Arginine Immunonutrition in Critically Ill Patients: A Clinical Dilemma

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

Disclosures

Am J Crit Care. 2004;13(1) 

In This Article

Role of Arginine Immunonutrition in Critically Ill Patients

Immunonutrition with arginine is a popular approach to augment the immune response of patients with critical illnesses. In early studies,[27,28,29,30] immunonutrition with arginine led to improvements in cellular immunity in patients with postoperative or posttraumatic stress. Zaloga[49] reviewed 13 prospective randomized clinical studies in which an enteral immunonutritional formula with arginine was compared with a standard one in surgical and critically ill patients. He reported that in 12 of the 13 studies, the experimental groups had improved outcomes. Specifically, hospital and ICU lengths of stay, number of days of mechanical ventilation required, and number of infections decreased after immunonutrition with arginine. Subsequently, the conclusions of 2 other meta-analyses, by Beale et al[2] and Heys et al,[3] were similar.

Heyland et al[1] did a more comprehensive meta-analysis of immunonutrition in which they examined the results of 22 individual studies in which an immunonutritional enteral formula was compared with a standard enteral formula in a total of 2419 surgical and critically ill patients. Using a scoring system to document the methodological limitations of the studies, Heyland et al found that although some of the investigators used an evidence-based approach, the study methods had many shortcomings, resulting in invalid conclusions and inferences. Thus, the findings of Heyland et al conflict with those of previous meta-analyses and suggest that immunonutrition in surgical and critically ill patients may decrease the rate of infectious complications but is not related to an over-all decrease in mortality. Specifically, Heyland et al concluded that the treatment effect of immunonutrition with arginine varies according to the type of enteral formula, the subset of patients, and the quality of the study method.

Heyland et al examined studies of patients under-going elective surgery, critically ill patients with severe trauma, critically ill patients with severe burns, and critically ill patients in an ICU. Analysis of the aggregated trials revealed that immunonutrition was associated with no mortality advantage. The aggregated results also indicated that patients given immunonutritional formulas had fewer infectious complications and shorter lengths of stay in the hospital than did patients given standard enteral formulas.

Studies were further examined by Heyland et al[1] to determine the effects of immunonutrition on mortality, infectious complications, and duration of ICU stay and mechanical ventilation in subgroups of critically ill patients. Treatment with formulas containing arginine had no effect on mortality or rate of infectious complications; it did result in a reduction in length of hospital stay. Mortality was higher in the studies in which formulas other than those high in arginine content were used. In addition, the number of infectious complications tended to be lower in studies in which formulas with high arginine content were used.

In critically ill patients with shock, sepsis, or organ failure, treatment effects differed significantly from those of surgical patients.[1] Although immunonutrition with arginine was associated with a significant reduction in the rate of infectious complications in surgical patients, it had no effect on mortality or rate of infectious complications in critically ill patients, indicating possibly a trend toward harm.[1] A possible explanation for this finding is that the use of immunonutrition with arginine can increase the release of proinflammatory cytokines and the production of nitric oxide, changes that may be detrimental in critically ill patients who are already experiencing a heightened inflammatory response. In patients with severe SIRS and sepsis, administration of enteral formulas containing arginine can cause transient hypo-tension, increases in cardiac index, and decreases in systemic and pulmonary vascular resistance.[50,51] Further research is needed to determine underlying deleterious mechanisms of immunonutrition with arginine in this vulnerable population of patients.

Findings from other studies also support the assumption that immunonutrition may be harmful in critically ill patients. Bower et al[9] compared the effect of Impact, an immunonutritional supplement with arginine, and Osmolite HN in 326 critically ill patients. Data on 47 patients were dropped from the primary analysis because of inconsistency in feedings. The results indicated that more deaths occurred in patients who received the arginine-supplemented formula (15.7%) than in the control group (8.4%; P=.055). Among the patients with sepsis who received the arginine supplement, the death rate was 3 times that of patients with sepsis who received the control feedings (25% vs 8.9%, P=.051).

The results from the studies[1,4] described do not support the use of currently available immunonutritional formulas with arginine in the most critically ill patients who have sepsis. The studies indicate that early immunonutrition in selected surgical patients may improve clinical outcomes, but the issue needs further study.

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