Daily Anesthesiology Research Analysis
Three notable anesthesiology papers stood out: a mechanistic mouse study mapped a supramammillary–medial septum glutamatergic circuit that facilitates emergence from isoflurane anesthesia; a large multinational RCT found no difference in postoperative delirium or 1-year cognitive decline between perioperative hypotension-avoidance versus hypertension-avoidance strategies; and a randomized, double-blind bronchoscopy trial showed ciprofol yields more stable hemodynamics and less injection pain tha
Summary
Three notable anesthesiology papers stood out: a mechanistic mouse study mapped a supramammillary–medial septum glutamatergic circuit that facilitates emergence from isoflurane anesthesia; a large multinational RCT found no difference in postoperative delirium or 1-year cognitive decline between perioperative hypotension-avoidance versus hypertension-avoidance strategies; and a randomized, double-blind bronchoscopy trial showed ciprofol yields more stable hemodynamics and less injection pain than propofol.
Research Themes
- Neural circuit mechanisms of anesthesia and emergence
- Perioperative hemodynamic strategies and neurocognitive outcomes
- Optimization of anesthetic induction for bronchoscopy
Selected Articles
1. Role of the Supramammillary Nucleus-Medial Septum Glutamatergic Pathway in Mediating the Effects of Isoflurane Anesthesia.
In mice, SuM glutamatergic neuron activity is suppressed by isoflurane and rebounds upon emergence. Optogenetic/chemogenetic activation of SuM→medial septum projections reduced EEG delta and burst suppression, increased arousal-related physiology, and markedly shortened emergence time. This identifies a discrete arousal circuit that can bidirectionally modulate anesthetic depth and emergence.
Impact: This work provides mechanistic, circuit-level evidence for controlling anesthetic states and emergence, opening avenues for targeted neuromodulation to hasten recovery from anesthesia.
Clinical Implications: While preclinical, the SuM→medial septum pathway could be a target to speed emergence, reduce burst suppression, or stabilize respiration under anesthesia. It may inform development of pro-emergence adjuncts or closed-loop depth-of-anesthesia algorithms.
Key Findings
- SuM glutamatergic activity decreased during isoflurane anesthesia and recovered with emergence.
- Optogenetic activation reduced EEG delta power (≈51% to ≈32%, n=8, P=0.002) and burst suppression ratio (≈82% to ≈45%, n=8, P=0.002).
- Activation enlarged pupil diameter, increased respiratory rate and blood pressure, and accelerated emergence (≈171 s to ≈60 s, n=8, P=0.007).
- Chemogenetic activation mirrored, and inhibition opposed, these effects.
- Stimulating SuM terminals in the medial septum replicated cortical/physiologic effects and increased medial septum glutamatergic neuron activity.
Methodological Strengths
- Multimodal approach (fiber photometry, optogenetics, chemogenetics) with convergent results
- Comprehensive physiologic readouts (EEG, pupil, respiration, blood pressure) and behavioral endpoints
Limitations
- Preclinical mouse model; translational validity to humans remains to be established
- Focused on isoflurane; generalizability to other anesthetics is uncertain
Future Directions: Test whether pharmacologic or neuromodulatory manipulation of SuM or medial septum can safely hasten emergence in larger animals/humans and integrate circuit biomarkers into closed-loop anesthesia systems.
BACKGROUND: Glutamatergic neurons in the supramammillary nucleus (SuM) have been recently identified as a key node in arousal system, yet their role in regulating general anesthesia remains unclear. The aim of the current study is to examine the role of the glutamatergic supramammillary neurons and their projections to the medial septum in mediating the effects of isoflurane anesthesia. METHODS: Fiber photometry recording was used to determine the changes in calcium signals of glutamatergic neurons in the SuM during isoflurane anesthesia. Optogenetic and chemogenetic approaches were employed to manipulate SuM glutamatergic neuron activity, and the effects on cortical activity, behavioral responses, and physiologic parameters-including pupil diameter, respiratory rate, and blood pressure-were examined in anesthetized mice. Both male and female mice were used in this study. RESULTS: The activities of SuM glutamatergic neurons decreased during isoflurane anesthesia and recovered after the emergence. Optogenetic activation of these neurons enhanced cortical activity, decreasing electroencephalogram delta power (mean ± SD, prestimulation vs . stimulation: 51.35 ± 7.26% vs . 32.08 ± 10.48%, n = 8, P = 0.002) and burst suppression ratio (81.82 ± 7.83% vs . 44.53 ± 28.62%, n = 8, P = 0.002). Furthermore, optogenetic activation altered physiologic parameters including enlarged pupil diameter (prestimulation vs. stimulation: 1.05 ± 0.08% vs. 1.95 ± 0.46%, n = 8, P < 0.001), increased respiratory rate (0.98 ± 0.08% vs. 1.57 ± 0.39%, n = 10, P < 0.001) and elevated blood pressure and induced behavioral responses including increased arousal scores and accelerated emergence (light off vs . light on, 171.40 ± 56.39 s to 59.88 ± 27.18 s, n = 8, P = 0.007). Moreover, chemogenetic activation produced similar effects, whereas inhibition led to opposite effects. Finally, optogenetically activating SuM glutamatergic terminals projecting to the medial septum mimicked the effects of activating SuM glutamatergic soma and increased the activity of medial septum glutamatergic neurons. CONCLUSIONS: This study identifies glutamatergic neurons of the SuM as key neural substrates regulating isoflurane anesthesia and facilitating emergence through their projections to the medial septum.
2. Effects of a Hypotension-Avoidance Versus a Hypertension-Avoidance Strategy on Neurocognitive Outcomes After Noncardiac Surgery.
In 2,603 high-vascular-risk patients across 54 centers, targeting higher intraoperative MAP (≥80 mmHg) with perioperative RAAS inhibitor withholding did not reduce postoperative delirium (7.3% vs 7.0%) or 1-year MoCA decline versus a lower MAP target (≥60 mmHg) with antihypertensive continuation. The hypotension-avoidance strategy reduced hypotension requiring intervention (19% vs 27%), mainly intraoperatively.
Impact: This large, multicenter RCT directly informs perioperative blood pressure and antihypertensive management, showing no neurocognitive benefit from a higher MAP target and RAAS inhibitor withholding.
Clinical Implications: Do not expect neurocognitive benefits from targeting higher intraoperative MAP or withholding RAAS inhibitors in this population; delirium prevention likely needs other strategies. The choice to aim higher MAP or withhold RAAS inhibitors may be driven by hemodynamic stability (fewer hypotension interventions) rather than cognitive endpoints.
Key Findings
- Delirium incidence was similar: 7.3% (hypotension-avoidance) vs 7.0% (hypertension-avoidance); RR 1.04 (95% CI 0.79–1.38).
- At 1 year, ≥2-point MoCA decline did not differ: 37.2% vs 33.1%; RR 1.13 (95% CI 0.92–1.38) among 701 completers.
- Hypotension requiring intervention was lower with hypotension-avoidance: 19% vs 27%; RR 0.63 (95% CI 0.52–0.76), predominantly intraoperative.
- Postoperative hypotension occurred in 5% in both groups.
- COVID-19 affected substudy participation; the 1-year cognitive outcome sample was smaller than planned.
Methodological Strengths
- Multinational, multicenter randomized design with prespecified outcomes and trial registration
- Algorithm-driven hemodynamic targets and standardized antihypertensive strategies
Limitations
- 1-year cognitive outcome completion was limited (701/2603), reducing power for that endpoint
- Pandemic-related site challenges; potential heterogeneity across 54 centers
Future Directions: Evaluate multimodal delirium prevention (e.g., analgesia-sedation bundles, sleep/mobilization, non-pharmacologic measures) and individualized MAP targets using autoregulation monitoring rather than fixed thresholds.
BACKGROUND: Perioperative hemodynamic abnormalities have been associated with neurocognitive outcomes after noncardiac surgery. OBJECTIVE: To compare the effects of perioperative hypotension-avoidance versus hypertension-avoidance strategies on delirium and 1-year cognitive decline after noncardiac surgery. DESIGN: Randomized controlled trial. (ClinicalTrials.gov: NCT03505723). SETTING: 54 centers, 19 countries. PARTICIPANTS: 2603 high-vascular-risk patients undergoing noncardiac surgery, receiving 1 or more chronic antihypertensive medications (mean age, 70 years). INTERVENTION: In the hypotension-avoidance strategy, the intraoperative mean arterial pressure (MAP) target was 80 mm Hg or greater; before and for 2 days after surgery, renin-angiotensin-aldosterone system inhibitors were withheld, and other chronic antihypertensive medications were administered for systolic blood pressures of 130 mm Hg or greater following an algorithm. In the hypertension-avoidance strategy, the intraoperative MAP target was 60 mm Hg or greater; all chronic antihypertensive medications were continued perioperatively. MEASUREMENTS: Delirium on postoperative day 1 to 3 (primary outcome); decline of 2 points or more at the Montreal Cognitive Assessment (MoCA) 1 year after surgery compared with baseline (secondary outcome). RESULTS: 95 of 1310 patients (7.3%) in the hypotension-avoidance and 90 of 1293 patients (7.0%) in the hypertension-avoidance group had delirium (relative risk [RR], 1.04 [95% CI, 0.79 to 1.38]). Among 701 patients who completed 1-year MoCA (full or telephone version), 129 of 347 (37.2%) in the hypotension-avoidance and 117 of 354 (33.1%) in the hypertension-avoidance group had a decline of 2 or more points (RR, 1.13 [CI, 0.92 to 1.38]). Nineteen percent in the hypotension-avoidance and 27% in the hypertension-avoidance strategy had hypotension requiring an intervention (RR, 0.63 [CI, 0.52 to 0.76]), mostly intraoperatively; only 5%, in both groups, had hypotension postoperatively. LIMITATION: The COVID-19 pandemic challenged site participation in the substudy; although large, the sample size was lower than expected. CONCLUSION: There was no evidence of a difference in neurocognitive outcomes between the hypotension-avoidance and hypertension-avoidance strategies. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research, Canada; National Health and Medical Research Council, Australia; Research Grant Council, Hong Kong SAR, China.
3. Effect of ciprofol compared with propofol on hemodynamics in bronchoscope procedures during anesthetic induction: a randomized double-blind controlled study.
In a randomized, double-blind trial of 250 bronchoscopy patients, ciprofol produced more stable blood pressure several minutes after induction and reduced injection pain compared with propofol, with favorable satisfaction across operators, anesthesiologists, and patients. Findings support ciprofol as an alternative induction agent for bronchoscopy under LMA.
Impact: Provides randomized evidence that a propofol analog can mitigate hemodynamic depression and injection pain in bronchoscopy, a high-volume procedural sedation context.
Clinical Implications: Ciprofol may be preferred over propofol for bronchoscopy induction in patients at risk for hypotension or when minimizing injection pain is desirable; dosing strategies and broader safety profiles need confirmation.
Key Findings
- Randomized, double-blind comparison (n=250) of ciprofol vs propofol for bronchoscopy induction under LMA.
- Ciprofol yielded higher (more stable) blood pressure 3 minutes after induction compared with propofol.
- Injection pain incidence was lower with ciprofol, with improved satisfaction among operators, anesthesiologists, and patients.
- Vasoactive drug use and airway events were assessed; overall hemodynamic impact favored ciprofol.
Methodological Strengths
- Randomized, double-blind, controlled design with adequate sample size for a procedural anesthesia study
- Multifaceted outcomes including hemodynamics, pain on injection, and stakeholder satisfaction
Limitations
- Single-center setting; generalizability across practices and populations is uncertain
- Partial reporting of quantitative hemodynamic differences in abstract; full data needed for effect size appraisal
Future Directions: Head-to-head trials across diverse procedural sedation settings, dose-finding studies, and safety comparisons (e.g., respiratory events) versus propofol in higher-risk cohorts.
OBJECTIVE: Propofol poses hemodynamic challenges and injection pain during anesthesia. This study compared the effects of propofol and ciprofol, a novel propofol analog, on hemodynamics in painless bronchoscopy during induction of general anesthesia. METHODS: A total of 250 patients underwent painless bronchoscopy anesthesia from October 2021 to June 2023. Randomly assigned to ciprofol or propofol groups, they received respective anesthesia. Changes in heart rate, blood pressure pre- and post-induction, after laryngeal mask airway placement, before and after fiberoptic scope insertion, incidence of choking and injection pain, vasoactive drug use, and satisfaction levels of operators, anesthesiologists, and patients were compared. RESULTS: Ciprofol group showed significantly higher blood pressure 3 min post-induction compared to propofol group (80.81 ± 12.49 mmHg vs. 84.47 ± 12.80 mmHg, CONCLUSION: Ciprofol exhibits less hemodynamic impact and injection pain than propofol, suggesting it as a viable alternative for anesthesia induction in bronchoscopy under general anesthesia with a laryngeal mask airway. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/, identifier [ChiCTR2200063048].