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To the Editors:
The article by Stechmiller and colleagues titled "Arginine Immunonutrition in Critically Ill Patients: A Clinical Dilemma" (January 2004:17–23) contains many of the same errors as have prior analyses of the data. After reviewing the studies evincing dietary arginine immune stimulation in animals and humans, the reviewers raise the possibility that arginine might pose a risk to septic patients. This speculation is largely based on studies demonstrating increased lability of blood pressure in lipopolysaccharide-treated or septic animals after arginine loading. The reviewers then note that although infection rates and hospital length of stay decreased in the surgical patients fed an enteral immunonutritional formula with arginine compared with patients who were enterally fed a standard formula, no similar benefit was observed in multicenter studies of critically ill patients. Indeed, patients randomized to arginine enteral regimens had a higher mortality rate than did patients receiving standard enteral feeding. The reviewers suggest, as did Heyland1 in a previous analysis, that the arginine diet might be harmful to critically ill patients. How else would one account for the difference between the surgical and intensive care unit studies?
These authors, like Heyland,1 fail to note the critical difference, namely the inability to feed patients adequate enteral formulas in studies such as Bower’s compared with the postoperative surgical studies.2 Most patients failed to receive adequate formula or early feeding in the Bower study. This group obscures any benefit derived from random assignment to an arginine-based diet.
Indeed, the mortality rate was inversely related to the formula—the more arginine-based formula patients were fed, the lower the mortality rate—hardly what one would expect if arginine had a standard sigmoid-shaped, dose-dependent toxicity curve in critically ill patients. Many of the deaths in the group of patients receiving the arginine formula were secondary to head injuries and occurred before any significant enteral feedings could be delivered.
Of the patients who tolerated the diet, the benefits to patients who received the arginine-based formula in the Bower study paralleled those observed by Daly3: a comparable reduction in length of hospital stay and infection rates compared with patients fed an equal volume of standard enteral feeding. It should be noted that this decreased length of stay was realized with equivalent mortality compared with control groups, thus refuting Heyland’s bon mot that the decreased length of stay is related to increased mortality.
The animal record is clear: casein-based diets are immunosuppressive, delaying cardiac allograft rejection and T cell maturation and decreasing host resistance to either bacterial or fungal pathogens. Blinded surgical studies document the benefit of arginine-based diets for patients. Critical care studies fail to support the contention that arginine-based diets are harmful; in fact, if patients tolerate the feeding, the outcomes are beneficial compared with control groups, as in the surgical studies. Patients at high risk for infection or inadequate wound healing should be provided substrates required for maintaining normal host immunity.
Houston, Tex
REFERENCES
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