Schomer Kendra J, Duby Jeremiah J, Firestone Rachelle L, Louie Erin L, Sebat Christian M, Love Dawn M, Cocanour Christine S, Albertson Timothy E
Department of Pharmacy, University of California Davis Medical Center, Scramento, CA.
Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, School of Medicine, University of California Davis Medical Center, Sacramento, CA.
Crit Care Explor. 2020 Mar 24;2(3):e0085. doi: 10.1097/CCE.0000000000000085. eCollection 2020 Mar.
To determine whether the use of flumazenil reverses hypoactive delirium and increases delirium-free days in critically ill patients who were exposed to benzodiazepine therapy during the ICU admission.
This was a single-center, double-blinded, randomized placebo-controlled pilot study.
Adult ICUs at a large academic medical center in the United States.
Adult, critically ill patients with benzodiazepine exposure and hypoactive delirium based on the Confusion Assessment Method-ICU and Richmond Agitation Sedation Scale assessments were considered for enrollment.
Patients received a test dose of flumazenil starting at 0.1 mg intravenously and titrated up every 5 minutes by 0.1 mg increments up to a maximum total dose of 2 mg. Patients who demonstrated a Richmond Agitation Sedation Scale score increase of greater than 1 point were considered responders and randomized to flumazenil (0.05-0.3 mg/hr) or placebo infusion for up to 72 hours. Confusion Assessment Method-ICU scores were assessed twice daily for resolution of delirium.
The trial was stopped early based on the observed size effect and power analysis. Twenty-two of the 25 patients responded to the flumazenil test dose (88%). The median number of delirium-free days alive without coma within 14 days of enrollment was similar between the two infusion groups (12.7 vs 9.2; = 0.19). There was no difference in the probability of delirium resolution within the first 14 days with 90% versus 70% in the flumazenil and placebo groups, respectively ( = 0.2). There was no statistical difference (odds ratio, 0.17; 95% CI, 0.022-1.23; = 0.079) in delirium- and coma-free days at the end of the study drug infusion. There was no difference between groups in ICU length of stay (7.8 ± 4.8 vs 7 ± 8; = 0.74). No serious adverse events occurred.
This study found that flumazenil test dose and infusion present a potential option for hypoactive delirium associated with benzodiazepine exposure; however, the possible benefit is unknown. Larger studies are warranted to further evaluate these findings.
为确定氟马西尼的使用是否能逆转危重症患者的活动减少型谵妄，并增加无谵妄天数，这些患者在入住重症监护病房（ICU）期间接受了苯二氮䓬类药物治疗。
这是一项单中心、双盲、随机安慰剂对照的试验性研究。
美国一家大型学术医疗中心的成人ICU。
根据重症监护谵妄筛查检查表（CAM-ICU）和里士满躁动镇静量表评估，有苯二氮䓬类药物暴露且存在活动减少型谵妄的成年危重症患者被纳入研究。
患者从静脉注射0.1毫克氟马西尼开始接受试验剂量，并每5分钟以0.1毫克的增量滴定，最大总剂量为2毫克。里士满躁动镇静量表评分增加超过1分的患者被视为有反应者，并随机分为氟马西尼组（0.05 - 0.3毫克/小时）或安慰剂输注组，持续72小时。每天两次评估重症监护谵妄筛查检查表评分以确定谵妄是否缓解。
基于观察到的效应量和效能分析，试验提前终止。25名患者中有22名对氟马西尼试验剂量有反应（88%）。两组输注组在入组后14天内无昏迷且无谵妄的存活天数中位数相似（12.7天对9.2天；P = 0.19）。氟马西尼组和安慰剂组在第14天内谵妄缓解的概率分别为90%和70%，无差异（P = 0.2）。在研究药物输注结束时，无谵妄和无昏迷天数无统计学差异（优势比，0.17；95%置信区间，0.022 - 1.23；P = 0.079）。两组在ICU住院时间上无差异（7.8 ± 4.8天对7 ± 8天；P = 0.74）。未发生严重不良事件。
本研究发现，氟马西尼试验剂量和输注是与苯二氮䓬类药物暴露相关的活动减少型谵妄的一种潜在选择；然而，其可能的益处尚不清楚。需要更大规模的研究来进一步评估这些发现。
