The influence of nimodipine and vasopressors on outcome in patients with delayed cerebral ischemia after spontaneous subarachnoid hemorrhage

Andrej Paľa MD1,2, Julia Schick MD1, Moritz Klein MD2, Benjamin Mayer Dr.biol.hum3, Bernd Schmitz MD, PhD4, Christian Rainer Wirtz MD, PhD1,2, Ralph König MD, PhD1,2, and Thomas Kapapa MD, PhD1,2
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  • 1 Department of Neurosurgery, University of Ulm;
  • | 2 Department of Neurosurgery, Bezirkskrankenhaus Günzburg, University of Ulm, Günzburg;
  • | 3 Institute of Epidemiology and Medical Biometry, University of Ulm; and
  • | 4 Section of Neuroradiology, University of Ulm, Günzburg, Germany
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OBJECTIVE

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

ABBREVIATIONS

AUC = area under the receiver operating characteristic curve; CRP = C-reactive protein; DCI = delayed cerebral ischemia; DSA = digital subtraction angiography; ICA = internal carotid artery; MAP = mean arterial pressure; mRS = modified Rankin Scale; SAH = subarachnoid hemorrhage; WFNS = World Federation of Neurosurgical Societies.

Illustration from Duan et al. (pp 1174–1181).

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Contributor Notes

Correspondence Andrej Paľa: Bezirkskrankenhaus Günzburg, University of Ulm, Günzburg, Germany. andrej.pala@uni-ulm.de.

INCLUDE WHEN CITING Published online March 8, 2019; DOI: 10.3171/2018.11.JNS182891.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

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