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.