Weekly Anesthesiology Research Analysis
This week highlights translational neuroscience linking peripheral barrier biology to chemotherapy neuropathy, practical hemodynamic management during anesthetic induction, and pediatric procedural sedation dosing. Mechanistic work identified netrin‑1/cortactin–mediated perineurial sealing as a recovery correlate for bortezomib neuropathy. Clinical trials support continuous norepinephrine infusion to stabilize MAP during induction in high‑risk patients, and adaptive randomized evidence defines o
Summary
This week highlights translational neuroscience linking peripheral barrier biology to chemotherapy neuropathy, practical hemodynamic management during anesthetic induction, and pediatric procedural sedation dosing. Mechanistic work identified netrin‑1/cortactin–mediated perineurial sealing as a recovery correlate for bortezomib neuropathy. Clinical trials support continuous norepinephrine infusion to stabilize MAP during induction in high‑risk patients, and adaptive randomized evidence defines optimal intranasal midazolam doses for young children.
Selected Articles
1. Neuronal toxicity and recovery from early bortezomib-induced neuropathy: blood-nerve barrier dysfunction without dorsal root ganglion damage.
Translational rat and patient data show early bortezomib neuropathy primarily involves perineurial/blood–nerve barrier leakiness with modest DRG change. Recovery correlated with resealing of the perineurial barrier, normalization of axonal morphology and skin innervation, and upregulation of cortactin and netrin‑1 — implicating barrier‑sealing biology as a therapeutic axis.
Impact: Defines barrier dysfunction (not DRG cell loss) as a mechanistic driver of early bortezomib neuropathy and identifies netrin‑1/cortactin–linked perineurial sealing as recovery correlates — opening targeted therapeutic avenues.
Clinical Implications: Consider monitoring small‑fiber loss in patients on bortezomib and investigate barrier‑repair strategies (e.g., netrin‑1 agonists or ECM modulators) in preclinical and early‑phase trials; pain management strategies should incorporate barrier biology.
Key Findings
- Early BTZ caused tactile and cold allodynia in rats with perineurial small-molecule leakiness that resealed during recovery.
- Nerve transcriptomics revealed circadian, ECM, and immune gene regulation; DRG changes were modest.
- Cortactin and netrin‑1 increased with pain resolution; patients with persistent pain had reduced skin innervation without netrin‑1 rise.
2. Continuous versus bolus norepinephrine administration and arterial blood pressure stability during induction of general anaesthesia in high-risk noncardiac surgery patients: a randomised trial.
In a single‑centre randomized trial (n=72), continuous norepinephrine infusion during induction reduced MAP variability (gARV) over the first 15 minutes compared with repeated manual boluses, demonstrating improved hemodynamic stability in high‑risk noncardiac surgery patients monitored with an arterial line.
Impact: Provides a simple, implementable strategy to reduce induction‑related MAP variability — a modifiable factor linked to organ injury — with high immediate clinical relevance for anesthetic practice.
Clinical Implications: Institutions should consider protocolizing continuous norepinephrine infusions during induction for high‑risk patients with arterial monitoring and pump availability; evaluate integration into induction bundles with preload optimization and anesthetic dosing.
Key Findings
- Continuous infusion reduced generalized average real variability (gARV) of MAP within 15 minutes post‑induction versus manual boluses.
- Arterial catheter continuous monitoring enabled precise hemodynamic assessment supporting the endpoint.
- Randomized allocation demonstrated feasibility and safety in a high‑risk cohort; organ outcomes not reported.
3. Optimal Dose of Intranasal Midazolam for Procedural Sedation in Children: A Randomized Clinical Trial.
A double‑blind adaptive randomized trial (n=101) in children 6 months–7 years undergoing laceration repair found 0.4 and 0.5 mg/kg intranasal midazolam met prespecified adequate sedation criteria while 0.2 and 0.3 mg/kg were eliminated; no serious adverse events occurred.
Impact: Provides high‑quality, adaptive randomized evidence to standardize dosing for a commonly used pediatric sedative, reducing practice variability and improving safety and workflow in emergency/procedural settings.
Clinical Implications: Adopt intranasal midazolam dosing of 0.4–0.5 mg/kg for procedural sedation in young children with appropriate monitoring; standardize timing and staffing around predictable onset and recovery profiles.
Key Findings
- Adaptive selection eliminated 0.2 and 0.3 mg/kg; 0.4 and 0.5 mg/kg satisfied the predefined adequate sedation composite endpoint.
- No serious adverse events across dosing arms and similar secondary outcomes between 0.4 vs 0.5 mg/kg.
- Design: double‑blind, adaptive Levin‑Robbins‑Leu sequential selection in a tertiary pediatric ED.