Daily Anesthesiology Research Analysis
Three perioperative studies stand out today: an RCT shows S-ketamine markedly reduces postoperative delirium after hip/knee arthroplasty under neuraxial anesthesia; a phase 3 RCT finds pathogen-reduced red blood cells are noninferior to conventional units for acute kidney injury after cardiac/aortic surgery; and a nationwide matched cohort links pre-operative SGLT2 inhibitor use with lower 30-day mortality and complications after surgery in type 2 diabetes.
Summary
Three perioperative studies stand out today: an RCT shows S-ketamine markedly reduces postoperative delirium after hip/knee arthroplasty under neuraxial anesthesia; a phase 3 RCT finds pathogen-reduced red blood cells are noninferior to conventional units for acute kidney injury after cardiac/aortic surgery; and a nationwide matched cohort links pre-operative SGLT2 inhibitor use with lower 30-day mortality and complications after surgery in type 2 diabetes.
Research Themes
- Perioperative neuroprotection and delirium prevention
- Transfusion innovation and blood safety
- Metabolic optimization in diabetic surgical patients
Selected Articles
1. Effect of S-Ketamine on Postoperative Delirium in Elderly Patients Undergoing Arthroplasty: A Randomized Controlled Trial.
Among 372 elderly arthroplasty patients under neuraxial anesthesia, S-ketamine reduced postoperative delirium within 3 days (8.06% vs 20.43%; adjusted OR 0.29, 95% CI 0.14–0.63; P=0.002). Early postoperative pain during activity and rescue analgesia use were lower with S-ketamine, whereas hallucinations, dizziness, and nightmares were more frequent. Other complications were uncommon and similar between groups.
Impact: This is a well-designed RCT demonstrating a substantial and clinically meaningful reduction in postoperative delirium with S-ketamine under neuraxial anesthesia, a high-risk scenario with limited proven preventive therapies.
Clinical Implications: Perioperative teams may consider S-ketamine as part of multimodal analgesia under neuraxial anesthesia to prevent postoperative delirium in elderly arthroplasty patients, balancing benefits against increased psychotomimetic adverse effects and ensuring monitoring and counseling.
Key Findings
- Postoperative delirium within 3 days: 8.06% (S-ketamine) vs 20.43% (placebo); adjusted OR 0.29 (95% CI 0.14–0.63; P=0.002).
- Lower pain during exercise/physical therapy and reduced need for rescue analgesia on postoperative day 1 with S-ketamine.
- Higher incidence of hallucinations, dizziness, and nightmares with S-ketamine; other complications were infrequent with no significant differences.
Methodological Strengths
- Randomized, placebo-controlled design with prespecified primary and secondary outcomes.
- Standardized perioperative protocols at a high-volume arthroplasty center and in-person assessments through postoperative day 3.
Limitations
- Single-center setting may limit generalizability; neuraxial anesthesia context may not extend to general anesthesia.
- Short follow-up (3 days) for delirium assessment; increased psychotomimetic adverse events require mitigation strategies.
Future Directions: Multicenter trials to validate efficacy across settings, dose-finding to minimize psychotomimetic effects, evaluation under general anesthesia, and longer-term cognitive/functional outcomes.
BACKGROUND: General anesthesia may counteract the neuroprotective effects of S-ketamine, so previous trials may have underestimated the efficacy of S-ketamine to reduce postoperative delirium (POD). The authors hypothesized that administration of S-ketamine in a non-general anesthesia setting would reduce the risk of POD. METHODS: This study was conducted at a high-volume arthroplasty referral center where standardized, evidence-based perioperative protocols are implemented with high fidelity. This study included 372 elderly patients undergoing total hip or knee arthroplasty under neuraxial anesthesia. Patients were enrolled from November 2023 to October 2024, and in-person follow-up assessments were conducted from admission to 3 days after surgery. Patients were randomized to receive either S-ketamine (n = 186) or normal saline placebo (n = 186). The primary outcome was risk of POD within 3 days after surgery. Secondary outcomes were number of POD episodes, POD onset time and duration, POD severity, POD subtype, pain score (numeric rating scale), opioid consumption, number of patients requiring rescue analgesia, sleep quality, clinical outcomes, and harms.
2. Transfusion of Amustaline/Glutathione Pathogen-reduced Red Blood Cells in Cardiac Surgery: A Randomized Phase 3 Clinical Trial.
Among 581 randomized patients (321 transfused), AKI within 48 h occurred in 29.3% (pathogen-reduced) vs 28.0% (conventional), meeting noninferiority (difference 0.7%; 95% CI −8.9 to 10.4%; P=0.001 for noninferiority). KDIGO 7-day AKI rates were similar; stage III trended higher in pathogen-reduced (9.4% vs 4.3%; P=0.075). Low-titer, specific antibodies occurred in 3.1% without hemolysis.
Impact: This phase 3 double-blind RCT supports the clinical viability of pathogen-reduced red cells in major cardiac/aortic surgery, addressing transfusion safety while maintaining renal outcomes comparable to conventional units.
Clinical Implications: Centers with access to amustaline/glutathione pathogen-reduced red cells may consider their perioperative use without increased AKI risk, with vigilance for rare low-titer alloantibodies and evaluation of broader safety (e.g., infection, TA-GVHD) and cost-effectiveness.
Key Findings
- AKI within 48 h: 29.3% (pathogen-reduced) vs 28.0% (conventional); noninferiority met (difference 0.7%; 95% CI −8.9 to 10.4%; P=0.001).
- KDIGO 7-day AKI similar (37.1% vs 34.0%; P=0.53); stage III tended higher with pathogen-reduced (9.4% vs 4.3%; P=0.075).
- Low-titer, specific red cell antibodies occurred in 3.1% of pathogen-reduced recipients without hemolysis; hemoglobin nadirs were comparable.
Methodological Strengths
- Phase 3, double-blinded, randomized noninferiority design with objective renal endpoints.
- Prespecified noninferiority margin and systematic safety monitoring (28-day AEs; 75-day antibody surveillance).
Limitations
- Only 55% of randomized patients were transfused with study RBCs; analyses focus on transfused population.
- Primary endpoint (AKI) is a surrogate; trend toward more stage III AKI warrants further study; long-term alloimmunization and infectious risk reduction not directly assessed.
Future Directions: Pragmatic trials assessing infection transmission, TA-GVHD, longer-term renal and immunologic outcomes, and cost-effectiveness across varied surgical populations.
BACKGROUND: Transfusion has a persistent low risk of transfusion-transmitted infection and transfusion-associated graft-versus-host disease that may be addressed using pathogen reduction. The Red Cell Pathogen Inactivation (ReCePI) trial tested whether amustaline/glutathione pathogen-reduced red cells are noninferior to conventional transfusions for support of acute surgical blood loss. METHODS: A phase 3, double-blinded, noninferiority trial randomized cardiac or thoracic-aorta surgery patients with increased risk of red cell transfusion to receive pathogen-reduced or conventional red cells during and for 7 days postsurgery. The primary endpoint was the proportion of patients with acute kidney injury (AKI), which is defined as an increase from baseline of greater than or equal to 0.3 mg/dl serum creatinine within 48 h of surgery. Noninferiority was claimed if the upper bound 95% CI of the treatment difference was less than half (50%) of the observed conventional arm incidence. Adverse events and treatment-emergent red cell antibodies were assessed for 28 and 75 days, respectively.
3. Association between pre-operative sodium-glucose cotransporter-2 inhibitor use and postoperative outcomes: a propensity score-matched analysis of the TriNetX database.
In 98,118 matched pairs of surgical patients with type 2 diabetes, pre-operative SGLT2 inhibitor use was associated with lower 30-day mortality (RR 0.61, 95% CI 0.55–0.67), reduced MACE (RR 0.89), AKI (RR 0.71), and DKA (RR 0.31). Benefits were more pronounced in females, those with obesity or proteinuria, and in cardiovascular surgery. Findings are observational and require randomized validation.
Impact: This very large, carefully matched cohort challenges prevailing concerns by linking pre-operative SGLT2 inhibitor exposure with improved postoperative survival and morbidity, informing perioperative decision-making for a widespread medication class.
Clinical Implications: For patients with type 2 diabetes facing surgery, perioperative teams should re-examine blanket discontinuation policies for SGLT2 inhibitors. Risk-stratified protocols with ketone monitoring and multidisciplinary coordination are warranted while awaiting randomized trials.
Key Findings
- 30-day all-cause mortality reduced with SGLT2 inhibitor use (RR 0.61, 95% CI 0.55–0.67; p<0.001).
- Lower risks of MACE (RR 0.89), AKI (RR 0.71), and DKA (RR 0.31) in the SGLT2 inhibitor group (all p<0.001).
- Greater mortality reduction in females, patients with obesity or proteinuria, and those undergoing cardiovascular surgery.
Methodological Strengths
- Nationwide cohort with very large sample size and propensity score matching to balance covariates.
- Consistent associations across multiple clinically relevant outcomes with subgroup analyses.
Limitations
- Observational design with residual confounding and potential misclassification of exposure/adherence.
- Medication timing relative to surgery and standardized perioperative management details were not available.
Future Directions: Randomized trials to define perioperative continuation/withholding strategies, optimal timing, and monitoring protocols to balance metabolic risks and cardiometabolic benefits.
INTRODUCTION: While sodium-glucose cotransporter-2 inhibitors offer cardiovascular and renal benefits, their peri-operative safety and effect profile remain unclear. This study aimed to evaluate the association between pre-operative sodium-glucose cotransporter-2 inhibitor use and postoperative adverse events in patients with type 2 diabetes mellitus. METHODS: This nationwide propensity-score matched cohort study utilised the TriNetX database to analyse data from patients with type 2 diabetes mellitus who underwent surgery in the USA. Patients were categorised based on whether they had received a prescription for sodium-glucose cotransporter-2 inhibitors 90 days before surgery. The primary outcome was 30-day all-cause mortality. Secondary outcomes included the incidence of major adverse cardiovascular events; acute kidney injury; and diabetic ketoacidosis.