Weekly Anesthesiology Research Analysis
This week highlighted translational advances spanning mechanistic neuroscience, perioperative analgesic innovation, and systems-level perioperative optimization. A high-impact animal study identified a convergent dmPAG glutamatergic arousal circuit across multiple anesthetics, offering a new target for emergence modulation. Large randomized human trials and meta-analyses showed perineural esketamine can prevent chronic postsurgical pain after TKA and exercise prehabilitation (especially inspirat
Summary
This week highlighted translational advances spanning mechanistic neuroscience, perioperative analgesic innovation, and systems-level perioperative optimization. A high-impact animal study identified a convergent dmPAG glutamatergic arousal circuit across multiple anesthetics, offering a new target for emergence modulation. Large randomized human trials and meta-analyses showed perineural esketamine can prevent chronic postsurgical pain after TKA and exercise prehabilitation (especially inspiratory muscle training) likely reduces postoperative complications and length of stay. Collectively these papers emphasize mechanisms-to-clinic translation and practical strategies to improve perioperative outcomes.
Selected Articles
1. The role of the dorsomedial periaqueductal gray glutamatergic neurons in promoting arousal under multiple general anesthetics in mice.
This mechanistic in vivo study used calcium imaging, optogenetic and chemogenetic manipulation, and EEG to show that dorsomedial PAG glutamatergic neurons are suppressed during anesthesia and activated during wakefulness across sevoflurane, propofol, ketamine and dexmedetomidine. Activation delayed induction, accelerated emergence, and reduced burst-suppression, indicating a convergent arousal substrate across agents.
Impact: Identifies a cross-agent neural circuit controlling anesthetic depth and emergence, providing a tangible mechanistic target to develop pharmacologic or neuromodulatory emergence strategies.
Clinical Implications: Although preclinical, the findings support exploration of dmPAG-targeted neuromodulation or drugs to accelerate emergence or treat delayed awakening, and motivate search for bedside biomarkers of dmPAG activity to inform individualized emergence protocols.
Key Findings
- dmPAG glutamatergic neurons are suppressed during anesthesia and activated during wakefulness across inhalational and intravenous agents.
- Optogenetic activation prolonged induction time and shortened emergence time under sevoflurane; it reduced burst-suppression ratio and produced wake-like EEG patterns.
- Inhibition of these neurons potentiated anesthetic effects across agents, indicating a shared arousal substrate.
2. Esketamine as an Adjuvant to Ropivacaine in Genicular Nerve and IPACK Blocks for Total Knee Arthroplasty: A Double-Blind Randomized Trial.
A multicenter double-blind RCT (n=367) randomized TKA patients to genicular/IPACK blocks with saline, ropivacaine, or ropivacaine plus perineural esketamine (0.2 mg/kg). At 6 months, chronic postsurgical pain (NRS≥4) was 4.9% in the esketamine group versus 17.9% (ropivacaine) and 27.0% (control); pain burden and early functional recovery also improved without increased adverse events.
Impact: Offers a pragmatic, scalable regional-anesthesia strategy that substantially reduces the incidence of chronic postsurgical pain after TKA — a major determinant of long-term recovery and quality of life.
Clinical Implications: Consider adding perineural esketamine (0.2 mg/kg) to genicular/IPACK blocks for TKA within multimodal analgesia pathways to reduce 6‑month CPSP and improve early recovery, while monitoring for neurotoxicity and documenting long-term safety.
Key Findings
- 6‑month CPSP incidence: 4.9% (esketamine) vs 17.9% (ropivacaine) vs 27.0% (control).
- Overall pain burden (AUC) and early functional outcomes (TUG, walking distance, QoR-15) improved in the esketamine arm.
- No increase in reported adverse events with perineural esketamine at studied dose.
3. Pooled Efficacy and Exploration of Effect Modifiers of Exercise Prehabilitation: A Systematic Review and Meta-regression Analysis of Randomized Controlled Trials.
A registered systematic review and meta-regression of 99 RCTs (n=8,222) found that exercise prehabilitation likely reduces postoperative complications (OR 0.54) and shortens length of stay (mean −0.90 days). Inspiratory muscle training was the sole consistent effect modifier enhancing both complication and LOS reductions, suggesting practical optimizations for ERAS programs.
Impact: Aggregates broad RCT evidence to show a modifiable preoperative program (especially inspiratory muscle training) can meaningfully reduce complications and hospital stay—highly actionable for perioperative services and ERAS implementation.
Clinical Implications: Incorporate structured exercise prehabilitation—prioritizing inspiratory muscle training—into perioperative pathways where feasible to reduce complications and LOS; standardize protocols and reporting to enable broader implementation and IPD synthesis.
Key Findings
- Pooled effect across 99 RCTs: postoperative complications reduced (OR 0.54, moderate certainty).
- Length of stay decreased by mean ~0.90 days (low certainty; heterogeneity present).
- Inspiratory muscle training was the only consistent effect modifier improving both complications and LOS.