Anesthesiology, November 2025 edition

BigpAK-2 randomized biomarker-enriched high-risk patients undergoing major surgery to a KDIGO-aligned prevention bundle or usual care. Moderate-to-severe AKI within 72 hours occurred in 14.4% versus 22.3% of patients, corresponding to an odds ratio of 0.57 and an approximate number needed to treat of 12, without an increase in major adverse events.

Impact: This large multinational randomized trial shows that biomarker-directed selection coupled with a pragmatic prevention bundle can reduce a common and clinically important postoperative complication.

Clinical Implications: High-risk surgical patients may benefit from urinary tubular-stress biomarker screening followed by a KDIGO-aligned bundle including hemodynamic optimization, avoidance of nephrotoxins and unnecessary contrast, appropriate volume and pressure management, and glycemic control.

High-resolution structures of the Ryanodine Receptor R12 domain revealed cooperative binding of dantrolene and azumolene with nucleotides, key tryptophan contacts, and ligand-induced clamshell closure. Structure-based screening identified additional binders at the same pocket, providing a rational platform for developing improved Ryanodine Receptor inhibitors.

Impact: The study provides a structural foundation for next-generation malignant hyperthermia therapies, potentially overcoming the pharmacologic, formulation, and safety limitations associated with current dantrolene-based treatment.

Clinical Implications: The findings primarily support medicinal chemistry and preclinical development rather than immediate clinical substitution of dantrolene. Future inhibitors should be evaluated for rapid onset, potency, hemodynamic safety, tissue distribution, and effectiveness in clinically relevant malignant hyperthermia models.

In a 2,200-patient, 28-country phase 3 randomized trial, high PEEP with recruitment during one-lung ventilation did not reduce postoperative pulmonary complications compared with lower PEEP without recruitment. High PEEP substantially increased intraoperative hypotension and new arrhythmias, whereas low PEEP required more hypoxemia rescue maneuvers.

Impact: This definitive international trial challenges routine application of high PEEP and recruitment during one-lung ventilation and provides a stronger evidence base for individualized rather than protocolized ventilation.

Clinical Implications: For patients similar to the trial population, routine high PEEP with recruitment should generally be avoided during one-lung ventilation. Lower PEEP with close oxygenation monitoring and individualized rescue maneuvers is reasonable, while higher PEEP may still be selectively considered in patients with specific recruitment or oxygenation needs.

In a randomized trial of 58 patients, personalized coached prehabilitation improved six-minute walk distance, reduced moderate-to-severe postoperative complications, and produced measurable changes in high-dimensional immune signaling compared with a standard paper-based program. The immune changes were characterized by dampened proinflammatory signaling in selected myeloid and T-cell subsets.

Impact: The study connects a scalable perioperative intervention with both functional improvement and biologically plausible immune modulation, supporting a more mechanistic and personalized approach to prehabilitation.

Clinical Implications: Personalized, coached prehabilitation may be incorporated into pathways for patients preparing for major surgery, particularly when functional reserve is limited. Immune phenotyping remains investigational but may eventually help determine intervention intensity, timing, and response.

In a randomized non-inferiority trial of 90 kidney transplant recipients, transversus abdominis plane plus rectus sheath blocks with patient-controlled intravenous analgesia were non-inferior to epidural analgesia for postoperative day 1 quality of recovery. Renal function and recovery through day 7 were comparable, although epidural analgesia reduced intraoperative opioid requirements and accelerated emergence.

Impact: This trial provides clinically relevant randomized evidence that a less invasive regional analgesia pathway can preserve early recovery quality after kidney transplantation while avoiding some contraindications and logistical demands of epidural placement.

Clinical Implications: TAP and rectus sheath blocks with patient-controlled intravenous analgesia may be considered when epidural analgesia is contraindicated, technically difficult, or resource-intensive. Clinicians should still account for the greater intraoperative opioid requirement and potentially slower emergence compared with epidural analgesia.