Previous studies indicate that isoflurane could be useful for the sedation of patients in the intensive care unit (ICU), but prospective studies evaluating isoflurane's efficacy have been small. The aim of this study was to test whether the sedation with isoflurane was non-inferior to sedation with propofol. This phase 3, randomised, controlled, open-label non-inferiority trial evaluated the efficacy and safety of up to 54 h of isoflurane compared with propofol in adults (aged ≥18 years) who were invasively ventilated in ICUs in Germany (21 sites) and Slovenia (three sites). Patients were randomly assigned (1:1) to isoflurane inhalation via the Sedaconda anaesthetic conserving device (ACD; Sedana Medical AB, Danderyd, Sweden; ACD-L [dead space 100 mL] or ACD-S [dead space 50 mL]) or intravenous propofol infusion (20 mg/mL) for 48 h (range 42–54) using permuted block randomisation with a centralised electronic randomisation system. The primary endpoint was percentage of time in Richmond Agitation–Sedation Scale (RASS) range –1 to –4, assessed in eligible participants with at least 12 h sedation (the per-protocol population), five or more RASS measurements, and no major protocol violations, with a non-inferiority margin of 15%. Key secondary endpoints were opioid requirements, spontaneous breathing, time to wake-up and extubation, and adverse events. Safety was assessed in all patients who received at least one dose. The trial is complete and registered with EudraCT, 2016–004551–67. Between July 2, 2017, and Jan 12, 2020, 338 patients were enrolled and 301 (89%) were randomly assigned to isoflurane (n=150) or propofol (n=151). 146 patients (97%) in each group completed the 24-h follow-up. 146 (97%) patients in the isoflurane group and 148 (98%) of patients in the propofol group were included in the per-protocol analysis of the primary endpoint. Least-squares mean percentage of time in RASS target range was 90·7% (95% CI 86·8–94·6) for isoflurane and 91·1% (87·2–95·1) for propofol. With isoflurane sedation, opioid dose intensity was 29% lower than with propofol for the overall sedation period (0·22 [0·12–0·34] 0·32 [0·21–0·42] mg/kg per h morphine equivalent dose, p=0·0036) and spontaneous breathing was more frequent on day 1 (odds ratio [OR] 1·72 [1·12–2·64], generalised mixed linear model p=0·013, with estimated rates of 50% of observations with isoflurane 37% with propofol). Extubation times were short and median wake-up was significantly faster after isoflurane on day 2 (20 min [IQR 10–30] 30 min [11–120]; Cox regression p=0·0011). The most common adverse events by treatment group (isoflurane propofol) were: hypertension (ten [7%] of 150 two [1%] of 151), delirium (eight [5%] seven [5%]), oliguria (seven [5%] six [4%]), and atrial fibrillation (five [3%] four [3%]). These results support the use of isoflurane in invasively ventilated patients who have a clinical need for sedation. Sedana Medical AB.

中文翻译：

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通过麻醉保存装置吸入异氟烷与异丙酚对德国和斯洛文尼亚重症监护病房的有创通气患者进行镇静：一项开放标签、3 期、随机对照、非劣效性试验


先前的研究表明，异氟烷可用于重症监护病房 (ICU) 患者的镇静，但评估异氟烷疗效的前瞻性研究很少。本研究的目的是测试异氟烷镇静是否不劣于异丙酚镇静。这项 3 期、随机、对照、开放标签非劣效性试验评估了在德国 ICU（21 个地点）接受有创通气的成人（年龄≥18 岁）中使用长达 54 小时的异氟烷与丙泊酚的疗效和安全性和斯洛文尼亚（三个地点）。患者被随机分配 (1:1) 通过 Sedaconda 麻醉保存装置吸入异氟烷（ACD；Sedana Medical AB，Danderyd，瑞典；ACD-L [死腔 100 mL] 或 ACD-S [死腔 50 mL]）或使用集中电子随机系统的置换区组随机化，静脉输注异丙酚（20 mg/mL）48小时（范围42-54）。主要终点是 Richmond 躁动-镇静量表 (RASS) 范围 –1 至 –4 的时间百分比，对至少 12 小时镇静的合格参与者（符合方案的人群）进行评估，进行 5 次或更多 RASS 测量，并且没有重大影响违反协议，非劣效裕度为 15%。关键的次要终点是阿片类药物的需求、自主呼吸、苏醒和拔管的时间以及不良事件。对所有接受至少一剂剂量的患者进行安全性评估。试验已完成并在 EudraCT 注册，2016-004551-67。 2017年7月2日至2020年1月12日期间，入组了338名患者，其中301名患者（89%）被随机分配至异氟烷（n=150）或异丙酚（n=151）组。每组中有 146 名患者（97%）完成了 24 小时随访。 主要终点的符合方案分析包括异氟醚组的 146 名患者 (97%) 和异丙酚组的 148 名患者 (98%)。异氟烷处于 RASS 目标范围内的最小二乘平均时间百分比为 90·7% (95% CI 86·8–94·6)，丙泊酚为 91·1% (87·2–95·1)。在整个镇静期间，使用异氟醚镇静时，阿片类药物剂量强度比丙泊酚低 29%（0·22 [0·12–0·34] 0·32 [0·21–0·42] mg/kg 每小时吗啡）等效剂量，p=0·0036），第 1 天自主呼吸更加频繁（比值比 [OR] 1·72 [1·12–2·64]，广义混合线性模型 p=0·013，估计发生率50% 的观察结果使用异氟醚，37% 的观察结果使用丙泊酚）。第 2 天使用异氟烷后，拔管时间很短，中位苏醒速度明显加快（20 分钟 [IQR 10–30] 30 分钟 [11–120]；Cox 回归 p=0·0011）。治疗组（异氟烷丙泊酚）最常见的不良事件是：高血压（150 例中的​​ 10 例 [7%]，151 例中的 2 例 [1%]）、谵妄（8 例 [5%] 7 例 [5%]）、少尿（7 例 [1%]）。 5%] 六 [4%]）和心房颤动（五 [3%] 四 [3%]）。这些结果支持在临床需要镇静的有创通气患者中使用异氟醚。塞达纳医疗公司。