Key Point

Use of glutamine in critically ill ICU patients for whom parenteral nutrition is prescribed is supported in the medical literature.

ORLANDO—Traditionally, glutamine is thought of as a metabolic fuel or a nonessential amino acid. Yet, for the critically ill, parenteral glutamine is a lifesaving “drug” that has been shown to significantly impact rates of infection and mortality, said Paul Wisch­meyer, MD, Director of Nutrition Support Services and Associate Professor of Anesthesiology at the University of Colorado Health Sciences Center, Denver, and the new editor of JPEN, Journal of Parenteral and Enteral Nutrition. His lecture outlining the positive effects of glutamine was part of a “pro/con” series (see also “Glutamine Use Cautioned Against,” page 14) presented at the Society of Critical Care Medicine annual meeting.

“Possible mechanisms for why glutamine is beneficial to critically ill patients include tissue protection, preservation of metabolism, attenuation of oxidant stress, and anti-inflammatory effects on the basic genetic level,” Dr. Wischmeyer noted. Furthermore, he added, most human studies support the use of glutamine in the critically ill, with results pertaining to “clinically relevant end points,” namely, survival, infection, and length of stay.

SORTING THROUGH THE LITERATURE

Dr. Wischmeyer cited a double-blind trial by Garrel and colleagues that involved 45 patients with severe burns. Patients were randomized to receive enteral gluta­mine or an isonitrogenous control mixture until complete healing occurred.

Positive blood culture was three times more frequent in controls than in patients who received glutamine treatment. Pseudo­monas aeruginosa was detected in six patients in the control group versus zero patients in the glutamine group. The mortality rate was significantly lower in the glutamine group than in controls: Two patients versus 12 patients, respectively, died in the intention-to-treat analysis, and zero versus eight died in the protocol analysis. Although length of hospital stay was not significantly different between the two groups in this study, other research has found that glutamine supplementation reduces length of stay, particularly among surgical patients.

A recently published trial by Dechelotte et al involving 114 trauma and surgical ICU patients showed that parenteral glutamine supplementation nutrition led to a statistically significant decrease in infectious complications and insulin resistance in critically ill patients.

In contrast, a study by Hall and colleagues did not show such benefits of gluta­mine administration. A total of 363 patients on mechanical ventilation—85 of whom were trauma patients—were randomized to 20 grams per day of enteral glutamine or an isocaloric and isonitrogenous control solution. As there were no statistically significant between-group differences in six-month mortality and severe sepsis rates, the study authors did not support the use of glutamine supplements for the critically ill.

Dr. Wischmeyer noted that the patients in this trial were not particularly sick, as evidenced by their low APACHE scores. He added that both the Garrel and the Hall studies had methodological flaws, including comparison of glutamine to an active control solution instead of to placebo. In addition, glutamine was given enterally at far too low a dose to show efficacy. “Human dosing studies show that enteral administration of glutamine is not as effective in increasing plasma levels over time as intravenous administration, which has a very dramatic effect,” Dr. Wisch­meyer stated.

“Most importantly, however, there is no study of glutamine to show evidence of harm,” Dr. Wischmeyer pointed out. For example, results of a single-center, open-label, dose-escalating clinical trial of glutamine and antioxidants, conducted by Heyland and associates, showed no adverse events attributable to the study nutrients.

UPDATED GUIDELINES, UPCOMING TRIALS

The Canadian Clinical Practice Guidelines for Nutrition Support, which were updated in January, reflect the growing evidence to support glutamine therapy. “Parenteral supplementation with glutamine, when parenteral nutrition is prescribed to critically ill patients, is clearly recommended: If you are not doing that, I would say that you are outside the standard of care,” Dr. Wischmeyer stated. In addition, the guidelines stress early initiation of enteral nutrition (ie, within 24 to 48 hours of ICU admission).

The REDOXS (REducing Deaths due to OXidative Stress) study,10 which was scheduled to commence in March, may help to shed more light on the subject, Dr. Wisch­meyer said. A total of 1,200 mechanically ventilated adult patients with severe organ dysfunction randomized to glutamine therapy, antioxidant therapy, glutamine and antioxidant therapy, or placebo are expected to be enrolled in this multicenter trial. The primary outcome is 28-day mortality; secondary outcomes are length of ICU stay, length of hospital stay, complications of infection, multiple organ dysfunction, duration of mechanical ventilation, and health-related quality of life at three and six months.           

—Adriene Marshall

Suggested Reading
Wischmeyer P, Buchman A. Pro/con: glutamine in critically ill patients. Presented at: 36th Critical Care Congress of the Society of Critical Care Medicine; February 19, 2007; Orlando, Florida.
Wischmeyer PE. The glutamine story: where are we now? Curr Opin Crit Care. 2006;12:142-148.
Garrel D, Patenaude J, Nedelec B, et al. Decreased mortality and infectious morbidity in adult burn patients given enteral glutamine supplements: a prospective, controlled, randomized clinical trial. Crit Care Med. 2003;31:2444-2449.
Novak F, Heyland DK, Avenell A, et al. Glutamine supplementation in serious illness: a systematic review of the evidence. Crit Care Med. 2002;30:2022-2029.
Dhaliwal R, Heyland DK. Nutrition and infection in the intensive care unit: what does the evidence show? Curr Opin Crit Care. 2005;11:461-467.
Dechelotte P, Hasselmann M, Cynober L, et al. L-alanyl-L-glutamine dipeptide-supplemented total paren­teral nutrition reduces infectious complications and glucose intolerance in critically ill patients: the French controlled, randomized, double-blind, multicenter study. Crit Care Med. 2006;34:598-604.
Hall JC, Dobb G, Hall J, et al. A prospective randomized trial of enteral glutamine in critical illness. Intensive Care Med. 2003;29:1710-1716.
Heyland DK, Dhaliwal R, Day A, et al. Optimizing the dose of glutamine dipeptides and antioxidants in critically ill patients: a phase I dose-finding study. JPEN J Parenter Enteral Nutr. 2007;31:109-118.
Critical Care Nutrition. Available at: www.criticalcarenutrition.com. Accessed March 13, 2007.
Heyland DK, Dhaliwal R, Day AG, et al, for the Canadian Critical Care Trials Group. REducing Deaths due to OXidative Stress (the REDOXS© study): rationale and study design for a randomized trial of glutamine and antioxidant supplementation in critically-ill patients. Proc Nutr Soc. 2006;65:250-263.

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