Hockel Konstantin, Diedler Jennifer, Steiner Jochen, Birkenhauer Ulrich, Danz Sören, Ernemann Ulrike, Schuhmann Martin U
Department of Neurosurgery, University Hospital Tübingen, University of Tübingen, Germany.
Department of Neurosurgery, University Hospital Tübingen, University of Tübingen, Germany.
World Neurosurg. 2016 Apr;88:104-112. doi: 10.1016/j.wneu.2015.11.081. Epub 2015 Dec 28.
Secondary vasospasm and disturbances in cerebrovascular autoregulation are associated with the development of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. An intra-arterial application of nimodipine has been shown to increase the vessel diameter, although this effect is transient. The feasibility of long-term, continuous, intra-arterial nimodipine treatment and its effects on macrovasospasm, autoregulation parameters, and outcome were evaluated in patients with refractory severe macrovasospasm.
Ten patients were included with refractory macrovasospasm despite bolus nimodipine application (n = 4) or with primary severe vasospasm (n = 6). The patients were assessed with continuous multimodal neuromonitoring (mean arterial pressure, intraceranial pressure, cerebral perfusion pressure, brain tissue oxygen tension probe), daily transcranial Doppler examinations, and computed tomography angiography/perfusion. Autoregulation indices, the pressure reactivity index, and oxygen reactivity index were calculated. Indwelling microcatheters were placed in the extracranial internal carotid arteries and 0.4 mg nimodipine was continuously infused at 50 mL/hour.
The duration of continuous, intra-arterial nimodipine ranged from 9 to 15 days. During treatment intracranial pressure remained stable, transcranial Doppler flow velocity decreased, and brain tissue oxygen tension improved by 37%. Macrovasospasm, as assessed via computed tomography angiography, had improved (n = 5) or disappeared (n = 5) at the end of treatment. Cerebrovascular autoregulation according to the pressure reactivity index and oxygen reactivity index significantly worsened during treatment. All patients showed a favorable outcome (median Glasgow Outcome Scale 5) at 3 months.
In well-selected patients with prolonged severe macrovasospasm, continuous intra-arterial nimodipine treatment can be applied as a rescue therapy with relative safety for more than 2 weeks to prevent secondary cerebral ischemia. The induced impairment of cerebrovascular autoregulation during treatment seems to have no negative effects.
继发性血管痉挛和脑血管自动调节功能障碍与动脉瘤性蛛网膜下腔出血后迟发性脑缺血的发生有关。动脉内应用尼莫地平已被证明可增加血管直径，尽管这种效果是短暂的。本研究评估了难治性严重血管痉挛患者长期、持续动脉内尼莫地平治疗的可行性及其对大血管痉挛、自动调节参数和预后的影响。
纳入10例患者，其中4例尽管已静脉推注尼莫地平仍存在难治性血管痉挛，6例为原发性严重血管痉挛。对患者进行连续多模态神经监测（平均动脉压、颅内压、脑灌注压、脑组织氧分压探头）、每日经颅多普勒检查以及计算机断层血管造影/灌注检查。计算自动调节指数、压力反应性指数和氧反应性指数。将留置微导管置于颅外颈内动脉，以50 mL/小时的速度持续输注0.4 mg尼莫地平。
动脉内持续应用尼莫地平的时间为9至15天。治疗期间颅内压保持稳定，经颅多普勒血流速度降低，脑组织氧分压提高了37%。治疗结束时，通过计算机断层血管造影评估的大血管痉挛有所改善（5例）或消失（5例）。根据压力反应性指数和氧反应性指数评估，治疗期间脑血管自动调节功能显著恶化。所有患者在3个月时均显示出良好的预后（格拉斯哥预后量表中位数为5）。
在精心挑选的长期严重血管痉挛患者中，连续动脉内尼莫地平治疗可作为一种挽救疗法相对安全地应用超过2周，以预防继发性脑缺血。治疗期间诱导的脑血管自动调节功能损害似乎没有负面影响。
