Daily Anesthesiology Research Analysis
Three impactful studies in anesthesiology and perioperative care stand out today: a double-blind RCT shows gastrodin infusion halves postoperative delirium after CABG; a controlled crossover trial in Anesthesiology quantifies remimazolam–remifentanil PK/PD interactions to guide sedation targeting; and a large cohort in Neurology suggests long-term epilepsy risk may be higher after general versus neuraxial anesthesia, emerging years later.
Summary
Three impactful studies in anesthesiology and perioperative care stand out today: a double-blind RCT shows gastrodin infusion halves postoperative delirium after CABG; a controlled crossover trial in Anesthesiology quantifies remimazolam–remifentanil PK/PD interactions to guide sedation targeting; and a large cohort in Neurology suggests long-term epilepsy risk may be higher after general versus neuraxial anesthesia, emerging years later.
Research Themes
- Prevention of postoperative neurocognitive complications in cardiac anesthesia
- Precision dosing and drug–drug interactions in modern anesthetic regimens
- Long-term neurological outcomes associated with anesthesia modality
Selected Articles
1. Efficacy and safety of gastrodin in preventing postoperative delirium following cardiac surgery: a randomized placebo controlled clinical trial.
In a double-blind RCT of 155 CABG patients, gastrodin infusion (600 mg twice daily through POD6) reduced postoperative delirium incidence from 35.9% to 19.5% and increased odds of hospital discharge without drug-related adverse events. POCD incidence was low and similar between groups.
Impact: This is one of the first adequately blinded RCTs to show a pharmacological reduction in postoperative delirium after cardiac surgery, a high-impact outcome lacking effective prophylaxis.
Clinical Implications: Gastrodin infusion may be considered as a prophylactic adjunct for delirium in CABG patients pending replication, with monitoring protocols and inclusion in multimodal delirium prevention bundles.
Key Findings
- Postoperative delirium incidence reduced to 19.5% with gastrodin versus 35.9% with placebo (RR 0.54, 95% CI 0.32–0.93).
- No increase in adverse events; none were drug related (9.1% vs 14.1%).
- Greater odds of discharge in the gastrodin group (subhazard ratio 1.20, 95% CI 1.00–1.84).
Methodological Strengths
- Double-blind, randomized, placebo-controlled design with trial registration.
- Modified intention-to-treat analysis with prespecified co-primary outcomes.
Limitations
- Single-country, single drug regimen; generalizability beyond CABG ± valve surgery is uncertain.
- Sample size modest; POCD outcomes were rare, limiting power for cognitive endpoints.
Future Directions: Multicenter, larger RCTs across cardiac and non-cardiac surgeries, dose–response assessments, mechanistic studies (GABAergic/anti-inflammatory pathways), and health economic evaluations.
2. Influence of Remifentanil on the Pharmacokinetics and Pharmacodynamics of Remimazolam in Healthy Volunteers.
In a 24-subject crossover trial, remifentanil altered remimazolam PK/PD, reducing CNS7054 clearance and synergistically deepening sedation across MOAAS and BIS endpoints. Modeling identified remimazolam targets of ~200–275 ng/mL with 0–0.5 ng/mL remifentanil to maximize moderate sedation (MOAAS 2–3) probabilities.
Impact: Provides quantitative PK/PD interaction data and actionable target concentrations for a widely adopted ultra–short-acting benzodiazepine–opioid combination, informing safer, precise titration.
Clinical Implications: Use lower remimazolam targets when co-administering remifentanil and anticipate deeper sedation and increased tolerance to stimulation; adjust TCI setpoints and monitoring (MOAAS/BIS) accordingly.
Key Findings
- Remifentanil decreased apparent clearance of remimazolam’s metabolite CNS7054 (half-max inhibition at 8.0 ng/mL).
- Pharmacodynamic interaction detected across MOAAS, BIS, TOL, and TOTS endpoints.
- Simulated optimal targets for moderate sedation: remimazolam 200–275 ng/mL with 0–0.5 ng/mL remifentanil (MOAAS 2–3 probability ~44–45%).
Methodological Strengths
- Three-period randomized crossover design with target-controlled infusions and dense PK/PD sampling.
- Nonlinear mixed-effects modeling enabling simulation of clinical target combinations.
Limitations
- Healthy volunteers; external validity to surgical patients limited.
- Exposure–response for TOL and TOTS not fully characterized by design constraints.
Future Directions: Validation in perioperative patients (including elderly and comorbid), effect on recovery profiles, respiratory safety, and integration into closed-loop sedation systems.
3. Epilepsy Risk Associated With the Receipt of General Anesthesia Relative to Neuraxial Anesthesia: A Retrospective Cohort Study.
In over 177,000 adults undergoing procedures amenable to either general or neuraxial anesthesia, weighted analyses showed a time-dependent increase in new-onset epilepsy risk with general anesthesia compared with neuraxial techniques, becoming significant after ~3 years of follow-up.
Impact: Addresses a critical, long-debated question of long-term neurological sequelae of anesthesia with a large, methodologically rigorous cohort, likely to stimulate guideline and research reconsiderations.
Clinical Implications: When feasible, neuraxial anesthesia may be preferred in patients concerned about long-term neurological risks; informed consent should acknowledge uncertainty and potential time-delayed risks after general anesthesia.
Key Findings
- Weighted epilepsy incidence: 48.8 vs 35.5 per 100,000 person-years (general vs neuraxial).
- Time-varying effect: HR at time 0 was 0.61, but risk increased over time (time interaction HR 1.36), becoming significantly higher after ~3 years for general anesthesia.
- Robust methodology: IPTW adjustment and Fine–Gray competing risk modeling.
Methodological Strengths
- Large population-based cohort with linkage of administrative databases.
- Advanced causal methods: inverse probability weighting and competing risk models.
Limitations
- Residual confounding and unmeasured differences (e.g., surgical indications) may remain.
- Onset of new epilepsy risk factors during follow-up could not be fully controlled.
Future Directions: Procedure-specific analyses, prospective registries capturing perioperative brain insults, and mechanistic studies to disentangle anesthesia effects from surgical/pathology contributors.