Abstracts From the 51st Annual Meeting of the Society for Neuroscience in Anesthesiology and Critical Care, September 8-10, 2023

[SNACC 1] Effects of Adrenergic Signalling on Anesthetic Sensitivity and Resistance to State Transition in Mice Andrew McKinstry-Wu, Timothy Jiang, Aden Mandel, Kofi Ayensu, Steven Thomas. University of Pennsylvania, Pennsylvania, United States Introduction: Adrenergic signaling plays a significant role in sleep-to-wake transitions, with increases in locus coeruleus (LC) activity preceding transitions to arousal and LC stimulation inducing those transitions. Animals lacking norepinephrine demonstrate increased sensitivity to anesthetics, and stimulation of LC signaling has been shown to speed emergence. Suppression of LC activity alone, however, has not been shown to have a sedative effect. Here, we investigate the effect of inhibition of adrenergic signaling on behavioral measures of sedation, and on dynamic and EEG measures of anesthetic response at isoflurane steady-state. Methods: Pupillometry: Male and female Dbh-Cre x stop-floxed hM4di (M4) mice (n=6) under 1.0% isoflurane had a camera trained on one eye. After 10 min baseline, they received saline or 20 μg/kg deschlorclozapine (DCZ) I.P. Pupil size was measured with video processing functions in Matlab 2022b. Spontaneous and Forced Movement: Mice previously trained on rotarod (n=17) were given IP DCZ/saline and evaluated on rotarod 20 minutes after injection, then placed in beam-break cages for 1 hour. Baseline, post-rotatrod testing, and post-beam break testing temperature was recorded, Righting Reflex (RR): M4 mice were warmed and exposed to continuous population EC20 isoflurane (n=17). RR was checked every 3 minutes starting after 90 min of isoflurane. After 90 min of baseline, IP saline or DCZ was given and RR checks resumed after 5 minutes for another 90 min. This was repeated in WT controls at EC50. EEG Spectral Analysis: M4 mice (n=7) implanted with 10-lead EEG were exposed to EC20 isoflurane for 2 hours with continuous EEG recording while being warmed. Mice then received 20 μg/kg DCZ IP and recording continued for 90 minutes. Noisy channels were removed, EEG mean rereferenced and filtered between 0.8-35 Hz, and artifacts manually removed. Signal from M1/M2 was analyzed using the Chronux package in Matlab 2022b, comparing spectra of the last 30 minutes baseline to 30-60 minutes after DCZ injection. Spectral slope was calculated as described previously(1) to compare anesthetic depth. Data Analysis: Markov matrix estimation and calculation of sensitivity and resistance to state transition (RST) performed with Matlab 2022b as described previously.(2) Spectral analysis performed using Matlab 2022b and the Chronux package. Statistical calculations used PRISM 9.5 or Matlab 2022b, using paired t-test, one-way ANOVA, or mixed-effect as appropriate with significance set at P< 0.05. Results: M4 mice showed significantly greater pupillary constriction (n=6, P< 0.05) in response to DCZ than saline control, indicating a decrease in central adrenergic tone (Fig. 1A.) This same line showed significant behavioral sedation with DCZ, with a decrease in forced and spontaneous movement (P< 0.0001, Fig. 1C, D.) M4 mice given DCZ also had decreased temperature after rotarod and beam break (P< 0.0001, 3 degree and 12 degree difference, Fig. 1B.) At steady-state isoflurane, DCZ exposure significantly increased population EC to a median 77, compared with no change to saline (P< 0.0001, Fig. 2A.) The change in anesthetic sensitivity DCZ was reflected in EEG spectra, with a greater negative slope induced by DCZ, indicating a deeper anesthetic state (Fig 2B-C.) RST significantly increased in response to DCZ (P< 0.05, Fig 2D.) In contrast, in WT controls, no changes occurred with DCZ (Fig 2E.).FIGURE 1: Decrease in Adrenergic Tone in Male and Female Dbh-Cre x stop-floxed hM4di mice with DCZ Results in Behavioral Sedation and Temperature Decrease. (A) M4 mice show significant pupilary constriction with DCZ.Discussion: We show for the first time behavioral sedation in response to inhibition of adrenergic neurons. Decrease in temperature may be a central adrenergic effect, given known common neural pathways controlling temperature and sedation in response to alpha-2 adrenergic agonists, but may also be a confounding factor in measuring sedation. We show for the first time that acute adrenergic inhibition sensitizes animals to anesthetic hypnosis and show the first change in neural activity, rather than a pharmacologic intervention, that alters RST. This is evidence for control of RST by a neural population implicated in similar sleep-to-wake transitions. Changes in RST and anesthetic sensitivity do not relate to temperature changes as those mice were kept at constant temperature. Decreasing Adrenergic Tone in M4 mice Increases Sensitivity to Isoflurane and Increases Resistance to State Transitions. Male and female M4 mice exposed to unchanging stead-state population EC20 Isoflurane show a profound increase in sensitivity in response to DCZ administration.[SNACC 2] Simultaneous Assessment of Cerebral Oxygenation in Multiple Brain Regions during Adult Shoulder Surgery Full-Head Coverage Multi-Channel Time-Resolved Near-Infrared Spectroscopy: A Pilot Study Farah Kamar, Jason Chui, Mamadou D, Darren D, Daniel M, John M, Leena N, Keith L. University of Western Ontario, Ontario, Canada Introduction: Perioperative stroke is associated with an 8-fold increase in perioperative mortality, prolonged length of hospital stay, and decreased quality of life.1 For shoulder surgery performed in the beach chair position, due to systemic hypotension, cerebral desaturation events occur in up to 80% of patients.2 However, current commercial cerebral oximeters have limitations, including non-specificity due to contamination from extracerebral tissue and only having two channels to monitor frontal lobe regions. Limited spatial coverage may result in undetected stroke. The current research project employed a novel full-head coverage, multi-channel, time-resolved (tr)-NIRS, Kernel Flow, to address these limitations.3 This high-density NIRS system contains 52 light sources, 312 detectors and can record 2206 measurement channels of oxyhemoglobin (HbO) and deoxyhemoglobin (HbR) simultaneously. As this system is a tr-NIRS device, the measurements have superior depth sensitivity compared to conventional NIRS devices. We conducted a pilot prospective cohort study with two objectives: (i) to assess the feasibility of using this device to monitor multiple brain regions during adult shoulder surgery, and (ii) to determine differences in cerebral oxygenation (StO2) between brain regions during surgery, specifically during periods of hypotension and following phenylephrine administration. Methods: After ethics approval, we prospectively recruited adult patients undergoing shoulder surgery in beach chair position from Oct 2022 to Mar 2023 in St. Joseph Hospital, London, Ontario, Canada. The Kernel Flow device was used to continuously measure StO2 that provides increased depth sensitivity (Fig. 1). Continuous blood pressure was measured by finger photoplethysmography (Finometer, Finapres Medical Systems, Enschede, and temperature and anesthetic depth were the were for quality and The changes in and StO2 were calculated for were and and were We differences during and phenylephrine 1: Kernel Flow The Kernel Flow device is of 52 in a can be in that the and on of the of a and at by detectors of is 10 from the The device light to light to or from the and The a is 10 and channels can also be has the and shown in an in shoulder surgery in the beach chair position under the Kernel Flow system was used to monitor a as shown in The was with and to the Kernel in A of patients have been in this patients were with the Kernel system one had by the were events of phenylephrine in 5 with an of After phenylephrine the significantly decreased by and StO2 decreased from to while significantly increased by The was was a of a desaturation in the frontal regions compared to the brain regions after the first of phenylephrine (Fig. was no cerebral desaturation in phenylephrine compared to the first The of StO2 changes also decreased with repeated of phenylephrine (Fig. A measurements of and regions after of phenylephrine in one The of oxyhemoglobin and deoxyhemoglobin changes time were Fig. the differences of differences in and The changes in frontal regions were than regions. Fig. the change in the of cerebral desaturation with repeated of phenylephrine in This has received of phenylephrine during the surgery and the cerebral desaturation was in the first This study the feasibility of and comparing StO2 in multiple brain regions during surgery, a to differences patients hypotension and was a in that the cerebral desaturation phenylephrine may have been by using tr-NIRS that the desaturation events of cerebral events were in frontal and were with repeated of However, due to the of events this pilot study may be We an analysis of the study a of these differences in [SNACC for in for and United States Introduction: The has in a increase in the of patients oxygenation This has in patients with while on during and This two of with 1: A female with and for and was for due to in the to A female with from a was placed on due to acute from and was performed in the position due to of in the to a and was placed in is a intervention, but including and is a in and and for and for the of using the or position for in patients on have and of can be with and as to the and of However, also has including and position has and from the but can to hypotension and blood to the brain in patients with between and is for and the or position is to the of or and of and with continuous of and is for and the In on and and for in this [SNACC Effects on Sedation with as by the United The Surgery States The between and the specifically the the of between these and the In has been to this with and the on and The of from to and measurements have been employed to demonstrate and and changes in following and sedation, the significance of these measurements has not been The is one to measure the of to is can demonstrate changes in from baseline, and differences between of or the same of used for sedation and as an to have been implicated as to and the of in the is a novel by the in for sedation in patients undergoing of 30 minutes in and to an differences greater exposure and is to and compare from those associated with used as Methods: In two 3 was compared to a for sedation of patients undergoing or were with at sedation was were also given a of and received for of patients received they of were a baseline minutes to and a was 5 minutes after The differences between and patients at 5 minutes were Results: Results from shown in 1 and Results were and similar between in a significant decrease in However, the in were greater in the patients the 1: Study that of received sedation with to of Study that of received sedation with to of to measure the a to assess the on from exposure to differences between can as we to the between and the changes in occurred after a exposure 30 may be with used in with for sedation. 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