Psychedelic concentrations of nitrous oxide reduce functional differentiation in frontoparietal and somatomotor cortical networks.

Despite the longstanding use of nitrous oxide and descriptions of its psychological effects more than a century ago, there is a paucity of neurobiological investigation of associated psychedelic experiences. We measure the brain's functional geometry (through analysis of cortical gradients) and temporal dynamics (through analysis of co-activation patterns) using human resting-state functional magnetic resonance imaging data acquired before and during administration of 35% nitrous oxide. Both analyses demonstrate that nitrous oxide reduces functional differentiation in frontoparietal and somatomotor networks. Importantly, the subjective psychedelic experience induced by nitrous oxide is inversely correlated with the degree of functional differentiation. Thus, like classical psychedelics acting on serotonin receptors, nitrous oxide flattens the functional geometry of the cortex and disrupts temporal dynamics in association with psychoactive effects.

Classical and non-classical psychedelic drugs induce common network changes in human cortex.

The neurobiology of the psychedelic experience is not fully understood. Identifying common brain network changes induced by both classical (i.e., acting at the 5-HT2 receptor) and non-classical 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 three drugs 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 qualitative aspects of experience. Thus, both classical and non-classical psychedelics modulate networks within an area of known relevance for consciousness, identifying a biologically plausible candidate for their subjective effects.

Correlation between brain tissue oxygen tension and regional cerebral oximetry in uninjured human brain under conditions of changing ventilation strategy.

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.

Trans-Ocular Brain Impedance Indices Predict Pressure Reactivity Index Changes in a Porcine Model of Hypotension and Cerebral Autoregulation Perturbation.

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Distinct and Dissociable EEG Networks Are Associated With Recovery of Cognitive Function Following Anesthesia-Induced Unconsciousness.

The temporal trajectories and neural mechanisms of recovery of cognitive function after a major perturbation of consciousness is of both clinical and neuroscientific interest. The purpose of the present study was to investigate network-level changes in functional brain connectivity associated with the recovery and return of six cognitive functions after general anesthesia. High-density electroencephalograms (EEG) were recorded from healthy volunteers undergoing a clinically relevant anesthesia protocol (propofol induction and isoflurane maintenance), and age-matched healthy controls. A battery of cognitive tests (motor praxis, visual object learning test, fractal-2-back, abstract matching, psychomotor vigilance test, digital symbol substitution test) was administered at baseline, upon recovery of consciousness (ROC), and at half-hour intervals up to 3 h following ROC. EEG networks were derived using the strength of functional connectivity measured through the weighted phase lag index (wPLI). A partial least squares (PLS) analysis was conducted to assess changes in these networks: (1) between anesthesia and control groups; (2) during the 3-h recovery from anesthesia; and (3) for each cognitive test during recovery from anesthesia. Networks were maximally perturbed upon ROC but returned to baseline 30-60 min following ROC, despite deficits in cognitive performance that persisted up to 3 h following ROC. Additionally, during recovery from anesthesia, cognitive tests conducted at the same time-point activated distinct and dissociable functional connectivity networks across all frequency bands. The results highlight that the return of cognitive function after anesthetic-induced unconsciousness is task-specific, with unique behavioral and brain network trajectories of recovery.

Volume of packed red blood cells and fresh frozen plasma is associated with intraoperative hypocalcaemia during large volume intraoperative transfusion.

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.

Anterior insula regulates brain network transitions that gate conscious access.

Conscious access to sensory information is likely gated at an intermediate site between primary sensory and transmodal association cortices, but the structure responsible remains unknown. We perform functional neuroimaging to determine the neural correlates of conscious access using a volitional mental imagery task, a report paradigm not confounded by motor behavior. Titrating propofol to loss of behavioral responsiveness in healthy volunteers creates dysfunction of the anterior insular cortex (AIC) in association with an impairment of dynamic transitions of default-mode and dorsal attention networks. Candidate subcortical regions mediating sensory gating or arousal (thalamus, basal forebrain) fail to show this association. The gating role of the AIC is consistent with findings in awake participants, whose conscious access is predicted by pre-stimulus AIC activity near perceptual threshold. These data support the hypothesis that AIC, situated at an intermediate position of the cortical hierarchy, regulates brain network transitions that gate conscious access.

Differential classification of states of consciousness using envelope- and phase-based functional connectivity.

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.

Recovery of consciousness and cognition after general anesthesia in humans.

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.

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.

Asymmetric neural dynamics characterize loss and recovery of consciousness.

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.

Brain network motifs are markers of loss and recovery of consciousness.

Motifs are patterns of inter-connections between nodes of a network, and have been investigated as building blocks of directed networks. This study explored the re-organization of 3-node motifs during loss and recovery of consciousness. Nine healthy subjects underwent a 3-h anesthetic protocol while 128-channel electroencephalography (EEG) was recorded. In the alpha (8-13 Hz) band, 5-min epochs of EEG were extracted for: Baseline; Induction; Unconscious; 30-, 10- and 5-min pre-recovery of responsiveness; 30- and 180-min post-recovery of responsiveness. We constructed a functional brain network using the weighted and directed phase lag index, on which we calculated the frequency and topology of 3-node motifs. Three motifs (motifs 1, 2 and 5) were significantly present across participants and epochs, when compared to random networks (p < 0.05). The topology of motifs 1 and 5 changed significantly between responsive and unresponsive epochs (p-values < 0.01; Kendall's W = 0.664 (motif 1) and 0.529 (motif 5)). Motif 1 was constituted of long-range chain-like connections, while motif 5 was constituted of short-range, loop-like connections. Our results suggest that anesthetic-induced unconsciousness is associated with a topological re-organization of network motifs. As motif topological re-organization may precede (motif 5) or accompany (motif 1) the return of responsiveness, motifs could contribute to the understanding of the neural correlates of consciousness.

Trans-ocular brain impedance index for assessment of cerebral autoregulation in a porcine model of cerebral hemodynamic perturbation.

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.

Intraoperative glycemic control in patients undergoing Orthotopic liver transplant: a single center prospective randomized study.

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.

Cerebrovascular Disease and Perioperative Neurologic Vulnerability: A Prospective Cohort Study.

Background: Stroke is a devastating perioperative complication without effective methods for prevention or diagnosis. The objective of this study was to analyze evidence-based strategies for detecting cerebrovascular vulnerability and injury in a high-risk cohort of non-cardiac surgery patients. Methods: This was a single-center, prospective cohort study. Fifty patients undergoing non-cardiac surgery were recruited -25 with known cerebrovascular disease and 25 matched controls. Neurologic vulnerability was measured with intraoperative cerebral oximetry as the primary outcome. Perioperative neurocognitive testing and serum biomarker analysis (S-100ß, neuron specific enolase, glial fibrillary acid protein, and matrix metalloproteinase-9) were measured as secondary outcomes. Results: Cerebral desaturation events (an oximetry decrease ≥20% from baseline or <50% absolute value for ≥3 min) occurred in 7/24 (29%) cerebrovascular disease patients and 2/24 (8.3%) controls (relative risk 3.5, 95% CI 0.81-15.2; P = 0.094). Cognitive function trends were similar in both groups, though overall scores (range: 1,500-7,197) were ~1 standard deviation lower in cerebrovascular patients across the entire perioperative period (-1,049 [95% CI -1,662, -436], P < 0.001). No significant serum biomarker differences were found between groups over time. One control patient experienced intraoperative hypoxic-ischemic injury, but no robust biomarker or oximetry changes were observed. Conclusions: Cerebrovascular disease patients did not demonstrate dramatic differences in cerebral oximetry, cognitive trajectory, or molecular biomarkers compared to controls. Moreover, a catastrophic hypoxic-ischemic event was neither predicted nor detected by any strategy tested. These findings support the need for novel research into cerebrovascular risk and vulnerability.

Brain imaging reveals covert consciousness during behavioral unresponsiveness induced by propofol.

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.

Promoting a Restrictive Intraoperative Transfusion Strategy: The Influence of a Transfusion Guideline and a Novel Software Tool.

BACKGROUND: 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%). METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.

Factors Associated with Postoperative Prolonged Mechanical Ventilation in Pediatric Liver Transplant Recipients.

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.

Network Efficiency and Posterior Alpha Patterns Are Markers of Recovery from General Anesthesia: A High-Density Electroencephalography Study in Healthy Volunteers.

Recent studies have investigated local oscillations, long-range connectivity, and global network patterns to identify neural changes associated with anesthetic-induced unconsciousness. These studies typically employ anesthetic protocols that either just cross the threshold of unconsciousness, or induce deep unconsciousness for a brief period of time-neither of which models general anesthesia for major surgery. To study neural patterns of unconsciousness and recovery in a clinically-relevant context, we used a realistic anesthetic regimen to induce and maintain unconsciousness in eight healthy participants for 3 h. High-density electroencephalogram (EEG) was acquired throughout and for another 3 h after emergence. Seven epochs of 5-min eyes-closed resting states were extracted from the data at baseline as well as 30, 60, 90, 120, 150, and 180-min post-emergence. Additionally, 5-min epochs were extracted during induction, unconsciousness, and immediately prior to recovery of consciousness, for a total of 10 analysis epochs. The EEG data in each epoch were analyzed using source-localized spectral analysis, phase-lag index, and graph theoretical techniques. Posterior alpha power was significantly depressed during unconsciousness, and gradually approached baseline levels over the 3 h recovery period. Phase-lag index did not distinguish between states of consciousness or stages of recovery. Network efficiency was significantly depressed and network clustering coefficient was significantly increased during unconsciousness; these graph theoretical measures returned to baseline during the 3 h recovery period. Posterior alpha power may be a potential biomarker for normal recovery of functional brain networks after general anesthesia.

Neurophysiologic Correlates of Ketamine Sedation and Anesthesia: A High-density Electroencephalography Study in Healthy Volunteers.

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.