Division of Neurocritical Care, Department of Neurology, University of Massachusetts Medical School, 55 Lake Avenue North, S5-412, Worcester, MA 01655, USA.
Stroke. 2011 May;42(5):1301-6. doi: 10.1161/STROKEAHA.110.603159. Epub 2011 Mar 31.
New therapies for cerebral vasospasm after subarachnoid hemorrhage are needed because of its high morbidity and mortality rates. We investigated the feasibility and safety of a single dose of intravenous dantrolene and its effect on transcranial Doppler in cerebral vasospasm after subarachnoid hemorrhage.
In a prospective, open-label, single-dose ascending safety trial, 5 patients received intravenous dantrolene 1.25 mg/kg and the next 5 patients received 2.5 mg/kg over the course of 60 minutes. All other infusions were kept steady and hemodynamic parameters were recorded. Transcranial Doppler was performed at 0, 45, 90, and 135 minutes relative to infusion start. Basic chemistries, serum osmolality, arterial blood gas, and liver enzymes were measured before and after.
Laboratory values and hemodynamic parameters remained unchanged except for a decrease in the systolic blood pressure in the low-dose group (-8 mm Hg; 95% CI, -26 to 10 mm Hg; P=0.027). After correcting for this decrease in blood pressure, peak systolic transcranial Doppler velocities decreased significantly (-26 cm/s; 95% CI, -47 to -5 cm/s; P=0.02), with a borderline change in mean velocities in the low-dose group (-16 cm/s; 95% CI, -36 to 4 cm/s; P=0.07) and peak systolic transcranial Doppler velocity in the high-dose group (-26 cm/s; 95% CI, -56 to 5 cm/s; P=0.05).
In this pilot study, a single dose of intravenous dantrolene in cerebral vasospasm after subarachnoid hemorrhage appears feasible while inhibiting vasoconstriction in the low-dose group, but it may lower blood pressure. Our study provides useful data for the design of larger future studies. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique identifier: NCT00964548.
由于蛛网膜下腔出血后脑血管痉挛的高发病率和死亡率，需要新的治疗方法。我们研究了单次静脉注射丹曲林治疗蛛网膜下腔出血后脑血管痉挛的可行性和安全性，以及其对经颅多普勒的影响。
在一项前瞻性、开放标签、单剂量递增安全性试验中，5 例患者接受静脉注射丹曲林 1.25mg/kg，随后 5 例患者接受 2.5mg/kg，持续 60 分钟。所有其他输液速度保持稳定，并记录血流动力学参数。在输液开始后 0、45、90 和 135 分钟进行经颅多普勒检查。在前后分别测量基本化学物质、血清渗透压、动脉血气和肝酶。
除了低剂量组的收缩压下降（-8mmHg；95%CI，-26 至 10mmHg；P=0.027）外，实验室值和血流动力学参数保持不变。在纠正血压下降后，经颅多普勒超声收缩峰速度显著下降（-26cm/s；95%CI，-47 至-5cm/s；P=0.02），低剂量组的平均速度也有明显变化（-16cm/s；95%CI，-36 至 4cm/s；P=0.07），高剂量组的经颅多普勒超声收缩峰速度也有下降（-26cm/s；95%CI，-56 至 5cm/s；P=0.05）。
在这项初步研究中，蛛网膜下腔出血后脑血管痉挛患者单次静脉注射丹曲林似乎是可行的，同时抑制了低剂量组的血管收缩，但可能会降低血压。我们的研究为未来更大规模的研究提供了有用的数据。临床试验注册- URL：http://clinicaltrials.gov。独特标识符：NCT00964548。
