Department of Internal Medicine, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland.
Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Rue du Bugnon 46, 1011, Lausanne, Switzerland.
CNS Drugs. 2023 Jun;37(6):523-529. doi: 10.1007/s40263-023-01012-9. Epub 2023 Jun 8.
Benzodiazepines are the first treatment line in status epilepticus (SE). Despite their well-established benefit, benzodiazepines are frequently underdosed with potential detrimental consequences. In some European countries, clonazepam (CLZ) is commonly used as the first line treatment. The aim of this study was to explore the correlation between CLZ loading doses and SE outcome.
This study included a retrospective analysis of a prospective registry in Lausanne, Switzerland (CHUV Lausanne University Hospital), including all SE episodes treated between February 2016 and February 2021. Only adults (> 16 years old) were included with CLZ used as the first treatment line. Post-anoxic SE were excluded because of significant differences in physiopathology and prognosis. Patient characteristics, SE features, the validated SE severity score (STESS), and treatment characteristics were prospectively recorded. We considered loading doses of 0.015 mg/kg or higher (following commonly recommended loading doses) as high doses. We analyzed outcome in terms of number of treatment lines after the CLZ, proportion of refractory episodes, intubation for airways protection, intubation for SE treatment, and mortality. We performed univariable analyses to investigate the association between loading doses and clinical response. A multivariable stepwise backward binary logistic regression was applied for adjusting for potential confounders. Multivariable linear regression was similarly used to analyze CLZ dose as a continuous variable.
We collected 251 SE episodes in 225 adult patients. Median CLZ loading dose was 0.010 mg/kg. CLZ high doses were used in 21.9% of SE episodes (in 43.8% for > 80% of the high dose). Thirteen percent of patients with SE were intubated for airways control, while intubation was needed in 12.7% for SE treatment. High CLZ loading doses were independently associated with younger age (median 62 versus 68 years old, p = 0.002), lesser weight (65 kg versus 75 kg, p = 0.001) and more frequent intubation for airways protection (23% vs 11%, p = 0.013), but differing CLZ dose was not associated with any outcome parameter.
CLZ high doses were more frequently used for SE treatment in younger patients with healthy weight and were more often associated with intubation for airways protection, probably as an adverse event. Varying CLZ dose did not alter outcome in SE, raising the possibility that commonly recommended doses are above what is needed, at least in some patients. Our results suggest that CLZ doses in SE may be individualized depending on the clinical setting.
苯二氮䓬类药物是癫痫持续状态（SE）的一线治疗药物。尽管其疗效已得到充分证实，但苯二氮䓬类药物的剂量常常不足，可能产生不利影响。在一些欧洲国家，氯硝西泮（CLZ）常用于一线治疗。本研究旨在探讨 CLZ 负荷剂量与 SE 结局之间的相关性。
本研究纳入了瑞士洛桑 CHUV 洛桑大学医院前瞻性登记的回顾性分析，包括 2016 年 2 月至 2021 年 2 月期间治疗的所有 SE 发作。仅纳入年龄>16 岁、CLZ 作为一线治疗的成年患者。由于病理生理学和预后存在显著差异，我们排除了缺氧后 SE。前瞻性记录患者特征、SE 特征、经验证的 SE 严重程度评分（STESS）和治疗特征。我们认为 0.015 mg/kg 或更高的负荷剂量（遵循常用的推荐剂量）为高剂量。我们根据 CLZ 后的治疗线数、难治性发作比例、气道保护插管、SE 治疗插管和死亡率来分析结局。我们进行单变量分析以研究负荷剂量与临床反应之间的关联。应用多变量逐步向后二元逻辑回归来调整潜在混杂因素。同样使用多元线性回归来分析 CLZ 剂量作为连续变量。
我们收集了 225 名成年患者的 251 例 SE 发作。CLZ 负荷剂量中位数为 0.010 mg/kg。21.9%的 SE 发作使用了 CLZ 高剂量（43.8%的患者使用了>80%的高剂量）。13%的 SE 患者需要插管进行气道控制，而 12.7%的 SE 患者需要插管进行 SE 治疗。CLZ 高剂量与年龄较小（中位年龄 62 岁 vs 68 岁，p=0.002）、体重较轻（65 kg vs 75 kg，p=0.001）和更频繁的气道保护插管（23% vs 11%，p=0.013）独立相关，但 CLZ 剂量不同与任何结局参数无关。
CLZ 高剂量在体重健康的年轻 SE 患者中更常被用于 SE 治疗，并且更常与气道保护插管相关，可能是一种不良事件。CLZ 剂量的变化并未改变 SE 的结局，这表明至少在某些患者中，常用的推荐剂量可能高于所需剂量。我们的结果表明，SE 中的 CLZ 剂量可能取决于临床情况而定个体化。
Zotero 插件