A Multicenter, Randomized, Double Blind, Placebo Controlled Study of the Effect of Sodium Bicarbonate on Postoperative Renal Function in Patients Undergoing Elective Cardiopulmonary Bypass
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 350
- 试验地点
- 4
- 主要终点
- Proportion of patients developing an increase in serum creatinine > 25% or >44µmicromol/L from baseline to peak level after adjustment for relevant baseline characteristics
研究概览
简要总结
With over one million operations a year, cardiac surgery with cardiopulmonary bypass is one of the most common major surgical procedures worldwide (1). Acute kidney injury is a common and serious postoperative complication of cardiopulmonary bypass and may affect 25% to 50% of patients (2-4). Acute kidney injury carries significant costs (4) and is independently associated with increased morbidity and mortality (2,3). Even minimal increments in plasma creatinine are associated with an increase in mortality (5,6).
Multiple causes of cardiopulmonary bypass-associated acute kidney injury have been proposed, including ischemia-reperfusion, generation of reactive oxygen species, hemolysis and activation of inflammatory pathways (7-10). COMT LL genotype appears to increase the risk of vasodilatory shock and AKI after cardiac surgery. To date, no simple, safe and effective intervention to prevent cardiopulmonary bypass-associated acute kidney injury in a broad patient population has been found (11-14).
Urinary acidity may enhance the generation and toxicity of reactive oxygen species induced by cardiopulmonary bypass (10,15). Activation of complement during cardiac surgery (16) may also participate in kidney injury. Urinary alkalinization may protect from kidney injury induced by oxidant substances, iron-mediated free radical pathways, complement activation and tubular hemoglobin cast formation (9,17,18). Of note, increasing urinary pH - in combination with N-acetylcysteine (19,20) or without (21) - has recently been reported to attenuate acute kidney injury in patients undergoing contrast-media infusion.
In a pilot double-blind, randomized controlled trial the investigators found sodium bicarbonate to be efficacious, safe, inexpensive and easy to administer. These findings now need to be confirmed or refuted by further clinical investigations in other geographic and institutional settings.
Accordingly, the investigators hypothesized that urinary alkalinization might protect kidney function in patients at increased risk of acute kidney injury undergoing cardiopulmonary bypass needs to be confirmed in an international multicenter, double-blind, randomized controlled trial of intravenous sodium bicarbonate.
详细描述
Renal impairment following cardiopulmonary bypass is common. While most of these patients do not require either short or long term renal replacement, the mortality of patients with acute renal failure is substantially greater than those who do not develop renal dysfunction.
In a pilot double-blind, randomized controlled trial we found sodium bicarbonate to be efficacious, safe, inexpensive and easy to administer. These findings now need to be confirmed or refuted by further clinical investigations in other geographic and institutional settings.
There is evidence that sodium bicarbonate affects the cardiovascular, respiratory and immune systems and may be of benefit to patients undergoing cardiac surgery.
Study Design - overview and rationale Patients will be randomised to receive sodium bicarbonate from the induction of anaesthesia until 24 hours postoperatively, or a placebo (sodium chloride).
Serum creatinine is the most commonly used clinical indicator of renal function along with urine output. Both will be measured for several days postoperatively - the time period during which renal impairment is most likely to develop.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Cardiac surgical patients in whom the use of cardiopulmonary bypass was planned and:
- •Written informed consent of patient
- •Age >18 years
- •And having at least one ore more of the following risk factors for postoperative AKI:
- •Age =/>70 years
- •Preoperative plasma creatinine >120 µmol/L New York Heart Association class III / IV or LVEF <35%
- •Insulin dependent diabetes mellitus
- •Valve surgery (with or without coronary artery bypass graft)
- •Redo cardiac surgery
排除标准
- •Cardiac surgical patients will not be considered eligible if:
- •An emergency operation is indicated (within 24 hours after hospital admission or on intra-aortic balloon pump) or
- •Pregnancy is confirmed or breastfeeding is present or
- •A renal allograft is present or
- •Preoperative acute renal failure within 6 weeks (acute rise in serum creatinine >50% from baseline) is present or
- •Pre-operative end stage renal disease (serum creatinine >300 µmol/L) is present or
- •Chronic moderate to high dose corticosteroid therapy (>10 mg/d prednisone or equivalent) is present
研究组 & 干预措施
2
sodium chloride at 0.5 mmol/kg loading pre-induction and then at 0.2 mmol/kg/hr over 24 hours after induction until the next day
干预措施: Sodium Chloride (Drug)
1
The active intervention is loading (05. mmol/kg) pre-surgery and continuous infusion of bicarbonate at 0.2 mmol/kg/hr for 24 hours after induction
干预措施: Sodium Bicarbonate (Drug)
结局指标
主要结局
Proportion of patients developing an increase in serum creatinine > 25% or >44µmicromol/L from baseline to peak level after adjustment for relevant baseline characteristics
时间窗: within first two-five postoperative days.
次要结局
- Length of ventilation(from commencement to end of intubation)
- Proportion of patients developing an increase in serum creatinine greater than 50% from baseline to peak level after adjustment for relevant baseline characteristics(within first two-five postoperative days)
- Proportion of patients developing an increase in serum creatinine greater than 100% from baseline to peak level after adjustment for relevant baseline characteristics(within first two-five postoperative days)
- Change in serum creatinine from baseline to peak level after adjustment for relevant baseline characteristics(within first two-five postoperative days)
- Proportion of patients developing any of the RIFLE criteria: R, I or F after adjustment for relevant baseline characteristics(within first five postoperative days)
- Proportion of patients developing any of the AKI stages: 1, 2 or 3 (using network definition)after adjustment for relevant baseline characteristics(within 48 hours postoperatively)
- Change in serum urea from baseline to peak(within first two-five postoperative days)
- Change in NGAL from baseline to peak(within first 24 postoperatively)
- Change in electrolyte status from baseline to peak(within first 24-48hrs postoperatively)
- Requirement of renal replacement therapy(within first postoperative days)
- Length of stay in Intensive care(from admission to discharge from Intensive care)
- Length of stay in hospital(from admission to discharge from hospital)
- Hospital-Mortality(during hospital stay)
- 90-day mortality(during 90 days postoperatively)
- COMT polymorphism(sampling at induction of anesthesia)
研究者
Rinaldo Bellomo
Director of ICU research
Austin Health