Does LOW Dose DEXmedetomidine After Cardiopulmonary Bypass Separation Decrease the Incidence of DELirium: A Double-blind Randomized Placebo-controlled Study (LOWDEXDEL Study)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 420
- 试验地点
- 1
- 主要终点
- The incidence of delirium
研究概览
简要总结
Delirium after cardiac surgery can occur in up to 50% of the patients and has been shown to be significantly associated with increased morbidity and mortality. Advanced age is a significant risk factor of delirium.
Numerous studies have shown that sedation with high doses of Dexmedetomidine in the ICU reduces the incidence of postoperative delirium. On the other hand animal studies have shown neuroprotective effects of Dexmedetomidine by means of stimulating alpha2A-adrenoceptors.
It is not clear whether the administration of a low dose Dexmedetomidine in cardiac surgery would have any neuroprotective effects by stimulating the alpha 2A-receptors and as such would decrease the incidence of postoperative delirium.
详细描述
Postoperative delirium (PD) is a common problem in cardiac surgical patients. Its incidence varies among studies and can reach up to 50% of the patients. PD is associated with increased morbidity and mortality. Its occurrence is the resultant between the predisposing factors and the precipitating factors. Age seems to be a significant predisposing factor. In this regard the pathophysiology of PD is not yet fully understood. There are several hypothetical mechanisms for the development of PD. The first hypothesis is cerebral ischemia and BBB breakdown. The second hypothesis is neuro-inflammation. Peripheral pro-inflammatory mediators especially released during surgery would interact with the brain. Otherwise there is the problem of sleep deprivation/fragmentation in patients admitted to the hospital.
Dexmedetomidine is a potent and more selective alpha2-adrenergic receptor than clonidine. Studies have demonstrated that it has neuroprotective and anti-inflammatory actions.
Numerous studies including trials in cardiac surgery have shown a decreased incidence of delirium when Dexmedetomidine was used as sedative in the ICU compared with other sedatives acting on the GABA receptors. However, in these studies high doses of Dexmedetomidine were used for periods up to 24h. Dexmedetomidine was started in the ICU and was not compared in a double-blind fashion with placebo. In a recent randomized double-blind placebo-controlled trial a very low dose of Dexmedetomidine decreased the occurrence of PD when compared to placebo. However this study was performed in non-cardiac patients. Moreover the patients were included after their arrival in the ICU, which means that those patients who were intubated at their arrival in the ICU were not included. And again the study medication was only started after arrival in the ICU.
The aim of this study is to elucidate whether the administration of Dexmedetomidine at a low dose would decrease the incidence of PD in elderly patients undergoing cardiac surgery. The hypothesis is that Dexmedetomidine at low doses, by only stimulating the alpha2A adrenoceptors,would have neuroprotective affects ans as such decrease the incidence of PD. Dexmedetomidine would also have anti-inflammatory effects and effects on the quality of sleep. Both mechanisms would play a role in the pathophysiology of PD.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 60 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients undergoing cardiac surgery with cardiopulmonary bypass
排除标准
- •Hepatic dysfunction (hepatic function tests 3 times the normal value)
- •Preoperative renal replacement therapy
- •Preoperative delirium
- •Emergency surgery not allowing neurologic evaluation by MMSE
- •Mini invasive cardiac surgery
- •Patients not speaking French
研究组 & 干预措施
Dexmedetomidine
Dexmedetomidine will be administered at 0.4ug/kg/h (5mL/h) starting at the closure of the chest and continued during 10h.
干预措施: Dexmedetomidine (Drug)
Placebo
NaCl 0.9% will be administered at 5mL/h starting at the closure of the chest and continued during 10h.
干预措施: Placebo (Drug)
结局指标
主要结局
The incidence of delirium
时间窗: Through study completion, an average of 30 days
The incidence of delirium detected by means of CAM-ICU and CAM
次要结局
- Total dose of vasopressors(Through study completion, an average of 30 days)
- Pace maker necessitation(Through study completion, an average of 30 days)
- Number of days spent in delirium(Through study completion, an average of 30 days)
- ICU stay(Through study completion, an average of 30 days)
- Total dose of analgesics(Through study completion, an average of 30 days)
- Hospital stay(Through study completion, an average of 30 days)
- Total dose sedatives(Through study completion, an average of 30 days)
- Total dose of inotropic agents(Through study completion, an average of 30 days)
研究者
Mona Momeni, MD, PhD
Professor
Cliniques universitaires Saint-Luc- Université Catholique de Louvain