Efficacy and Safety of Glutamine-supplemented Parenteral Nutrition in Surgical ICU Patients: An American Multicenter Randomized Controlled Trial

Abstract

Objective: To determine whether glutamine (GLN)-supplemented parenteral nutrition (PN) improves clinical outcomes in surgical intensive care unit (SICU) patients.

Summary background data: GLN requirements may increase with critical illness. GLN-supplemented PN may improve clinical outcomes in SICU patients.

Methods: A parallel-group, multicenter, double-blind, randomized, controlled clinical trial in 150 adults after gastrointestinal, vascular, or cardiac surgery requiring PN and SICU care. Patients were without significant renal or hepatic failure or shock at entry. All received isonitrogenous, isocaloric PN [1.5 g/kg/d amino acids (AAs) and energy at 1.3× estimated basal energy expenditure]. Controls (n = 75) received standard GLN-free PN (STD-PN); the GLN group (n = 75) received PN containing alanyl-GLN dipeptide (0.5 g/kg/d), proportionally replacing AA in PN (GLN-PN). Enteral nutrition (EN) was advanced and PN weaned as indicated. Hospital mortality and infections were primary endpoints.

Results: Baseline characteristics, days on study PN and daily macronutrient intakes via PN and EN, were similar between groups. There were 11 hospital deaths (14.7%) in the GLN-PN group and 13 deaths in the STD-PN group (17.3%; difference, -2.6%; 95% confidence interval, -14.6% to 9.3%; P = 0.66). The 6-month cumulative mortality was 31.4% in the GLN-PN group and 29.7% in the STD-PN group (P = 0.88). Incident bloodstream infection rate was 9.6 and 8.4 per 1000 hospital days in the GLN-PN and STD-PN groups, respectively (P = 0.73). Other clinical outcomes and adverse events were similar.

Conclusions: PN supplemented with GLN dipeptide was safe, but did not alter clinical outcomes among SICU patients.

Trial registration: ClinicalTrials.gov NCT00248638.

Figure 1. CONSORT diagram

The progress through the phases (enrollment, intervention allocation, follow-up and data analysis) of a double-blind, randomized controlled trial in surgical intensive care unit (SICU) patients requiring parenteral nutrition (PN) comparing standard, glutamine (GLN)-free PN (STD-PN) with PN supplemented with alanyl-GLN dipeptide (GLN-PN) are shown.

Figure 2. A. Administration of amino acids (AA; g/kg/day) from study PN, shown as median and 25^th and 75^th percentiles, during the initial 14 days after entry

Intake was similar between the STD-PN and GLN-PN groups, and also for the entire 28-day period of observation (not shown). B. Study PN kcal intake, shown as median and 25^th and 75^th percentiles. Intake was similar between the STD-PN and GLN-PN groups during the initial 14 days and also for the entire 28-day period of observation (not shown). The steady decrease in study PN AA and kcal over time reflected the GLND standard of care protocol for weaning from PN to EN as tolerated.

Figure 2. A. Administration of amino acids (AA; g/kg/day) from study PN, shown as median and 25^th and 75^th percentiles, during the initial 14 days after entry

Intake was similar between the STD-PN and GLN-PN groups, and also for the entire 28-day period of observation (not shown). B. Study PN kcal intake, shown as median and 25^th and 75^th percentiles. Intake was similar between the STD-PN and GLN-PN groups during the initial 14 days and also for the entire 28-day period of observation (not shown). The steady decrease in study PN AA and kcal over time reflected the GLND standard of care protocol for weaning from PN to EN as tolerated.

Figure 3. Plasma glutamine (GLN) concentrations over time

Mean plasma GLN concentrations were in the low to low-normal range at entry in both groups (44). With GLN-PN, plasma GLN levels rose significantly (≈30%) by day 3 but were unchanged in the STD-PN group. Plasma GLN concentrations remained significantly higher in the GLN-PN group compared to the STD-PN subjects through day 14. With STD-PN, plasma GLN levels rose slowly over time.

Figure 4. Kaplan-Meier cumulative mortality curve through 6 months after entry

There were no differences in mortality between the STD-PN and the GLN-PN groups over time.