Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA.
J Clin Anesth. 2010 Jun;22(4):260-7. doi: 10.1016/j.jclinane.2009.08.007.
To evaluate the safety of intravenous (IV) fospropofol when used to provide minimal to moderate sedation in patients undergoing minor surgical procedures.
Phase 3, open-label, single-arm study.
Multi-center.
123 ASA physical status I, II, III, and IV patients, aged>or=18 years.
Patients were pretreated with fentanyl 50 microg before receiving an initial dose of IV fospropofol 6.5 mg/kg. Patients could receive up to 5 supplemental doses of fospropofol 1.63 mg/kg to reach a Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score<or=4 to allow the start of the procedure and to maintain adequate sedation levels during the procedure.
Study endpoints included measures of sedation depth, requirement for supplemental sedative doses, use of alternative sedatives, and the frequency and nature of treatment-emergent and sedative-related adverse events.
A mean of 2.4 supplemental doses of fospropofol was administered, and in 60% of patients, two or fewer supplemental doses of fospropofol were sufficient to initiate and complete the procedure. Alternative sedative medication was administered in 6 of 123 patients (4.9%). Mean (SD) MOAA/S score during the procedure was 3.8 (0.5). Sixty-one percent (61%) of patients had a MOAA/S score of 5 (fully alert) within two minutes after the end of the procedure. Few patients (7 of 123; 5.7%) had MOAA/S scores of 0 to 1 (deep sedation) during the procedure, and all 7 were either ASA physical status I (n=1) or II (n=6). The most common treatment-related adverse events (TRAEs) were self-limited: paresthesias (62.6%) and pruritus (27.6%). Five patients experienced sedation-related adverse events, including hypotension (n=4), bradycardia (concurrently with hypotension and managed with atropine; n=1), or hypoxemia (less than one min and managed with chin lift and verbal stimulation; n=1). Twenty patients with previous or existing hepatic disease (ranging from minimal to severe) and 5 patients with severe renal impairment had adverse events similar to the overall population. No deaths were reported, and no patient discontinued the study due to adverse events.
An initial dose of IV fospropofol 6.5 mg/kg with supplemental doses was safe and well-tolerated as moderate sedation for use in minor surgical procedures.
评估静脉注射（IV）磷丙泊酚在接受小手术的患者中提供轻度至中度镇静时的安全性。
III 期、开放标签、单臂研究。
多中心。
123 例 ASA 身体状况 I、II、III 和 IV 患者，年龄>或=18 岁。
患者在接受初始剂量 6.5mg/kg IV 磷丙泊酚前预先接受芬太尼 50μg。患者可接受多达 5 次补充剂量 1.63mg/kg 的磷丙泊酚，以达到改良的观察者评估警觉/镇静评分（MOAA/S）<或=4，从而开始手术并在手术过程中维持足够的镇静水平。
研究终点包括镇静深度、补充镇静剂量的要求、替代镇静药物的使用，以及治疗中出现的和与镇静相关的不良事件的频率和性质。
平均给予 2.4 次补充剂量的磷丙泊酚，在 60%的患者中，两次或更少的补充剂量的磷丙泊酚足以开始和完成手术。在 123 例患者中有 6 例（4.9%）使用了替代镇静药物。手术过程中平均（SD）MOAA/S 评分为 3.8（0.5）。61%（61%）的患者在手术后两分钟内 MOAA/S 评分为 5（完全警觉）。在手术过程中，少数患者（123 例中的 7 例；5.7%）的 MOAA/S 评分为 0 至 1（深度镇静），所有 7 例均为 ASA 身体状况 I（n=1）或 II（n=6）。最常见的与治疗相关的不良事件（TRAEs）是自限性的：感觉异常（62.6%）和瘙痒（27.6%）。5 例患者出现与镇静相关的不良事件，包括低血压（n=4）、心动过缓（与低血压同时发生，并用阿托品治疗；n=1）或低氧血症（不到一分钟，用 chin lift 和口头刺激治疗；n=1）。20 例有既往或现有肝脏疾病（从轻度到重度）和 5 例严重肾功能损害的患者的不良事件与总体人群相似。无死亡报告，也无患者因不良事件而退出研究。
初始剂量 6.5mg/kg IV 磷丙泊酚联合补充剂量作为轻度镇静剂，用于小手术是安全且耐受良好的。
