A Randomised, Double Blind, Placebo Controlled Pilot Study of the Effect of Sodium Bicarbonate on Postoperative Renal Function and Oxidative Stress in Patients Undergoing Elective Cardiopulmonary Bypass.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- Proportion of patients developing an increase in serum creatinine greater than 25% from baseline to peak level within first five postoperative days.
研究概览
简要总结
Many patients develop kidney failure after cardiac surgery. Although this kidney failure can usually be treated effectively, a longer stay in intensive care is often required. While many patients suffer no long term ill effects after developing post-operative kidney failure, some require long term kidney dialysis. We also know that patients who develop post-operative kidney failure are much more likely to die before they leave hospital.
Why some people develop kidney failure after cardiac surgery is not known. However, doctors suspect that the process of cardiopulmonary bypass (where the functions of the heart and lungs are taken over by a machine during the operation, to allow the surgeon to operate) overactivates some of the same mechanisms the body uses to defend itself against severe infection.
Many of the cell changes by which severe infection causes kidney failure also occur after cardiopulmonary bypass. One of the main overactive defence mechanisms is the release of highly toxic compounds derived from oxygen - a process called 'oxidative stress'.
The investigators believe that sodium bicarbonate might reduce the oxidative stress, which occurs during cardiac surgery, and so prevent or decrease the kidney failure, which occurs in many patients.
The investigators hope to give sodium bicarbonate (in similar doses to those used safely for treatment of acidosis) to patients during, and for 24 hours after cardiac surgery, and to compare the effects with patients who have not had sodium bicarbonate. The drug, or a placebo, will be given through the drip, which is present in all cardiac surgery patients. Whether a particular patient receives the drug or placebo will be decided at random, and neither the patient nor the investigators will know which has been given. We will measure kidney function before and after the operation using the standard blood tests.
The investigators will also take four 20ml samples of blood, spaced before, during, and after the operation, from the arterial catheter routinely inserted in every patient. This blood would be used to measure oxidative stress, and also some of the proteins inside the blood cells, which are responsible for creating the toxic oxygen compounds. In this way we will discover not only the effect of sodium bicarbonate, but also the mechanism of that effect.
Sodium bicarbonate is commonly used to treat metabolic acidosis in severe renal disease, circulatory insufficiency due to shock or severe dehydration and has been shown to be an effective drug in preventing contrast-induced nephropathy.
Sodium bicarbonate is considered to be safe in the setting of intensive care treatment and is often used in the treatment of patients with metabolic acidosis without any discernible adverse clinical effects.
This is a pilot study. If the drug proves effective in this context, further studies on a larger scale would be required to justify its general use.
There will be no extra risk to a patient who participates in the study, and no discomfort other than that normally associated with cardiac surgery.
Informed consent will be obtained from the patient prior to the operation by one of the investigators or the ICU research nurse. The clinical care of a patient who does not consent for any reason will not be affected.
详细描述
Renal impairment following cardiopulmonary bypass is common. 11.4% to 42% of patients with previously normal renal function show a postoperative rise in serum creatinine. 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 dysfunction1.
Cardiopulmonary bypass activates components of the non-specific immune system, which leads to the generation of compounds containing oxygen free radicals. A study of 14 patients undergoing cardiac surgery found increased levels of serum lipid peroxidation products (thiobarbituric acid reactive substances) within 15 minutes of the commencement of cardiopulmonary bypass, which returned to preoperative levels by the following morning. The total serum antioxidative capacity was correspondingly decreased intraoperatively, and remained decreased at 24 hours postoperatively. A similar study of total plasma antioxidant status showed decreased levels up to 72 hours postoperatively. It is clear that cardiopulmonary bypass causes oxidative stress and depletion of antioxidant capacity.
N-Nitrosation of oxygenated nitric oxide (NO.) solutions was previously shown to be significantly inhibited by the strong scavenging ability of NaBic presumably by anion scavenging of nitrosating agents. At physiologic concentrations, NaBic scavenges peroxynitrite and reactive oxygen species generated from nitric oxide. This may contribute to a reduction in the deleterious effects of NO generating agents. NaBic is therefore a potential regulator of NO-induced toxicity. NaBic is considered to be safe in the setting of intensive care treatment and is often used in the treatment of patients with metabolic acidosis without any discernible adverse clinical effects. NaBic increases the pH-level by buffering of hydrogen ions, which can cause electrolyte balance shifts, e.g. Potassium will be shifted increasingly intracellular. Frequent control of pH and potassium levels is required to prevent alkalosis and hypokalemia. These adverse effects are uncommon or typically only biochemical in nature.
Oxidative stress can be produced experimentally using hypertonic glycerol. Intramuscular injection of hypertonic glycerol in rats precipitates acute renal failure associated with a marked decrease in renal reduced levels of antioxidative agents. Pre-treatment with NaBic is more protective than sodium chloride in animal models of acute renal failure secondary to ischaemia or doxorubicin.
Radio-contrast dye commonly causes renal dysfunction, in part through oxidative stress in the kidney. While not an approved indication, intravenous sodium bicarbonate has been used successfully to attenuate radiocontrast-induced nephropathy, and was more effective than standard intravenous fluid prophylaxis. Hydration with NaBic before contrast exposure is more effective than hydration with sodium chloride for prophylaxis of contrast-induced renal failure. By increasing medullary pH in the kidneys, NaBic might protect from oxygen injury by slowing pH-dependent radical production.
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
- Double
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
- •Age above 70 years
- •Preexisting renal impairment (preoperative serum creatinine level >120µmol/L
- •New York Heart Association class III/IV or Moderate to poor left ventricular dysfunction
- •Valve surgery or complex cardiac surgery
- •Redo cardiac surgery
- •Insulin-dependent diabetes mellitus
排除标准
- •Age <18 years
- •Emergency cardiac surgery
- •Planned off-pump cardiac surgery
- •Enrolled in conflicting research study
- •Known blood-borne infectious disease
- •Chronic inflammatory disease on immunosuppression
- •Chronic moderate to high dose corticosteroid therapy (>10mg/d prednisone or equivalent)
- •End stage renal disease (serum creatinine >300µmol/L)
- •Thiamine deficiency will be excluded on medical and dietary history.
结局指标
主要结局
Proportion of patients developing an increase in serum creatinine greater than 25% from baseline to peak level within first five postoperative days.
次要结局
- Proportion of patients developing an increase in serum creatinine greater than 50% from baseline to peak level within first five postoperative days.
- Relative change in serum creatinine,
- Urinary output,
- Use of renal replacement therapy (RRT),
- Acute renal dysfunction,
- Duration of ventilation,
- Chest tube drainage,
- Need for return to operating room,
- Incidence of post-operative atrial fibrillation (AF),
- Duration of stay in the intensive care unit (ICU)
- Duration of stay in hospital