Glutamine supplementation of parenteral nutrition does not improve intestinal permeability, nitrogen balance, or outcome in newborns and infants undergoing digestive-tract surgery: results from a double-blind, randomized, controlled trial

Abstract

Objective: To assess the effect of isocaloric isonitrogenous parenteral glutamine supplementation on intestinal permeability and nitrogen loss in newborns and infants after major digestive-tract surgery.

Summary background data: Glutamine supplementation in critically ill and surgical adults may normalize intestinal permeability, attenuate nitrogen loss, improve survival, and lower the incidence of nosocomial infections. Previous studies in critically ill children were limited to very-low-birthweight infants and had equivocal results.

Methods: Eighty newborns and infants were included in a double-blind, randomized trial comparing standard parenteral nutrition (sPN; n = 39) to glutamine-supplemented parenteral nutrition (GlnPN; glutamine target intake, 0.4 g kg day; n = 41), starting on day 2 after major digestive-tract surgery. Primary endpoints were intestinal permeability, as assessed by the urinary excretion ratio of lactulose and rhamnose (weeks 1 through 4); nitrogen balance (days 4 through 6), and urinary 3-methylhistidine excretion (day 5). Secondary endpoints were mortality, length of stay in the ICU and the hospital, number of septic episodes, and usage of antibiotics and ICU resources.

Results: Glutamine intake plateaued at 90% of the target on day 4. No differences were found between patients assigned sPN and patients assigned GlnPN regarding any of the endpoints. Glutamine supplementation was not associated with adverse effects.

Conclusions: In newborns and infants after major digestive-tract surgery, we did not identify beneficial effects of isonitrogenous, isocaloric glutamine supplementation of parenteral nutrition. Glutamine supplementation in these patients therefore is not warranted until further research proves otherwise.

FIGURE 1. Flow chart including primary endpoints. PN, parenteral nutrition; 3-MH, 3-methylhistidine.

FIGURE 2. Intake of nitrogen (left panel) and nonprotein calories (right panel) on days 2 to 6 after surgery, as a percentage of the target (mean ± SEM). Open circles, patients assigned sPN; closed circles, patients assigned GlnPN. Note that in patients assigned GlnPN, nitrogen intake values equal glutamine intake values.

FIGURE 3. Cumulative TISS (mean ± SEM) from days 0 through 31 after surgery. Open circles, patients assigned sPN; closed circles, patients assigned GlnPN. Note that patients discharged from the ICU have a daily TISS of zero.