Chau Lily, Davis Herbert T, Jones Thomas, Greene-Chandos Diana, Torbey Michel, Shuttleworth C William, Carlson Andrew P
Department of Neurology, University of New Mexico, Albuquerque, NM 87131, USA.
Department of Internal Medicine, University of New Mexico, Albuquerque, NM 87131, USA.
J Pers Med. 2022 Sep 1;12(9):1447. doi: 10.3390/jpm12091447.
Spreading depolarization (SD) occurs nearly ubiquitously in malignant hemispheric stroke (MHS) and is strongly implicated in edema progression and lesion expansion. Due to this high burden of SD after infarct, it is of great interest whether SD in MHS patients can be mitigated by physiologic or pharmacologic means and whether this intervention improves clinical outcomes. Here we describe the association between physiological variables and risk of SD in MHS patients who had undergone decompressive craniectomy and present an initial case of using ketamine to target SD in MHS.
We recorded SD using subdural electrodes and time-linked with continuous physiological recordings in five subjects. We assessed physiologic variables in time bins preceding SD compared to those with no SD.
Using multivariable logistic regression, we found that increased ETCO2 (OR 0.772, 95% CI 0.655-0.910) and DBP (OR 0.958, 95% CI 0.941-0.991) were protective against SD, while elevated temperature (OR 2.048, 95% CI 1.442-2.909) and WBC (OR 1.113, 95% CI 1.081-1.922) were associated with increased risk of SD. In a subject with recurrent SD, ketamine at a dose of 2 mg/kg/h was found to completely inhibit SD.
Fluctuations in physiological variables can be associated with risk of SD after MHS. Ketamine was also found to completely inhibit SD in one subject. These data suggest that use of physiological optimization strategies and/or pharmacologic therapy could inhibit SD in MHS patients, and thereby limit edema and infarct progression. Clinical trials using individualized approaches to target this novel mechanism are warranted.
扩散性去极化（SD）在恶性半球性卒中（MHS）中几乎普遍存在，并且与水肿进展和病灶扩大密切相关。由于梗死灶后SD负担较重，因此MHS患者的SD能否通过生理或药物手段减轻以及这种干预是否能改善临床结局备受关注。在此，我们描述了接受减压颅骨切除术的MHS患者生理变量与SD风险之间的关联，并介绍了首例使用氯胺酮靶向治疗MHS患者SD的病例。
我们使用硬膜下电极记录了5名受试者的SD，并将其与连续的生理记录进行时间关联。我们评估了SD发生前时间间隔内的生理变量，并与未发生SD的情况进行比较。
通过多变量逻辑回归分析，我们发现呼气末二氧化碳分压（ETCO2）升高（比值比[OR]0.772，95%置信区间[CI]0.655 - 0.910）和舒张压（DBP）升高（OR 0.958，95% CI 0.941 - 0.991）对SD具有保护作用，而体温升高（OR 2.048，95% CI 1.442 - 2.909）和白细胞计数（WBC）升高（OR 1.113，95% CI 1.081 - 1.922）与SD风险增加相关。在一名复发性SD患者中，发现剂量为2 mg/kg/h的氯胺酮可完全抑制SD。
生理变量的波动可能与MHS后SD风险相关。还发现氯胺酮可在一名受试者中完全抑制SD。这些数据表明，采用生理优化策略和/或药物治疗可能抑制MHS患者的SD，从而限制水肿和梗死进展。有必要开展采用个体化方法靶向这一新机制的临床试验。
