Yearly ReportJan 1 – Dec 31, 2025
Anesthesiology, 2025 edition
We read 1835 papers and selected 10.
Summary
The landmark anesthesiology research of 2025 was defined by a transition from universal perioperative protocols toward individualized, physiology-guided, biomarker-enriched, and mechanism-based care. Large randomized trials demonstrated that capillary refill time can guide septic-shock resuscitation, biomarker enrichment can reduce postoperative acute kidney injury, and routine high PEEP with recruitment may cause harm without improving pulmonary outcomes. Translational neuroscience and structural biology produced major advances in understanding emergence, opioid receptor activation, pain, and malignant hyperthermia pharmacology. Dynamic ARDS phenotyping illustrated how temporal biological classification may replace static diagnostic labels in treatment selection. Computational infrastructure, including EHR-omics transfer learning, expanded the methodological foundation for precision perioperative research. Clinical blood-management evidence also strengthened the case for selected prothrombin complex concentrate use in cardiac surgery. Across the year, the most durable contributions combined rigorous comparative trials with discoveries that could redirect future therapeutic development. Negative and de-implementation trials were equally important because they separated improved surrogate physiology from improved patient outcomes.
Selected Articles
1. A preventive care strategy to reduce moderate or severe acute kidney injury after major surgery (BigpAK-2); a multinational, randomised clinical trial.
This multinational randomized trial demonstrated that biomarker enrichment can identify surgical patients who benefit from a KDIGO-aligned prevention bundle, converting risk prediction into effective perioperative organ protection.
Impact: It is one of the clearest demonstrations that biomarker-guided enrichment can produce a clinically meaningful reduction in postoperative organ injury.
Clinical Implications: High-risk surgical patients identified by urinary tubular-stress biomarkers may benefit from hemodynamic optimization, nephrotoxin avoidance, and protocolized volume and pressure management.
Key Findings
- Moderate-to-severe AKI occurred in 14.4% with the intervention versus 22.3% with usual care.
- The intervention had an odds ratio of approximately 0.57 and an approximate number needed to treat of 12.
- Major adverse events did not increase with the prevention bundle.
Methodological Strengths
- Multinational randomized clinical trial with biomarker-enriched enrollment.
- Patient-centered kidney outcome and safety assessment.
Limitations
- Generalizability depends on availability and validation of the tubular-stress biomarker.
- The bundle contained multiple components, preventing attribution to a single intervention.
Future Directions: Future studies should validate the biomarker algorithm across health systems, compare implementation strategies, and determine whether earlier or less intensive bundles are effective.
BigpAK-2 randomized biomarker-enriched high-risk surgical patients to a KDIGO-aligned prevention bundle or usual care. Moderate-to-severe AKI was reduced from 22.3% to 14.4% without an increase in major adverse events.
2. Personalized Hemodynamic Resuscitation Targeting Capillary Refill Time in Early Septic Shock: The ANDROMEDA-SHOCK-2 Randomized Clinical Trial.
ANDROMEDA-SHOCK-2 provided high-level evidence that a simple bedside perfusion marker can guide individualized septic-shock resuscitation and reduce the duration of vasopressor, ventilatory, and kidney-replacement support.
Impact: It converted bedside microcirculatory assessment into a prospectively tested precision-resuscitation strategy with international applicability.
Clinical Implications: Serial capillary refill assessment can complement blood pressure, echocardiography, and fluid-responsiveness testing in early septic shock.
Key Findings
- The hierarchical composite outcome improved with a win ratio of 1.16.
- The principal benefit involved shorter vasopressor, ventilation, and kidney-replacement durations.
- The trial enrolled 1,467 patients across 86 centers in 19 countries.
Methodological Strengths
- Large international randomized clinical trial.
- Multimodal algorithm combining a simple bedside measure with advanced hemodynamic assessment.
Limitations
- Capillary refill measurement may have interobserver variability.
- The hierarchical outcome was driven substantially by duration of organ support rather than mortality.
Future Directions: Research should standardize measurement, evaluate training requirements, and determine which patient phenotypes derive the greatest benefit from capillary refill-guided resuscitation.
This international randomized trial of 1,467 patients tested a capillary refill time–guided algorithm integrated with blood pressure, pulse pressure, fluid responsiveness, and echocardiography. The strategy improved a hierarchical 28-day outcome, mainly by reducing durations of organ support.
3. Non-equilibrium snapshots of ligand efficacy at the μ-opioid receptor.
This structural-biology study captured receptor activation as a dynamic trajectory rather than a static conformation, providing a framework for designing analgesics that separate desired efficacy from respiratory depression.
Impact: It is a fundamental mechanistic advance with broad implications for next-generation opioid design and pharmacology.
Clinical Implications: The findings are not immediately practice-changing but may enable safer signaling-selective opioids with less respiratory toxicity.
Key Findings
- Time-resolved cryo-EM captured intermediate MOR-G-protein activation states.
- Partial, full, and super-agonists produced distinguishable activation trajectories.
- Structural dynamics linked ligand efficacy to receptor signaling.
Methodological Strengths
- Time-resolved high-resolution structural analysis.
- Direct comparison of ligands with different efficacy profiles.
Limitations
- The study does not establish in vivo analgesic or respiratory safety.
- Structural trajectories may not capture all cell-type and tissue-context effects.
Future Directions: Future work should connect the observed conformational trajectories to downstream signaling, analgesia, tolerance, and respiratory depression in vivo.
Time-resolved cryo-electron microscopy captured intermediate μ-opioid receptor–G-protein states during activation. Partial, full, and super-agonists produced distinct structural trajectories, linking ligand efficacy to dynamic receptor signaling.
4. Effects of intraoperative higher versus lower positive end-expiratory pressure during one-lung ventilation for thoracic surgery on postoperative pulmonary complications (PROTHOR): a multicentre, international, randomised, controlled, phase 3 trial.
PROTHOR was a definitive trial showing that routine high PEEP with recruitment during one-lung ventilation does not improve postoperative pulmonary outcomes and increases hemodynamic harm.
Impact: It directly challenged a widely accepted physiologic strategy using a large international phase 3 trial and patient-important outcomes.
Clinical Implications: Routine high PEEP with recruitment should generally be avoided in similar patients; lower PEEP with close monitoring and selective rescue is more defensible.
Key Findings
- Postoperative pulmonary complications were similar: 53.6% versus 56.4%.
- High PEEP increased hypotension from 14.3% to 37.3%.
- New arrhythmias increased from 3.9% to 9.9% with high PEEP.
Methodological Strengths
- Large phase 3, international, multicenter randomized design.
- Assessment of pulmonary and hemodynamic patient-important outcomes.
Limitations
- The findings may not apply to patients with substantially different baseline lung mechanics.
- The low-PEEP strategy required more rescue interventions for hypoxemia.
Future Directions: Future studies should identify patients who benefit from higher PEEP and develop individualized ventilation algorithms balancing oxygenation and hemodynamic tolerance.
In 2,200 patients from 28 countries, high PEEP with recruitment did not reduce postoperative pulmonary complications compared with low PEEP without recruitment. High PEEP increased hypotension and arrhythmias, whereas low PEEP required more rescue maneuvers for hypoxemia.
5. Temporal stability of phenotypes of acute respiratory distress syndrome: clinical implications for early corticosteroid therapy and mortality.
This study combined open-source AI, temporal reassessment, and causal-inference methods to show that ARDS phenotypes can change over time and may modify the effect of corticosteroids.
Impact: It offers a generalizable framework for replacing static critical-care labels with dynamic treatment-response phenotypes.
Clinical Implications: The findings support research use of serial phenotype classification but do not yet justify routine phenotype-guided corticosteroid therapy.
Key Findings
- Approximately 39% of cases were classified as hyperinflammatory and 61% as hypoinflammatory.
- Corticosteroid effects on mortality differed across phenotypes.
- Nearly half of baseline hyperinflammatory patients changed phenotype over time.
Methodological Strengths
- Open-source classifier using routinely available clinical variables.
- Integration of temporal phenotyping with target-trial emulation.
Limitations
- Treatment effects were estimated observationally rather than in a randomized phenotype-guided trial.
- Classifier performance and treatment interactions require prospective external validation.
Future Directions: Prospective trials should randomize treatment within dynamically reassessed phenotypes and determine whether serial classification improves outcomes.
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.
6. A machine learning approach to leveraging electronic health records for enhanced omics analysis.
COMET established reusable computational infrastructure for integrating large-scale EHR data with smaller omics cohorts, enabling more granular biological phenotyping and discovery.
Impact: Its principal contribution is methodological: it can influence many future anesthesiology and critical-care studies rather than only one disease area.
Clinical Implications: COMET is not a clinical decision tool but may support discovery-stage models for delirium, AKI, pulmonary complications, and other perioperative outcomes.
Key Findings
- COMET combines EHR pretraining with adaptive clinical-omics fusion.
- It improved predictive modeling and biological discovery in two independent datasets.
- It enabled patient stratification beyond binary case-control labels.
Methodological Strengths
- Transfer learning leverages large real-world EHR datasets.
- Validation across independent datasets and integration of multimodal data.
Limitations
- The framework is not yet prospectively validated for clinical decisions.
- Performance may depend on data quality, coding practices, and population transportability.
Future Directions: Future studies should externally validate COMET-derived phenotypes, assess fairness and calibration, and test whether implementation improves patient outcomes.
COMET is a transfer-learning framework that pretrains on large observational EHR datasets and integrates clinical and omics data from smaller cohorts. Across two independent datasets, it improved prediction and biological discovery and enabled more granular patient stratification than binary case-control classification.
7. Antibody-secreting cell repertoires hold high-affinity anti-rocuronium specificities that can induce anaphylaxis in vivo.
This translational study provided direct molecular and structural evidence for rocuronium-specific IgE-mediated anaphylaxis and created a foundation for epitope-resolved perioperative allergy diagnostics.
Impact: It transformed a clinically recognized but incompletely understood perioperative emergency into a structurally defined and testable immunologic problem.
Clinical Implications: The findings may improve evaluation of suspected neuromuscular-blocker allergy and support future epitope-specific diagnostics and alternative-agent selection.
Key Findings
- More than 500 VH-VL pairs included antibody families with subnanomolar affinity for rocuronium.
- Human IgE versions activated mast cells and basophils and caused severe anaphylaxis in humanized mice.
- Cocrystal structures identified distinct rocuronium-binding modes involving the ammonium group.
Methodological Strengths
- Integration of single-cell sequencing, structural crystallography, and humanized in vivo models.
- Mechanistic triangulation from antibody repertoire to effector-cell activation and anaphylaxis.
Limitations
- Clinical diagnostic performance and prevalence of the identified epitopes remain unconfirmed.
- Humanized mouse responses may not reproduce the full complexity of perioperative anaphylaxis.
Future Directions: Clinical studies should validate epitope-specific assays, define their predictive value, and test whether they improve perioperative allergy evaluation.
Using single-cell VH/VL sequencing, structural crystallography, and FcεRI-humanized mice, this translational study identified high-affinity human-format anti-rocuronium antibodies. These antibodies activated human effector cells and caused severe anaphylaxis in vivo, while structural analyses mapped distinct epitopes involving the ammonium moiety.
8. The role of the dorsomedial periaqueductal gray glutamatergic neurons in promoting arousal under multiple general anesthetics in mice.
This causal neuroscience study identified a convergent arousal circuit that regulates induction, maintenance-related burst suppression, and emergence across multiple anesthetic classes.
Impact: It provides a unified circuit-level model for anesthetic state transitions and a potential target for active control of delayed emergence.
Clinical Implications: Translation to humans is uncertain, but the circuit could eventually support treatments that reduce delayed emergence and excessive burst suppression.
Key Findings
- dmPAG glutamatergic activity was suppressed during anesthesia and increased during wakefulness.
- Activation accelerated emergence across multiple anesthetic agents.
- Activation reduced burst suppression from approximately 50% to 2.15%.
Methodological Strengths
- Causal optogenetic and chemogenetic manipulation.
- Testing across four mechanistically diverse anesthetic classes.
Limitations
- The study was conducted in mice and may not reflect human arousal circuitry.
- Clinical effects of manipulating this circuit, including agitation or autonomic instability, are unknown.
Future Directions: Human neurophysiologic studies should test whether analogous circuit activity predicts emergence and whether pharmacologic modulation is safe.
In mice, dorsomedial periaqueductal gray glutamatergic neurons were suppressed during anesthesia and activated during wakefulness across four anesthetic classes. Optogenetic or chemogenetic activation delayed induction, accelerated emergence, and reduced burst suppression.
9. Vascular motion in the dorsal root ganglion sensed by Piezo2 in sensory neurons triggers episodic pain.
This study identified a vascular-neural mechanism for episodic neuropathic pain and connected angiogenesis, pericyte remodeling, mechanotransduction, and neuronal firing to a non-opioid therapeutic strategy.
Impact: It introduced a paradigm-level explanation for spontaneous neuropathic pain that differs from conventional inflammation- or injury-centered models.
Clinical Implications: Peripherally restricted Piezo2 modulators or vascular-targeted therapies may eventually address refractory spontaneous pain, but human translation is required.
Key Findings
- Microvascular motion in injured dorsal root ganglia triggered spontaneous pain and clustered neuronal firing.
- Piezo2 in sensory neurons was necessary for sensing vascular motion.
- Anti-VEGF or Piezo2-targeted interventions suppressed angiogenesis-linked pain amplification in mice.
Methodological Strengths
- Integration of vascular imaging, neuronal activity, genetic manipulation, and behavioral testing.
- Mechanistic convergence on Piezo2 and angiogenic signaling.
Limitations
- The evidence is preclinical and based primarily on mouse models.
- Human dorsal-root-ganglion vascular biology and safety of Piezo2 inhibition remain unknown.
Future Directions: Human tissue studies and peripherally restricted pharmacologic programs should test whether the vascular-Piezo2 mechanism is present in patients with neuropathic pain.
This mechanistic preclinical study showed that dynamic microvascular motion within injured dorsal root ganglia triggers episodic spontaneous neuropathic pain through Piezo2 mechanotransduction in sensory neurons. Angiogenesis and pericyte alterations amplified clustered neuronal firing, while anti-VEGF or Piezo2-targeting approaches reduced pain behaviors in mice.
10. Prothrombin Complex Concentrate vs Frozen Plasma for Coagulopathic Bleeding in Cardiac Surgery: The FARES-II Multicenter Randomized Clinical Trial.
FARES-II provided high-level randomized evidence that four-factor PCC can improve hemostatic effectiveness while reducing transfusion exposure in selected cardiac-surgical bleeding.
Impact: It linked factor-replacement strategy to clinically meaningful hemostatic and organ-safety outcomes and challenged plasma-centered blood-management algorithms.
Clinical Implications: Selected cardiac-surgery patients with coagulopathic bleeding may be considered for viscoelastic- or laboratory-guided PCC pathways with thrombosis surveillance.
Key Findings
- Hemostatic effectiveness was 77.9% with PCC versus 60.4% with frozen plasma.
- PCC reduced allogeneic transfusion requirements.
- Serious adverse events, including postoperative AKI, were lower through day 30.
Methodological Strengths
- Pragmatic multicenter randomized clinical trial.
- Assessment of hemostasis, transfusion exposure, and postoperative safety outcomes.
Limitations
- Results may depend on local transfusion algorithms and availability of viscoelastic testing.
- Thrombotic outcomes require continued surveillance and broader external confirmation.
Future Directions: Future trials should define optimal dosing, identify patients at greatest benefit, and compare PCC pathways across diverse cardiac-surgery systems.
In a pragmatic multicenter randomized trial of approximately 528 analyzed patients, 4-factor PCC was superior to frozen plasma for hemostatic effectiveness during coagulopathic bleeding in cardiac surgery. PCC also reduced allogeneic transfusion exposure and serious adverse events, including postoperative acute kidney injury through day 30.