Daily Anesthesiology Research Analysis
Analyzed 3 papers and selected 3 impactful articles.
Summary
Analyzed 3 papers and selected 3 impactful articles.
Selected Articles
1. The role of the dorsomedial periaqueductal gray glutamatergic neurons in promoting arousal under multiple general anesthetics in mice.
dmPAG glutamatergic neurons were suppressed by diverse anesthetics and activated during wakefulness. Optogenetic/chemogenetic activation delayed induction, hastened emergence, and reduced burst-suppression during maintained anesthesia; inhibition enhanced anesthetic effects across agents, suggesting a shared arousal substrate.
Impact: This study identifies a convergent neural circuit modulating anesthetic depth and emergence across distinct agents, offering a mechanistic substrate for future targeted arousal strategies.
Clinical Implications: Targeting dmPAG glutamatergic circuits could inform pharmacologic or neuromodulatory approaches to accelerate emergence or counter delayed awakening, though translation from mice to humans remains to be established.
Key Findings
- dmPAG glutamatergic activity is suppressed during anesthesia and elevated during wakefulness across sevoflurane, propofol, ketamine, and dexmedetomidine.
- Optogenetic activation prolonged induction (≈219 vs 373 s) and shortened emergence (≈231 vs 135 s) under sevoflurane (both P<0.001).
- Activation induced wake-like EEG with a markedly reduced burst-suppression ratio (≈50% vs 2.15%, P<0.001); inhibition potentiated anesthetic effects across agents.
Methodological Strengths
- Multimodal approach combining in vivo calcium imaging, optogenetics/chemogenetics, and EEG.
- Cross-agent validation across inhalational and intravenous anesthetics in both sexes.
Limitations
- Preclinical mouse model limits direct clinical translation.
- Detailed sample sizes and potential off-target effects of neuromodulation are not fully delineated in the abstract.
Future Directions: Test dmPAG-targeted neuromodulation/pharmacology in large animals and explore biomarkers of dmPAG activity during anesthesia to guide individualized emergence protocols.
2. Blood biomarkers for the prediction of outcome after cardiac arrest: an international prospective observational study within the Targeted Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial.
Among 819 analyzed patients (51% poor outcome), neurofilament light (NfL) best predicted 6‑month functional outcome with AUROCs 0.92–0.93 at 24–72 h, significantly outperforming GFAP, and exceeding NSE and S100. Findings support incorporating serial NfL into multimodal prognostication after cardiac arrest.
Impact: Provides robust, head-to-head validation of NfL superiority over commonly used biomarkers for neuroprognostication after cardiac arrest, informing practice and guideline development.
Clinical Implications: Serial NfL measurements at 24–72 h can refine prognostic accuracy and counseling, and should be integrated with clinical exam, electrophysiology, and imaging in multimodal algorithms.
Key Findings
- NfL AUROC was 0.92 at 24 h and 0.93 at 48–72 h for predicting 6‑month functional outcome; it significantly outperformed GFAP at 24, 48, and 72 h (p<0.0001).
- GFAP showed AUROCs 0.87 at 24–72 h; NSE 0.78–0.86; S100 0.74–0.84 depending on timepoint.
- Prospective, multicenter sampling at 0/24/48/72 h within TTM2; 418 of 819 patients had poor outcomes.
Methodological Strengths
- Prospective, international, multicenter design with standardized Elecsys assays and serial timepoints.
- Direct head-to-head comparison across four leading biomarkers with predefined statistical comparisons.
Limitations
- Observational design cannot establish causal effects or treatment implications.
- Generalizability may be influenced by inclusion within TTM2 sites; optimal clinical cutoffs still require external validation.
Future Directions: Define and validate clinically actionable NfL thresholds, evaluate combination with EEG/CT/MRI markers, and assess impact on shared decision-making and withdrawal-of-care protocols.
3. Effect of ketamine/esketamine on postoperative delirium and cognitive dysfunctions: A systematic review and meta-analysis of randomised trials.
Across 16 RCTs (n=2,536), perioperative (es)ketamine reduced postoperative delirium (OR 0.62) but did not significantly affect overall POND; psychological adverse effects increased (OR 1.72). Subgroups suggested esketamine lowered delirium risk while racemic ketamine may reduce neurocognitive disorder, without differences in PONV, pain, LOS, or extubation time.
Impact: Synthesizes randomized evidence on an accessible perioperative intervention with competing neuroprotective and neuropsychiatric effects, informing risk–benefit discussions and protocol design.
Clinical Implications: Consider (es)ketamine as part of multimodal strategies to reduce delirium in high-risk patients, with proactive monitoring and mitigation of psychological adverse effects; dosing, timing, and patient selection remain key.
Key Findings
- Perioperative (es)ketamine reduced POD (OR 0.62, 95% CI 0.42–0.92; I²=51%).
- No significant effect on overall POND (OR 0.41, 95% CI 0.14–1.21; I²=74%), but subgroup signals: esketamine reduced delirium (OR 0.68) and racemic ketamine reduced neurocognitive disorder (OR 0.35).
- Psychological adverse effects increased (OR 1.72), with no differences in PONV, pain, hospital stay, or extubation time.
Methodological Strengths
- Systematic synthesis of randomized controlled trials with subgroup and sensitivity analyses and meta-regression.
- Comprehensive outcomes including neurocognitive endpoints and adverse effects.
Limitations
- Substantial heterogeneity (I² up to 74%) and limited sample size for POND (n=453) reduce certainty.
- Variability in dosing, timing, and delirium assessment tools across trials.
Future Directions: Pragmatic trials to define optimal dosing/timing, phenotype-specific benefits (e.g., frailty, cardiac surgery), and strategies to minimize psychological adverse effects while preserving anti-delirium efficacy.