Antioxidant therapy in critically ill patients

The increased oxidative stress in critically ill patients could exert pathophysiological role in the pathogenesis of multiple organ failures, as suggested by recent clinical trials of antioxidant therapies. Prophylactic administration of antioxidant vitamins or glutamine, incorporated in the nutritional support or given as sepasituation and could be influenced by several current therapeutic interventions, including the nutritional status. The bio-availability of some anti oxidants administered enterally could also be impaired. Third, the issue of timing of anti oxidant administration is probably a key factor, as the repletion of antioxidant would probably achieve a greater efficacy if given before a massive oxidative injury (major surgery, shock, severe sepsis). Therefore, the anti-oxidant approach can be considered as a preventive as well as a therapeutic modality. The purpose of the present article is to briefly review the basic mechanisms involved in the production and neutralisation of ROS, to summarize the current knowledge on oxidative stress in critically ill patients, and to present recently published data on the effects of antioxidants administration. Sources of reactive oxygen species. Stricto sensu, a free radical or reactive species is an unstable atom with an unpaired electron. ROS include superoxide (O2-.), hydrogen peroxide (H2O2) and the hydroxyl radical (OH.). In critically ill patients, ROS can be produced from 4 different pathways : 1. The mitochondrial respiratory chain produces O 2 -. as a byproduct of the reaction of molecular oxygen with semi-ubiquinone. In case of severe mitochondrial dysfunction, as observed during septic shock [4], this pathway could be up-regulated and massive amounts of O 2 -. could be released. From the Department of Intensive Care, Centre hospitalo-universitaire du Sart-Tilman, Liège, Belgium.(Drs. Jean-Charles Preiser and Robin Lovat). Address requests for reprints to: Jean-Charles PREISER, M.D., Ph.D., Department of Intensive Care, CHU Liege Domaine Universitaire du Sart Tilman B35, 4000 LIEGE 1, BELGIUM Tel : +3243667495. Fax : +3243668898 E-mail : [email protected] rate medications, efficiently attenuates the oxidative stress and in some studies, decreases the incidence of organ failures and ultimately improves the outcome of critically ill patients. Patients at risk of organ failures could benefit from the early adjunction of antioxidant treatment, including vitamins and glutamine. Review Articles