Track topics on Twitter Track topics that are important to you
N-acetylcysteine is a medication that has most commonly been used in the past to prevent liver damage after an acetaminophen overdose. N-acetylcysteine has also been used in patients with pre-existing kidney damage to prevent further kidney damage resulting from dye that is used in tests such as angiograms (dye studies). This study hopes to prove that this medication may also help to protect kidneys from the damage caused by the heart-lung machine during cardiac surgery. This damage to the kidneys happens to patients undergoing cardiac surgery requiring the use of the heart-lung machine. Kidney failure after surgery is a serious complication (2-30% of patients with kidney problems can develop it) and it can lead to short term and long-term dialysis as well as death (there is up to a 30% death rate once kidney failure develops). The study will test if intravenous N-acetylcysteine is safe and effective in preventing kidney problems after cardiac surgery using the heart-lung machine. Approximately 104 patients will be enrolled at Sunnybrook and Women’s College Health Science Centre. The study has been reviewed and approved by the ethics committee at Sunnybrook and Women’s College Health Science Centre. The study will compare the effects of N-acetylcysteine with those of placebo (salt solution). The study medication (either N-acetylcysteine or placebo) will be given in addition to your usual medication and surgical procedures.
N-acetylcysteine (NAC) is an oral or intravenous agent that replenishes glutathione which in turn allows for the formation of glutathione peroxidase, an important enzyme in the degradation cascade of reactive free oxygen radicals. NAC has been shown to reduce recurrent cardiac events in the setting of ischemic injury, and help prevent progression of renal dysfunction in patients with chronic renal failure exposed to nephrotoxic dye for radiographic studies. Cardiopulmonary bypass (CPB) has been shown be nephrotoxic that may be through the production of oxygen free radicals produced as a consequence of: a systemic inflammatory response to the pump, renal hypoperfusion and loss of pulsatile flow to the kidney during CPB. Renal dysfunction post cardiac surgery can lead to short or long term dialysis, and an increase in mortality rate. NAC therefore may be an ideal agent to preserve renal function in those patients who require exposure to CPB and are at high risk of developing postoperative renal dysfunction. The hypothesis tested in this study is that IV NAC may minimize postoperative renal dysfunction sustained by exposure to the cardiopulmonary bypass circuit.
This study will answer the question of whether perioperative intravenous N-Acetylcysteine (NAC) will be effective in reducing postoperative renal dysfunction as measured by a change peak creatinine from baseline values greater than or equal to 50μmol/L between placebo and NAC groups in adult, elective patients at high risk of renal insufficiency following exposure to cardiopulmonary bypass (CPB). This study is a randomized, placebo controlled, double blind trial that addresses the following objective:
1.To determine if intravenous N-Acetylcysteine (NAC) is effective in reducing post cardiopulmonary bypass renal dysfunction.
It is hypothesized that IV NAC will provide renal protection and may be an effective prophylactic option for patients at high risk of postoperative renal failure after exposure to CPB, and avoiding the ensuing high mortality rate associated with this.
This study will consist of a single centre, randomized, stratified, double blind, placebo controlled trial of intraoperative use of placebo or IV N-acetylcysteine (n=104 patients).
Includes those patients with preoperative renal dysfunction (serum creatinine level 140 μmol/L or greater or a calculated glomerular filtration rate of 50 mL/min or less), or a risk factor score for postoperative renal dysfunction that adds up to 6 or more based on the following scale:
Score Risk Factor:
3 scheduled for redo cardiac surgery 3 scheduled for valve surgery 2 age greater than 69 at time of surgery 2 known diabetic (Type I or II) 2 congestive heart failure 2 treated hypertension 2 chronic obstructive pulmonary disease 2 preoperative stroke
1 left ventricular function –grade 3 or 4 (seen on echo or angiogram)
1 New York Heart Association Class 3 or 4
Patient is participating in another trial
- Patient has received NAC in the past 48 hours.
- Patient has allergy to N-acetylcysteine.
- Patient scheduled for off-pump surgery or an extracardiac procedure (pericardiectomy etc.)
- Patient requires emergent surgery
- Patient scheduled for a procedure involving circulatory arrest.
- Patient requires chronic dialysis (peritoneal or hemodialysis)
- Patient unable to give informed consent (dementia, does not speak English, etc.)
- Patient has a recent history of cancer (in last five years) or untreated cancer
Patients will be randomized to either placebo or IV NAC (one to one allocation). There will be four strata. The four strata consist of the major divisions of isolated CABG surgery and valve surgery and the subdivisions of risk factor only patients, and patients with preoperative renal insufficiency. The patients will be randomized to each of these three strata using a permuted-block randomization with block sizes of 4. The randomization number will be kept by pharmacy personnel and be available for unblinding in case of any emergencies which would include anaphylaxis, hypotension (mean bp less than 60 mmHg), and liver failure. Blinding will be preserved as the IV NAC and placebo will be dispensed in identical IV solution bags that cannot be distinguished.
Patients will be randomized to receive either NAC (150 mg/kg bolus over 15 minutes after induction and 50 mg/kg/hr infusion during cardiopulmonary bypass) or placebo (same amount of saline both for bolus and infusion).
We also have provided standard guidelines suggested in the perioperative management of these patients as it pertains to renal protection including the use of co-interventions such as IV fluid management, pulsatile CPB, and use of vasopressors to maintain adequate perfusion pressures both during and following CPB.
The patients and caregivers will be blinded to the treatment group as the placebo will be identical to the IV NAC in appearance. The research personnel collecting data will also be blinded. The pharmacy personnel will be the only ones aware of the treatment assignments. Blinding will not be breached except for emergency situations as outlined above. The cardiac surgeon and anesthetist will be asked if they believe their patient is on study drug to ensure blinding has been preserved.
Intention to Treat:
The study will include those patients who do not tolerate NAC and do not receive the full NAC dosage because of adverse events in an intention to treat manner. These patients who have not have the full maneuver will therefore be included in the final analysis.
The primary outcome that will be compared between NAC and placebo groups will be the increase in serum creatinine from preoperative baseline level after exposure to CPB. The secondary outcomes will include glomerular filtration rate (as calculated by serum creatinine, and demographic variables as well as serum cystatin C), blood urea nitrogen, early dialysis (in-hospital), in-hospital mortality, postoperative myocardial infarction (MI), peak troponin, stroke, and postoperative low output syndrome. Adverse events such as hypotension, anaphylaxis and alteration of coagulation parameters will be documented.
Implication of Potential Results:
If this study shows renal protection with IV NAC it could be used as an effective prophylactic option for patients at high risk of postoperative renal failure and the ensuing high mortality rate associated with this.
Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double-Blind, Primary Purpose: Prevention
Sunnybrook Health Sciences Centre
Published on BioPortfolio: 2014-08-26T22:50:13-0400
This is a randomised controlled trial to investigate the efficacy of preventive regimen of hydration with high dose oral N-acetylcysteine and intravenous sodium bicarbonate pretreatment in...
OBJECTIVES: I. Determine the safety and efficacy of a short course (72 hours) of intravenous acetylcysteine in patients with acute liver failure for whom no antidote or specific tr...
The purposes of the study are to determine whether oxidative stress causes the muscle of dialysis patients to tire more quickly than muscle of people without kidney disease and to determin...
The objective of this study is to determine whether the administration of N-acetylcysteine (NAC) improves oxidative stress. To determine this, the study will assess the impact of oral tre...
We have completed patient enrollment in the the double blind, randomized, placebo-controlled trial of intravenous (IV) N-acetylcysteine (NAC) vs. placebo for the treatment of non-acetamino...
Intravenous immunoglobulin has been shown to decrease the risk of post-transplant infections in heart recipients with IgG hypogammaglobulinemia, however the use of subcutaneous immunoglobulin has not ...
Although HDL cholesterol concentrations are strongly and inversely associated with risk of coronary heart disease, interventions that raise HDL cholesterol do not reduce risk of coronary heart disease...
Urocortin 2 (UCn2) peptide infusion increases cardiac function in patients with heart failure, but chronic peptide infusion is cumbersome, costly, and provides only short-term benefits. Gene transfer ...
The correlation between heart murmur and congenital heart disease (CHD) is complex and varies with observed population.
Genetic disorders, such as heterotaxy, first provided a link between cilia and developmental heart defects. Now, a genetic screen in mice shows that ciliary dysfunction may indeed be the major contrib...
Inflammation of the ENDOCARDIUM caused by BACTERIA that entered the bloodstream. The strains of bacteria vary with predisposing factors, such as CONGENITAL HEART DEFECTS; HEART VALVE DISEASES; HEART VALVE PROSTHESIS IMPLANTATION; or intravenous drug use.
Cardiac manifestation of systemic rheumatological conditions, such as RHEUMATIC FEVER. Rheumatic heart disease can involve any part the heart, most often the HEART VALVES and the ENDOCARDIUM.
Disease-related laceration or tearing of tissues of the heart, including the free-wall MYOCARDIUM; HEART SEPTUM; PAPILLARY MUSCLES; CHORDAE TENDINEAE; and any of the HEART VALVES. Pathological rupture usually results from myocardial infarction (HEART RUPTURE, POST-INFARCTION).
Fluid propulsion systems driven mechanically, electrically, or osmotically that are used to inject (or infuse) over time agents into a patient or experimental animal; used routinely in hospitals to maintain a patent intravenous line, to administer antineoplastic agents and other drugs in thromboembolism, heart disease, diabetes mellitus (INSULIN INFUSION SYSTEMS is also available), and other disorders.
The hemodynamic and electrophysiological action of the left HEART VENTRICLE. Its measurement is an important aspect of the clinical evaluation of patients with heart disease to determine the effects of the disease on cardiac performance.
Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...
Hepatology is the study of liver, gallbladder, biliary tree, and pancreas, and diseases associated with them. This includes viral hepatitis, alcohol damage, cirrhosis and cancer. As modern lifestyles change, with alcoholism and cancer becoming more promi...
Diabetes Diabetes Endocrine Obesity Oxycontin Renal Disease Thyroid Disorders Endocrinology is the study of the endocrine glands and the hormones that they secrete (Oxford Medical Dictionary). There are several groups of h...
kidney protective dose of acetylcysteinenac n cetil cystein iv renal protectionnac n cetil cystein iv renal protectionacetylcysteine as kidney protectantacetylcysteine as kidney protectantmucomyst renal protection after procedureAcetylcysteine for Kidney ProtectionIV Acetylcysteine for Renal ProtectionAcetylcysteine for Kidney Protection