Monthly ReportDec 1–31, 2025
Anesthesiology, December 2025 edition
We read 847 papers and selected 5.
Summary
December 2025 anesthesiology research emphasized precision, selective intervention, and the de-implementation of routine strategies that improve surrogate physiology without improving patient outcomes. Major randomized trials challenged routine high PEEP with recruitment maneuvers, ketamine-based intubation for presumed survival benefit, propofol for oncologic advantage, and extended postoperative goal-directed hemodynamic therapy. At the same time, clinically actionable advances supported phenotype-directed sepsis immunotherapy, multimodal regional analgesia, exercise prehabilitation, and improved recovery pathways. Mechanistic and digital innovations—including time-resolved opioid-receptor structural biology, neural-circuit studies of emergence, AI-based prediction, and biomarker-guided prognostication—indicated a continued shift toward individualized perioperative and critical-care medicine. Weekly scores were normalized to each week's highest selected score and adjusted using recency weights of 1.05, 1.10, 1.15, and 1.20 for weeks 1 through 4.
Selected Articles
1. Non-equilibrium snapshots of ligand efficacy at the μ-opioid receptor.
This mechanistic Nature study used time-resolved cryo-EM to capture intermediate states during GTP-driven activation of the μ-opioid receptor coupled to G proteins. Partial, full, and super-agonists produced distinct receptor activation trajectories, linking ligand efficacy to dynamic structural transitions. The work provides a molecular framework for designing future analgesics with improved separation between analgesia and respiratory depression.
Impact: The study introduces a high-resolution structural explanation for why opioid ligands with different efficacies produce different signaling outputs, addressing a central challenge in safer analgesic development.
Clinical Implications: The findings are not immediately practice-changing, but they may enable rational development of efficacy-selective or signaling-biased opioids that preserve analgesia while reducing respiratory depression and other adverse effects.
Key Findings
- Time-resolved cryo-EM captured intermediate MOR-G protein activation states after GTP loading.
- Partial, full, and super-agonists produced distinguishable activation trajectories.
- Structural intermediates linked ligand efficacy to receptor signaling dynamics.
2. 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 sevoflurane, propofol, ketamine, and dexmedetomidine exposure. Optogenetic or chemogenetic activation delayed induction, accelerated emergence, and reduced burst suppression. The findings identify a possible shared arousal circuit across multiple anesthetic classes.
Impact: This rigorous multimodal mechanistic study identifies a convergent neural substrate that may regulate loss and recovery of consciousness across several anesthetic agents.
Clinical Implications: The results may eventually support neuromodulatory or pharmacologic strategies to accelerate emergence, reduce excessive burst suppression, and manage delayed awakening, although translation from mice to humans remains unproven.
Key Findings
- dmPAG glutamatergic activity was suppressed during anesthesia and elevated during wakefulness across four anesthetic agents.
- Optogenetic activation shortened emergence and modified anesthetic sensitivity.
- Activation reduced the burst-suppression ratio from approximately 50% to 2.15%.
3. Intrathecal Morphine for Enhanced Recovery After Laparoscopic Colorectal Surgery: A Randomized Clinical Trial.
In a double-blind randomized trial of 252 adults undergoing laparoscopic colorectal surgery within an ERAS pathway, intrathecal morphine at 3 μg/kg added to liposomal-bupivacaine TAP block improved 24-hour QoR-15 scores and reduced opioid consumption. Nausea decreased, but pruritus increased substantially. The findings support a practical multimodal analgesic modification with a clinically meaningful early-recovery benefit.
Impact: This large double-blind trial provides patient-centered evidence for a feasible modification of ERAS analgesia and demonstrates a meaningful improvement in early quality of recovery.
Clinical Implications: Intrathecal morphine combined with TAP block can be considered for laparoscopic colorectal surgery, provided that clinicians counsel patients about pruritus and monitor for neuraxial opioid-related adverse effects.
Key Findings
- 24-hour QoR-15 improved by 12.21 points with intrathecal morphine plus TAP block.
- Postoperative morphine-equivalent consumption decreased by 6.59 mg.
- Pruritus increased from 3.2% to 19.0%, while nausea decreased.
4. Esketamine as an Adjuvant to Ropivacaine in Genicular Nerve and IPACK Blocks for Total Knee Arthroplasty: A Double-Blind Randomized Trial.
In a double-blind randomized trial of 367 total knee arthroplasty patients, adding perineural esketamine 0.2 mg/kg to ropivacaine for genicular and IPACK blocks reduced six-month chronic postsurgical pain to 4.9%, compared with 17.9% with ropivacaine alone and 27.0% with control. Pain burden and early functional recovery also improved without an increase in reported adverse events.
Impact: The study reports a large reduction in chronic postsurgical pain using a practical regional-anesthesia adjunct, addressing a clinically important outcome often insufficiently prevented by standard perioperative analgesia.
Clinical Implications: Perineural esketamine could be considered as an adjuvant to ropivacaine in genicular and IPACK blocks for selected knee arthroplasty patients, but multicenter confirmation and longer-term safety evaluation are needed.
Key Findings
- Six-month chronic postsurgical pain was 4.9% with esketamine, versus 17.9% with ropivacaine alone and 27.0% with control.
- Pain burden and early functional outcomes improved with the esketamine regimen.
- No increase in adverse events was reported in the esketamine group.
5. Individualised Perioperative Blood Pressure and Fluid Therapy in Oesophagectomy: A Prospective, Single-Blind Randomised Controlled Trial.
In a single-center randomized trial of 100 patients undergoing esophagectomy, extending goal-directed fluid therapy through the first postoperative morning and targeting each patient's nighttime baseline MAP increased fluid balance, norepinephrine exposure, and MAP but did not reduce 30-day morbidity. The study demonstrates that improved physiologic targets do not necessarily translate into better patient outcomes.
Impact: This rigorous negative trial directly challenges routine extension of individualized postoperative hemodynamic optimization and highlights the importance of outcome-based rather than surrogate-based protocol adoption.
Clinical Implications: Routine extension of this individualized goal-directed fluid and blood-pressure protocol after esophagectomy should not be assumed to improve outcomes. Clinicians should balance potential benefits against additional fluids, vasopressors, monitoring burden, and treatment-related risks.
Key Findings
- The intervention increased postoperative fluid balance by 516 mL.
- Norepinephrine use was higher with extended individualized therapy: 7,894 versus 4,611 μg median.
- Thirty-day Comprehensive Complication Index was unchanged: 39.0 versus 39.2.