Quarterly ReportOct 1 – Dec 31, 2025
Anesthesiology, Q4 2025 edition
We read 1036 papers and selected 10.
Summary
The quarter marked a clear transition from universal perioperative protocols toward individualized, physiology- and biomarker-guided care. Large randomized trials supported capillary refill time–guided septic-shock resuscitation and biomarker-enriched prevention of postoperative acute kidney injury, while PROTHOR showed that routine high PEEP with recruitment does not improve pulmonary outcomes and increases hemodynamic harm. Mechanistic advances were substantial, including time-resolved structural analysis of μ-opioid receptor activation, identification of a shared arousal circuit for emergence, and structure-guided development of malignant hyperthermia inhibitors. Regional and neuraxial analgesic strategies produced clinically meaningful improvements in recovery and chronic postsurgical pain, although confirmatory multicenter studies remain necessary. Negative trials concerning extended hemodynamic therapy and selective digestive decontamination reinforced the importance of outcome-based de-implementation and ecological safety. Overall, the quarter advanced precision anesthesiology through pragmatic trials, translational biology, and selective rather than routine intervention.
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.
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.
Impact: It demonstrates that biomarker-based enrichment can make a pragmatic preventive bundle clinically effective for postoperative AKI.
Clinical Implications: Urinary tubular-stress biomarker screening followed by hemodynamic optimization, nephrotoxin avoidance, and appropriate volume and pressure management may be considered for high-risk surgery.
Key Findings
- Moderate-to-severe AKI occurred in 14.4% versus 22.3%.
- The intervention had an odds ratio of 0.57 and an approximate number needed to treat of 12.
- Major adverse events did not increase.
2. Personalized Hemodynamic Resuscitation Targeting Capillary Refill Time in Early Septic Shock: The ANDROMEDA-SHOCK-2 Randomized Clinical Trial.
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.
Impact: It provides high-level evidence that a simple bedside perfusion marker can guide individualized septic-shock resuscitation.
Clinical Implications: Serial capillary refill assessment can be integrated with echocardiography and fluid-responsiveness testing, provided staff are trained in reproducible measurement.
Key Findings
- The hierarchical composite outcome improved with a win ratio of 1.16.
- The main benefit involved shorter vasopressor, ventilation, and kidney-replacement durations.
- The trial enrolled 1,467 patients across 86 centers in 19 countries.
3. Non-equilibrium snapshots of ligand efficacy at the μ-opioid receptor.
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.
Impact: This study provides a high-resolution mechanistic framework for separating analgesic efficacy from respiratory depression during future opioid design.
Clinical Implications: The findings are not immediately practice-changing, but they may enable development of signaling-selective opioids with improved safety profiles.
Key Findings
- Time-resolved cryo-EM captured intermediate MOR-G-protein activation states.
- Different agonist classes produced distinguishable activation trajectories.
- Structural dynamics linked ligand efficacy to receptor signaling.
4. Crystal structures of Ryanodine Receptor reveal dantrolene and azumolene interactions guiding inhibitor development.
High-resolution structures of the ryanodine receptor R12 domain revealed cooperative binding of dantrolene and azumolene and identified residues important for ligand interaction. Structure-based screening found additional binders at the same pocket.
Impact: The study establishes a rational structural platform for next-generation malignant hyperthermia therapies.
Clinical Implications: The results support preclinical medicinal chemistry and do not justify replacing dantrolene before testing onset, potency, safety, and clinical efficacy.
Key Findings
- Dantrolene and azumolene bound cooperatively within a pseudosymmetric cleft.
- Trp880 and Trp994 were key ligand-interacting residues.
- Structure-based screening identified additional pocket binders.
5. The role of the dorsomedial periaqueductal gray glutamatergic neurons in promoting arousal under multiple general anesthetics in mice.
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.
Impact: It identifies a convergent arousal circuit that may explain recovery from mechanistically diverse anesthetics.
Clinical Implications: Translation to humans is uncertain, but the circuit may eventually support strategies to reduce delayed emergence and excessive burst suppression.
Key Findings
- dmPAG glutamatergic activity was suppressed during anesthesia.
- Activation accelerated emergence across multiple anesthetic agents.
- Activation reduced burst suppression from approximately 50% to 2.15%.
6. 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.
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.
Impact: This definitive trial challenges routine high-PEEP ventilation and supports individualized balancing of oxygenation against hemodynamic harm.
Clinical Implications: Routine high PEEP with recruitment should generally be avoided in similar patients; lower PEEP with monitoring and selective rescue is reasonable.
Key Findings
- 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.
7. Selective Decontamination of the Digestive Tract during Ventilation in the ICU.
This international cluster-randomized crossover trial of 9,289 patients found no mortality benefit from selective digestive decontamination. Although bloodstream infections and cultured resistant organisms decreased at the patient level, the ecological noninferiority criterion for new resistant organisms was not met.
Impact: The study resolves part of a longstanding ICU policy question while demonstrating that patient-level infection reduction does not establish ecological safety.
Clinical Implications: Routine adoption for mortality reduction is unsupported; any selected use requires resistance surveillance and antimicrobial-stewardship oversight.
Key Findings
- Ninety-day mortality was 27.9% versus 29.5%, with no significant difference.
- Patient-level bloodstream infections and resistant organisms decreased.
- Ecological noninferiority for new resistant organisms was not demonstrated.
8. Intrathecal Morphine for Enhanced Recovery After Laparoscopic Colorectal Surgery: A Randomized Clinical Trial.
In a double-blind randomized trial of 252 patients within an ERAS pathway, intrathecal morphine added to a liposomal-bupivacaine TAP block improved 24-hour QoR-15 scores and reduced opioid consumption. Pruritus increased, while nausea decreased.
Impact: It provides patient-centered randomized evidence for a feasible modification of multimodal ERAS analgesia.
Clinical Implications: The regimen may be considered for laparoscopic colorectal surgery with monitoring and counseling regarding pruritus and neuraxial opioid effects.
Key Findings
- QoR-15 improved by 12.21 points at 24 hours.
- Morphine-equivalent consumption decreased by 6.59 mg.
- Pruritus increased from 3.2% to 19.0%.
9. Effect of S-Ketamine on Postoperative Delirium in Elderly Patients Undergoing Arthroplasty: A Randomized Controlled Trial.
In 372 elderly arthroplasty patients under neuraxial anesthesia, perioperative S-ketamine reduced delirium within three postoperative days from 20.43% to 8.06% and reduced pain and rescue analgesic use. Hallucinations, dizziness, and nightmares were more frequent.
Impact: It offers a large randomized signal for pharmacologic prevention of postoperative delirium while clearly defining relevant neuropsychiatric trade-offs.
Clinical Implications: S-ketamine may be considered in selected elderly arthroplasty patients, with appropriate contraindication screening and monitoring for psychotomimetic effects.
Key Findings
- Delirium occurred in 8.06% versus 20.43%.
- Adjusted odds ratio for delirium was 0.29.
- Hallucinations, dizziness, and nightmares were more frequent.
10. Individualised Perioperative Blood Pressure and Fluid Therapy in Oesophagectomy: A Prospective, Single-Blind Randomised Controlled Trial.
In 100 esophagectomy patients, extending goal-directed fluid therapy and targeting an individualized postoperative MAP increased fluid balance, norepinephrine exposure, and MAP but did not reduce 30-day morbidity.
Impact: This rigorous negative trial demonstrates that tighter physiologic control may increase treatment burden without improving patient-centered outcomes.
Clinical Implications: Routine extension of this postoperative protocol should not be assumed to improve outcomes; fluids, vasopressors, and monitoring should be individualized.
Key Findings
- Postoperative fluid balance increased by 516 mL.
- Median norepinephrine exposure was 7,894 versus 4,611 micrograms.
- Thirty-day Comprehensive Complication Index was unchanged: 39.0 versus 39.2.