Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Pediatric Neurology Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel.
LivaNova PLC (or a subsidiary), London, Great Britain, United Kingdom.
Epilepsy Behav. 2022 Sep;134:108861. doi: 10.1016/j.yebeh.2022.108861. Epub 2022 Aug 10.
Common titration strategies for vagus nerve stimulation (VNS) prioritize monitoring of tolerability during small increases in stimulation intensity over several months. Prioritization of tolerability is partially based on how quickly side effects can be perceived and reported by patients, and the delayed onset of clinical benefits from VNS. However, many practices assess the clinical benefit of VNS at one year after implantation, and excessive caution during the titration phase can significantly delay target dosing or prevent a patient from reaching a therapeutic dose entirely.
This study aimed to characterize the relationship between titration speed and the onset of clinical response to VNS.
To assess differences between more aggressive titration strategies and more conservative ones, we analyzed the relationship between time-to-dose and time-to-response using a weighted Cox regression. The target dose was empirically defined as 1.625 mA output current delivered at 250 microsecond pulse widths at 20 Hz. Patient-level outcomes and dosing data were segregated into fast (<3 months), medium (3-6 months), and slow (>6 months) cohorts based on their titration speed.
The statistical model revealed a significant relationship between titration speed and onset of clinical response, defined as a 50% reduction from baseline in seizure frequency. Frequency of adverse events reported between each cohort trended toward higher rates of adverse events in adults who were titrated quickly; however, the pediatric population appeared to be more tolerant of titration at any speed.
This analysis indicates that faster titration yields faster onset of clinical benefit and is especially practical in the pediatric population, though attempts to accelerate adult titration may still be warranted.
迷走神经刺激（VNS）的常见滴定策略优先监测在几个月内刺激强度小幅度增加时的耐受性，而对耐受性的重视部分取决于患者对副作用的感知和报告的速度，以及 VNS 的临床获益的延迟出现。然而，许多实践在植入后一年评估 VNS 的临床获益，并且在滴定阶段过于谨慎可能会大大延迟目标剂量或完全阻止患者达到治疗剂量。
本研究旨在描述滴定速度与 VNS 临床反应开始之间的关系。
为了评估更积极的滴定策略与更保守的策略之间的差异，我们使用加权 Cox 回归分析了剂量与反应时间之间的关系。目标剂量被定义为在 20Hz 时以 250 微秒脉冲宽度输出 1.625mA 的电流。根据滴定速度，将患者水平的结局和剂量数据分为快速（<3 个月）、中速（3-6 个月）和慢速（>6 个月）队列。
统计模型显示，滴定速度与临床反应开始之间存在显著关系，临床反应开始定义为癫痫发作频率比基线降低 50%。在每个队列之间报告的不良事件频率趋势表明，快速滴定的成年人中不良事件的发生率更高；然而，在任何速度下，儿科人群似乎都更能耐受滴定。
这项分析表明，更快的滴定速度会更快地产生临床获益，在儿科人群中尤其实用，尽管加速成人滴定速度可能仍然是必要的。
