Optogenetic activation of dopamine neurons in the ventral tegmental area induces reanimation from general anesthesia

Dopamine (DA) promotes wakefulness, and DA transporter inhibitors such as dextroamphetamine and methylphenidate are effective for increasing arousal and inducing reanimation, or active emergence from general anesthesia. DA neurons in the ventral tegmental area (VTA) are involved in reward processing, motivation, emotion, reinforcement, and cognition, but their role in regulating wakefulness is less clear. The current study was performed to test the hypothesis that selective optogenetic activation of VTA DA neurons is sufficient to induce arousal from an unconscious, anesthetized state. Floxed-inverse (FLEX)-Channelrhodopsin2 (ChR2) expression was targeted to VTA DA neurons in DA transporter (DAT)-cre mice (ChR2+ group; n = 6). Optical VTA stimulation in ChR2+ mice during continuous, steady-state general anesthesia (CSSGA) with isoflurane produced behavioral and EEG evidence of arousal and restored the righting reflex in 6/6 mice. Pretreatment with the D1 receptor antagonist SCH-23390 before optical VTA stimulation inhibited the arousal responses and restoration of righting in 6/6 ChR2+ mice. In control DAT-cre mice, the VTA was targeted with a viral vector lacking the ChR2 gene (ChR2− group; n = 5). VTA optical stimulation in ChR2− mice did not restore righting or produce EEG changes during isoflurane CSSGA in 5/5 mice. These results provide compelling evidence that selective stimulation of VTA DA neurons is sufficient to induce the transition from an anesthetized, unconscious state to an awake state, suggesting critical involvement in behavioral arousal.United States. National Institutes of Health (TR01-GM104948)United States. National Institutes of Health (T32-GM07592

Physostigmine and Methylphenidate Induce Distinct Arousal States During Isoflurane General Anesthesia in Rats

BACKGROUND: Although emergence from general anesthesia is clinically treated as a passive process driven by the pharmacokinetics of drug clearance, agents that hasten recovery from general anesthesia may be useful for treating delayed emergence, emergence delirium, and postoperative cognitive dysfunction. Activation of central monoaminergic neurotransmission with methylphenidate has been shown to induce reanimation (active emergence) from general anesthesia. Cholinergic neurons in the brainstem and basal forebrain are also known to promote arousal. The objective of this study was to test the hypothesis that physostigmine, a centrally acting cholinesterase inhibitor, induces reanimation from isoflurane anesthesia in adult rats. METHODS: The dose-dependent effects of physostigmine on time to emergence from a standardized isoflurane general anesthetic were tested. It was then determined whether physostigmine restores righting during continuous isoflurane anesthesia. In a separate group of rats with implanted extradural electrodes, physostigmine was administered during continuous inhalation of 1.0% isoflurane, and the electroencephalogram changes were recorded. Finally, 2.0% isoflurane was used to induce burst suppression, and the effects of physostigmine and methylphenidate on burst suppression probability (BSP) were tested. RESULTS: Physostigmine delayed time to emergence from isoflurane anesthesia at doses ≥0.2 mg/kg (n = 9). During continuous isoflurane anesthesia (0.9% ± 0.1%), physostigmine did not restore righting (n = 9). Blocking the peripheral side effects of physostigmine with the coadministration of glycopyrrolate (a muscarinic antagonist that does not cross the blood-brain barrier) produced similar results (n = 9 each). However, during inhalation of 1.0% isoflurane, physostigmine shifted peak electroencephalogram power from δ ( < 4 Hz) to θ (4-8 Hz) in 6 of 6 rats. During continuous 2.0% isoflurane anesthesia, physostigmine induced large, statistically significant decreases in BSP in 6 of 6 rats, whereas methylphenidate did not. CONCLUSIONS: Unlike methylphenidate, physostigmine does not accelerate time to emergence from isoflurane anesthesia and does not restore righting during continuous isoflurane anesthesia. However, physostigmine consistently decreases BSP during deep isoflurane anesthesia, whereas methylphenidate does not. These findings suggest that activation of cholinergic neurotransmission during isoflurane anesthesia produces arousal states that are distinct from those induced by monoaminergic activation.National Institutes of Health (U.S.) (Grant TR01-GM104948)National Institutes of Health (U.S.) (Grant DP1-OD003646)National Institutes of Health (U.S.) (Grant K08-GM094394

Optogenetic activation of cholinergic neurons in the PPT or LDT induces REM sleep

Rapid eye movement (REM) sleep is an important component of the natural sleep/wake cycle, yet the mechanisms that regulate REM sleep remain incompletely understood. Cholinergic neurons in the mesopontine tegmentum have been implicated in REM sleep regulation, but lesions of this area have had varying effects on REM sleep. Therefore, this study aimed to clarify the role of cholinergic neurons in the pedunculopontine tegmentum (PPT) and laterodorsal tegmentum (LDT) in REM sleep generation. Selective optogenetic activation of cholinergic neurons in the PPT or LDT during non-REM (NREM) sleep increased the number of REM sleep episodes and did not change REM sleep episode duration. Activation of cholinergic neurons in the PPT or LDT during NREM sleep was sufficient to induce REM sleep.National Institutes of Health (U.S.) (Grant DP1-OD003646)National Institutes of Health (U.S.) (Grant TR01-GM104948)National Institutes of Health (U.S.) (Grant T32-HL07901)Massachusetts General Hospital (Executive Committee on Research Fellowship)Massachusetts General Hospital. Dept. of Anesthesia, Critical Care, and Pain Medicin

Retrospective Review of Outcomes in Non-Invasive Mucinous Appendiceal Neoplasms with and without Peritoneal Spread: A Cohort Study

Patients treated surgically for local non-invasive mucinous appendiceal neoplasm (NI-MAN) may recur with the development of peritoneal dissemination (PD). The risk of recurrence and predictive factors are not well studied. Patients with NI-MAN, with or without peritoneal dissemination at presentation, were included. Patients with limited disease underwent surgical resection only. Patients with peritoneal dissemination underwent cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC). Patients without PD (nPD) were compared to those who presented with PD. Thirty-nine patients were included, 25 in nPD and 14 in PD. LAMN was diagnosed in 96% and 93% of patients in nPD and PD, respectively. Acellular mucin on the peritoneal surface was seen in 16% of nPD patients vs. 50% of PD patients (p = 0.019). Two (8%) patients in the nPD group who had LAMN without wall rupture recurred, at 57 and 68 months, with a PCI of 9 and 22. The recurrence rate in the PD group was 36%. All recurred patients underwent CRS+HIPEC. A peritoneal recurrence is possible in NI-MANs confined to the appendix even with an intact wall at initial diagnosis. The peritoneal disease may occur with significant delay, which is longer than a conventional follow-up

Performance expectancy drives health professionals’ acceptance of digital tools for antimicrobial prescribing

Background: The digitisation of hospitals has presented new opportunities to curb antimicrobial misuse. However, access to digital tools does not guarantee use. Performance expectancy, from the unified theory of acceptance and use of technology (UTAUT), a common technology acceptance model, is the strongest predictor of users’ intention to use technology. Aim: Synthesise and understand health professionals’ expectations related to performance of digital tools for antimicrobial prescribing.Methods: A systematic review was conducted to identify qualitative studies that explored user perceptions of digital tools for antimicrobial prescribing. User perceptions were extracted from each paper and classified using the UTAUT model and as either facilitators or barriers to use.Results: Thirteen studies met the inclusion criteria. Twelve of these reported user perceptions related to performance expectancy, highlighting users were more likely to use digital tools if they believed systems helped them achieve gains in job performance. The majority of perceptions related to the perceived usefulness of digital tools or whether tools were seen as better than their precursors. Reported facilitators to use included digital tools being trusted/credible sources of information, improving the performance of tasks, or increasing efficiency. A key reported barrier was tools providing information/recommendations not useful for a setting (e.g., emergency department), or patient condition(s). Conclusions: To ensure use of antimicrobial digital tools in hospitals, organisations need to consider health professionals’ performance expectations. Conveying benefits resulting from the use of digital tools to users, and ensuring utility matches expectations, could increase use of digital tools for antimicrobial prescribing

Building Rapport and Earning the Surgical Patient\u27s Trust in the Era of Social Distancing: Teaching Patient-Centered Communication During Video Conference Encounters to Medical Students.

BACKGROUND: Effective physician communication improves care, and many medical schools and residency programs have adopted communication focused curricula. The COVID-19 pandemic has shifted the doctor-patient communication paradigm with the rapid adoption of video-based medical appointments by the majority of the medical community. The pandemic has also necessitated a sweeping move to online learning, including teaching and facilitating the practice of communication skills remotely. We aimed to identify effective techniques for surgeons to build relationships during a video consult, and to design and pilot a class that increased student skill in communicating during a video consult. METHODS: Fourth-year medical students matched into a surgical internship attended a 2-hour class virtually. The class provided suggestions for building rapport and earning trust with patients and families by video, role play sessions with a simulated patient, and group debriefing and feedback. A group debriefing generated lessons learned and best practices for telemedicine communication in surgery. RESULTS: Students felt the class introduced new skills and reinforced current ones; most reported higher self-confidence in target communication skills following the module. Students were particularly appreciative of opportunity for direct observation of skills and immediate faculty feedback, noting that the intimate setting was unique and valuable. Several elements of virtual communications required increased focus to communicate empathy and concern. Proper lighting and positioning relative to the camera were particularly important and body movement required narration to minimize misinterpretation. A patient\u27s distress was more difficult to interpret; asking direct questions was recommended to understand the patient\u27s emotional state. CONCLUSIONS: There is a need to teach video-conference communication skills to enable surgical teams to build rapport in this distinct form of consultation. Our training plan appears effective at engaging learners and improving skills and confidence, and identifies areas of focus when teaching virtual communication skills

Carotid Endarterectomy Under Local Anesthesia Has Less Risk of Myocardial Infarction Compared to General Anesthesia: An Analysis of National Surgical Quality Improvement Program Database

Objectives As carotid endarterectomy (CEA) is being increasingly compared to carotid artery stenting and the best current medical management, it has become important to revisit variables that might affect the outcomes of the procedure. Multiple studies have evaluated the effect of anesthesia type on CEA with inconsistent results. Our study compared 30 day postoperative myocardial infarction (MI), stroke and mortality between CEA under local or regional anesthesia (LA) and CEA under general anesthesia (GA) utilizing National Surgical Quality Improvement Program (NSQIP) database. Methods All patients listed in NSQIP database that underwent CEA under GA and LA from 2005-2011 were included with the exception of patients undergoing simultaneous CEA and CABG. Postoperative MI, stroke, and death at 30 days were compared between the two groups using simple and multiple logistic regression. Results A total of 42,265 CEA cases were included. 37,502 (88.7%) were performed under GA and 4763 (11.3%) under LA. CEA under LA had a significantly decreased risk of 30 day postoperative MI when compared to CEA under GA (0.4% vs 0.86%; P = .012). No statistically significant differences were found in postoperative stroke or mortality ( Table). Conclusions CEA under LA carries a decreased risk of postoperative MI when compared to CEA under GA. Patients with multiple comorbidities at risk of postoperative MI should be considered for CEA under LA. Table Comparison of 30-day postoperative MI, stroke, and death for CEA under LA vs GA with and without adjustment for confounding factors CEA under LA (n = 4763)CEA under GA (n = 37,502)Unadjusted P valueAdjusted P value MI, No. (%) 20 (0.40) 323 (0.86) .002 .012 Stroke, No. (%) 66 (1.39) 592 (1.58) .318 .540 Death, No. (%) 32 (0.67) 315 (0.84) .227 .66