The Study of Pharmacokinetics and Pharmacodynamics of a Loading Dose Cisatracurium in Critically Ill Patients
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Total plasma concentration-time data
研究概览
简要总结
Pathophysiological changes influenced by multiple factors in critically ill patients, has a significant impact on pharmacokinetics (PK) and pharmacodynamics (PD) of cisatracurium. In order to understand better and find an appropriate dosing regimen, the purpose of this study is to investigate the PK and PD of a loading dose cisatracurium in critically ill patients.
Cisatracurium, nondepolarizing neuromuscular blocking agents (NMBAs), are commonly used in intensive care units because of a lesser effect on hemodynamic parameters and a reduction in mortality rate in ARDS patients. Loading dose recommended in clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient is 0.1-0.2 mg/kg. Then, maintenance dose of 1-3 mcg/kg/min is followed regarding indications, such as ARDS. However, this recommended loading dose might not be adequate in critically ill patients, the study in this specific population might be needed.
详细描述
Neuromuscular blocking agents (NMBAs) are commonly used in critically ill patients, especially in adult respiratory distress syndrome (ARDS). Use of NMBAs to facilitate mechanical ventilation, to control patient/ventilator asynchrony and to reduce uncontrolled muscle tone in special conditions including tetanus, therapeutic hypothermia, and status epilepticus were increasingly found in current clinical practice.
Cisatracurium, 1Rcis-1'Rcis isomer of atracurium, is benzylisoquinolium nondepolarizing NMBAs which is three to five folds higher potency than atracurium besylate. The degradation of cisatracurium by hofmann elimination and ester hydrolysis in plasma generates laudanosine and a monoquaternary acrylate metabolite. Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient published in year 2016 strongly recommended cisatracurium due to a reduction in incidence of prolonged blockade, cardiovascular related adverse events and anaphylactic reactions. Moreover, recent evidence showed that early use of cisatracurium in early severe ARDS patients led to a significant reduction in mortality.
Regarding pharmacokinetics and pharmacodynamics of cisatracurium in critically ill patients, there were multiple factors affected cisatracurium blood concentration and neuromuscular blockade actions. Several reports demonstrated that pathophysiological changes, such as age, hypothermia/ hyperthermia, electrolyte imbalance and acid-base disturbances, had a significant impact on PK and PD of cisatracurium. Currently, there were an increasing data of slow response and less paralysis effect in critically ill patients receiving standard dose of cisatracurium. These may be explained by inadequate drug concentration at target organ, therefore, treatment failures regarding recommended dose of cisatracurium has been reported. Consequently, higher cisatracurium dose with higher drug concentration level might overcome a problem of inadequate level and therapeutic failure while receiving a standard dose of cisatracurium (a loading dose of 0.1-0.2 mg/kg, followed by a maintenance dose of 1-3 mcg/kg/min)
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
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
- •Age greater than 18 years
- •Admission for ICU care
- •Require paralysis with cisatracurium as part of their clinical care
- •Patients or legal representatives who are able to understand and are willing and able to give their signed informed consent before any trial-related procedures are performed
排除标准
- •Lactating women
- •Pregnancy women
- •Documented history of hypersensitivity to cisatracurium
- •Pre-existing neuromuscular disease
- •Patients with burn lesions
- •Currently diagnosed of hypothermia condition (tympanic body temperature ≤ 36 °C)
- •Patients currently receiving intravenous bolus or push of cisatracurium within 24 hours or receiving intravenous continuous infusion of cisatracurium within 48 hours prior to enrollment
- •Patients who have to receive intravenous continuous infusion of cisatracurium within 30 minutes after given intravenous bolus of 0.2 mg/ kg cisatracurium
研究组 & 干预措施
Cisatracurium
Patients who require paralysis with cisatracurium as part of their clinical care in ICU
干预措施: cisatracurium (Drug)
结局指标
主要结局
Total plasma concentration-time data
时间窗: Pre-dose through 60 minutes post-dose
Data will be collected in case-record form and managed by Microsoft Office Excel. Statistical analyses will be performed using SPSS.
The degree of neuromuscular block by train-of-four-watch monitor - time data
时间窗: Pre-dose through 60 minutes post-dose
Data will be collected in case-record form and managed by Microsoft Office Excel. Statistical analyses will be performed using SPSS.
Patient-ventilator asynchrony - time data
时间窗: Pre-dose through 60 minutes post-dose
Data will be collected in case-record form and managed by Microsoft Office Excel. Statistical analyses will be performed using SPSS.
次要结局
- Clearance(Pre-dose through 60 minutes post-dose)
- Time to maximum block(Pre-dose through 60 minutes post-dose)
- Elimination rate constant(Pre-dose through 60 minutes post-dose)
- Time to patient-ventilator synchrony(Pre-dose through 60 minutes post-dose)
- Percentage of maximum block(Pre-dose through 60 minutes post-dose)
- Time to maximum concentration(Pre-dose through 60 minutes post-dose)
- Half-life(Pre-dose through 60 minutes post-dose)
研究者
Panadda Panusitthikorn
Principal Investigator
Mahidol University