Please select the eligibility criteria that correspond to the clinical trial below.
Title: High-Dose N-Acetylcysteine in Cardiac Surgery Patients at High-Risk of Postoperative Renal Dysfunction.
Brief Summary: At least 14% of 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. The investigators 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'.

Another well-known cause of oxidative stress is paracetamol (Panadol) overdose. In large doses the oxidative stress caused by paracetamol damages cells in the liver, where it is digested, and the kidney. N-acetylcysteine is a drug in common use for the treatment of paracetamol overdose. Patients who would otherwise die of liver failure are routinely saved by N-acetylcysteine, which acts as a strong anti-oxidant.

The investigators believe that N-acetylcysteine might similarly 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 N-acetylcysteine (in similar doses to those used safely for paracetamol poisoning) to patients during, and for a day after cardiac surgery, and compare the effects with patients who have not had N-acetylcysteine. The drug, or a 5% glucose 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. The investigators will measure kidney function before and after the operation using the standard tests which are performed for the purposes of clinical care of every patient. Also, the investigators will do an extra test involving the collection of urine (from the urinary catheter every patient has after cardiac surgery), which provides an even better measure of kidney function. This is a potential benefit to the patient, as while this test is not routinely performed, the results will be available to the doctors in the intensive care unit. 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 is an insignificant amount of blood compared to that taken for other tests, and would have no adverse effects. 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 the investigators will discover not only the effect of N-acetylcysteine, but the mechanism of that effect.

N-acetylcysteine is routinely used to treat paracetamol overdose with few side effects. An itchy skin rash is the only common side effect. Sometimes patients develop nausea and vomiting, but the treatment for this is usually very effective, and the drug will be stopped if it occurs. Rarely, as with all drugs, allergic reactions have been reported, but there are no other reported adverse effects.

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. The itchy rash which occasionally develops with N-acetylcysteine would occur under anaesthetic, and would almost certainly be gone by the time the patient wakes up.

Informed consent will be obtained from the patient prior to the operation by one of the investigators or the ICU research nurse.


Options:
A: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.
B: Inclusion Criteria:

* Pts with baseline chronic kidney disease (eGFR\<60 ml/min/1.73m2)undergoing cardiac surgery

Exclusion Criteria:

* Patients on hemodialysis preoperatively
* IV contrast within 4 days prior to surgery
* Urgent/emergent surgery
* History of renal transplantation
C: Inclusion Criteria:

* CABG surgery under cardiopulmonary bypass AND/OR Valve replacement/repair surgery under cardiopulmonary bypass
* Preoperative creatinine clearance (Cockcroft-Gault equation) \<= 60 mL/min.
* Age above 18 years
* Informed consent

Exclusion Criteria:

* Preoperative need for renal replacement therapy
* Preoperative serum creatinine concentration \>= 300 mmol/L
* Prior adverse reaction to NAC with significant systemic symptoms (generalized rash, urticaria, bronchospasm, hypotension)
* Preoperative intra-aortic balloon pump support and/or inotropes/vasopressors
* Recent coronary angiography or intravenous dye exposure (\<= 24 hours) preceding surgery
* Planned intraoperative deep hypothermic circulatory arrest
* Pregnancy
* Chronic hepatitis or hepatic cirrhosis
D: Inclusion Criteria:

* 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

Exclusion Criteria:

* Age \<18 years
* Known allergy or hypersensitivity to N-acetylcysteine
* 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)
* Patients receiving pre-op IV nitrates

Answer: D