLE), a measure of phase relation diversity, was estimated and the topography of PLE was analyzed. To measure the distance from criticality, the PLE topography at a critical state was compared with those of the EEG data from baseline consciousness, isoflurane anesthesia, ketamine anesthesia, vegetative state/unresponsive wakefulness syndrome, and minimally conscious state. We demonstrate that the partial phase locking at criticality shapes the functional connectivity and asymmetric anterior-posterior PLE topography, with low (high) PLE for high (low) degree nodes. The topographical similarity and the strength of PLE differentiates various pharmacologic and pathologic states of consciousness. Moreover, this model-based EEG network analysis provides a novel metric to quantify how far a pharmacologically or pathologically perturbed brain network is away from critical state, rather than merely determining whether it is in a critical or non-critical state.

Anesthetics are known to disrupt neural interactions in cortical and subcortical brain circuits. While the effect of anesthetic drugs on consciousness is reversible, the neural mechanism mediating induction and recovery may be different. Insight into these distinct mechanisms can be gained from a systematic comparison of neural dynamics during slow induction of and emergence from anesthesia. To this end, we used functional magnetic resonance imaging (fMRI) data obtained in healthy volunteers before, during, and after the administration of propofol at incrementally adjusted target concentrations. We analyzed functional connectivity of corticocortical and subcorticocortical networks and the temporal autocorrelation of fMRI signal as an index of neural processing timescales. We found that en route to unconsciousness, temporal autocorrelation across the entire brain gradually increased, whereas functional connectivity gradually decreased. In contrast, regaining consciousness was associated with an abrupt restoration of cortical but not subcortical temporal autocorrelation and an abrupt boost of subcorticocortical functional connectivity. Pharmacokinetic effects could not account for the difference in neural dynamics between induction and emergence. We conclude that the induction and recovery phases of anesthesia follow asymmetric neural dynamics. A rapid increase in the speed of cortical neural processing and subcorticocortical neural interactions may be a mechanism that reboots consciousness.

Background Severe hypocalcaemia is associated with increased transfusion in the trauma population. Furthermore, trauma patients developing severe hypocalcaemia have higher mortality and coagulopathy. Electrolyte abnormalities associated with massive transfusion have been less studied in the surgical population. Here, we tested the primary hypothesis that volume of packed red blood cells and fresh frozen plasma transfused intraoperatively is associated with lower nadir ionised calcium in the surgical population receiving massive resuscitation. Methods We performed a retrospective observational study at an academic quaternary care centre to characterise hypocalcaemia following large volume (4 or more units packed red blood cells) intraoperative transfusion. We used multivariable linear regression to assess if volume of transfusion with packed red blood cells and fresh frozen plasma were independently associated with a lower ionised calcium. We then used multivariable logistic regressions to assess the association between ionised calcium and transfusion with: (i) mortality, (ii) acute kidney injury, and (iii) postoperative coagulopathy. Results Hypocalcaemia following large volume resuscitation in the operating room is a very frequent occurrence (70% of cases). After controlling for demographic variables and intraoperative variables, the volume transfused intraoperative was independently associated with hypocalcaemia on multivariable linear regression. Hypocalcaemia, intraoperative transfusion of packed red blood cells, and intraoperative transfusion of fresh frozen plasma were not shown to be associated with clinical outcomes. Conclusions Hypocalcaemia was associated with increased transfusion volume in this single-centre study. Unlike the trauma population, hypocalcaemia was not associated with increased mortality during surgical care. Our findings suggest that despite improved practice patterns of calcium supplementation, intraoperative hypocalcaemia occurs with relatively high frequency following large volume intraoperative transfusion.

Understanding how the brain recovers from unconsciousness can inform neurobiological theories of consciousness and guide clinical investigation. To address this question, we conducted a multicenter study of 60 healthy humans, half of whom received general anesthesia for 3 hr and half of whom served as awake controls. We administered a battery of neurocognitive tests and recorded electroencephalography to assess cortical dynamics. We hypothesized that recovery of consciousness and cognition is an extended process, with differential recovery of cognitive functions that would commence with return of responsiveness and end with return of executive function, mediated by prefrontal cortex. We found that, just prior to the recovery of consciousness, frontal-parietal dynamics returned to baseline. Consistent with our hypothesis, cognitive reconstitution after anesthesia evolved over time. Contrary to our hypothesis, executive function returned first. Early engagement of prefrontal cortex in recovery of consciousness and cognition is consistent with global neuronal workspace theory., eLife digest Anesthesia is a state of reversable, controlled unconsciousness. It has enabled countless medical procedures. But it also serves as a tool for scientists to study how the brain regains consciousness after disruptions such as sleep, coma or medical procedures requiring general anesthesia. It is still unclear how exactly the brain regains consciousness, and less so, why some patients do not recover normally after general anesthesia or fail to recover from brain injury. To find out more, Mashour et al. studied the patterns of reemerging consciousness and cognitive function in 30 healthy adults who underwent general anesthesia for three hours. While the volunteers were under anesthesia, their brain activity was measured with an EEG; and their sleep-wake activity was measured before and after the experiment. Each participant took part in a series of cognitive tests designed to measure the reaction speed, memory and other functions before receiving anesthesia, right after the return of consciousness, and then every 30 minutes thereafter. Thirty healthy volunteers who did not have anesthesia also completed the scans and tests as a comparison group. The experiments showed that certain normal EEG patterns resumed just before a person wakes up from anesthesia. The return of thinking abilities was an extended, multistep process, but volunteers recovered their cognitive abilities to nearly the same level as the volunteers within three hours of being deeply anesthetized. Mashour et al. also unexpectedly found that abstract problem-solving resumes early in the process, while other functions such as reaction time and attention took longer to recover. This makes sense from an evolutionary perspective. Sleep leaves individuals vulnerable. Quick evaluation and decision-making skills would be key to respond to a threat upon waking. The experiments confirm that the front of the brain, which handles thinking and decision-making, was especially active around the time of recovery. This suggests that therapies targeting this part of the brain may help people who experience loss of consciousness after a brain injury or have difficulties waking up after anesthesia. Moreover, disorders of cognition, such as delirium, in the days following surgery may be caused by factors other than the lingering effects of anesthetic drugs on the brain.

The development of sophisticated computational tools to quantify changes in the brain's oscillatory dynamics across states of consciousness have included both envelope- and phase-based measures of functional connectivity (FC), but there are very few direct comparisons of these techniques using the same dataset. The goal of this study was to compare an envelope-based (i.e. Amplitude Envelope Correlation, AEC) and a phase-based (i.e. weighted Phase Lag Index, wPLI) measure of FC in their classification of states of consciousness. Nine healthy participants underwent a three-hour experimental anesthetic protocol with propofol induction and isoflurane maintenance, in which five minutes of 128-channel electroencephalography were recorded before, during, and after anesthetic-induced unconsciousness, at the following time points: Baseline; light sedation with propofol (Light Sedation); deep unconsciousness following three hours of surgical levels of anesthesia with isoflurane (Unconscious); five minutes prior to the recovery of consciousness (Pre-ROC); and three hours following the recovery of consciousness (Recovery). Support vector machine classification was applied to the source-localized EEG in the alpha (8–13 Hz) frequency band in order to investigate the ability of AEC and wPLI (separately and together) to discriminate i) the four states from Baseline; ii) Unconscious (“deep” unconsciousness) vs. Pre-ROC (“light” unconsciousness); and iii) responsiveness (Baseline, Light Sedation, Recovery) vs. unresponsiveness (Unconscious, Pre-ROC). AEC and wPLI yielded different patterns of global connectivity across states of consciousness, with AEC showing the strongest network connectivity during the Unconscious epoch, and wPLI showing the strongest connectivity during full consciousness (i.e., Baseline and Recovery). Both measures also demonstrated differential predictive contributions across participants and used different brain regions for classification. AEC showed higher classification accuracy overall, particularly for distinguishing anesthetic-induced unconsciousness from Baseline (83.7 ± 0.8%). AEC also showed stronger classification accuracy than wPLI when distinguishing Unconscious from Pre-ROC (i.e., “deep” from “light” unconsciousness) (AEC: 66.3 ± 1.2%; wPLI: 56.2 ± 1.3%), and when distinguishing between responsiveness and unresponsiveness (AEC: 76.0 ± 1.3%; wPLI: 63.6 ± 1.8%). Classification accuracy was not improved compared to AEC when both AEC and wPLI were combined. This analysis of source-localized EEG data demonstrates that envelope- and phase-based FC provide different information about states of consciousness but that, on a group level, AEC is better able to detect relative alterations in brain FC across levels of anesthetic-induced unconsciousness compared to wPLI.

Cerebrovascular autoregulation (CA) is a protective mechanism that enables the cerebral vasculature to automodulate tone in response to changes in cerebral perfusion pressure to ensure constant levels of cerebral blood flow (CBF) and oxygen delivery. CA can be impaired after neurological injury and contributes to secondary brain injury. In this study, we report novel impedance indices using trans-ocular brain impedance (TOBI) during controlled systemic hemorrhage and hypotension to assess CA in comparison with pressure reactivity index (PRx).Yorkshire swine were instrumented to record intracranial pressure (ICP), mean arterial pressure (MAP), and CBF. TOBI was recorded using electrocardiographic electrodes placed on the closed eyelids. Impedance changes (dz) were recorded in response to introducing an alternating current (0.4 mA) through the electrodes. MAP, ICP, and CBF were also measured. Animals were subjected to a controlled hemorrhage to remove 30-40% of each animal's total blood volume over 25-35 min. Hemorrhage was titrated to reach an MAP of approximately 35 mm Hg and end-tidal carbon dioxide above 28 mm Hg. PRx was calculated as a moving Pearson correlation between MAP and ICP. TOBI indices were calculated as the amplitude of the respiratory-induced changes in dz. DZx was calculated as a moving Pearson correlation between dz and MAP. TOBI indices (dz and DZx) were compared with hemodynamic indicators and PRx.dz was shown to be highly correlated with MAP, ICP, cerebral perfusion pressure, and CBF (r = - 0.823, - 0.723, - 0.813, and - 0.726), respectively (p 0.0001). During hemorrhage, cerebral perfusion pressure and CBF had a mean percent decrease (standard deviation) from baseline of - 54.2% (12.5%) and - 28.3% (14.7%), respectively, whereas dz increased by 277% (268%). Receiver operator characteristics and precision-recall curves demonstrated high predictive performance of DZx when compared with PRx with an area under the curve above 0.82 and 0.89 for receiver operator characteristic and precision-recall curves, respectively, with high sensitivity and positive predictive power.TOBI indices appear to track changes in PRx and hemodynamics that affect CA during hemorrhage-induced hypotension. TOBI may offer a suitable, less invasive surrogate to PRx for monitoring and assessing CA.

Cerebrovascular autoregulation (CA) is often impaired following traumatic brain injury. Established technologies and metrics used to assess CA are invasive and conducive for measurement, but not for continuous monitoring. We developed a trans-ocular brain impedance (TOBI) method that may provide non-invasive and continuous indices to assess CA. In this study, we monitored impedance metrics such as respiratory-induced impedance amplitude changes (dz) as well as a novel impedance index (DZx), which is a moving Pearson correlation between mean arterial pressure (MAP) and dz. Yorkshire swine were instrumented to continuously record ICP, MAP, and cerebral blood flow (CBF). TOBI was recorded by placement of standard ECG electrodes on closed eyelids and connected to a data acquisition system. MAP, ICP and CBF were manipulated utilizing an intravenous vasopressor challenge. TOBI indices (dz and DZx) were compared to the hemodynamic indicators as well as pressure reactivity index (PRx). During the vasopressor challenge, dz was highly correlated with ICP, CPP, and CBF (r = - 0.49, p 0.0001). ICP, CPP, and CBF had a mean percent increase (standard deviation) from baseline of 29(23.2)%, 70(25)%, and 37(72.6)% respectively while dz decreased by 31(15.6)%. Receiver operator curve test showed high predictive performance of DZx when compared to PRx with area under the curve above 0.86, with high sensitivity and specificity. Impedance indices appear to track changes in PRx and hemodynamics that affect cerebral autoregulation. TOBI may be a suitable less invasive surrogate to PRx and capable of tracking cerebral autoregulation.

Background: Motifs are patterns of inter-connections between nodes of a complex network, and have been investigated as the basic building blocks of directed networks. This study explored the re-organization of 3-node (i.e. 3-electrode) network motifs during anesthetic-induced loss and recovery of consciousness. We hypothesized that motif frequency and topography would change across states of consciousness, and that the frequency and topography associated with consciousness would recover prior to the return of behavioral responsiveness. Methods: Nine healthy subjects underwent a 3-hour controlled anesthetic protocol (propofol induction; isoflurane maintenance) in an operating room, while brain activity was recorded through 128-channel electroencephalography (EEG). In the alpha (8-13 Hz) frequency band, five-minute epochs of EEG were extracted for: baseline; induction; unconsciousness; 30-, 10- and 5-minutes pre-recovery of consciousness; 30- and 180-minutes post-recovery of consciousness. We constructed a functional brain network using the weighted phase lag index and the directed phase lag index, which were then used to calculate graph theoretical brain network properties and the frequency and topography of 3-node (i.e. 3-electrode) motifs. Results: Three motifs (motifs 1, 2 and 5) were significantly present across participants and epochs, when compared to random networks (p

The effect of neither transfusion guidelines nor decision support tools on intraoperative transfusion has been previously evaluated. The University of Michigan introduced a transfusion guideline in 2009, and in 2011, the Department of Anesthesiology developed a transfusion decision support tool. The primary aim of this study was to assess the associations of the transfusion guideline and the optional use of the software transfusion tool with intraoperative behaviors; pretransfusion hematocrit assessment (whether or not a hematocrit was checked before each red cell unit) and restrictive red cell use (withholding transfusion unless the hematocrit was ≤21%).This was a before-after retrospective study without a concurrent control group of patients transfused 1-3 units of red cells intraoperatively. Three phases were studied to provide data both before and after the implementation of the transfusion guideline and the intraoperative software tool. Within each phase, trends of checking hematocrits before transfusion and restrictive transfusion were charted against time. F tests were used to measure differences of slopes. The difference between means of each phase was measured using Mann-Whitney U tests. Independent associations were measured using mixed-effects multivariable logistic regression. A secondary outcome analysis was conducted for 30-day mortality, myocardial infarction, renal injury, and their combination.The transfusion guideline was associated with increased pretransfusion hematocrit evaluation (67.4%, standard deviation [SD] 3.9 vs 76.5%, SD 2.7; P.001) and restrictive transfusion practice (14.0%, SD 7.4 vs 33.3%, SD 4.4; P = .001). After adjustment for confounders, the guideline phase was independently associated with increased hematocrit checking (odds ratio, 1.72; 95% confidence interval, 1.46-2.03; P.001) and restrictive red cell transfusion (odds ratio, 2.95; 95% confidence interval, 2.46-3.54; P.001). The software tool was not associated with either transfusion behavior. There was no significant change in the rate of renal injury (16.06%), myocardial injury (4.93%), 30-day mortality (5.47%), or a composite (21.90%).The introduction of a transfusion guideline was independently associated with increased intraoperative pretransfusion hematocrit assessment and restrictive transfusion. The use of a software tool did not further influence either behavior.

BACKGROUND: Despite its designation as a ‘dissociative anaesthetic,’ the dissociative and psychoactive effects of ketamine remain incompletely understood. The goal of this study was to characterise the subjective experiences and accompanying EEG changes with subanaesthetic doses of ketamine. METHODS: High-density EEG was recorded in 15 human volunteers before, during, and after subanaesthetic ketamine infusion (0.5 mg kg(−1) over 40 min), with self-reported measures of altered states of consciousness obtained after ketamine exposure. Sensor- and source-level EEG changes were analysed with a focus on spectral power and regional changes. RESULTS: Ketamine-induced altered states were characterised predominantly by dissociative experiences such as disembodiment and ego transcendence; sensory disturbances were also common. Ketamine broadly decreased low-frequency power, with mean reductions largest at alpha (8–12 Hz) in parietal (−0.94 dB, P

Neurologic complications of surgery can be devastating. The authors review neurologic considerations and complications associated with liver transplantation and discuss strategies to prevent, identify, and treat such adverse outcomes in the perioperative period.

Background Previous studies have demonstrated inconsistent neurophysiologic effects of ketamine, although discrepant findings might relate to differences in doses studied, brain regions analyzed, coadministration of other anesthetic medications, and resolution of the electroencephalograph. The objective of this study was to characterize the dose-dependent effects of ketamine on cortical oscillations and functional connectivity. Methods Ten healthy human volunteers were recruited for study participation. The data were recorded using a 128-channel electroencephalograph during baseline consciousness, subanesthetic dosing (0.5 mg/kg over 40 min), anesthetic dosing (1.5 mg/kg bolus), and recovery. No other sedative or anesthetic medications were administered. Spectrograms, topomaps, and functional connectivity (weighted and directed phase lag index) were computed and analyzed. Results Frontal theta bandwidth power increased most dramatically during ketamine anesthesia (mean power ± SD, 4.25 ± 1.90 dB) compared to the baseline (0.64 ± 0.28 dB), subanesthetic (0.60 ± 0.30 dB), and recovery (0.68 ± 0.41 dB) states; P < 0.001. Gamma power also increased during ketamine anesthesia. Weighted phase lag index demonstrated theta phase locking within anterior regions (0.2349 ± 0.1170, P < 0.001) and between anterior and posterior regions (0.2159 ± 0.1538, P < 0.01) during ketamine anesthesia. Alpha power gradually decreased with subanesthetic ketamine, and anterior-to-posterior directed connectivity was maximally reduced (0.0282 ± 0.0772) during ketamine anesthesia compared to all other states (P < 0.05). Conclusions Ketamine anesthesia correlates most clearly with distinct changes in the theta bandwidth, including increased power and functional connectivity. Anterior-to-posterior connectivity in the alpha bandwidth becomes maximally depressed with anesthetic ketamine administration, suggesting a dose-dependent effect.

Background Burst suppression occurs in the EEG during coma and under general anaesthesia. It has been assumed that burst suppression represents a deeper state of anaesthesia from which it is more difficult to recover. This has not been directly demonstrated, however. Here, we test this hypothesis directly by assessing relationships between EEG suppression in human volunteers and recovery of consciousness. Methods We recorded the EEG of 27 healthy humans (nine women/18 men) anaesthetised with isoflurane 1.3 minimum alveolar concentration (MAC) for 3 h. Periods of EEG suppression and non-suppression were separated using principal component analysis of the spectrogram. After emergence, participants completed the digit symbol substitution test and the psychomotor vigilance test. Results Volunteers demonstrated marked variability in multiple features of the suppressed EEG. In order to test the hypothesis that, for an individual subject, inclusion of features of suppression would improve accuracy of a model built to predict time of emergence, two types of models were constructed: one with a suppression-related feature included and one without. Contrary to our hypothesis, Akaike information criterion demonstrated that the addition of a suppression-related feature did not improve the ability of the model to predict time to emergence. Furthermore, the amounts of EEG suppression and decrements in cognitive task performance relative to pre-anaesthesia baseline were not significantly correlated. Conclusions These findings suggest that, in contrast to current assumptions, EEG suppression in and of itself is not an important determinant of recovery time or the degree of cognitive impairment upon emergence from anaesthesia in healthy adults.

Background Perioperative hyperglycemia is associated with poor outcomes yet evidence to guide intraoperative goals and treatment modalities during non-cardiac surgery are lacking. End-stage liver disease is associated with altered glucose homeostasis; patients undergoing liver transplantation display huge fluctuations in blood glucose (BG) and represent a population of great interest. Here, we conduct a randomized trial to compare the effects of strict versus conventional glycemic control during orthotopic liver transplant (OLT). Methods Following approval by the Institutional Review Board of the University of Michigan Medical School and informed consent, 100 adult patients undergoing OLT were recruited. Patients were randomized to either strict (target BG 80–120 mg/dL) or conventional (target BG 180–200 mg/dL) BG control with block randomization for diabetic and nondiabetic patients. The primary outcomes measured were 1-year patient and graft survival assessed on an intention to treat basis. Graft survival is defined as death or needing re-transplant (www.unos.org). Three and 5-year patient and graft survival, infectious and biliary complications were measured as secondary outcomes. Data were examined using univariate methods and Kaplan-Meir survival analysis. A sensitivity analysis was performed to compare patients with a mean BG of ≤120 mg/dL and those > 120 mg/dL regardless of treatment group. Results There was no statistically significant difference in patient survival between conventional and strict control respectively;1 year, 88% vs 88% (p-0.99), 3 years, 86% vs 84% (p- 0.77), 5 years, 82% vs 78. % (p-0.36). Graft survival was not different between conventional and strict control groups at 1 year, 88% vs 84% (p-0.56), 3 years 82% vs 76% (p-0.46), 5 years 78% vs 70% (p-0.362). Conclusion There was no difference in patient or graft survival between intraoperative strict and conventional glycemic control during OLT. Trial registration Clinical trial number and registry: www.clinicaltrials.gov NCT00780026. This trial was retrospectively registered on 10/22/2008.

Detecting covert consciousness in behaviorally unresponsive patients by brain imaging is of great interest, but a reproducible model and evidence from independent sources is still lacking. Here we demonstrate the possibility of using general anesthetics in a within-subjects study design to test methods or statistical paradigms of assessing covert consciousness. Using noninvasive neuroimaging in healthy volunteers, we identified a healthy study participant who was able to exhibit the specific fMRI signatures of volitional mental imagery while behaviorally unresponsive due to sedation with propofol. Our findings reveal a novel model that may accelerate the development of new approaches to reproducibly detect covert consciousness, which is difficult to achieve in patients with heterogeneous and sometimes clinically unstable neuropathology.

Background: Beach chair positioning during general anesthesia is associated with cerebral oxygen desaturation. Changes in cerebral oxygenation resulting from the interaction of inspired oxygen fraction (Fio2), end-tidal carbon dioxide (PETco2), and anesthetic choice have not been fully evaluated in anesthetized patients in the beach chair position. Methods: This is a prospective interventional within-group study of patients undergoing shoulder surgery in the beach chair position that incorporated a randomized comparison between two anesthetics. Fifty-six patients were randomized to receive desflurane or total intravenous anesthesia with propofol. Following induction of anesthesia and positioning, Fio2 and minute ventilation were sequentially adjusted for all patients. Regional cerebral oxygenation (rSo2) was the primary outcome and was recorded at each of five set points. Results: While maintaining Fio2 at 0.3 and PETco2 at 30 mmHg, there was a decrease in rSo2 from 68% (SD, 12) to 61% (SD, 12) (P < 0.001) following beach chair positioning. The combined interventions of increasing Fio2 to 1.0 and increasing PETco2 to 45 mmHg resulted in a 14% point improvement in rSo2 to 75% (SD, 12) (P Conclusions: Increasing Fio2 and PETco2 resulted in a significant increase in rSo2 that overcomes desaturation in patients anesthetized in the beach chair position and that appears independent of anesthetic choice.

Previous studies have demonstrated inconsistent neurophysiologic effects of ketamine, although discrepant findings might relate to differences in doses studied, brain regions analyzed, coadministration of other anesthetic medications, and resolution of the electroencephalograph. The objective of this study was to characterize the dose-dependent effects of ketamine on cortical oscillations and functional connectivity.Ten healthy human volunteers were recruited for study participation. The data were recorded using a 128-channel electroencephalograph during baseline consciousness, subanesthetic dosing (0.5 mg/kg over 40 min), anesthetic dosing (1.5 mg/kg bolus), and recovery. No other sedative or anesthetic medications were administered. Spectrograms, topomaps, and functional connectivity (weighted and directed phase lag index) were computed and analyzed.Frontal theta bandwidth power increased most dramatically during ketamine anesthesia (mean power ± SD, 4.25 ± 1.90 dB) compared to the baseline (0.64 ± 0.28 dB), subanesthetic (0.60 ± 0.30 dB), and recovery (0.68 ± 0.41 dB) states; P0.001. Gamma power also increased during ketamine anesthesia. Weighted phase lag index demonstrated theta phase locking within anterior regions (0.2349 ± 0.1170, P0.001) and between anterior and posterior regions (0.2159 ± 0.1538, P0.01) during ketamine anesthesia. Alpha power gradually decreased with subanesthetic ketamine, and anterior-to-posterior directed connectivity was maximally reduced (0.0282 ± 0.0772) during ketamine anesthesia compared to all other states (P0.05).Ketamine anesthesia correlates most clearly with distinct changes in the theta bandwidth, including increased power and functional connectivity. Anterior-to-posterior connectivity in the alpha bandwidth becomes maximally depressed with anesthetic ketamine administration, suggesting a dose-dependent effect.

Introduction. Almost all pediatric orthotopic liver transplant (OLT) recipients require mechanical ventilation in the early postoperative period. Prolonged postoperative mechanical ventilation (PPMV) may be a marker of severe disease and may be associated with morbidity and mortality. We determined the incidence and risk factors for PPMV in children who underwent OLT. Methods. This was a retrospective analysis of data collected on 128 pediatric OLT recipients. PPMV was defined as postoperative ventilation ≥ 4 days. Perioperative characteristics were compared between cases and control groups. Multivariable logistic regression analysis was used to calculate odds ratios for PPMV after controlling for relevant cofactors. Results. An estimated 25% (95% CI, 17.4%–32.6%) required PPMV. The overall incidence of PPMV varied significantly by age group with the highest incidence among infants. PPMV was associated with higher postoperative mortality (p=0.004) and longer intensive care unit (p<0.001) and hospital length of stay (p<0.001). Multivariable analysis identified young patient age, preoperative hypocalcemia, and increasing duration of surgery as independent predictors of PPMV following OLT. Conclusion. The incidence of PPMV is high and it was associated with prolonged ICU and hospital LOS and higher posttransplant mortality. Surgery duration appears to be the only modifiable predictor of PPMV.

Background Intraoperative awareness with explicit recall occurs in approximately 0.15% of all surgical cases. Efficacy trials based on the Bispectral Index® (BIS) monitor (Covidien, Boulder, CO) and anesthetic concentrations have focused on high-risk patients, but there are no effectiveness data applicable to an unselected surgical population. Methods We conducted a randomized controlled trial of unselected surgical patients at three hospitals of a tertiary academic medical center. Surgical cases were randomized to alerting algorithms based on either BIS values or anesthetic concentrations. The primary outcome was the incidence of definite intraoperative awareness; prespecified secondary outcomes included postanesthetic recovery variables. Results The study was terminated because of futility. At interim analysis the incidence of definite awareness was 0.12% (11/9,376) (95% CI: 0.07-0.21%) in the anesthetic concentration group and 0.08% (8/9,460) (95% CI: 0.04-0.16%) in the BIS group (P = 0.48). There was no significant difference between the two groups in terms of meeting criteria for recovery room discharge or incidence of nausea and vomiting. By post hoc secondary analysis, the BIS protocol was associated with a 4.7-fold reduction in definite or possible awareness events compared with a cohort receiving no intervention (P = 0.001; 95% CI: 1.7-13.1). Conclusion This negative trial could not detect a difference in the incidence of definite awareness or recovery variables between monitoring protocols based on either BIS values or anesthetic concentration. By post hoc analysis, a protocol based on BIS monitoring reduced the incidence of definite or possible intraoperative awareness compared with routine care.

THE USE OF echocardiography provides real-time, highyield information concerning valve and chamber function and allows intravascular volume assessment as well as an estimate of pulmonary and systemic vascular resistances. As such, the use of intraoperative transesophageal echocardiography (TEE) is recommended to facilitate the diagnosis for patients with hemodynamic instability undergoing noncardiac surgery. Pleural effusion is a common postoperative complication following cardiac surgery and mostly resolves with conservative management. Large pleural effusions can cause hemodynamic compromise, but this has not been reported previously in patients who display normal respiratory mechanics under positive-pressure ventilation. The authors present a case report of a known pleural effusion causing unanticipated hemodynamic compromise during general anesthesia. They postulate that the transition from negativeto positive-pressure mechanical ventilation was a pivotal contributing factor for the development of cardiac tamponade physiology. The emergent use of TEE provided for a rapid diagnosis and facilitated treatment of a pleural effusion with restoration of hemodynamic function.

Background: Hyperglycemia, defined as blood glucose (BG) levels above 200 mg/dl (11.1 mM), is associated with increased postoperative morbidity. Yet, the treatment standard for intraoperative glycemic control is poorly defined for noncardiac surgery. Little is known of the interindividual treatment variability or methods to modify intraoperative glycemic management behaviors. AlertWatch (AlertWatch, USA) is a novel audiovisual alert system that serves as a secondary patient monitor for use in operating rooms. The authors evaluated the influence of use of AlertWatch on intraoperative glycemic management behavior. Methods: AlertWatch displays historical patient data (risk factors and laboratory results) from multiple networked information systems, combined with the patient’s live physiologic data. The authors extracted intraoperative data for 19 months to evaluate the relationship between AlertWatch usage and initiation of insulin treatment for hyperglycemia. Outcome associations were adjusted for physical status, case duration, procedural complexity, emergent procedure, fasting BG value, home insulin therapy, patient age, and primary anesthetist. Results: Overall, 2,341 patients had documented intraoperative hyperglycemia. Use of AlertWatch (791 of 2,341; 33.5%) was associated with 55% increase in insulin treatment (496 of 791 [62.7%] with and 817 of 1,550 [52.7%] without AlertWatch; adjusted odds ratio [95% CI], 1.55 [1.23 to 1.95]; P < 0.001) and 44% increase in BG recheck after insulin administration (407 of 791 [51.5%] with AlertWatch and 655 of 1,550 [42.3%] in controls; adjusted odds ratio [95% CI], 1.44 [1.14 to 1.81]; P = 0.002). Conclusion: AlertWatch is associated with a significant increase in desirable intraoperative glycemic management behavior and may help achieve tighter intraoperative glycemic control.

Superiority of the modified Brice interview over quality assurance techniques in detecting intraoperative awareness with explicit recall has not been demonstrated definitively.We studied a single patient cohort to compare the detection of definite awareness using a single modified Brice interview (postoperative day 28-30) versus quality assurance data (postoperative day 1).The incidence of awareness based on the modified Brice interview was 19 per 18,847 or 0.1%. Fewer awareness cases (incidence 0.02%) were detected by the quality assurance approach (P0.0001).The modified Brice interview is the preferred modality for assessing intraoperative awareness with explicit recall.

Background Videolaryngoscopy presents a new approach for the management of the difficult and rescue airway. There is little available evidence to compare the performance features of these devices in true difficult laryngoscopy. Methods A prospective randomized crossover study was performed comparing the performance features of the Macintosh Laryngoscope, Glidescope, Storz CMAC and Storz DCI videolaryngoscope. Thirty anesthesia providers attempted intubation with each of the 4 laryngoscopes in a high fidelity difficult laryngoscopy manikin. The time to successful intubation (TTSI) was recorded for each device, along with failure rate, and the best view of the glottis obtained. Results Use of the Glidescope, CMAC and Storz videolaryngoscopes improved the view of the glottis compared with use of the Macintosh blade (GEE, p = 0.000, p = 0.002, p = 0.000 respectively). Use of the CMAC resulted in an improved view compared with use of the Storz VL (Fishers, p = 0.05). Use of the Glidescope or Storz videolaryngoscope blade resulted in a longer TTSI compared with either the Macintosh (GLM, p = 0.000, p = 0.029 respectively) or CMAC blades (GLM, p = 0.000, p = 0.033 respectively). Conclusions Unsurprisingly, when used in a simulated difficult laryngoscopy, all the videolaryngoscopes resulted in a better view of the glottis than the Macintosh blade. However, interestingly the CMAC was found to provide a better laryngoscopic view that the Storz DCI Videolaryngoscope. Additionally, use of either the Glidescope or Storz DCI Videolaryngoscope resulted in a prolonged time to successful intubation compared with use of the CMAC or Macintosh blade. The use of the CMAC during manikin simulated difficult laryngoscopy combined the efficacy of attainment of laryngoscopic view with the expediency of successful intubation. Use of the Macintosh blade combined expedience with success, despite a limited laryngoscopic view. The limitations of a manikin model of difficult laryngoscopy limits the conclusions for extrapolation into clinical practice.

Early liver transplantation was marred by excessive blood loss and routinely required massive blood transfusion. Surgical techniques have evolved to improve patient safety and achieve better outcomes for the transplanted organ. In this chapter we review the physiology of caval cross-clamping and explore surgical options to safely establish hepatectomy and transplantation including piggyback technique and venovenous bypass (VVB).

BACKGROUND: Carotid endarterectomy surgery can be performed under regional anaesthesia alone or under general anaesthesia. However, there are several types of regional block available and reported complication rates after superficial cervical plexus blocks are significantly lower than deep blocks. It is not known if subcutaneous and intermediate blocks are equally effective, although anatomical evidence suggests that the latter (where the injectate diffuses below the deep cervical fascia) might provide superior quality of intraoperative anaesthesia. METHODS: Forty-four patients were randomized to receive either subcutaneous or intermediate cervical plexus blocks for carotid endarterectomy. The primary endpoint was supplemental lidocaine requirement during surgery. Secondary outcome measures included: total amount of fentanyl administered during surgery, recall of pain scores during surgery, complications, and patient and surgeon satisfaction. RESULTS: There was no statistically significant difference for median (range) lidocaine supplementation between the subcutaneous and intermediate groups 65 (20-170) mg vs. 85 (30-345) mg, respectively; P=0.31. There were no statistical differences in the secondary outcome measures and no major complications during the study. CONCLUSIONS: Intermediate and subcutaneous cervical plexus blocks are equally effective for carotid endarterectomy. This study adds to the body of evidence supporting the safe use of superficial blocks for this type of surgery.

Objectives. Optimizing cerebral oxygenation is of paramount importance in certain intraoperative situations. There is, however, a paucity of published data pertaining to changes in cerebral oxygenation seen with increases in the inspired fraction of oxygen (Fio2) or end-tidal carbon dioxide (Petco2) in anesthetized patients without vascular disease. Here we tested the hypothesis that changes in Fio2 or Petco2 correlate to a significant change in regional cerebral oxygenation (rSO2) in anesthetized patients without vascular disease. Methods. This was a prospective pilot study approved by the IRB. We measured rSO2 using the INVOS 5100B monitor in ten anesthetized patients. Patients were excluded if they had a history of or risk factors for vascular disease, suffered from respiratory failure, or did not speak English. Following induction of anesthesia and intubation, Fio2 and minute ventilation were sequentially adjusted. At each set point, rSO2 was recorded and arterial blood gas analysis was performed. Each patient acted as their own control. A paired-sample t test was used to evaluate the change in rSO2 resultant upon each intervention. Results. The baseline rSO2 was measured with patients awake, breathing room air and varied between 48 and 72%. While maintaining Petco2 in the range 30–35 mmHg, rSO2 was 8% higher when 100% oxygen was delivered compared to Fio2 30% (P = 0.021). While maintaining Petco2 in the range 40–45 mmHg, rSO2 was 7% higher when 100% oxygen is delivered compared to Fio2 30% (P = 0.032). While maintaining Fio2 at 100%, rSO2 was 2% higher when Petco2 was in the range 40–45 mmHg compared to Petco2 30–35 mmHg (P = 0.017). While maintaining Fio2 at 30%, rSO2 was not statistically different between PECO2 40–45 mmHg and Petco2 30–35 mmHg. Conclusions. Modulating oxygenation and ventilation in anesthetized patients without vascular disease leads to measurable changes in rSO2.

Ten to fifteen percent of awake patients develop neurological deficits secondary to cerebral hypoperfusion after carotid artery cross-clamping. The reversal of such deficits by increasing the inspired oxygen fraction (Fio(2)) has been demonstrated, and regional cerebral oxygenation (rSO(2)) has been shown to improve during carotid cross-clamping in awake patients by increasing Fio(2). Paradoxical improvements in cerebral blood flow during carotid endarterectomy (CEA) at the time of cross-clamping and normalization of post-cross-clamp electroencephalographic abnormalities have been induced by hypocapnia. We performed this study to determine the influence of Fio(2) and end-tidal carbon dioxide (Petco(2)) on rSO(2) in patients undergoing CEA with general anesthesia during carotid cross-clamping.Twenty patients were recruited. Ten underwent elective shunting. Patients received standardized general anesthesia. rSO(2) was measured using the INVOS 5100B monitor (Somanetics Corporation, Troy, MI). After carotid cross-clamping, Fio(2) and minute ventilation were sequentially adjusted: 1) Fio(2) 30%, Petco(2) 30-35 mm Hg; 2) Fio(2) 100%, Petco(2) 30-35 mm Hg; and 3) Fio(2) 100%, Petco(2) 40-45 mm Hg. At each point, rSO(2) was recorded from both operative and nonoperative sides, and arterial blood gas analysis was performed.Results from shunted and unshunted patients were analyzed separately. Increasing Fio(2): Administration of 100% oxygen while maintaining Petco(2) in the range 30-35 mm Hg in unshunted patients resulted in an 8% increase (P = 0.008) in rSO(2) on the operative side and a 6% increase (P = 0.011) on the nonoperative side compared with an Fio(2) of 30%. In shunted patients, administration of 100% oxygen while maintaining the Petco(2) in the range 30-35 mm Hg resulted in a 4% increase in rSO(2) on both the operative side (P = 0.008) and the nonoperative side (P = 0.011) compared with an Fio(2) of 30%. Increasing Petco(2): In unshunted patients, there was a 6% (P = 0.008) increase in rSO(2) on the operative side and a 5% increase (P = 0.024) on the nonoperative side at Petco(2) 40-45 mm Hg compared with Petco(2) 30-35 mm Hg maintaining Fio(2) at 100%. In shunted patients, there was a 3% increase (P = 0.018) in rSO(2) on the operative side and a 4% increase (P = 0.007) on the nonoperative side at Petco(2) 40-45 mm Hg compared with Petco(2) 30-35 mm Hg maintaining Fio(2) at 100%.rSO(2) is reliably improved during carotid cross-clamping by increasing Fio(2) in patients undergoing CEA with general anesthesia. Additional improvement in rSO(2) may be gained by increasing Petco(2).