L-Arginine supplementation in sepsis: beneficial or harmful?

Abstract

Recent results are reviewed on the effects of L-arginine supplements in excess of standard nutritional practices during severe sepsis and septic shock. Septic shock has been alternatively viewed as an L-arginine-deficient state or as a syndrome caused by excess nitric oxide, a vasoactive product of L-arginine metabolism. L-Arginine has many physiologic and pharmacologic effects that indicate its potential to affect survival in septic patients. Animal studies have documented immunologic effects of L-arginine and of commercial 'immune-enhancing' diets. However, survival studies in small animals have not consistently favored L-arginine. L-Arginine monotherapy in a canine model of septic shock found significant harm at infusion rates of less than twice that administered in standard formulations of total parenteral nutrition. Meanwhile, clinical studies have suffered from lack of statistical power, patient heterogeneity, randomization failures, and use of complex nutritional formulas. Meta-analyses have noted heterogeneity between the effects of immune-enhancing diets in surgical versus medical patients and mixed critically ill populations that include subjects with sepsis, indicating that these results may not be reliably pooled. To date, published evidence has not established the safety and efficacy of L-arginine at doses above standard dietary practices in severe sepsis or septic shock.