Paľa Andrej, Schick Julia, Klein Moritz, Mayer Benjamin, Schmitz Bernd, Wirtz Christian Rainer, König Ralph, Kapapa Thomas
1Department of Neurosurgery, University of Ulm.
2Department of Neurosurgery, Bezirkskrankenhaus Günzburg, University of Ulm, Günzburg.
J Neurosurg. 2019 Mar 8;132(4):1096-1104. doi: 10.3171/2018.11.JNS182891. Print 2020 Apr 1.
Delayed cerebral ischemia (DCI) is a major factor contributing to the inferior outcome of patients with spontaneous subarachnoid hemorrhage (SAH). Nimodipine and induced hypertension using vasopressors are an integral part of standard therapy. Consequences of the opposite effect of nimodipine and vasopressors on blood pressure on patient outcome remain unclear. The authors report the detailed general characteristics and influence of nimodipine and vasopressors on outcome in patients with SAH.
The authors performed a 2-center, retrospective, clinical database analysis of 732 SAH patients treated between 2008 and 2016. Demographic and clinical data such as age, sex, World Federation of Neurosurgical Societies (WFNS) grade, BMI, Fisher grade, history of arterial hypertension and smoking, aneurysm location, C-reactive protein (CRP) level, and detailed dosage of vasopressors and nimodipine during the treatment period were evaluated. Clinical outcome was analyzed using the modified Rankin Scale (mRS) 6 months after treatment. Univariate and multivariate regression analyses were performed. Additionally, mean arterial pressure (MAP), age, nimodipine, and vasopressor dose cutoff were evaluated with regard to outcome. The level of significance was set at ≤ 0.05.
Follow-up was assessed for 397 patients, 260 (65.5%) of whom achieved a good outcome (defined as an mRS score of 0-3). Univariate and multivariate analyses confirmed that nimodipine (p = 0.049), age (p = 0.049), and CRP level (p = 0.002) are independent predictors of good outcome. WFNS grade, Fisher score, hypertension, initial hydrocephalus, and total vasopressor dose showed significant influence on outcome in univariate analysis, and patient sex, smoking status, BMI, and MAP showed no significant association with outcome. A subgroup analysis of patients with milder initial SAH (WFNS grades I-III) revealed that initial hydrocephalus (p = 0.003) and CRP levels (p = 0.001) had significant influence on further outcome. When evaluating only patients with WFNS grade IV or V, age, CRP level (p = 0.011), vasopressor dose (p = 0.030), and nimodipine dose (p = 0.049) were independent predictors of patient outcome. Patients with an MAP < 93 mm Hg, a nimodipine cutoff dose of 241.8 mg, and cutoff total vasopressor dose of 523 mg had better outcomes.
According to the authors' results, higher doses of vasopressors can safely provide a situation in which the maximum dose of nimodipine could be administered. Cutoff values of the total vasopressor dose were more than 3 times higher in patients with severe SAH (WFNS grade IV or V), while the nimodipine cutoff remained similar in patients with mild and severe SAH. Hence, it seems encouraging that a maximum nimodipine dosage can be achieved despite the need for a higher vasopressor dose in patients with SAH.
迟发性脑缺血（DCI）是导致自发性蛛网膜下腔出血（SAH）患者预后不良的主要因素。尼莫地平和使用血管升压药诱导高血压是标准治疗的重要组成部分。尼莫地平和血管升压药对血压的相反作用对患者预后的影响尚不清楚。作者报告了SAH患者的详细一般特征以及尼莫地平和血管升压药对预后的影响。
作者对2008年至2016年间治疗的732例SAH患者进行了一项双中心、回顾性临床数据库分析。评估了人口统计学和临床数据，如年龄、性别、世界神经外科协会联合会（WFNS）分级、体重指数（BMI）、Fisher分级、动脉高血压和吸烟史、动脉瘤位置、C反应蛋白（CRP）水平以及治疗期间血管升压药和尼莫地平的详细剂量。使用改良Rankin量表（mRS）在治疗6个月后分析临床结局。进行了单因素和多因素回归分析。此外，还评估了平均动脉压（MAP）、年龄、尼莫地平和血管升压药剂量阈值对预后的影响。显著性水平设定为≤0.05。
对397例患者进行了随访，其中260例（65.5%）取得了良好结局（定义为mRS评分为0 - 3）。单因素和多因素分析证实，尼莫地平（p = 0.049）、年龄（p = 0.049）和CRP水平（p = 0.002）是良好结局的独立预测因素。WFNS分级、Fisher评分、高血压、初始脑积水和血管升压药总剂量在单因素分析中对结局有显著影响，而患者性别、吸烟状况、BMI和MAP与结局无显著关联。对初始SAH较轻（WFNS I - III级）患者的亚组分析显示，初始脑积水（p = 0.003）和CRP水平（p = 0.001）对进一步结局有显著影响。仅评估WFNS IV级或V级患者时，年龄、CRP水平（p = 0.011）、血管升压药剂量（p = 0.030）和尼莫地平剂量（p = 0.049）是患者预后的独立预测因素。MAP < 93 mmHg、尼莫地平阈值剂量为241.8 mg和血管升压药总阈值剂量为523 mg的患者预后较好。
根据作者的结果，更高剂量的血管升压药可以安全地提供一种情况，使尼莫地平能够给予最大剂量。严重SAH（WFNS IV级或V级）患者的血管升压药总剂量阈值比轻度SAH患者高出3倍以上，而轻度和严重SAH患者的尼莫地平阈值相似。因此，尽管SAH患者需要更高剂量的血管升压药，但仍能达到最大尼莫地平剂量，这似乎令人鼓舞。
