Weekly Anesthesiology Research Analysis
This week’s anesthesiology literature highlights three high-impact findings: a randomized trial showing low-dose neostigmine infusion reduced systemic inflammation and 28-day mortality in septic shock; a translational demonstration that extensively gene-edited pig livers can provide extracorporeal liver support in human decedent models, advancing xenogeneic organ perfusion; and a large cohort-plus-meta-analysis clarifying risk factors for postoperative pneumonia after cardiac surgery and exposin
Summary
This week’s anesthesiology literature highlights three high-impact findings: a randomized trial showing low-dose neostigmine infusion reduced systemic inflammation and 28-day mortality in septic shock; a translational demonstration that extensively gene-edited pig livers can provide extracorporeal liver support in human decedent models, advancing xenogeneic organ perfusion; and a large cohort-plus-meta-analysis clarifying risk factors for postoperative pneumonia after cardiac surgery and exposing limits of current predictive models. Together these studies push clinical translation of organ-support technologies, revive immunomodulation strategies in critical care, and underscore gaps in perioperative risk prediction that demand targeted prevention.
Selected Articles
1. Effect of Neostigmine on Attenuation of Proinflammatory Cytokines When Given as an Adjuvant Therapy in Septic Shock: A Randomized Control Trial.
A single-center, double-blind randomized trial found continuous low-dose neostigmine (0.2 mg/hr for 5 days) significantly reduced TNF-α at day 5, improved SOFA trajectories, and decreased 28-day mortality (26% vs 54%) in septic shock patients, supporting cholinergic anti-inflammatory pathway augmentation as an adjunctive therapy.
Impact: High-quality randomized evidence of mortality benefit with an inexpensive, widely available drug via a defined immunomodulatory mechanism—potentially practice-changing if replicated.
Clinical Implications: Consideration of neostigmine infusion as an adjunct in septic shock protocols may be warranted pending multicenter replication and expanded safety profiling; monitor hemodynamics and anticholinesterase effects closely.
Key Findings
- Day-5 TNF-α markedly lower with neostigmine vs placebo (40±36 vs 67±43 pg/mL; p=0.002).
- SOFA scores improved and 28-day mortality reduced (26% vs 54%; p=0.02) in the neostigmine arm.
2. Extracorporeal liver cross-circulation using transgenic xenogeneic pig livers with brain-dead human decedents.
In four human decedent experiments, extensively gene-edited pig livers (triple glycan KO, seven human transgenes, PERV inactivation) supported physiologic metabolism and bile production during prolonged extracorporeal liver cross-circulation; one hepatectomized decedent received 48 hours of xenogeneic-only support with maintained metabolic parameters under minimal immunosuppression.
Impact: Provides a translational feasibility demonstration for xenogeneic extracorporeal organ support, lowering a translational barrier toward clinical trials for temporary liver support when human grafts are unavailable.
Clinical Implications: If safety and durability translate to living patients, xenogeneic extracorporeal liver platforms could become bridges to transplant or recovery for acute liver failure; careful immunomodulation and longer-duration studies are required before clinical adoption.
Key Findings
- Gene-edited pig livers maintained bile production and metabolic homeostasis during 48–84 h extracorporeal cross-circulation in human decedents.
- Minimal immunosuppression was associated with preserved parenchymal architecture and only mild immune infiltration on biopsy.
3. Preoperative and Intraoperative Risk Factors for Postoperative Pneumonia After Cardiac Surgery: An Ancillary Study of the STERNOCAT (Catheter Outcomes With Sternotomy Cardiac Operated) Randomized Trial and a Systematic Review With Meta-Analysis.
An ancillary cohort (n=1,470) plus a systematic review/meta-analysis (24 studies, n=172,079) identified ischemic cardiomyopathy, longer cardiopulmonary bypass duration, and catecholamine use as independent risk factors for postoperative pneumonia; most identified predictors are non-modifiable and preoperative-only models performed poorly on external validation, emphasizing perioperative optimization over static pre-op risk scores.
Impact: Large-scale synthesis with external validation clarifies limited modifiable drivers of post-cardiac surgery pneumonia and warns against reliance on preoperative-only prediction models—informing priorities for preventive bundles.
Clinical Implications: Focus on perioperative optimization—minimize CPB duration, judicious transfusion practices, and targeted pulmonary prevention bundles in high-risk patients—rather than relying solely on preoperative risk scores for pneumonia prevention.
Key Findings
- STERNOCAT cohort POP incidence 5.3%; independent risk factors included ischemic cardiomyopathy (OR 1.89), longer CPB time (OR 1.10 per unit), and catecholamine use (OR 4.07).
- Systematic review (24 studies) identified 14 risk factors, but most were non-modifiable; preoperative-only predictive models validated poorly.