Arginine Immunonutrition in Critically Ill Patients: A Clinical Dilemma

Joyce K. Stechmiller, PhD, ARNP; Beverly Childress, MSN; Tricia Porter, BSN


Am J Crit Care. 2004;13(1) 

In This Article

Abstract and Introduction


Commercial enteral nutritional formulas for enhancement of the immune system are widely used in critical care. Immunonutrition with arginine can enhance inflammatory and immunologic responses in animal models and in humans. Although clinical improvements in surgical patients have been reported, benefits in critically ill patients with systemic inflammatory response syndrome, sepsis, or organ failure are less clear. Recent meta-analyses on the use of immunonutrition with arginine in critically ill and surgical patients revealed methodological weaknesses in most published studies. Specifically, a meta-analysis indicated that critically ill patients with preexisting severe sepsis may have an increased mortality rate when fed an immunonutritional enteral formula that contains arginine. These findings brought about confusion and controversy over the use of immunonutritional formulas in subsets of critically ill patients. A review of the literature on the function of arginine, its effect on the immune system, its roles in immunonutrition and in the clinical outcomes of critically ill patients, and the implications for nursing practice indicated that the benefits of immunonutrition with arginine in critically ill patients are unproven and warrant further study. Until more information is available, nutritional support should focus primarily on preventing nutritional deficiencies rather than on immunomodulation.


Infectious complications in critically ill patients can cause increased morbidity and mortality. Recent advances in nutritional support involved enhancing immune function through the beneficial effects and therapeutic actions of amino acids. In the past decade, many investigators[1,2,3,4,5,6,7,8,9,10,11,12,13] compared nutritional formulas supplemented with arginine, n-3 fatty acids, structured lipids, and nucleotides with standard enteral formulas to determine the efficacy of the supplemented formulas in critically ill patients. The results revealed reduced occurrence of infections, reduced length of stay in the hospital or intensive care unit (ICU), reduced duration of mechanical ventilation, and decreased hospital costs for patients given the supplemented formulas. Unfortunately, the safety and efficacy of immunonutrition in critically ill patients have not been clearly established, because flaws in the methods in previous studies limit generalizations of the findings to clinical practice.[1,4] Interpreting the results of clinical trials in critical care patients is difficult because the severity of illness varies, resulting in a heterogeneous population of patients.[1,4] Moreover, except for a few randomized prospective clinical studies, the investigations have not included the most severely ill patients.[1,4] Therefore, accurate inferences cannot be drawn, and the use of enteral immunonutritional formulas in critically ill patients remains controversial.

The amino acid arginine, which is classified as a semiessential amino acid and conditionally as an essential nutrient for adults in injured or stressed states, is important in a number of biological and physiological processes. In trauma and sepsis states, its bioavailability is reduced.[14,15] In clinical studies,[16,17] arginine supplementation enhanced nitrogen retention and protein synthesis in animals and in healthy human subjects. Nutritional formulas with arginine can enhance immune parameters after stress and surgery.[10,11,12,13] However, immunonutrition with arginine has also been implicated in an intensification of the systemic inflammatoryresponse system in critically ill patients, resulting in increased morbidity.[1,2,3,4] In patients with shock, sepsis or organ failure, immunonutrition with arginine may not be beneficial and may actually have harmful effects.[1,4]

In this article, we review the function of arginine, its effect on the immune system, and its role in the immunonutrition of critically ill patients. We discuss key studies on the efficacy of arginine immunonutrition and on the clinical outcomes of critically ill patients given enteral formulas containing arginine. Finally, we discuss the implications for nursing practice and review how to assess patients for indications of adverse reactions to immunonutrition with arginine.


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