Weekly Anesthesiology Research Analysis
This week’s anesthesiology literature emphasized mechanistic insights into arousal circuits and anesthetic neurotoxicity, pragmatic perioperative interventions that alter long-term pain and recovery, and high-level evidence supporting preoperative optimization. A high-impact preclinical study identified dorsomedial periaqueductal gray glutamatergic neurons as a convergent arousal substrate across anesthetic classes. Randomized trials showed perineural esketamine dramatically lowered chronic post
Summary
This week’s anesthesiology literature emphasized mechanistic insights into arousal circuits and anesthetic neurotoxicity, pragmatic perioperative interventions that alter long-term pain and recovery, and high-level evidence supporting preoperative optimization. A high-impact preclinical study identified dorsomedial periaqueductal gray glutamatergic neurons as a convergent arousal substrate across anesthetic classes. Randomized trials showed perineural esketamine dramatically lowered chronic postsurgical pain after TKA, and a large meta-regression supported exercise prehabilitation (especially inspiratory muscle training) to reduce complications and length-of-stay.
Selected Articles
1. The role of the dorsomedial periaqueductal gray glutamatergic neurons in promoting arousal under multiple general anesthetics in mice.
Using in vivo calcium imaging, optogenetic/chemogenetic manipulation, and EEG across sevoflurane, propofol, ketamine, and dexmedetomidine, the study shows dmPAG glutamatergic neurons are suppressed by anesthetics and activated during wakefulness. Activation delayed induction, accelerated emergence, and reduced burst-suppression, while inhibition potentiated anesthetic effects, indicating a convergent arousal substrate across agents.
Impact: Identifies a causal, cross-agent neural circuit that modulates anesthetic depth and emergence; this mechanistic insight can anchor future pharmacologic or neuromodulatory strategies to control emergence and delayed awakening.
Clinical Implications: Although preclinical, the discovery motivates development of dmPAG-targeted neuromodulation or biomarker-guided emergence protocols and cautions translation studies in larger animals and humans to assess safety and efficacy.
Key Findings
- dmPAG glutamatergic neurons are suppressed during anesthesia and active during wakefulness across multiple agents.
- Optogenetic activation prolonged induction (~219 → 373 s) and shortened emergence (~231 → 135 s) under sevoflurane (P<0.001).
- Activation markedly reduced burst-suppression ratio and inhibition potentiated anesthetic effects across agents.
2. Esketamine as an Adjuvant to Ropivacaine in Genicular Nerve and IPACK Blocks for Total Knee Arthroplasty: A Double-Blind Randomized Trial.
In a double-blind RCT of 367 unilateral TKA patients, adding 0.2 mg/kg perineural esketamine to 0.5% ropivacaine for genicular and IPACK blocks reduced 6‑month chronic postsurgical pain to 4.9% versus 17.9% (ropivacaine alone) and 27.0% (saline). Pain burden (AUC) and early functional recovery metrics improved without increased adverse events.
Impact: Demonstrates a pragmatic, scalable regional-anesthesia adjuvant strategy that substantially lowers chronic postsurgical pain after TKA — a meaningful long-term outcome with direct implementation potential.
Clinical Implications: Consider perineural esketamine (0.2 mg/kg) as an adjuvant in genicular/IPACK blocks for TKA to reduce CPSP risk and improve early recovery, while continuing surveillance for potential local or neurotoxic effects in broader populations.
Key Findings
- 6‑month CPSP incidence: 4.9% (esketamine) vs 17.9% (ropivacaine) vs 27.0% (control).
- Reduced overall pain burden (AUC) and improved early function (TUG, walking distance, QoR-15).
- No increase in reported adverse events with perineural esketamine in the trial.
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/meta-regression of 99 RCTs (n=8,222) found exercise prehabilitation likely reduces postoperative complications (OR 0.54) and shortens length of stay (mean −0.90 days). Inspiratory muscle training was the only consistent effect modifier enhancing both outcomes. Authors recommend multicenter IPD trials to refine optimal program characteristics.
Impact: Provides high-level, cross-procedure evidence that exercise prehabilitation—particularly with inspiratory muscle training—can meaningfully reduce complications and LOS, informing ERAS and preoperative optimization programs.
Clinical Implications: Integrate structured exercise prehabilitation into perioperative pathways with emphasis on inspiratory muscle training; prioritize standardization and multicenter evaluation to optimize delivery and cost-effectiveness.
Key Findings
- Across 99 RCTs (n=8,222), prehabilitation likely reduced postoperative complications (OR 0.54).
- Length of stay was shortened by a pooled mean of 0.90 days (low certainty overall).
- Inspiratory muscle training was the only consistent effect modifier for improved outcomes.