Ketanserin Effects on Peripheral Temperature and Lactate (KoPTaL)
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 120
- 主要终点
- Delta Temperature
研究概览
简要总结
A high blood lactate and a high peripheral to central temperature difference (deltaT) are associated with a higher mortality in critically ill patients. Both measures are signs of a reduced microcirculatory bloodflow or vasoconstriction and are associated with shock. It is unknown which medication can best be used to improve deltaT and lactate clearance.
Ketanserin is being used in the intensive care setting for decades to optimize circulatory parameters. Ketanserin is a serotonin type 2-receptor blocker (5-HT2). Blocking the 5-HT2 receptor with ketanserin can attenuate pathological vasoconstriction. In these ways ketanserin can reduce vasoconstriction and can improve the microcirculation. As a consequence, the enhanced blood flow in the skin will increase the peripheral temperature and decrease deltaT. At the same time an increased flow in the microcirculation may lead to a reduction in lactate production.
Objective:
To determine the effects of a continuous ketanserin infusion on peripheral temperature and lactate clearance in critically ill patients with either a high lactate or a high deltaT.
详细描述
Rationale:
A high blood lactate and a high peripheral to central temperature difference (deltaT) are associated with a higher mortality in critically ill patients. Both measures are signs of a reduced microcirculatory bloodflow or vasoconstriction and are associated with shock. On the other hand, it has not been shown yet that interventions leading to improvement of this temperature gap reduces mortality or improves any other outcome measurement. Moreover, it is unknown which medication can best be used to improve deltaT and lactate clearance.
Ketanserin is being used in the intensive care setting for decades to optimize circulatory parameters. Ketanserin is a serotonin type 2-receptor blocker (5-HT2). Blocking the 5-HT2 receptor with ketanserin can attenuate pathological vasoconstriction. In these ways ketanserin can reduce vasoconstriction and can improve the microcirculation. As a consequence, the enhanced blood flow in the skin will increase the peripheral temperature and decrease deltaT. At the same time an increased flow in the microcirculation may lead to a reduction in lactate production.
Objective:
To determine the effects of a continuous ketanserin infusion on peripheral temperature and lactate clearance in critically ill patients with either a high lactate or a high deltaT.
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)
盲法说明
Placebo medication
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
- •DeltaTemperature greater that 6.0 °C.
- •Age 18 years or older
- •Admitted to the ICU for any reason
- •Signed informed consent from the patient or legal representative
排除标准
- •Pregnancy
- •No possibility to obtain informed consent
- •QTc above 550 msec,
- •Arrhythmias, including bradycardia defined as a heart rate below 50/min; 2nd and 3rd degree AV block; ventricular tachycardia
- •Blood Potassium level < 3.5 mmol/l
- •Blood Magnesium level <0.5 mmol/l
- •Allergy for ketanserin
- •DeltaT less than 6°C.
- •Patients undergoing therapeutic hypothermia
- •Patients admitted after cardiac arrest
- •Patients admitted after cardiac surgery
研究组 & 干预措施
Ketanserin
Ketanserin is a serotonin type 2-receptor blocker (5-HT2). In normal endothelium, the 5-HT1 effects (vasodilation) are the most prominent [Dabire 1990]. In endothelium that is damaged, which is the case in sepsis, the 5HT2 effects (vasoconstriction) surpass the 5-HT1 effects. Blocking the 5-HT2 receptor with ketanserin can attenuate this pathological vasoconstriction. In addition, ketanserin has favourable α1-adrenergic blocking properties in the endothelium (vasodilation) that may further reverse the pathological vasoconstriction. In these ways ketanserin can reduce vasoconstriction and can improve the microcirculation.
干预措施: Ketanserin (Drug)
Placebo
The placebo is a standard glucose 5% solution.
干预措施: Placebo (Other)
结局指标
主要结局
Delta Temperature
时间窗: 8 hours (after start of the study medication)
Delta Temperature is calculated from the difference between central (rectal) and peripheral (forefoot) temperature
次要结局
- Lactate clearance(8 hours (after start of the study medication)
- mortality(6 months after start of study medication)
- ICU mortality(6 months after start of study medication)
- hospital length of stay(6 months after start of study medication)
- ICU length of stay(6 months after start of study medication)
研究者
PHJ van der Voort
Prof. dr. P. H. J. van der Voort
Onze Lieve Vrouwe Gasthuis