The use of N-acetylcysteine in intensive care.

OBJECTIVE: To review the actions and clinical use of serum N-acetylcysteine in the critically ill patient. DATA SOURCES: A review of articles published on the mechanisms of action and clinical use of N-acetylcysteine. SUMMARY OF REVIEW: N-acetylcysteine (NAC) is an amino acid with a MW of 163.2. It acts as an antioxidant, both directly as a glutathione substitute and indirectly as a precursor for glutathione. It also causes vasodilation by increasing cyclic guanosine monophosphate levels, inhibits platelet aggregation, acts as a sulphydryl donor to regenerate endothelial-derived relaxing factor and reduces IL-8 and TNF-alpha production. While there is evidence for its effectiveness as an antidote to paracetamol poisoning, its use in other disorders has only experimental or anecdotal support. For example, in hepatic failure, there are few studies in man showing improved outcome following NAC therapy. There is also conflicting evidence for the use of NAC in sepsis or ARDS and while there is some evidence to suggest that NAC may be of benefit in acute myocardial infarction, the patient numbers are small. It may also be of use in ameliorating nitrate tolerance. It is also possible that NAC may confer benefit in reducing the risks of radiographic contrast nephropathy, although the study suggesting this was probably insufficiently powered to review all patient subsets (e.g. diabetics). N-acetylcysteine would also appear to enhance T cell function in HIV infected patients. However, the use of NAC for immunomodulation in HIV patients has not yet undergone prospective randomised controlled trials and therefore cannot be recommended as routine therapy in HIV infected, or other immune deficient, patients. There is currently insufficient evidence to propose NAC for the treatment of carbon monoxide poisoning. Whilst there is experimental evidence for a variety of novel roles for NAC, further clinical studies are required before it can be recommended for the routine management of any disorders other than that of paracetamol poisoning.
CONCLUSIONS: N-acetylcysteine has antioxidant properties that may be useful in many clinical conditions. Currently, however, it can only be recommended as therapy for paracetamol poisoning, in all other disorders it is still under evaluation.