Renoprotective Effects of Dexmedetomidine Pharmacological Preconditioning in Patients Undergoing Coronary Artery Bypass Grafting With Cardiopulmonary Bypass: A Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Incidence of postoperative acute kidney injury (KDIGO serum creatinine criterion)
研究概览
简要总结
Acute kidney injury (AKI) is one of the most frequent complications of coronary artery bypass graft (CABG) surgery performed with cardiopulmonary bypass (CPB). Even small postoperative rises in serum creatinine are associated with longer intensive care stay and higher mortality. Ischemia-reperfusion injury, the systemic inflammatory response elicited by contact of blood with the bypass circuit, and heightened perioperative sympathetic activity are believed to contribute to its development.
Dexmedetomidine is a selective alpha-2 adrenergic receptor agonist used as a sedative and anesthetic adjunct. It attenuates sympathetic outflow and has shown anti-inflammatory and organ-protective properties in experimental models and in some cardiac surgical populations, but whether it reduces AKI after on-pump CABG surgery has not been established.
This is a prospective, randomized, double-blind, placebo-controlled, single-center trial in adults undergoing elective CABG surgery with CPB. One hundred patients aged 18-80 years, ASA physical status II or III, with a preoperative serum creatinine below 1.5 mg/dL are allocated 1:1 to a dexmedetomidine group (n=50) or a control group (n=50). Patients in the dexmedetomidine group receive a loading dose of 1 microgram/kg over 15 minutes after central venous catheterization, followed by a maintenance infusion of 0.5 microgram/kg/h until the start of CPB. Patients in the control group receive an equal volume of 0.9% sodium chloride over the same period and with the same infusion scheme. In both groups the infusion is stopped when CPB begins; no study drug is given during bypass or postoperatively. Anesthesia, surgery, CPB conduct, fluid and vasoactive therapy, and postoperative intensive care follow a standardized protocol with identical numerical thresholds in both groups, applied by clinicians unaware of group allocation.
The primary outcome is the incidence of postoperative AKI within the first 72 hours, staged according to the serum creatinine criteria of the KDIGO 2012 classification. Secondary outcomes are systemic inflammatory markers (white blood cell count, neutrophils, lymphocytes, neutrophil-to-lymphocyte ratio, C-reactive protein, procalcitonin), vasoactive drug requirement quantified by the vasoactive-inotropic score, need for renal replacement therapy, time to extubation, intensive care unit and hospital length of stay, and 30-day and 90-day mortality. All patients are followed until postoperative day 90.
All variables assessed in the study are parameters obtained as part of routine clinical care in this patient population; no additional intervention or additional laboratory test is performed for study purposes.
详细描述
Acute kidney injury (AKI) is one of the most frequent complications of coronary artery bypass graft (CABG) surgery performed with cardiopulmonary bypass (CPB). Even small postoperative rises in serum creatinine are associated with longer intensive care stay and higher mortality. Ischemia-reperfusion injury, the systemic inflammatory response elicited by contact of blood with the bypass circuit, and heightened perioperative sympathetic activity are believed to contribute to its development.
Dexmedetomidine is a selective alpha-2 adrenergic receptor agonist used as a sedative and anesthetic adjunct. It attenuates sympathetic outflow and has shown anti-inflammatory and organ-protective properties in experimental models and in some cardiac surgical populations, but whether it reduces AKI after on-pump CABG surgery has not been established.
This is a prospective, randomized, double-blind, placebo-controlled, single-center trial in adults undergoing elective CABG surgery with CPB. One hundred patients aged 18-80 years, ASA physical status II or III, with a preoperative serum creatinine below 1.5 mg/dL are allocated 1:1 to a dexmedetomidine group (n=50) or a control group (n=50). Patients in the dexmedetomidine group receive a loading dose of 1 microgram/kg over 15 minutes after central venous catheterization, followed by a maintenance infusion of 0.5 microgram/kg/h until the start of CPB. Patients in the control group receive an equal volume of 0.9% sodium chloride over the same period and with the same infusion scheme. In both groups the infusion is stopped when CPB begins; no study drug is given during bypass or postoperatively. Anesthesia, surgery, CPB conduct, fluid and vasoactive therapy, and postoperative intensive care follow a standardized protocol with identical numerical thresholds in both groups, applied by clinicians unaware of group allocation.
The primary outcome is the incidence of postoperative AKI within the first 72 hours, staged according to the serum creatinine criteria of the KDIGO 2012 classification. Secondary outcomes are systemic inflammatory markers (white blood cell count, neutrophils, lymphocytes, neutrophil-to-lymphocyte ratio, C-reactive protein, procalcitonin), vasoactive drug requirement quantified by the vasoactive-inotropic score, need for renal replacement therapy, time to extubation, intensive care unit and hospital length of stay, and 30-day and 90-day mortality. All patients are followed until postoperative day 90.
All variables assessed in the study are parameters obtained as part of routine clinical care in this patient population; no additional intervention or additional laboratory test is performed for study purposes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 to 80 years
- •Scheduled for elective coronary artery bypass graft surgery with cardiopulmonary bypass at the study center
- •American Society of Anesthesiologists (ASA) physical status class II or III
- •Preoperative serum creatinine below 1.5 mg/dL
- •Written informed consent obtained at the preoperative visit
排除标准
- •Left main coronary artery stenosis greater than 50%
- •Severe valvular dysfunction
- •Severe left ventricular hypertrophy or cardiomyopathy
- •Arrhythmia causing significant hemodynamic compromise
- •Left ventricular ejection fraction below 35%
- •Acute coronary syndrome or cardiovascular surgery within the preceding month
- •Estimated glomerular filtration rate below 15 mL/min/1.73 m2
- •Nephropathy due to uncontrolled hypertension and/or diabetes mellitus
- •Treatment of hypertension with a combination of an angiotensin-converting enzyme inhibitor, a diuretic and an alpha-2 adrenergic agonist
- •Morbid obesity
- •Hepatic dysfunction attributable to substance abuse or alcoholism
- •Previous severe drug allergy during administration of dexmedetomidine
研究组 & 干预措施
Dexmedetomidine
Patients undergoing elective coronary artery bypass graft surgery with cardiopulmonary bypass (CPB) who receive intravenous dexmedetomidine in the pre-bypass period. After central venous catheterization and a subsequent 5-minute period of hemodynamic stabilization, a loading dose of 1 microgram/kg is infused over 15 minutes, followed by a maintenance infusion of 0.5 microgram/kg/h until the start of CPB. The infusion is terminated with the initiation of CPB; no study drug is given during bypass or postoperatively. All other aspects of anesthesia, surgery, CPB conduct, fluid and vasoactive therapy, and postoperative intensive care follow a standardized protocol identical to that used in the control arm.
干预措施: Dexmedetomidine (Drug)
Control Group
Patients undergoing elective coronary artery bypass graft surgery with cardiopulmonary bypass (CPB) who receive an equal volume of 0.9% sodium chloride instead of dexmedetomidine. The placebo infusion is started after central venous catheterization and the subsequent 5-minute period of hemodynamic stabilization and is given over the same time intervals and with the same infusion scheme as in the dexmedetomidine arm (15-minute loading infusion followed by a maintenance infusion), and is terminated with the initiation of CPB. All other aspects of anesthesia, surgery, CPB conduct, fluid and vasoactive therapy, and postoperative intensive care follow the same standardized protocol as in the dexmedetomidine arm.
干预措施: 0.9 % sodium chloride (Drug)
结局指标
主要结局
Incidence of postoperative acute kidney injury (KDIGO serum creatinine criterion)
时间窗: From the preoperative baseline measurement to postoperative hour 72
Number and percentage of participants developing acute kidney injury (AKI) of any stage (stage 1 or higher) according to the serum creatinine criterion of the KDIGO 2012 classification. The preoperative serum creatinine value is taken as the baseline; serum creatinine is measured at postoperative hours 0, 24, 48 and 72. AKI is defined as an increase in serum creatinine of 0.3 mg/dL or more from baseline within 48 hours, or a rise to 1.5 times baseline or higher, or the need for renal replacement therapy. The urine output criterion of the KDIGO classification is not applied.
次要结局
- Vasoactive-inotropic score(After separation from cardiopulmonary bypass, at intensive care unit admission (postoperative hour 0) and at postoperative hour 24)
- Systemic immune-inflammatory response(Preoperative baseline, at intensive care unit admission (postoperative hour 0) and at postoperative hour 24)
- Time to extubation(From ICU admission to extubation, assessed up to postoperative day 7)
- Length of intensive care unit stay(From ICU admission to ICU discharge, assessed up to postoperative day 30)
- Length of hospital stay(From surgery to hospital discharge, assessed up to postoperative day 30)
研究者
eralp çevikkalp
Associate ,professor
Bursa City Hospital