Inotropic Effects of Vasopressin Versus Noradrenaline In Patients With Vasoplegic Syndrome After Cardiac Surgery
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 350
- 试验地点
- 1
- 主要终点
- Change in inotropic function assessed by cardiac output between T0 and T1
研究概览
简要总结
This is a randomized, double-blind clinical trial designed to compare the inotropic effects of vasopressin versus norepinephrine in patients who develop vasoplegic syndrome in the immediate postoperative period following cardiac surgery.
Vasoplegic syndrome is characterized by severe hypotension due to systemic vasodilation, despite adequate fluid resuscitation and preserved or elevated cardiac output. Vasopressors are essential in restoring hemodynamic stability in this context; however, their impact on myocardial performance remains uncertain. While norepinephrine is the standard first-line agent, vasopressin has shown potential benefits, including reduced catecholamine exposure and fewer adverse cardiovascular effects.
This study aims to assess changes in cardiac output and other echocardiographic and hemodynamic parameters after administration of either vasopressin or norepinephrine. The findings are expected to contribute to optimizing vasopressor selection in vasoplegic patients after cardiac surgery and improving clinical outcomes.
详细描述
This prospective, randomized, double-blind clinical trial investigates the inotropic effects of vasopressin versus norepinephrine in patients who develop vasoplegic syndrome (VS) in the immediate postoperative period following cardiac surgery.
Vasoplegic syndrome is characterized by severe hypotension with low systemic vascular resistance despite adequate cardiac output, often unresponsive to standard fluid resuscitation and catecholamine vasopressors. It is associated with significant morbidity and mortality, especially in cardiac surgery patients. In recent years, vasopressin has been explored as an alternative or adjunctive treatment due to its different mechanism of action and potentially fewer adverse effects compared to catecholamines.
Eligible patients (≥18 years) undergoing coronary artery bypass grafting or valve surgery, who develop vasoplegic syndrome within 24 hours postoperatively, will be randomized in a 1:1 ratio to receive vasopressin or norepinephrine. Drug allocation will be blinded to the clinical and research teams, with identically prepared infusion bags.
The study protocol includes a detailed vasopressor infusion regimen, beginning at 5 mL/h with titration every 10 minutes to a maximum of 30 mL/h, aiming for a target mean arterial pressure (MAP) ≥65 mmHg. Hemodynamic parameters (SBP, DBP, MAP, HR, lactate, SVO₂, CO₂ gap) and echocardiographic indices (LVEF, TAPSE, VTI, CO, SVR) will be collected at baseline (T0) and upon reaching the MAP goal (T1).
Primary endpoint: Comparative assessment of the inotropic effects between the two vasopressors based on echocardiographic and hemodynamic changes from T0 to T1.
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
The study is double-blinded. Vasopressin and norepinephrine solutions will be prepared by the pharmacy in identical intravenous bags, labeled only with the participant's identification code. The pharmacy team will be the only party unblinded to treatment allocation. All other clinical staff, investigators, research personnel, participants, and their families will remain blinded throughout the study period.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patients undergoing coronary artery bypass grafting, valve surgery or both, with a diagnosis of vasoplegic syndrome in the immediate postoperative period (<24 hours), defined as mean arterial pressure < 65 mmHg (measured using an invasive blood pressure catheter) and resistance to fluid replacement - at least 1000ml of crystalloids.
排除标准
- •Pregnancy or breastfeeding.
- •Aortic surgery.
- •Surgeries to correct congenital heart disease.
- •Heart transplants.
- •Emergency surgery.
- •Use of vasopressor therapy in the preoperative period.
- •Presence of a ventricular assist device other than an intra-aortic balloon in the postoperative period.
- •Severe hyponatremia in the postoperative period (serum sodium less than 130mEq/l).
- •Postoperative acute coronary syndrome.
- •Mesenteric ischemia in the postoperative period.
- •History of Raynaud's disease.
- •History of neoplasia.
研究组 & 干预措施
Vasopressin
Participants randomized to this arm will receive vasopressin intravenously in a blinded solution prepared by the pharmacy (final concentration: 0.12 U/mL in 250 mL of 5% glucose solution). The infusion will start at 5 mL/h and will be titrated by 2.5 mL/h every 10 minutes up to a maximum of 30 mL/h, corresponding to doses between 0.01 and 0.06 U/min. The infusion will be maintained until the target mean arterial pressure (MAP) ≥65 mmHg is achieved. If this target is not reached, open-label norepinephrine may be initiated. Hemodynamic and laboratory parameters will be collected at the start (T0) and after achieving target pressure (T1).
干预措施: Vasopressin intravenous infusion (Drug)
Noradrenaline
Participants randomized to this arm will receive norepinephrine intravenously in a blinded solution prepared by the pharmacy (final concentration: 120 µg/mL in 250 mL of 5% glucose solution). The infusion will start at 5 mL/h and will be titrated by 2.5 mL/h every 10 minutes up to a maximum of 30 mL/h, corresponding to doses between 10 and 60 µg/min. The infusion will be maintained until the target mean arterial pressure (MAP) ≥65 mmHg is achieved. If this target is not reached, additional open-label norepinephrine may be started. Hemodynamic and laboratory parameters will be collected at the start (T0) and after achieving target pressure (T1).
干预措施: Norepinephrine intravenous infusion (Drug)
结局指标
主要结局
Change in inotropic function assessed by cardiac output between T0 and T1
时间窗: Up to 1 hour after initiation of vasopressor therapy
The primary outcome is the variation in cardiac output (CO), measured by transthoracic echocardiography, from the beginning of the vasopressor infusion (T0) until the achievement of target mean arterial pressure ≥65 mmHg (T1), in patients with vasoplegic syndrome after cardiac surgery. This measurement reflects the inotropic effect of vasopressin versus norepinephrine
次要结局
- Need for additional open-label norepinephrine(During initial vasopressor titration (up to 1 hour))
- Change in left ventricular ejection fraction (LVEF) between T0 and T1(Up to 1 hour after vasopressor initiation)
- Time to achieve target mean arterial pressure (MAP ≥65 mmHg)(Up to 1 hour)
- Change in heart rate (HR) between T0 and T1(Up to 1 hour)
- Change in arterial lactate levels between T0 and T1(Up to 1 hour)
- Change in central venous oxygen saturation (SvO₂)(Up to 1 hour)
- Change in CO₂ gap (central venous-to-arterial CO₂ difference)(Up to 1 hour)
研究者
Ludhmila Abrahão Hajjar MD, PhD
Full Professor
University of Sao Paulo