Daily Anesthesiology Research Analysis
A double-blind pilot RCT shows a multi-drug anti-inflammatory bundle markedly reduces postoperative delirium after hip fracture surgery. A multicenter ICU study quantifies that 10.7% of prepared IV medications are discarded, highlighting sustainability and cost targets. Preclinical work identifies GDF15-driven microglial activation as a mechanistic driver of sepsis-associated cognitive impairment, with anti-GDF15 therapy improving cognition in mice.
Summary
A double-blind pilot RCT shows a multi-drug anti-inflammatory bundle markedly reduces postoperative delirium after hip fracture surgery. A multicenter ICU study quantifies that 10.7% of prepared IV medications are discarded, highlighting sustainability and cost targets. Preclinical work identifies GDF15-driven microglial activation as a mechanistic driver of sepsis-associated cognitive impairment, with anti-GDF15 therapy improving cognition in mice.
Research Themes
- Delirium prevention via multi-target anti-inflammatory modulation
- Sustainable critical care and medication waste reduction
- Neuroinflammation mechanisms in sepsis-associated encephalopathy
Selected Articles
1. Effect of combination of multiple anti-inflammatory drugs strategy on postoperative delirium among older patients undergoing hip fracture surgery: a pilot randomized controlled trial.
In a dual-center, double-blind pilot RCT (n=132 randomized; 123 analyzed), a perioperative anti-inflammatory bundle (dexmedetomidine, glucocorticoid, ulinastatin, NSAIDs) reduced postoperative delirium from 44% to 15% (RR 0.33; P=0.001) without major adverse events. Lower postoperative CRP partially mediated the effect, supporting inflammation as a causal pathway.
Impact: This rigorously blinded pilot RCT demonstrates a substantial reduction in postoperative delirium using a pragmatic, multi-target anti-inflammatory strategy, a leading cause of morbidity in older surgical patients.
Clinical Implications: If replicated, anesthesiologists could adopt protocolized anti-inflammatory bundles to prevent delirium in high-risk geriatric fracture surgery, integrating dexmedetomidine sedation, a single perioperative steroid dose, ulinastatin, and NSAIDs with careful patient selection and monitoring.
Key Findings
- Postoperative delirium was reduced from 44% (27/61) to 15% (9/62) with the anti-inflammatory bundle (RR 0.33; 95% CI 0.17–0.64; P=0.001).
- No major adverse events occurred in either group, supporting safety of the bundled approach.
- Postoperative CRP levels were significantly lower with the bundle, and mediation analysis implicated systemic inflammation in the protective effect.
Methodological Strengths
- Dual-center, double-blind, placebo-controlled randomized design
- Predefined primary outcome with mediation analysis linking CRP to clinical effect
Limitations
- Pilot sample size and two-center setting limit generalizability
- Bundle design precludes disentangling the contribution of individual drugs; short (3-day) delirium follow-up
Future Directions: Conduct adequately powered, multicenter RCTs to confirm efficacy, optimize dosing/timing, assess long-term cognitive and functional outcomes, and evaluate cost-effectiveness and safety in broader populations.
2. Growth differentiation factor 15 aggravates sepsis-induced cognitive and memory impairments by promoting microglial inflammatory responses and phagocytosis.
In LPS-induced murine sepsis, CSF GDF15 rose markedly; intracerebroventricular anti-GDF15 (ponsegromab) mitigated cognitive and memory deficits, reduced microglial activation/phagocytosis, and prevented synaptic loss. In vitro, GDF15 enhanced microglial inflammatory cytokines and phagocytic activity, supporting a causal role.
Impact: Identifies GDF15 as a mechanistic driver of neuroinflammation and cognitive impairment in sepsis and demonstrates target engagement with a therapeutic antibody, opening a translational pathway for SAE.
Clinical Implications: While preclinical, these data suggest GDF15 blockade could become a therapeutic strategy for sepsis-associated encephalopathy. Future clinical translation will need systemic delivery approaches, safety evaluation, and biomarker-guided patient selection.
Key Findings
- CSF GDF15 levels increased significantly after LPS-induced sepsis in mice.
- Intracerebroventricular anti-GDF15 (ponsegromab) improved fear-conditioning and novel object recognition performance.
- GDF15 promoted microglial inflammatory cytokine production and phagocytosis; antibody treatment reduced microglial activation and protected synapses.
Methodological Strengths
- Convergent in vivo behavioral, histological, and in vitro mechanistic assays
- Target engagement using a clinically developed monoclonal antibody
Limitations
- LPS model may not capture the full complexity of polymicrobial sepsis
- Intracerebroventricular delivery limits immediate clinical translatability; sample sizes not detailed in abstract
Future Directions: Evaluate systemic anti-GDF15 strategies, validate in polymicrobial sepsis models, define dosing windows, and assess interaction with sedation/analgesia regimens and long-term cognitive outcomes.
3. Discarded intravenous medication in the ICU: the GAME-OVER multicenter prospective observational study.
Across 81 ICUs and 1,076 patients, 10.7% of prepared IV medication volume was discarded during a 24-hour snapshot, with 90% of waste concentrated in 25 drugs and an estimated national annual cost of €2.74 million. Patient/flow factors (admissions/discharges, SOFA≥7, intubation, RRT, BMI) were associated with waste, underscoring system-level interventions.
Impact: Provides the first large-scale, prospective quantification of ICU IV medication waste with cost attribution and risk factors, enabling targeted sustainability and stewardship strategies.
Clinical Implications: Hospitals can prioritize high-yield interventions: ready-to-administer dosing, unit-dose preparation, on-demand compounding, pharmacy-ICU workflow redesign, and analytics to target the 25 key drugs driving 90% of waste.
Key Findings
- 10.7% (95% CI 9.9–11.5) of prepared IV medication volume was discarded across 81 ICUs and 1,076 patients.
- Ninety percent of waste was attributable to 25 drugs; estimated national annual cost €2,737,163.
- Admission/discharge volume, elective surgery admission, SOFA≥7, intubation, renal replacement therapy, and BMI were independently associated with increased waste.
Methodological Strengths
- Prospective multicenter design with pre-registered protocol
- Large sample capturing diverse ICU settings and standardized primary metric
Limitations
- Single 24-hour snapshot per ICU may miss temporal variability
- Conducted in France; generalizability to other health systems may vary; no linkage to patient outcomes
Future Directions: Test targeted stewardship interventions (e.g., ready-to-administer formats, predictive preparation) in pragmatic trials, incorporate environmental life-cycle assessment, and integrate waste metrics into quality dashboards.