Coppler Patrick J, Gagnon David J, Flickinger Katharyn L, Elmer Jonathan, Callaway Clifton W, Guyette Francis X, Doshi Ankur, Steinberg Alexis, Dezfulian Cameron, Moskowitz Ari L, Donnino Michael, May Teresa L, Seder David B, Rittenberger Jon C
Department of Emergency Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Critical Care Services, Maine Medical Center, Portland, ME, USA.
Clin Exp Emerg Med. 2024 Jun;11(2):205-212. doi: 10.15441/ceem.23.158. Epub 2024 Jan 29.
We hypothesized that the administration of amantadine would increase awakening of comatose patients resuscitated from cardiac arrest.
We performed a prospective, randomized, controlled pilot trial, randomizing subjects to amantadine 100 mg twice daily or placebo for up to 7 days. The study drug was administered between 72 and 120 hours after resuscitation and patients with absent N20 cortical responses, early cerebral edema, or ongoing malignant electroencephalography patterns were excluded. Our primary outcome was awakening, defined as following two-step commands, within 28 days of cardiac arrest. Secondary outcomes included length of stay, awakening, time to awakening, and neurologic outcome measured by Cerebral Performance Category at hospital discharge. We compared the proportion of subjects awakening and hospital survival using Fisher exact tests and time to awakening and hospital length of stay using Wilcoxon rank sum tests.
After 2 years, we stopped the study due to slow enrollment and lapse of funding. We enrolled 14 subjects (12% of goal enrollment), seven in the amantadine group and seven in the placebo group. The proportion of patients who awakened within 28 days after cardiac arrest did not differ between amantadine (n=2, 28.6%) and placebo groups (n=3, 42.9%; P>0.99). There were no differences in secondary outcomes. Study medication was stopped in three subjects (21.4%). Adverse events included a recurrence of seizures (n=2; 14.3%), both of which occurred in the placebo group.
We could not determine the effect of amantadine on awakening in comatose survivors of cardiac arrest due to small sample size.
我们假设给予金刚烷胺可增加心脏骤停复苏后昏迷患者的觉醒。
我们进行了一项前瞻性、随机、对照试验，将受试者随机分为每日两次服用100毫克金刚烷胺组或安慰剂组，持续7天。研究药物在复苏后72至120小时之间给药，排除N20皮质反应缺失、早期脑水肿或持续恶性脑电图模式的患者。我们的主要结局是觉醒，定义为在心脏骤停后28天内能够执行两步指令。次要结局包括住院时间、觉醒情况、觉醒时间以及出院时用脑功能分类法测量的神经学结局。我们使用Fisher精确检验比较觉醒受试者的比例和医院生存率，使用Wilcoxon秩和检验比较觉醒时间和住院时间。
2年后，由于入组缓慢和资金耗尽，我们停止了研究。我们招募了14名受试者（占目标入组人数的12%），金刚烷胺组7名，安慰剂组7名。心脏骤停后28天内觉醒的患者比例在金刚烷胺组（n = 2，28.6%）和安慰剂组（n = 3，42.9%；P>0.99）之间没有差异。次要结局也没有差异。三名受试者（21.4%）停止了研究药物治疗。不良事件包括癫痫复发（n = 2；14.3%），均发生在安慰剂组。
由于样本量小，我们无法确定金刚烷胺对心脏骤停昏迷幸存者觉醒的影响。
