Weekly Anesthesiology Research Analysis
This week’s anesthesiology literature highlights practice‑relevant randomized trials, translational mechanistic work, and large safety/epidemiologic studies. Top clinical trials show S‑ketamine reduces postoperative delirium after neuraxial arthroplasty and a phase‑3 trial supports pathogen‑reduced red cells as noninferior for perioperative AKI. Mechanistic science (propofol acting presynaptically in the locus coeruleus) and large registries/cohorts further refine perioperative risk stratificati
Summary
This week’s anesthesiology literature highlights practice‑relevant randomized trials, translational mechanistic work, and large safety/epidemiologic studies. Top clinical trials show S‑ketamine reduces postoperative delirium after neuraxial arthroplasty and a phase‑3 trial supports pathogen‑reduced red cells as noninferior for perioperative AKI. Mechanistic science (propofol acting presynaptically in the locus coeruleus) and large registries/cohorts further refine perioperative risk stratification and organ‑protection strategies.
Selected Articles
1. Effect of S-Ketamine on Postoperative Delirium in Elderly Patients Undergoing Arthroplasty: A Randomized Controlled Trial.
In a randomized, placebo‑controlled trial of 372 elderly patients undergoing hip or knee arthroplasty under neuraxial anesthesia, perioperative S‑ketamine reduced postoperative delirium within 3 days (8.06% vs 20.43%; adjusted OR 0.29). It also reduced early activity‑related pain and rescue analgesia use, though psychotomimetic adverse events (hallucinations, dizziness, nightmares) were more common.
Impact: Largest high‑quality RCT this week showing a clinically meaningful reduction in postoperative delirium — an outcome with major functional and resource implications for elderly surgical patients.
Clinical Implications: Consider adding S‑ketamine to multimodal perioperative care for elderly arthroplasty patients under neuraxial anesthesia to reduce delirium risk, while planning monitoring and mitigation for psychotomimetic effects and counseling patients/families.
Key Findings
- S‑ketamine reduced postoperative delirium within 3 days: 8.06% vs 20.43% (adjusted OR 0.29; 95% CI 0.14–0.63).
- Reduced pain during activity and lower rescue analgesia use on POD1.
- Increased incidence of hallucinations, dizziness, and nightmares; other complications similar between groups.
2. Propofol inhibits norepinephrine release in vivo at presynaptic varicosities of locus coeruleus neurones in zebrafish larvae.
Using in vivo electrophysiology, chemogenetics and optical imaging in zebrafish larvae, this mechanistic study demonstrates that propofol directly suppresses presynaptic norepinephrine release from locus coeruleus varicosities, revealing a presynaptic noradrenergic mechanism contributing to anesthetic hypnosis.
Impact: Provides novel mechanistic insight into anesthetic action at presynaptic noradrenergic terminals that may explain clinical effects on arousal, cardiovascular tone, and delirium, guiding future drug development and translational studies.
Clinical Implications: Although preclinical, the findings support targeting the locus coeruleus–noradrenergic axis in sedative development and may inform interpretation of clinical effects (arousal, hemodynamics, delirium) associated with propofol and noradrenergic agents.
Key Findings
- Propofol directly inhibited norepinephrine release at presynaptic varicosities of locus coeruleus neurons in vivo.
- Combined in vivo whole‑cell recordings, chemogenetics, and time‑lapse imaging provided cellular resolution evidence.
3. Transfusion of Amustaline/Glutathione Pathogen-reduced Red Blood Cells in Cardiac Surgery: A Randomized Phase 3 Clinical Trial.
A double‑blind phase‑3 RCT randomized cardiac/aortic surgery patients to pathogen‑reduced vs conventional red blood cells and demonstrated noninferiority for 48‑hour AKI (29.3% vs 28.0%; noninferiority met). KDIGO 7‑day AKI rates were similar; a numerical increase in stage III AKI in the pathogen‑reduced arm trended but did not reach statistical significance.
Impact: Phase‑3 evidence that pathogen‑reduced RBCs are clinically viable for major cardiac surgery addresses transfusion safety concerns and may influence blood‑product policies and perioperative transfusion protocols.
Clinical Implications: Centers with access to amustaline/glutathione pathogen‑reduced RBCs can consider perioperative use without increased short‑term AKI risk, while monitoring for rare low‑titer alloantibodies and tracking longer‑term renal and immunologic outcomes.
Key Findings
- 48‑hour AKI: 29.3% (pathogen‑reduced) vs 28.0% (conventional); noninferiority met (difference 0.7%; 95% CI −8.9 to 10.4%).
- KDIGO 7‑day AKI similar; stage III AKI trended higher in pathogen‑reduced group (9.4% vs 4.3%; P=0.075).
- Low‑titer specific red‑cell antibodies occurred in 3.1% without hemolysis; hemoglobin nadirs comparable.