Department of Anesthesiology, University of Miami/Jackson Memorial Hospital, R-C370, 1611 NW 12th Avenue, Miami, FL 33101, USA.
Anesth Analg. 2011 Sep;113(3):550-6. doi: 10.1213/ANE.0b013e31821d7faf. Epub 2011 May 19.
Current drugs for induction and maintenance of sedation in mechanically ventilated patients in the intensive care unit have limitations. Fospropofol, a prodrug of propofol, has not been studied as a sedative in the ICU setting.
In this randomized, open-label pilot study, patients received 1 of 3 regimens with a goal of maintaining a Ramsay Sedation Score of 2 to 5: (1) fospropofol IV infusion with a bolus and increased infusion rate for agitation events (infusion/bolus); (2) fospropofol IV infusion with an increased infusion rate for agitation events (infusion only); or (3) propofol IV infusion with an increased infusion rate for agitation events.
Sixty patients received study drug and were included in the safety and efficacy analyses. Because incidence rates for adverse events were similar between fospropofol groups, and because the study was not powered to determine significant differences between treatment groups for safety variables, adverse events for both fospropofol groups were combined. In the fospropofol groups, 28 out of 38 patients (74%) experienced treatment-emergent adverse events in comparison with 14 out of 22 patients (64%) in the propofol group. The most common treatment-emergent adverse events with fospropofol were procedural pain (21.1%) and nausea (13.2%). Two patients (1 each in the fospropofol infusion/bolus and the propofol groups) experienced hypotension during the study as a potential sedation-related adverse event. Mean plasma formate levels were not significantly different among groups. Patients in all 3 treatment groups maintained Ramsay Sedation Scores of 2 to 5 for >90% of the time they were sedated.
This pilot study suggests that fospropofol, administered in either an infusion/bolus or infusion-only regimen, is tolerable and effective for short-term induction and maintenance of sedation in mechanically ventilated intensive care unit patients.
目前用于重症监护病房机械通气患者诱导和维持镇静的药物存在局限性。福司泊酚是丙泊酚的前体药物，尚未在 ICU 环境中作为镇静剂进行研究。
在这项随机、开放标签的初步研究中，患者接受了以下 3 种方案中的 1 种，以维持 Ramsay 镇静评分 2 至 5：（1）福司泊酚静脉输注，出现激惹事件时给予推注和增加输注率（输注/推注）；（2）福司泊酚静脉输注，出现激惹事件时增加输注率（仅输注）；或（3）丙泊酚静脉输注，出现激惹事件时增加输注率。
60 名患者接受了研究药物治疗，并纳入了安全性和疗效分析。由于福司泊酚组的不良事件发生率相似，并且该研究没有足够的效力来确定治疗组在安全性变量方面的显著差异，因此将福司泊酚组的不良事件合并在一起。在福司泊酚组中，38 名患者中有 28 名（74%）出现治疗期间出现的不良事件，而 22 名患者中有 14 名（64%）在丙泊酚组中出现。福司泊酚最常见的治疗期间出现的不良事件是程序性疼痛（21.1%）和恶心（13.2%）。有 2 名患者（福司泊酚输注/推注组和丙泊酚组各 1 名）在研究期间出现低血压，可能与镇静相关的不良事件有关。各组间的平均血浆甲酸盐水平无显著差异。所有 3 个治疗组的患者在接受镇静治疗时，Ramsay 镇静评分维持在 2 至 5 分，超过 90%的时间。
这项初步研究表明，福司泊酚以输注/推注或输注方案给药，在机械通气的重症监护病房患者中诱导和维持短期镇静是可耐受且有效的。
