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.
BACKGROUND: General anesthesia may involve shared neural mechanisms. The periaqueductal gray (PAG) plays a critical role in physiological, instinctive behaviors, as well as sleep-wake regulation. However, the role of the dorsomedial PAG (dmPAG) in regulating the anesthesia-awakening state remains unclear. The study aims to investigate the role of dmPAG glutamatergic neurons in promoting arousal under multiple general anesthetics. METHODS: Multiple general anesthetics, including sevoflurane, propofol, ketamine, and dexmedetomidine, were administered to mice of both sexes. Calcium imaging was employed to monitor activity changes in glutamatergic neurons within the dmPAG during anesthesia and arousal. Optogenetic and chemogenetic approaches were used to manipulate neuronal activity and evaluate their effects on anesthesia induction, maintenance, and recovery. Additionally, electroencephalogram (EEG) recordings were analyzed to assess alterations in spectral power and the burst-suppression ratio under anesthesia. RESULTS: Glutamatergic neuronal activity in the dmPAG was suppressed during sevoflurane anesthesia but increased during wakefulness, with similar patterns observed for all intravenous anesthetics tested. Optogenetic activation of dmPAG glutamatergic neurons significantly prolonged anesthesia induction time (GFP vs. ChR2, 218.8 ± 50.83 s vs. 372.5 ± 40.18 ;s, P<0.001) and shortened emergence time (GFP vs. ChR2, 230.8 ± 40.44 s vs. 135 ± 19.82 s, P<0.001) under sevoflurane anesthesia.
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.
BACKGROUND: Prognostication of recovery in patients who are unconscious following cardiac arrest can be guided by concentrations of brain injury biomarkers in the blood. The optimal biomarker and cutoff concentrations for the prediction of outcome remain unknown. In this study, we aimed to evaluate which biomarker of brain injury is most accurate for predicting functional outcome after cardiac arrest, and to evaluate cutoff levels for the prediction of good and poor outcome. METHODS: This study was a prospective, international, observational biomarker study within the international Targeted Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial including adults aged 18 years or older with a presumed cardiac cause or unknown cause of arrest. Patients were recruited from 24 European hospitals. Serum samples were collected at 0, 24, 48, and 72 h after admission to intensive care units. Concentrations of neuron-specific enolase, S100, neurofilament light, and glial fibrillary acidic protein were analysed with Elecsys electrochemiluminescence immunoassays. The primary outcome was 6-month good (modified Rankin Scale 0-3) or poor (modified Rankin Scale 4-6) functional outcome.
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.
BACKGROUND AND AIMS: Postoperative delirium (POD) and postoperative neurocognitive dysfunction (POND) are common neurological complications after general anaesthesia. This study aimed to evaluate the effect of perioperative ketamine or esketamine on POD and POND. METHODS: We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library for randomised controlled trials investigating perioperative use of ketamine or esketamine versus placebo or no treatment. The primary outcomes included the incidence of POD and POND. Secondary outcomes included postoperative nausea and vomiting, pain scores, length of hospital stay, extubation time, and psychological adverse effects. The pooled estimates were quantified using odds ratios (ORs) and 95% confidence intervals (CIs), and between-study variability was quantified by the I² index, and sensitivity, subgroup analyses, and meta-regression were used to explore effect modifiers. RESULTS: Sixteen studies (2536 patients) demonstrated that ketamine significantly reduced POD risk (OR = 0.62, 95% CI: 0.42, 0.92; I² =51%), while seven studies (453 patients) showed no significant effect on POND (OR = 0.41, 95% CI: 0.14, 1.21; I² =74%). (es)ketamine administration was associated with increased psychological adverse effects (OR = 1.72, 95% CI: 1.24, 2.37; I² =0%). Subgroup analyses revealed that esketamine reduced delirium risk (OR = 0.68, 95% CI: 0.47, 0.98), whereas ketamine prevented neurocognitive disorder (OR = 0.35, 95% CI: 0.20, 0.61). No significant differences were observed in secondary outcomes including nausea/vomiting, pain intensity, hospital stay, or extubation time.