Anesthesiology Research Analysis
October anesthesiology research balanced pragmatic perioperative trials with high-impact translational science. A large single-cell genomics study mapped chronic pain risk to specific cortical glutamatergic neurons and hDRG nociceptors, guiding precision analgesic target discovery. Multiple randomized trials emphasized implementable perioperative strategies (e.g., IV esketamine for pediatric emergence and subcutaneous nitroglycerin for radial artery occlusion) and produced neutral evidence again
Summary
October anesthesiology research balanced pragmatic perioperative trials with high-impact translational science. A large single-cell genomics study mapped chronic pain risk to specific cortical glutamatergic neurons and hDRG nociceptors, guiding precision analgesic target discovery. Multiple randomized trials emphasized implementable perioperative strategies (e.g., IV esketamine for pediatric emergence and subcutaneous nitroglycerin for radial artery occlusion) and produced neutral evidence against ambulatory-derived individualized intraoperative MAP targets. A phase-3 trial of a full-spectrum cannabis extract showed modest but significant pain reduction, expanding multimodal analgesic options.
Selected Articles
1. The cell-type-specific genetic architecture of chronic pain in brain and dorsal root ganglia.
Integrating GWAS (n≈1.24M) with human single-cell transcriptomic and chromatin data, the study localizes chronic pain heritability to glutamatergic neurons in prefrontal cortex, hippocampus and amygdala and to a specific hDRG nociceptor subtype (hPEP.TRPV1/A1.2), highlighting kinase signaling, GABAergic synapses, and axon guidance pathways as candidate mechanisms for targeted analgesic development.
Impact: Provides the first large-scale cell-type map linking chronic pain GWAS signals to discrete CNS and PNS neuronal populations, enabling precision target discovery and prioritizing translational programs.
Clinical Implications: Guides targeted analgesic strategy development and biomarker selection focused on glutamatergic cortical circuits and hDRG TRPV1/A1.2 nociceptors; informs research prioritization rather than immediate practice change.
Key Findings
- Pain GWAS variants enriched in glutamatergic neurons (prefrontal cortex, hippocampus CA1–3, amygdala).
- Human DRG hPEP.TRPV1/A1.2 nociceptor subtype shows robust enrichment of pain risk variants.
- Gene-level pathways implicate kinase activity, GABAergic synapses, axon guidance, and neuron projection development.
2. Full-spectrum extract from Cannabis sativa DKJ127 for chronic low back pain: a phase 3 randomized placebo-controlled trial.
A multicenter phase‑3 randomized, placebo‑controlled trial (n=820) found that a full‑spectrum Cannabis sativa extract (VER‑01) produced a modest but statistically significant reduction in mean numeric rating scale pain over 12 weeks versus placebo and improved neuropathic symptom scores in a predefined subgroup. Adverse events were more frequent but mainly mild‑to‑moderate; no dependence or withdrawal signals were observed.
Impact: First large phase‑3 evidence that a standardized full‑spectrum cannabis extract can reduce chronic low back pain and neuropathic symptoms, informing analgesic options beyond traditional opioids and NSAIDs.
Clinical Implications: Consider VER‑01 as a potential adjunct in multimodal chronic low back pain management after discussing modest effect size and higher rates of mostly mild adverse events; monitor for tolerability and long‑term safety.
Key Findings
- Met primary endpoint: mean NRS pain reduction −1.9 in VER‑01; mean difference vs placebo −0.6 (95% CI −0.9 to −0.3; P<0.001).
- Neuropathic pain subgroup (PainDETECT>18) had larger NPSI improvement (MD vs placebo −7.3; P=0.017).
- Adverse events higher with VER‑01 (83.3% vs 67.3%) but mostly mild–moderate; no dependence/withdrawal detected.
3. Intravenous esketamine for the prevention of emergence delirium and negative behavioural changes after paediatric adenotonsillectomy: a randomised controlled trial.
A single‑center, double‑blind RCT (n=228) in children 3–7 years undergoing adenotonsillectomy found intraoperative low‑dose IV esketamine (0.2 mg/kg) reduced emergence delirium (17% vs 43%) and day‑7 negative behavioral changes (42% vs 61%) without increasing adverse events; benefits persisted at day 30 with improved analgesia and parental satisfaction.
Impact: Pragmatic randomized evidence for a simple intraoperative intervention that reduces pediatric emergence delirium and early maladaptive behaviours with minimal safety concerns.
Clinical Implications: Consider protocolizing low‑dose IV esketamine in pediatric adenotonsillectomy to reduce emergence delirium and early behavioral disturbances, with routine monitoring and local adaptation.
Key Findings
- Emergence delirium: 17% (esketamine) vs 43% (saline); RR 0.40; p<0.001.
- Negative behavioural changes day 7: 42% vs 61%; RR 0.70; p=0.009; benefits persisted to day 30.
- No increase in adverse events; improved analgesia and parental satisfaction.
4. Subcutaneous Nitroglycerin to Prevent Radial Artery Occlusion in Pediatric Patients: A Randomized Clinical Trial.
A double‑blind RCT in children <3 years undergoing radial artery catheterization (per‑protocol n=132) demonstrated that subcutaneous nitroglycerin (5 μg/kg) before cannulation and removal reduced radial artery occlusion after catheter removal from 73.8% to 25.4% (absolute risk reduction ≈48.5%) without hypotension or local adverse effects and improved flow metrics.
Impact: Shows a low-cost, simple, and highly effective preventive measure against a common pediatric vascular complication with a large absolute risk reduction and favorable safety.
Clinical Implications: Adopt subcutaneous nitroglycerin (5 μg/kg) before ultrasound‑guided radial arterial cannulation and prior to removal in infants/toddlers to prevent RAO while monitoring standard hemodynamics.
Key Findings
- RAO incidence: 25.4% with nitroglycerin vs 73.8% with placebo; OR 0.12; absolute risk reduction ~48.5%.
- Improved post‑removal radial artery peak flow velocity and perfusion index; no hypotension or local adverse effects.
- Per‑protocol analysis included 132 of 200 randomized due to protocol exclusions.
5. Individualized Perioperative Blood Pressure Management in Patients Undergoing Major Abdominal Surgery: The IMPROVE-multi Randomized Clinical Trial.
In 1,142 high‑risk major abdominal surgery patients across 15 centers, individualized MAP targets based on preoperative nighttime ambulatory MAP did not reduce a 7‑day composite of AKI, myocardial injury, nonfatal cardiac arrest, or death versus routine MAP ≥65 mmHg (RR 1.10; 95% CI 0.93–1.30). No secondary outcomes differed, challenging use of ambulatory-derived personalized BP targets intraoperatively.
Impact: A large multicenter RCT directly testing ambulatory-derived personalized MAP targets that found no clinical benefit, providing high-level evidence against routine implementation.
Clinical Implications: Maintain standard intraoperative MAP targets (e.g., ≥65 mmHg) in major abdominal surgery rather than adopting ambulatory-derived personalized targets; redirect efforts to perfusion- and autoregulation-guided strategies.
Key Findings
- No reduction in 7‑day composite organ-injury endpoint with individualized MAP vs routine care (RR 1.10; 95% CI 0.93–1.30; P=.31).
- No differences across 22 secondary outcomes including infections and 90‑day major adverse events.
- Intervention used preoperative mean nighttime MAP from ambulatory monitoring to set intraoperative targets; control targeted MAP ≥65 mmHg.