Effect of Dexmedetomidine on Mortality, Duration of Mechanical Ventilation and Multi-organ Function in Sepsis Patients Under Lighter Sedation by Randomized Control Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 203
- 试验地点
- 1
- 主要终点
- mortality
研究概览
简要总结
Background:
Dexmedetomidine, a highly selective arfa2-adrenergic agonist, is known to be a unique sedative agent which causes less acute tolerance, drug addiction and withdrawal compared with gamma-aminobutyrate (GABA) agonists. Dexmedetomidine was approved for short-term ICU sedation in 2004 in Japan, and it has been used particularly for surgical ICU patients. In August 2010 dexmedetomidine was approved in Japan for sedation lasting more than 24 hours.
Recent evidence demonstrated that dexmedetomidine has organ protective effects including neuroprotection, cardioprotection, renal protection, gastrointestinal tract action, and anti-inflammatory action. Dexmedetomidine was shown to significantly decrease the infarct size in isolated rat hearts. Additionally, dexmedetomidine exhibited a preconditioning effect against ischemic injury in hippocampal slices, and this result was considered an apoptosis suppression effect of dexmedetomidine. Aydin C et al reported that dexmedetomidine enhanced the spontaneous contractions of the ileum in peritonitis rats compared with propofol and midazolam. Taniguchi and colleagues demonstrated that dexmedetomidine reduced high mortality rates and the plasma cytokine concentrations, interleukin-6 and tumor necrosis factor alpha in endotoxemic rats.
A meta-analysis has shown that perioperative alfa2-adrenergic agonists, including dexmedetomidine infusion, decreased cardiovascular events on patients undergoing cardiac surgery. Dexmedetomidine treated patients undergoing thoracotomy indicated increase in urine output, reduction in serum creatinine, and the suppression of diuretics in a randomized placebo-controlled double-blind study. Septic patients receiving dexmedetomidine had improved 28-day mortality rates compared with septic patients receiving lorazepam in a sub-group analysis of MENDS randomized controlled trial.
These positive effects of dexmedetomidine on the cardiovascular system, neurons, kidneys, gastrointestinal tract action, and an anti-inflammatory action, are expected to improve mortality in septic patients. However, large clinical research studies have not been conducted yet. We designed and conducted the DESIRE trial (DExmedetomidine for Sepsis in ICU Randomized Evaluation trial) to test a hypothesis that dexmedetomidine may improve clinical outcome and has these organ protective effects on septic patients.
Objective:
To determine whether dexmedetomidine improves clinical outcome and has organ protective effects on septic patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •transferred to ICU
- •anticipation of a need for mechanical ventilation at least 24 hours
排除标准
- •sever chronic liver disease (Child B or C)
- •acute myocardial infarction, heart disease (NYHA 4)
- •Drug dependence, alcoholism
- •Psychological illness, severe cognitive dysfunction
- •patients who have allergy for dexmedetomidine
- •attending physician's decision
研究组 & 干预措施
Dexmedetomidine
administer dexmedetomidine (0.1-0.7ug/kg/h) from the beginning of ICU treatment
干预措施: Dexmedetomidine (Drug)
non-Dexmedetomidine
administer sedatives except Dexmedetomidine
干预措施: Dexmedetomidine (Drug)
结局指标
主要结局
mortality
时间窗: on 28 days
mortality of patients on 28 days or on a day of discharge if patients are discharged earlier than 28 days
duration of mechanical ventilation
时间窗: up to 28 days
duration of mechanical ventilation in the ICU involving non-invasive ventilation
次要结局
- length of stay in the ICU(up to 28 days)
- length of stay in the hospital(up to 28 days)
- Evaluation of restlessness and delirium(up to 28 days in the ICU)
- Evaluation of cognitive function(on 28 days or on the day of discharge)
- Occurrence of arrythmia or myocardial ischemia(up to 28 days in the ICU)
- infection control(within 28 days until discharge)
- inflammation marker(for 14days)
- organ failure control(up to 28 days in the ICU)
- coagulopathy control(for 14 days)
- nutrition control(up to 28 days in the ICU)
- sedation control(up to 28 days in the ICU)
- Renal function(up to 28 days in the ICU)
研究者
Yu Kawazoe
Assistant Professor
Tohoku University