Simultaneous Administration of Norepinephrine, Angiotensin II, and Vasopressin in Septic Shock Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 79
- 试验地点
- 4
- 主要终点
- Rate of change in renin levels
研究概览
简要总结
The goal of this prospective randomized controlled trial is to compare the effects of classic stepwise vs. early balanced multimodal vasopressor strategies in septic shock.
详细描述
CONTROL GROUP(Classic stepwise vasopressor administration):
Patients will be started on norepinephrine with increases of 0.05-0.1 mcg/kg/min up to 0.5 mcg/kg/min, followed by vasopressin (administered at a fixed dose of 0.03 IE/min). If MAP remains < 65 mmHg, norepinephrine will be titrated above dose of 0.5 mcg/kg/min until MAP ≥ 65 mmHg. Initiation of additional vasoactive drugs (epinephrine, Ang II, methylene blue or dopamine) as per clinical team decision. Initiation of inotropes (dobutamine, milrinone, levosimendan) as per clinical team decision.
EXPERIMENTAL GROUP(Balanced multimodal vasopressor administration):
Early, simultaneous start of norepinephrine, angiotensin II and vasopressin at equivalent starting doses (equivalent to approximately 0.05 mcg/kg/min of norepinephrine). Increments of 0.05 mcg/kg/min of equivalent doses of all three vasopressors every 3-5 min until MAP ≥ 65 mmHg is reached (vasopressin will be administered at a maximum dose of 0.03 IE/min, Ang II will be administered at maximum dose of 100ng/kg/min). Initiation of additional vasoactive drugs (epinephrine, methylene blue or dopamine) as per clinical team decision. Initiation of inotropes (dobutamine, milrinone, levosimendan) as per clinical team decision.
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
- Single (Participant)
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
- •Adult patients (≥18 years).
- •Sepsis (an acute change in total Sequential Organ Failure Assessment (SOFA) score ≥2 points consequent to infection) with persisting hypotension requiring vasopressors to maintain MAP ≥65 mm Hg and having a serum lactate level >2 mmol/L despite adequate volume resuscitation (20-30ml/kg in 3 hours).
- •Vasopressor requirement of ≥0,15 μg/kg/min equivalent of norepinephrine base.
- •Patients are required to have central venous access and an arterial line present, and these are expected to remain present for at least the initial 72 hours of study.
- •Patients are required to have an urinary catheter present, and it is expected to remain present for at least the initial 72 hours of study.
- •Patients must have cardiac index (CI) >2.3 L/min/m2 (measured by bedside echocardiography, pulse contour cardiac output (PiCCO) or Swan-Ganz catheter).
排除标准
- •Death expected <24 hours.
- •Pregnancy (suspected or confirmed).
- •Surgery expected for source of infection.
- •Inter-hospital transfer expected during first 72 hours of hospitalization.
- •Liver failure with a Model for End-Stage Liver Disease (MELD) score of ≥
- •Patients with acute mesenteric ischemia or a history of mesenteric ischemic.
- •Patients with Raynaud's phenomenon, systemic sclerosis or vasospastic disease.
- •Patients with active bleeding and an anticipated need (within 48 hours of initiation of the study) for transfusion of >4 units of packed red blood cells.
- •Patients with a known allergy to mannitol.
- •Patients on veno-arterial (VA) ECMO.
结局指标
主要结局
Rate of change in renin levels
时间窗: 72 hours
There is an increasing amount of data that renin is the best marker of tissue hypoperfusion and predictor of ICU mortality in patients with sepsis and septic shock, even outperforming lactate. Renin increased between the first and third day in non-survivors, but dropped in survivors. The rate of change in renin concentration but not lactate concentration in ICU patients over first 72 hours is associated with in hospital mortality.
Rate of change in renin levels
时间窗: 72 hours
There is an increasing amount of data that renin is the best marker of tissue hypoperfusion and predictor of ICU mortality in patients with sepsis and septic shock, even outperforming lactate. Renin increased between the first and third day in non-survivors, but dropped in survivors. The rate of change in renin concentration but not lactate concentration in ICU patients over first 72 hours is associated with in hospital mortality.
次要结局
- Compare lactate levels(72h)
- Compare acute kidney injury rate(72 hours)
- Compare Δ Sequential Organ Failure Assessment (SOFA) score(72 hours)
- Compare Δ Sequential Organ Failure Assessment (SOFA) score(72 hours)
- Compare acute kidney injury rate(72 hours)
研究者
Ziga Kalamar
Principal Investigator
University Medical Centre Maribor