Efficacy of parenteral nutrition supplemented with glutamine dipeptide to decrease hospital infections in critically ill surgical patients

Abstract

Background: Nosocomial infections are an important cause of morbidity and mortality in the surgical intensive care unit (SICU). Clinical benefits of glutamine-supplemented parenteral nutrition may occur in hospitalized surgical patients, but efficacy data in different surgical subgroups are lacking. The objective was to determine whether glutamine-supplemented parenteral nutrition differentially affects nosocomial infection rates in selected subgroups of SICU patients.

Methods: This was a double-blind, randomized, controlled study of alanyl-glutamine dipeptide-supplemented parenteral nutrition in SICU patients requiring parenteral nutrition and SICU care after surgery for pancreatic necrosis, cardiac, vascular, or colonic surgery. Subjects (n = 59) received isocaloric/isonitrogenous parenteral nutrition, providing 1.5 g/kg/d standard glutamine-free amino acids (STD-PN) or 1.0 g/kg/d standard amino acids + 0.5 g/kg/d glutamine dipeptide (GLN-PN). Enteral feedings were advanced as tolerated. Nosocomial infections were determined until hospital discharge.

Results: Baseline clinical/metabolic data were similar between groups. Plasma glutamine concentrations were low in all groups and were increased by GLN-PN. GLN-PN did not alter infection rates after pancreatic necrosis surgery (17 STD-PN and 15 GLN-PN patients). In nonpancreatic surgery patients (12 STD-PN and 15 GLN-PN), GLN-PN was associated with significantly decreased total nosocomial infections (STD-PN 36 vs GLN-PN 13, P < .030), bloodstream infections (7 vs 0, P < .01), pneumonias (16 vs 6, P < .05), and infections attributed to Staphylococcus aureus (P < .01), fungi, and enteric Gram-negative bacteria (each P < .05).

Conclusions: Glutamine dipeptide-supplemented parenteral nutrition did not alter infection rates following pancreatic necrosis surgery but significantly decreased infections in SICU patients after cardiac, vascular, and colonic surgery.

Figure 1

Plasma glutamine (GLN) concentrations: Patients in the pancreatic necrosis surgery subgroup (n = 32) demonstrated significantly higher mean baseline plasma GLN concentrations than patients in the nonpancreatic (n = 27) surgery subgroup (457 ± 22 vs 385 ± 20; t test P < .05). Plasma GLN levels did not change from baseline to day 8 of study in the subjects in either surgical subgroup who received standard, GLN-free parenteral nutrition (PN). However, subjects who received GLN-PN demonstrated a significant increase of plasma GLN into the normal range. *P < .07.

Figure 2

Total nosocomial infections. The total number of hospital-acquired infections was determined from the day of study PN initiation until hospital discharge, as outlined in the methods. The total number of nosocomial infections was unchanged with GLN-PN in patients who underwent pancreatic necrosis surgery but was markedly decreased in patients given GLN-PN after cardiac, abdominal vascular, or colonic surgery compared with patients in this subgroup given STD-PN (3-fold; Poisson regression P value = .030). Interaction P value = .190. Number of patients in each group is shown.

Figure 3

Bloodstream infections (BSIs): Positive blood cultures for bacterial or fungal species during hospitalization did not occur in 15 surgical intensive care unit patients given glutamine-supplemented parenteral nutrition (GLN-PN) after cardiac, abdominal vascular, or colonic surgery compared with 5 of 12 patients (42%) in this subgroup given standard glutamine-free parenteral nutrition (STD-PN), who developed 7 BSIs (Fisher exact test P = .010). There were no differences in the number of BSIs between study groups in the pancreatic surgery cohort (STD-PN 18% [n=17] vs GLN-PN 27% [n=15]; P = .687). Breslow-Day interaction test P = .011.

Figure 4

Hospital mortality. There were no hospital deaths after pancreatic surgery: standard glutamine-free parenteral nutrition (STD-PN; n = 17) vs glutamine-supplemented parenteral nutrition (GLN-PN; n = 15). In contrast, in the nonpancreatic surgery cohort, 5 of 12 patients in the STD-PN group developed sepsis-associated acute respiratory distress syndrome and died (42%), compared with only 1 death in 15 patients in this subgroup randomized to GLN-PN (7%; Fisher exact test P = .060). Breslow-Day interaction test was not possible because there were no hospital deaths after pancreatic surgery.

Figure 5

D-xylose absorption studies. D-xylose tests were done in a total of 27 patients: 16 in the pancreatic necrosis surgery subgroup (n = 7 STD-PN and 9 GLN-PN) and 11 in the nonpancreatic surgery subgroup (n =5 STD-PN and 6 GLN-PN). D-xylose absorption indices (2-hour serum value and 5-hour urinary excretion) were below the normal range after a 25-g enteral D-xylose load in the total group of 27 patients studied. Serum values for D-xylose at 2 hours after administration were significantly higher in patients given GLN-PN vs STD-PN (t test P = .033). Pancreatic necrosis patients did not demonstrate differences between the 2 study groups for 2-hour serum D-xylose concentrations or 5-hour urinary D-xylose excretion (not shown). In nonpancreatic surgery patients, 5-hour urinary D-xylose excretion was similar between study groups. However, the 2-hour serum D-xylose concentration was markedly higher with GLN-PN than with STD-PN (P = .001).