Anesthesiology Research Analysis
Across 2025-Q2, anesthesiology research converged on blood management, ICU sedation in ARDS, opioid-sparing analgesia, and precision methods. Practice-defining RCTs supported a PCC-first approach for coagulopathic bleeding and cautioned against volatile-based ICU sedation in moderate–severe ARDS. Pragmatic perioperative stewardship advanced through an EHR-ready transfusion model and a blinded RCT validating hypovolemic phlebotomy to expedite low CVP and reduce liver transection bleeding. Mechani
Summary
Across 2025-Q2, anesthesiology research converged on blood management, ICU sedation in ARDS, opioid-sparing analgesia, and precision methods. Practice-defining RCTs supported a PCC-first approach for coagulopathic bleeding and cautioned against volatile-based ICU sedation in moderate–severe ARDS. Pragmatic perioperative stewardship advanced through an EHR-ready transfusion model and a blinded RCT validating hypovolemic phlebotomy to expedite low CVP and reduce liver transection bleeding. Mechanistic and translational advances included 7T fMRI mapping of sedatives’ memory and pain-network effects, quantitative PK resolving intranasal oxytocin exposure with an open dosing simulator, and a preclinical arrestin-biased NTSR1 analgesic pointing to non-opioid pathways. An international Delphi refined ARDS definitions and prioritized subphenotyping, aligning with the quarter’s emphasis on phenotype-guided trials. Cardiorenal protection also progressed with a randomized trial of perioperative inhaled nitric oxide in CKD cardiac surgery patients.
Selected Articles
1. Prothrombin Complex Concentrate vs Frozen Plasma for Coagulopathic Bleeding in Cardiac Surgery: The FARES-II Multicenter Randomized Clinical Trial.
A multicenter RCT showed 4-factor PCC improved hemostatic effectiveness versus FFP in coagulopathic bleeding during cardiac surgery, reduced allogeneic transfusion, and lowered serious adverse events including AKI through 30 days.
Impact: Definitive randomized evidence reframes perioperative bleeding management toward factor-concentrate, stewardship-aligned strategies.
Clinical Implications: Use PCC as first-line factor replacement for coagulopathic bleeding in cardiac surgery while monitoring thromboembolic safety; update transfusion pathways to leverage reduced exposure and AKI risk.
Key Findings
- Higher hemostatic effectiveness with PCC vs FFP (difference ~17.6%).
- Reduced allogeneic transfusion requirements with PCC.
- Lower serious adverse events including AKI through day 30.
2. Arrestin-biased allosteric modulator of neurotensin receptor 1 alleviates acute and chronic pain.
Preclinical SBI-810, a β-arrestin–biased positive allosteric modulator of NTSR1, produced robust analgesia across postoperative, inflammatory, and neuropathic rodent models with mechanistic specificity and reduced opioid-like liabilities.
Impact: Introduces a mechanistically distinct, non-opioid analgesic trajectory with translational potential across perioperative and chronic pain.
Clinical Implications: Supports IND-enabling work toward early-phase trials; if efficacy translates, perioperative pain strategies could shift away from opioids with fewer adverse effects.
Key Findings
- Analgesia across multiple pain models via systemic and local routes.
- Dependence on NTSR1 and β-arrestin-2 with NMDA/ERK suppression and reduced Nav1.7 surface expression.
- Lower reward, constipation, and withdrawal-like behaviors than opioids.
3. Effects of Sedative Doses of Propofol, Dexmedetomidine, and Fentanyl on Memory and Pain in Healthy Young Adults: A Randomized, Controlled, Single-blind Crossover Study Using Functional Magnetic Resonance Imaging at 7 Tesla.
In a randomized crossover study with 7T fMRI, propofol most impaired recollection and attenuated hippocampal/amygdala encoding and pain-network responses; dexmedetomidine largely preserved recollection; fentanyl showed distinct somatosensory/limbic patterns.
Impact: High-resolution mapping links sedatives to memory and nociceptive networks, enabling cognition-aligned drug selection.
Clinical Implications: Choose sedatives according to cognitive goals (strong amnesia with propofol vs memory preservation with dexmedetomidine) while considering generalizability beyond healthy adults.
Key Findings
- Propofol reduced next-day recollection and hippocampal/amygdala encoding activity.
- Dexmedetomidine preserved recollection with limited hippocampal disruption.
- Fentanyl induced distinct somatosensory and limbic activation patterns.
4. Plasma pharmacokinetics of intravenous and intranasal oxytocin in nonpregnant adults.
Using LC/MS and population PK modeling, this study found intranasal oxytocin has very low bioavailability (~0.7%) with high variability, while IV oxytocin follows a robust two-compartment model; a public dosing simulator was released.
Impact: Resolves longstanding uncertainty regarding intranasal systemic exposure and provides an open methodology to redesign dosing and routes.
Clinical Implications: Reconsider intranasal oxytocin in research and practice; prefer IV or redesign intranasal regimens using the simulator while accounting for very low bioavailability.
Key Findings
- Intranasal oxytocin bioavailability ≈0.7% with high intersubject variability.
- IV oxytocin PK fits a two-compartment model with low bias.
- LC/MS concentrations exceeded ELISA; public dosing simulator released.
5. Inhaled Sedation in Acute Respiratory Distress Syndrome: The SESAR Randomized Clinical Trial.
In a multicenter phase 3 RCT of adults with moderate–severe ARDS, inhaled sevoflurane sedation resulted in fewer ventilator-free days at day 28 and lower 90-day survival compared with propofol, with higher early mortality and fewer ICU-free days.
Impact: Provides practice-directing randomized evidence that redirects ICU sedation away from volatile agents in severe ARDS.
Clinical Implications: Favor intravenous propofol over inhaled sevoflurane for deep sedation in moderate–severe ARDS; reassess protocols endorsing volatile sedation.
Key Findings
- Fewer ventilator-free days at day 28 with sevoflurane vs propofol.
- Lower 90-day survival with sevoflurane (HR ~1.31).
- Higher 7-day mortality and fewer ICU-free days with sevoflurane.
6. Pharmacotherapy and non-invasive neuromodulation for neuropathic pain: a systematic review and meta-analysis.
NeuPSIG’s preregistered meta-analysis of 313 double-blind RCTs reprioritized neuropathic pain therapies toward TCAs, α2δ-ligands, and SNRIs as first-line options and downgraded opioids and rTMS given lower certainty.
Impact: Definitive synthesis with practical effect–harm metrics that supports opioid-sparing strategies across perioperative and chronic pain.
Clinical Implications: Prioritize non-opioid first-line agents and align formularies and care pathways with quantified benefit–harm profiles.
Key Findings
- Synthesis of 313 double-blind RCTs (48,789 adults).
- TCAs, α2δ-ligands, and SNRIs ranked as first-line options.
- Opioids, BTX-A, and rTMS recommended as later-line due to lower certainty.
7. Perioperative Nitric Oxide Conditioning Reduces Acute Kidney Injury in Cardiac Surgery Patients with Chronic Kidney Disease (the DEFENDER Trial): A Randomized Controlled Trial.
In CKD patients undergoing CPB cardiac surgery, perioperative inhaled nitric oxide (80 ppm intraop and 6 h postop) reduced 7-day AKI and improved 6-month GFR with acceptable safety.
Impact: Demonstrates an actionable organ-protective strategy with early and sustained renal benefits in a high-risk group.
Clinical Implications: Consider protocolized inhaled NO for CKD patients undergoing CPB with appropriate monitoring for methemoglobin and NO2.
Key Findings
- Reduced AKI within 7 days (RR ~0.59).
- Improved 6-month GFR and fewer postoperative pneumonias.
- No signals of methemoglobinemia or NO2 toxicity.
8. Defining and subphenotyping ARDS: insights from an international Delphi expert panel.
An international multi-round Delphi achieved consensus on a conceptual model and essential components for ARDS definitions and prioritized subphenotyping to mitigate heterogeneity and guide trials.
Impact: Provides a harmonized research framework to standardize diagnosis, stratification, and phenotype-guided therapy development.
Clinical Implications: Adopt the consensus model in studies and registries and accelerate biomarker/imaging-based subphenotyping programs.
Key Findings
- Consensus conceptual model and defining components for ARDS across clinical and research settings.
- Strong endorsement to advance subphenotyping to address heterogeneity.
- Diverse global expert participation in a rigorous multi-round process.
9. Development and Validation of a Risk Model to Predict Intraoperative Blood Transfusion.
The TRANSFUSE model, using 24 preoperative variables and validated across 816,618 surgeries, achieved AUC 0.93 and NPV 99.7%, enabling targeted crossmatch orders and outperforming existing tools.
Impact: EHR-ready, transportable prognostic tool that operationalizes patient blood management at scale.
Clinical Implications: Embed into preoperative workflows to right-size crossmatching and prioritize conservation for high-risk patients.
Key Findings
- External validation across 816,618 surgeries with AUC 0.93.
- High overall NPV (99.7%) enabling safe reduction of unnecessary crossmatches.
- Outperformed established risk tools using 24 readily available predictors.
10. Impact of Hypovolemic Phlebotomy with Low Central Venous Pressure on Intraoperative Blood Loss in Open Liver Resection: A Double-Blind Randomized Controlled Trial.
A double-blind RCT demonstrated that protocolized hypovolemic phlebotomy expedited low CVP, reduced parenchymal transection blood loss, and improved bleeding scores without increasing transfusions or complications.
Impact: Validates a controllable, pragmatic intraoperative maneuver for blood conservation during open hepatectomy.
Clinical Implications: Adopt controlled phlebotomy with tight hemodynamic monitoring to achieve low CVP and minimize bleeding during transection.
Key Findings
- Reduced transection blood loss (median 300 vs 500 mL).
- Faster achievement of low CVP (~50 vs 107.5 minutes).
- Independent protection against >500 mL blood loss (AOR ~0.19).