Quarterly ReportJul 1 – Sep 30, 2025
Anesthesiology, Q3 2025 edition
We read 261 papers and selected 10.
Summary
The third quarter of 2025 shifted anesthesiology toward precision, mechanism-based, and pragmatic perioperative science. Large randomized trials challenged routine use of BIS-guided anesthesia and supported simple safety interventions such as lateral positioning during procedural sedation, while other trials refined regional anesthesia and pediatric ICU sedation choices. Translational studies identified potentially reversible biological mechanisms involving myocardial membrane cholesterol, RIPK1-JAK1-STAT3 signaling, the blood-nerve barrier, and Apelin-APJ signaling. Dynamic phenotyping and AI-assisted classification emerged as important methodological directions, particularly for ARDS treatment selection. Neuromodulation expanded from noninvasive postpartum analgesia to implantable autonomic support after spinal cord injury. Collectively, the quarter emphasized moving from universal protocols toward individualized treatment, while distinguishing promising mechanistic hypotheses from interventions supported by mature clinical evidence.
Selected Articles
1. Temporal stability of phenotypes of acute respiratory distress syndrome: clinical implications for early corticosteroid therapy and mortality.
An open-source AI classifier identified hyperinflammatory and hypoinflammatory ARDS phenotypes from routine clinical variables. Target trial emulation suggested that corticosteroids may reduce mortality in persistent hyperinflammatory ARDS but increase mortality in hypoinflammatory disease.
Impact: The study offers a practical framework for dynamic, phenotype-guided critical-care treatment rather than static ARDS classification.
Clinical Implications: Phenotype-guided corticosteroid use is promising for research and specialized care but requires prospective validation before routine adoption.
Key Findings
- Approximately 39% of cases were classified as hyperinflammatory and 61% as hypoinflammatory.
- Corticosteroids were associated with divergent mortality effects across phenotypes.
- Nearly half of baseline hyperinflammatory patients changed phenotype over time.
2. Sepsis-induced hypocholesterolemia is linked to low cardiomyocyte membrane cholesterol and impaired catecholamine responsiveness.
Human ICU observations and a longitudinal rat model linked early HDL-C decline and reduced cardiomyocyte membrane cholesterol to impaired dobutamine responsiveness. HDL or liposomal cholesterol restored membrane cholesterol and inotropic responsiveness in animals.
Impact: It identifies a measurable and potentially reversible mechanism of catecholamine-refractory septic shock.
Clinical Implications: HDL-related measures may support future phenotyping, but cholesterol replacement requires controlled clinical safety and efficacy trials.
Key Findings
- Early HDL-C decline was associated with worse outcomes in septic patients and rats.
- Low cardiomyocyte membrane cholesterol correlated with reduced dobutamine responsiveness.
- HDL or liposomal cholesterol restored adrenergic and inotropic responses in animals.
3. RIPK1 Drives JAK1-STAT3 Signaling to Promote CXCL1-Mediated Neutrophil Recruitment in Sepsis-Induced Lung Injury.
Multi-omics and functional preclinical studies identified RIPK1 activation in type II alveolar epithelial cells as an amplifier of JAK1-STAT3-CXCL1 signaling. Genetic or pharmacologic inhibition reduced neutrophil recruitment, preserved the epithelial barrier, and improved survival in septic mice.
Impact: The paper defines a cell-specific and experimentally druggable inflammatory pathway in sepsis-induced lung injury.
Clinical Implications: RIPK1 inhibition merits pharmacologic, toxicologic, and biomarker-enrichment studies before human testing.
Key Findings
- RIPK1 activation in type II alveolar epithelial cells increased CXCL1 through JAK1-STAT3 signaling.
- RIPK1 inhibition reduced neutrophil infiltration and alveolar damage.
- Genetic or pharmacologic inhibition improved survival in septic mice.
4. Neuronal toxicity and recovery from early bortezomib-induced neuropathy: blood-nerve barrier dysfunction without dorsal root ganglion damage.
Translational rat and patient data indicated that early bortezomib neuropathy is driven primarily by perineurial and blood-nerve barrier leakiness rather than major dorsal root ganglion injury. Recovery correlated with barrier resealing and changes in cortactin and netrin-1.
Impact: It reframes chemotherapy neuropathy as a potentially reversible barrier disorder and proposes molecular targets for repair.
Clinical Implications: Blood-nerve barrier and small-fiber measures may support early phenotyping, while barrier-repair therapies require clinical development.
Key Findings
- Early bortezomib exposure caused perineurial leakiness and allodynia with modest ganglion changes.
- Recovery correlated with blood-nerve barrier resealing.
- Netrin-1 and cortactin changes suggested candidate repair mechanisms.
5. An implantable system to restore hemodynamic stability after spinal cord injury.
Epidemiologic analysis and first-in-human testing evaluated thoracic epidural electrical stimulation for autonomic hypotension after spinal cord injury. In 14 participants, targeted stimulation generated pressor responses, reduced hypotensive complications, and improved quality of life and activities of daily living.
Impact: It represents an important first-in-human translation of targeted neuromodulation for a severe and undertreated autonomic disorder.
Clinical Implications: The system may become an option for selected refractory cases, but larger controlled studies and long-term device evaluation are required.
Key Findings
- A substantial burden of chronic hypotension was documented in 1479 patients with spinal cord injury.
- Lower thoracic stimulation produced immediate pressor responses.
- Participants experienced fewer hypotensive complications and improved functional outcomes.
6. Effect of lateral versus supine positioning on hypoxaemia in sedated adults: multicentre randomised controlled trial.
A pragmatic multicenter randomized trial of approximately 2143 adults found that lateral positioning during procedural sedation reduced hypoxaemia and airway rescue interventions without an apparent safety trade-off.
Impact: It provides high-level evidence for an inexpensive, scalable, and immediately implementable sedation-safety intervention.
Clinical Implications: Lateral positioning should be considered when feasible during adult procedural sedation, with usual oxygenation and airway monitoring maintained.
Key Findings
- Lateral positioning reduced the incidence and severity of hypoxaemia.
- Fewer airway rescue interventions were required.
- Benefits were consistent across participating centers without an identified safety compromise.
7. Inhaled isoflurane for sedation of mechanically ventilated children in intensive care (IsoCOMFORT): a multicentre, randomised, active-control, assessor-masked, non-inferiority phase 3 trial.
The phase 3 IsoCOMFORT trial randomized 96 mechanically ventilated children and found inhaled isoflurane non-inferior to intravenous midazolam for time within the target sedation range, with comparable safety across 19 PICUs.
Impact: It supplies unusually strong multicenter evidence for an implementable alternative to intravenous pediatric ICU sedation.
Clinical Implications: Isoflurane may be considered where vaporizers, scavenging, monitoring, and trained staff are available.
Key Findings
- Isoflurane was non-inferior to midazolam for time in the target COMFORT-B range.
- Serious adverse events were similar between groups.
- The trial included 19 PICUs with approximately 48 hours of standardized titration.
8. Transcutaneous Auricular Vagus Nerve Stimulation for Postpartum Contraction Pain During Elective Cesarean Delivery: A Randomized Clinical Trial.
A sham-controlled randomized trial of 156 women found that taVNS reduced moderate-to-severe uterine contraction pain on postoperative day 3 and improved incision pain, mood, recovery quality, and sleep without major safety concerns.
Impact: It provides randomized evidence for a scalable, nonpharmacologic, patient-centered analgesic strategy.
Clinical Implications: taVNS could be an adjunct to standard cesarean analgesia within enhanced recovery pathways after further validation.
Key Findings
- Moderate-to-severe uterine contraction pain occurred in 5.1% with taVNS versus 28.2% with sham stimulation.
- Incision pain, depression, anxiety, recovery quality, and sleep improved.
- No major treatment-related safety signal was reported.
9. Bispectral Index-guided Anesthesia for Older Patients Having Noncardiac Surgery: A Randomized Multicenter Trial.
In 6982 older patients, BIS-guided titration targeting 40-60 did not reduce one-year mortality or 30-day moderate-to-severe complications compared with routine management. Achieved BIS values were nearly identical between groups.
Impact: This large trial directly tested whether a widely used monitoring strategy improves hard outcomes in older surgical patients.
Clinical Implications: Routine BIS use solely to reduce mortality or major complications is not supported, although selected awareness-risk or TIVA cases may still benefit.
Key Findings
- One-year mortality was 10.2% with BIS guidance and 10.0% with routine management.
- Thirty-day moderate-to-severe complications were similar between groups.
- Mean achieved BIS values were 47 and 46, respectively.
10. Continuous versus bolus norepinephrine administration and arterial blood pressure stability during induction of general anaesthesia in high-risk noncardiac surgery patients: a randomised trial.
In 72 high-risk patients, continuous norepinephrine during induction reduced mean arterial pressure variability compared with repeated manual boluses. The intervention was feasible with invasive arterial monitoring, although postoperative organ outcomes were not assessed.
Impact: It tests a simple, protocol-compatible approach to reduce induction-related hemodynamic instability.
Clinical Implications: Continuous norepinephrine may be considered in selected high-risk patients, pending trials of organ outcomes and dosing algorithms.
Key Findings
- Continuous norepinephrine reduced mean arterial pressure variability during the first 15 minutes after induction.
- Arterial monitoring enabled precise assessment of blood pressure stability.
- The study demonstrated feasibility but did not establish postoperative organ benefit.