Antioxidant therapy in critical care--is the microcirculation the primary target?
This review presents the rationale for the therapeutic use of antioxidants in treating critically ill patients; it is not a systematic review of the clinical evidence that has been assessed recently by others. Clinical and nonclinical evidence is presented to support the notion that natural antioxidants are of therapeutic value in treating cardiovascular shock. Oxidative stress is a major promoter and mediator of the systemic inflammatory response. The microcirculation is particularly susceptible to oxidative stress that causes hemodynamic instability, leading to multiple organ failure due to systemic inflammatory response syndrome. Vitamin C is the antioxidant used experimentally to demonstrate oxidative stress as a key pathophysiologic factor in septic shock. Pharmacologic studies reveal that vitamin C (as ascorbate), at supraphysiologic doses, significantly affects the bioavailability of nitric oxide during acute inflammation, including inhibiting nitric oxide synthetase induction. Parenteral high-dose vitamin C inhibits endotoxin-induced endothelial dysfunction and vasohyporeactivity in humans and reverses sepsis-induced suppression of microcirculatory control in rodents. In severe burn injury, in both animals and patients, parenteral high-dose vitamin C significantly reduces resuscitation fluid volumes. Therefore, a significant body of pharmacologic evidence and sound preliminary clinical evidence supports the biological feasibility of using the exemplary antioxidant, vitamin C, in the treatment of the critically ill.
Biesalski
Hans Konrad
HK
Department of Biological Chemistry and Nutrition, University Hohenheim, Germany. biesal@uni-hohenheim.de
McGregor
Gerard Patrick
GP
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology / Q000627:therapeutic use; D016638:Critical Illness; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008833:Microcirculation / Q000187:drug effects*; D009102:Multiple Organ Failure / Q000188:drug therapy / Q000209:etiology; D018384:Oxidative Stress; D012772:Shock, Septic / Q000188:drug therapy; D018746:Systemic Inflammatory Response Syndrome / Q000150:complications / Q000188:drug therapy; D014664:Vasodilation / Q000187:drug effects; D014815:Vitamins / Q000494:pharmacology / Q000627:therapeutic use; D014947:Wounds and Injuries / Q000188:drug therapy
D000975:Antioxidants; D014815:Vitamins; D001205:Ascorbic Acid