Liu Yongjun, Zuo Lingyun, Li Xiaoyun, Nie Yao, Chen Chuanxi, Liu Ning, Chen Minying, Wu Jianfeng, Guan Xiangdong
Department of Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
Guangdong Clinical Research Center for Critical Care Medicine, No. 58 Zhongshan 2nd Road, Guangzhou, 510080, China.
Ann Intensive Care. 2024 Oct 26;14(1):164. doi: 10.1186/s13613-024-01390-3.
Ciprofol was approved for use in intensive care unit (ICU) patients requiring sedation during mechanical ventilation in July 2022. A pooled post-hoc analysis of phase 2 and phase 3 trials was conducted primarily to explore hypotension-free outcome in ICU patients who required mechanical ventilation and achieved the target light sedation goal at an early stage after being sedated with ciprofol or propofol.
All eligible ICU patients who were expected to require sedation for 6-24 h were randomly assigned in a 2:1 ratio to either a ciprofol or propofol group. Ciprofol or propofol was initially infused at loading doses of 0.5 or 1.0 mg/kg followed by maintenance doses of 0.3 or 1.5 mg/kg/h. Ciprofol or propofol dosages were adjusted up or down at rates of 0.05-0.10 mg/kg/h or 0.25-0.50 mg/kg/h, respectively, to achieve the target light sedation (a Richmond Agitation-Sedation Scale of -2 to + 1). The primary post-hoc outcome was the hypotension-free rate in patients who had achieved the target sedation goal after 30-min administration of ciprofol or propofol.
In total, 174 patients were enrolled for pooled post-hoc analysis, of whom 116 and 58 were assigned to the ciprofol and propofol groups, respectively. The hypotension-free rate was significantly higher in patients who achieved the target sedation goal after 30-min administration of ciprofol (93.0% vs. 81.0%, P = 0.018), and especially in the subgroups of males and patients aged < 65 years. Multivariable analysis revealed that ciprofol treatment, a younger age and lower baseline body mass index were independent favorable predictors for a higher hypotension-free rate in patients who achieved the target sedation goal after 30-min of drug administration. Moreover, hypotension-free patients who reached the target sedation level after 30 min had a more favorable short-term prognosis including a lower incidence of drug-related treatment-emergent adverse events, shorter time to extubation and fewer dose adjustments of ciprofol or propofol (all P < 0.05).
ICU patients undergoing mechanical ventilation and sedated with ciprofol had significantly lower rate of hypotension during the early phase of achieving light sedation during a 6-24 h period, leading to a more favorable short-term prognosis (within 24 h).
Phase 2 trial (clinicaltrials.gov, NCT04147416. Registered November 1, 2019, https://classic.
gov/ct2/show/NCT04147416 ) and phase 3 trial (clinicaltrials.gov, NCT04620031. Registered November 6, 2020, https://classic.
gov/ct2/show/NCT04620031 ).
环泊酚于2022年7月被批准用于在机械通气期间需要镇静的重症监护病房（ICU）患者。进行了一项2期和3期试验的汇总事后分析，主要目的是探讨在使用环泊酚或丙泊酚镇静后早期达到目标轻度镇静目标的需要机械通气的ICU患者的无低血压结局。
所有预计需要镇静6 - 24小时的符合条件的ICU患者按2:1的比例随机分配至环泊酚组或丙泊酚组。环泊酚或丙泊酚最初以0.5或1.0mg/kg的负荷剂量输注，随后以0.3或1.5mg/kg/h的维持剂量输注。环泊酚或丙泊酚剂量分别以0.05 - 0.10mg/kg/h或0.25 - 0.50mg/kg/h的速率上调或下调，以达到目标轻度镇静（里士满躁动 - 镇静量表为 -2至 +1）。主要事后结局是在给予环泊酚或丙泊酚30分钟后达到目标镇静目标的患者的无低血压率。
总共174例患者被纳入汇总事后分析，其中116例和58例分别被分配至环泊酚组和丙泊酚组。在给予环泊酚30分钟后达到目标镇静目标的患者中，无低血压率显著更高（93.0%对81.0%，P = 0.018），尤其是在男性和年龄<65岁的患者亚组中。多变量分析显示，环泊酚治疗、年龄较小和基线体重指数较低是在给药30分钟后达到目标镇静目标的患者无低血压率较高的独立有利预测因素。此外，在30分钟后达到目标镇静水平的无低血压患者有更有利的短期预后，包括药物相关治疗突发不良事件的发生率较低、拔管时间较短以及环泊酚或丙泊酚的剂量调整较少（所有P < 0.05）。
在6 - 24小时期间达到轻度镇静的早期阶段，接受环泊酚镇静的机械通气ICU患者的低血压发生率显著较低，导致更有利的短期预后（24小时内）。
2期试验（clinicaltrials.gov，NCT04147416。2019年11月1日注册，https://classic.
gov/ct2/show/NCT04147416 ）和3期试验（clinicaltrials.gov，NCT04620031。2020年11月6日注册，https://classic.
gov/ct2/show/NCT04620031 ）。
