Stoehr Kaitlyn A, Bartolome David, Jayasundara Sithmi, Thinzar Pwint, Vargas David, Kim Jennifer, Magid-Bernstein Jessica, O'Keefe Lena M, de Havenon Adam, Hebert Ryan, Matouk Charles, Sheth Kevin N, Gilmore Emily J, Ortega-Gutierrez Santiago, Petersen Nils H
Department of Neurology, Yale School of Medicine, New Haven, CT, USA.
Department of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
Neurocrit Care. 2025 Aug 22. doi: 10.1007/s12028-025-02338-6.
Impairment of cerebral autoregulation following aneurysmal subarachnoid hemorrhage (aSAH) increases susceptibility to secondary injury from blood pressure (BP) fluctuations. Although nimodipine is recommended to improve neurological outcomes, it is frequently associated with BP reduction. In this observational cohort study, we examined the effect of nimodipine-induced BP reductions that exceed autoregulatory capacity on functional outcome following aSAH.
Autoregulatory function was measured continuously following aneurysm securement by correlating near-infrared spectroscopy-derived regional oxygen saturation with mean arterial pressure (MAP). The resulting autoregulatory index was used to derive the lower and upper limits of autoregulation (LLA and ULA). Physiologic parameters were compared between the hour before and the hour after nimodipine administration using linear mixed-effects models. Ordinal regression was used to assess the relationship between time with MAP below the LLA and functional outcome, as measured by the modified Rankin scale at 90 days post discharge.
Analysis included 682 nimodipine administrations among 31 patients with moderate to severe aSAH (mean age 57 ± 14 years, 71% female, median Hunt & Hess score 4 [interquartile range (IQR) 2-4], modified Fisher grade 4 [IQR 3-4], monitoring time 5.5 ± 4.7 days). Following nimodipine, MAP decreased from a mean ± SEM of 105.9 ± 0.7 to 100.1 ± 0.7 mm Hg (p < 0.001), resulting in increased time below the LLA from a mean ± SEM of 5.3 ± 0.5 to 13.9 ± 0.7 min (p < 0.001). Mean time below the LLA was significantly associated with worse functional outcome at 90 days (odds ratio for 10-min increase 3.6, 95% confidence interval 1.6-8.0, p = 0.0015). This association remained significant after adjusting separately for age, Hunt & Hess score, modified Fisher grade, delayed cerebral ischemia, and the magnitude of BP response to nimodipine.
Nimodipine-induced BP reductions below personalized limits of autoregulation may be associated with worse functional outcome after aSAH. Further prospective studies are warranted to explore how autoregulatory sensitivity to nimodipine can be used to identify vulnerable patients and maximize benefits from current clinical interventions.
动脉瘤性蛛网膜下腔出血（aSAH）后脑血管自动调节功能受损会增加血压（BP）波动导致继发性损伤的易感性。尽管推荐使用尼莫地平改善神经功能结局，但它常与血压降低相关。在这项观察性队列研究中，我们研究了尼莫地平引起的血压降低超过自动调节能力对aSAH后功能结局的影响。
在动脉瘤夹闭后，通过将近红外光谱衍生的局部氧饱和度与平均动脉压（MAP）相关联，连续测量自动调节功能。所得的自动调节指数用于得出自动调节的下限和上限（LLA和ULA）。使用线性混合效应模型比较尼莫地平给药前1小时和给药后1小时的生理参数。使用有序回归评估MAP低于LLA的时间与功能结局之间的关系，功能结局通过出院后90天的改良Rankin量表进行测量。
分析纳入了31例中重度aSAH患者（平均年龄57±14岁，71%为女性，Hunt & Hess评分中位数4[四分位间距（IQR）2 - 4]，改良Fisher分级4[IQR 3 - 4]，监测时间5.5±4.7天）的682次尼莫地平给药情况。给予尼莫地平后，MAP从平均±SEM的105.9±0.7降至100.1±0.7 mmHg（p < 0.001），导致低于LLA的时间从平均±SEM的5.3±0.5分钟增加至13.9±0.7分钟（p < 0.001）。低于LLA的平均时间与90天时较差的功能结局显著相关（每增加10分钟的比值比为3.6，95%置信区间1.6 - 8.0，p = 0.0015）。在分别调整年龄、Hunt & Hess评分、改良Fisher分级、迟发性脑缺血以及血压对尼莫地平的反应幅度后，这种关联仍然显著。
尼莫地平引起的血压降低至个性化自动调节极限以下可能与aSAH后较差的功能结局相关。有必要进行进一步的前瞻性研究，以探索如何利用对尼莫地平的自动调节敏感性来识别易损患者，并使当前临床干预的益处最大化。
