Zhou Yongfang, Jin Xiaodong, Kang Yan, Liang Guopeng, Liu Tingting, Deng Ni
Crit Care. 2014 Jun 16;18(3):R122. doi: 10.1186/cc13922.
Midazolam and propofol used alone for long-term sedation are associated with adverse effects. Sequential use may reduce the adverse effects, and lead to faster recovery, earlier extubation and lower costs. This study evaluates the effects, safety, and cost of midazolam, propofol, and their sequential use for long-term sedation in critically ill mechanically ventilated patients.
A total of 135 patients who required mechanical ventilation for >3 days were randomly assigned to receive midazolam (group M), propofol (group P), or sequential use of both (group M-P). In group M-P, midazolam was switched to propofol until the patients passed the spontaneous breathing trial (SBT) safety screen. The primary endpoints included recovery time, extubation time and mechanical ventilation time. The secondary endpoints were pharmaceutical cost, total cost of ICU stay, and recollection to mechanical ventilation-related events.
The incidence of agitation following cessation of sedation in group M-P was lower than group M (19.4% versus 48.7%, P = 0.01). The mean percentage of adequate sedation and duration of sedation were similar in the three groups. The recovery time, extubation time and mechanical ventilation time of group M were 58.0 (interquartile range (IQR), 39.0) hours, 45.0 (IQR, 24.5) hours, and 192.0 (IQR, 124.0) hours, respectively; these were significantly longer than the other groups, while they were similar between the other two groups. In the treatment-received analysis, ICU duration was longer in group M than group M-P (P = 0.016). Using an intention-to-treat analysis and a treatment-received analysis, respectively, the pharmaceutical cost of group M-P was lower than group P (P <0.01) and its ICU cost was lower than group M (P <0.01; P = 0.015). The proportion of group M-P with unbearable memory of the uncomfortable events was lower than in group M (11.7% versus 25.0%, P <0.01), while the proportion with no memory was similar (P >0.05). The incidence of hypotension in group M-P was lower than group (P = 0.01).
Sequential use of midazolam and propofol was a safe and effective sedation protocol, with higher clinical effectiveness and better cost-benefit ratio than midazolam or propofol used alone, for long-term sedation of critically ill mechanically ventilated patients.
Current Controlled Trials ISRCTN01173443. Registered 25 February 2014.
单独使用咪达唑仑和丙泊酚进行长期镇静会产生不良反应。序贯使用可能会减少不良反应，并加快恢复速度、提前拔管并降低成本。本研究评估了咪达唑仑、丙泊酚及其序贯使用对重症机械通气患者长期镇静的效果、安全性和成本。
总共135例需要机械通气超过3天的患者被随机分配接受咪达唑仑（M组）、丙泊酚（P组）或两者序贯使用（M-P组）。在M-P组中，在患者通过自主呼吸试验（SBT）安全筛查之前，将咪达唑仑换为丙泊酚。主要终点包括恢复时间、拔管时间和机械通气时间。次要终点为药物成本、ICU住院总成本以及对机械通气相关事件的回忆。
M-P组镇静停止后躁动的发生率低于M组（19.4%对48.7%，P = 0.01）。三组中充分镇静的平均百分比和镇静持续时间相似。M组的恢复时间、拔管时间和机械通气时间分别为58.0（四分位间距（IQR），39.0）小时、45.0（IQR，24.5）小时和192.0（IQR，124.0）小时；这些明显长于其他组，而其他两组之间相似。在接受治疗分析中，M组的ICU住院时间长于M-P组（P = 0.016）。分别采用意向性分析和接受治疗分析，M-P组的药物成本低于P组（P <0.01），其ICU成本低于M组（P <0.01；P = 0.015）。M-P组对不适事件有难以忍受记忆的比例低于M组（11.7%对25.0%，P <0.01），而无记忆的比例相似（P >0.05）。M-P组低血压的发生率低于P组（P = 0.01）。
对于重症机械通气患者的长期镇静，咪达唑仑和丙泊酚序贯使用是一种安全有效的镇静方案，与单独使用咪达唑仑或丙泊酚相比，具有更高的临床有效性和更好的成本效益比。
当前受控试验ISRCTN01173443。2014年2月25日注册。
