Effect of Flumazenil on Hypoactive Delirium in the ICU: A Double-Blind, Placebo-Controlled Pilot Study
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Number of Delirium-free Days
研究概览
简要总结
Delirium within the intensive care unit (ICU) is associated with poor outcomes such as increased mortality, ICU and hospital length of stay (LOS), and time on mechanical ventilation. Benzodiazepine (BZD) exposure is an independent risk factor for development of delirium. Reversal of hypoactive delirium represents a potential opportunity for reducing duration of delirium and subsequent complications.
This is a single-center randomized, double-blind, placebo-controlled study of critically ill adult patients with benzodiazepine-associated hypoactive delirium. The hypothesis is that flumazenil continuous infusion may reverse hypoactive delirium associated with BZD exposure and thereby reduce duration of delirium and ICU LOS.
详细描述
Benzodiazepines are commonly used for discomfort, anxiety, agitation, and alcohol withdrawal syndrome (AWS) in the ICU. End organ dysfunction and extended exposure can increase the risk of complications associated with BZDs, which include increased ICU LOS, time on mechanical ventilation, and mortality.
Flumazenil as a 1, 4-imidazobenzodiazepine is a competitive antagonist for the benzodiazepine binding site with weak intrinsic or partial agonistic activity on the GABA receptor. Multiple studies have confirmed the safety and effectiveness of flumazenil for the reversal of sedation. Pilot studies have demonstrated safe reversal of over-sedation and statistically significant improvements in patient cooperation and time to extubation. The current standard for suspected BZD-associated hypoactive delirium is cessation of benzodiazepine administration and supportive care.
The role of continuous infusion flumazenil for rapid and sustained reversal of hypoactive delirium in the ICU has not been evaluated prospectively and therefore remains poorly defined.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •critically ill adults
- •RASS score of -3 to 0 after receiving benzodiazepine therapy
- •CAM-ICU positive
- •no benzodiazepine therapy within the previous 12 hours
排除标准
- •contraindications to flumazenil including hypersensitivity
- •receipt of benzodiazepines for control of potentially life-threatening conditions (e.g., control of intracranial pressure or status epilepticus)
- •active seizure disorder or on current anti-convulsant therapy for history of seizure disorder. Seizures secondary to alcohol withdrawal will NOT be excluded.
- •history of traumatic brain injury complicated by seizures
- •acute episode (within prior 30 days) of severe traumatic brain injury
- •history of structural lesion (e.g. subarachnoid hemorrhage, cerebrovascular accident, intra-parenchymal hemorrhage) complicated by seizures
- •acute episode (within prior 14 days) of structural lesion (e.g. subarachnoid hemorrhage, cerebrovascular accident, intra-parenchymal hemorrhage)
- •brain tumor complicated by seizure
- •history of anoxic brain injury
- •third-degree burn with total body surface area (TBSA) burn greater than 20%
- •chronic benzodiazepine (clonazepam:lorazepam:diazepam approximately 4:8:40 mg per day) for 7 consecutive days with no taper
- •chronic delirium that is attributable to other causes
- •anticipated to transfer to lower level of care within 24 hours
- •admitted for polysubstance overdose as determined by initial drug toxicity screening
- •recent exposure (prior 7 days) to pro-convulsant medications (identified via medication list, medication reconciliation performed by PI/pharmacy medication reconciliation team, or urine drug screening)
- •children, incarcerated individuals, and pregnant women
- •unable to provide consent and the legally authorized representative is unable to provide consent
研究组 & 干预措施
Flumazenil Infusion
The flumazenil continuous infusion is started at an initial dose of 0.1 mg/hr., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.
干预措施: Flumazenil (Drug)
Placebo Infusion
The placebo continuous infusion is started at an initial dose of 0.1 mg/hr (2 ml/hr)., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Delirium-free Days
时间窗: up to 14 days after randomization
Defined by the number of days in the 14-day period after randomization that the patient was alive and not delirious (i.e. CAM-ICU negative). Zero delirium-free days will be observed for patients that die within the 14-day period.
次要结局
- Number of Participants With Delirium Resolution(up to 14 days after randomization)
- Intensive Care Unit Length of Stay(duration of admission to the intensive care unit)
- Occurrence of Agitation Requiring Use of Rescue Sedatives While on Study Infusion(up to 72 hours after the start of the infusion)
- Average Maximum Rate of Study Infusion(up to 72 hours after the start of the infusion)
- Number of Mechanical Ventilator Free Days(up to 28 days after randomization)
- Average Duration of Study Infusion(up to 72 hours after the start of the infusion)