Dexmedetomidine Prolongs Lidocaine Intravenous Regional Anesthesia in Rats by Blocking the Hyperpolarization-Activated Cation Current.

Purpose: Intravenous regional anesthesia (IVRA) using lidocaine provides effective localized analgesia but its duration is limited. The mechanism by which dexmedetomidine enhances lidocaine IVRA is unclear but may involve modulation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Materials and Methods: Lidocaine IVRA with varying dexmedetomidine concentrations was performed in the tails of Sprague-Dawley rats. Tail-flick and tail-clamping tests assessed IVRA analgesia and anesthesia efficacy and duration. Contributions of α2 adrenergic receptors and HCN channels were evaluated by incorporating an α adrenergic receptor antagonist, the HCN channel inhibitor ZD7288, and the HCN channel agonist forskolin. Furthermore, whole-cell patch clamp electrophysiology quantified the effects of dexmedetomidine on HCN channels mediating hyperpolarization-activated cation current (Ih) in isolated dorsal root ganglion neurons. Results: Dexmedetomidine dose-dependently extended lidocaine IVRA duration and analgesia, unaffected by α2 receptor blockade. The HCN channel inhibitor ZD7288 also prolonged lidocaine IVRA effects, while the HCN channel activator forskolin shortened effects. In dorsal root ganglion neurons, dexmedetomidine concentration-dependently inhibited Ih amplitude and shifted the voltage-dependence of HCN channel activation. Conclusion: Dexmedetomidine prolongs lidocaine IVRA duration by directly inhibiting HCN channel activity, independent of α2 adrenergic receptor activation. This HCN channel inhibition represents a novel mechanism underlying the anesthetic and analgesic adjuvant effects of dexmedetomidine in IVRA.

Ultra-high b-value DWI accurately identifies isocitrate dehydrogenase genotypes and tumor subtypes of adult-type diffuse gliomas.

OBJECTIVES: To distinguish isocitrate dehydrogenase (IDH) genotypes and tumor subtypes of adult-type diffuse gliomas based on the fifth edition of the World Health Organization classification of central nervous system tumors (WHO CNS5) in 2021 using standard, high, and ultra-high b-value diffusion-weighted imaging (DWI). MATERIALS AND METHODS: This prospective study enrolled 70 patients with adult-type diffuse gliomas who underwent multiple b-value DWI. Apparent diffusion coefficient (ADC) values including ADCb500/b1000, ADCb500/b2000, ADCb500/b3000, ADCb500/b4000, ADCb500/b6000, ADCb500/b8000, and ADCb500/b10000 in tumor parenchyma (TP) and contralateral normal-appearing white matter (NAWM) were calculated. The ADC ratios of TP/NAWM were assessed for correlations with IDH genotypes, tumor subtypes, and Ki-67 status; diagnostic performances were compared. RESULTS: All ADCs were significantly higher in IDH mutant gliomas than in IDH wild-type gliomas (p < 0.01 for all); ADCb500/b8000 had the highest area under the curve (AUC) of 0.866. All ADCs were significantly lower in glioblastoma than in astrocytoma (p < 0.01 for all). ADCs other than ADCb500/b1000 were significantly lower in glioblastoma than in oligodendroglioma (p < 0.05 for all). ADCb500/b8000 and ADCb500/b10000 were significantly higher in oligodendroglioma than in astrocytoma (p = 0.034 and 0.023). The highest AUCs were 0.818 for ADCb500/b6000 when distinguishing glioblastoma from astrocytoma, 0.979 for ADCb500/b8000 and ADCb500/b10000 when distinguishing glioblastoma from oligodendroglioma, and 0.773 for ADCb500/b10000 when distinguishing astrocytoma from oligodendroglioma. Additionally, all ADCs were negatively correlated with Ki-67 status (p < 0.05 for all). CONCLUSION: Ultra-high b-value DWI can reliably separate IDH genotypes and tumor subtypes of adult-type diffuse gliomas using WHO CNS5 criteria. CLINICAL RELEVANCE STATEMENT: Ultra-high b-value diffusion-weighted imaging can accurately distinguish isocitrate dehydrogenase genotypes and tumor subtypes of adult-type diffuse gliomas, which may facilitate personalized treatment and prognostic assessment for patients with glioma. KEY POINTS: • Ultra-high b-value diffusion-weighted imaging can accurately distinguish subtle differences in water diffusion among biological tissues. • Ultra-high b-value diffusion-weighted imaging can reliably separate isocitrate dehydrogenase genotypes and tumor subtypes of adult-type diffuse gliomas. • Compared with standard b-value diffusion-weighted imaging, high and ultra-high b-value diffusion-weighted imaging demonstrate better diagnostic performances.

Regional versus systemic dexmedetomidine as an adjuvant to lidocaine for intravenous regional anaesthesia in healthy volunteers: a randomized crossover study.

BACKGROUND: Dexmedetomidine enhances the quality and duration of lidocaine intravenous regional anaesthesia (IVRA). However, the two administration routes have not been directly compared regarding effects on tourniquet tolerance time with lidocaine IVRA. Additionally, it remains unclear whether the prolonged tourniquet tolerance stems from the direct peripheral action of dexmedetomidine or indirect systemic analgesic effects. METHODS: We conducted forearm IVRA in 12 healthy volunteers using a crossover design on two separate study days. One day, the systemic dexmedetomidine group received an intravenous infusion of 0.5 µg/kg dexmedetomidine (20 mL) in one arm, followed by 0.5% lidocaine (25 mL) forearm IVRA in the contralateral arm. On the other day, the regional dexmedetomidine group received an intravenous 0.9% saline infusion (20 mL) in one arm, followed by combined 0.5% lidocaine (25 mL) and 0.5 µg/kg dexmedetomidine forearm IVRA in the opposite arm. After a two-week washout period, participants crossed over to receive the alternate treatment. The primary outcome was tourniquet tolerance time, from initiating IVRA until the patient-reported tourniquet pain numerical rating scale exceeded three. RESULTS: The tourniquet tolerance time was longer with regional versus systemic dexmedetomidine (36.9 ± 7.6 min vs 23.3 ± 6.2 min, respectively), with a 13.6 min mean difference (95% CI: 10.8 to 16.4 min, p < 0.001). Regional dexmedetomidine also hastened sensory onset and extended sensory recovery compared to systemic administration. Delayed sedation after tourniquet release occurred in 5 of 12 subjects receiving regional dexmedetomidine. CONCLUSION: The addition of regional dexmedetomidine to lidocaine prolonged tourniquet tolerance time in forearm IVRA to a greater extent compared to systemic dexmedetomidine in healthy volunteers. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2300067978.

The addition of regional dexmedetomidine prolongs tourniquet tolerance time with lidocaine forearm IVRA.Regional dexmedetomidine accelerates sensory block onset time and extends sensory block recovery time when supplemented with lidocaine forearm IVRA.Delayed sedative effects following tourniquet release were witnessed in some participants administered regional dexmedetomidine.