Monthly ReportMay 1–31, 2025
Anesthesiology, May 2025 edition
We read 102 papers and selected 5.
Summary
May 2025 anesthesiology research was characterized by a convergence of mechanistic neuroscience, precision perioperative management, and pragmatic randomized evidence. Studies identified orexin–nucleus accumbens and central amygdala circuits as potential targets for controlling emergence and anesthesia-related antinociception, while a novel NTSR1 modulator provided a promising preclinical non-opioid analgesic strategy. Clinically, cipepofol improved hemodynamic stability during induction in patients with severe aortic stenosis, and stellate ganglion block reduced arteriovenous fistula complications in hemodialysis patients. Overall, the month emphasized individualized anesthetic drug selection, regional techniques that preserve function or organ integrity, and translation of neurobiological mechanisms into safer perioperative care.
Selected Articles
1. Arrestin-biased allosteric modulator of neurotensin receptor 1 alleviates acute and chronic pain.
This preclinical study identified SBI-810, a beta-arrestin-biased positive allosteric modulator of NTSR1, as an analgesic in postoperative, inflammatory, and neuropathic rodent pain models. Its effects required NTSR1 and beta-arrestin-2 and involved suppression of NMDA/ERK signaling, reduced Nav1.7 surface expression, and decreased neuronal firing without the behavioral liabilities typically associated with opioids.
Impact: SBI-810 introduces a mechanistically distinct non-opioid analgesic strategy with broad activity across acute and chronic pain models and a potentially favorable behavioral profile.
Clinical Implications: The compound supports IND-enabling toxicology, pharmacokinetic/pharmacodynamic studies, and early-phase human trials. It could eventually expand multimodal analgesia and reduce opioid exposure, but clinical translation remains uncertain.
Key Findings
- SBI-810 produced analgesia in postoperative, inflammatory, and neuropathic pain models through systemic and local administration.
- Analgesia required NTSR1 and beta-arrestin-2 and involved NMDA/ERK suppression and reduced Nav1.7 surface expression.
- Behavioral testing showed reduced opioid reward, constipation, and withdrawal-like behaviors.
2. General Anesthesia-activated Neurons in the Central Amygdala Mediate Antinociception: Distinct Roles in Acute versus Chronic Phases of Nerve Injury.
Using TRAP2 labeling, electrophysiology, and chemogenetics in mice, this study identified a GABAergic central amygdala population activated by general anesthesia that increased nociceptive thresholds in normal and subacute nerve-injury states. Antinociception was weaker in chronic injury, which was associated with hyperexcitability of Fos-negative neurons and downregulation of KCC2.
Impact: The study links anesthesia-induced analgesia to a defined amygdala circuit and identifies impaired KCC2-dependent chloride regulation as a possible mechanism of pain chronification.
Clinical Implications: The findings support future development of circuit- or KCC2-directed interventions for patients at risk of persistent postsurgical pain. However, the evidence remains preclinical and requires validation in human pain phenotypes and perioperative trials.
Key Findings
- Isoflurane activated a GABAergic central amygdala neuronal population identified using TRAP2.
- Activation of these neurons increased nociceptive thresholds in naive and subacute nerve-injury mice.
- Chronic nerve injury was associated with reduced antinociception, Fos-negative neuronal hyperexcitability, and KCC2 downregulation.
3. Orexin signalling in the nucleus accumbens promotes arousal from isoflurane anaesthesia and restores communication between the nucleus accumbens and frontal cortex.
This preclinical study used multimodal approaches to show that orexinergic inputs to the nucleus accumbens are activated during arousal from isoflurane anesthesia. Optogenetic or pharmacologic activation shortened emergence, reduced burst suppression, and restored communication between the nucleus accumbens and frontal cortex through OX1R signaling in D1 receptor-positive neurons.
Impact: The study defines a specific arousal circuit and receptor mechanism that could eventually be targeted to modulate emergence from general anesthesia.
Clinical Implications: The findings provide a mechanistic basis for exploring orexinergic or OX1R-targeted agents to shorten emergence or modulate emergence-related EEG patterns. Translation to clinical practice will require human pharmacology, cardiovascular and neurobehavioral safety assessment, and evaluation of emergence agitation risk.
Key Findings
- Orexinergic afferents in the nucleus accumbens were wake-active during isoflurane anesthesia and emergence.
- Optogenetic activation reduced burst suppression and shortened emergence.
- Orexin-A effects were mediated by OX1R on D1 receptor-positive neurons and restored nucleus accumbens–frontal cortex communication.
4. Hemodynamic Impact of Cipepofol vs Propofol During Anesthesia Induction in Patients With Severe Aortic Stenosis: A Randomized Clinical Trial.
In a single-center randomized trial of 122 patients with severe aortic stenosis undergoing TAVR, cipepofol produced a smaller mean arterial pressure deficit during the first 15 minutes after induction than propofol. Post-induction hypotension occurred less frequently and norepinephrine requirements were lower with cipepofol at comparable anesthetic depth.
Impact: This study provides directly actionable randomized evidence for selecting an induction agent in a population in whom hypotension can cause substantial myocardial and cerebral risk.
Clinical Implications: Cipepofol may be considered as an alternative to propofol for induction in severe aortic stenosis or TAVR, particularly when preserving arterial pressure is critical. Multicenter studies should assess myocardial injury, neurologic outcomes, recovery, cost, and generalizability.
Key Findings
- Cipepofol produced a smaller mean arterial pressure deficit area under the curve during the first 15 minutes after induction.
- Post-induction hypotension occurred in 70.5% with cipepofol versus 88.5% with propofol.
- Median norepinephrine use was lower with cipepofol while BIS values were comparable.
5. Stellate ganglion block for preserving arteriovenous fistula in hemodialysis patients undergoing major lower limb orthopedic surgeries: randomized control trial.
In a double-blind, sham-controlled randomized trial of 50 hemodialysis patients, preemptive ultrasound-guided stellate ganglion block before spinal anesthesia increased arteriovenous fistula flow and Doppler velocities. It also reduced thrombosis from 36% to 8% and functional fistula failure from 64% to 32%.
Impact: This randomized evidence identifies a readily available regional anesthesia intervention that may protect vascular access in a particularly vulnerable dialysis population.
Clinical Implications: A stellate ganglion block may be considered before neuraxial anesthesia for selected hemodialysis patients undergoing major limb surgery, with ultrasound guidance, Doppler surveillance, and adherence to standard vascular-access protection protocols.
Key Findings
- Stellate ganglion block increased arteriovenous fistula flow on postoperative days 1 and 7.
- Doppler flow velocities and vascular resistance indices improved compared with sham treatment.
- Thrombosis was 8% versus 36%, and functional failure was 32% versus 64%.