Glutamine is the most abundant amino acid in the body and has been considered non-essential in the past because it can be synthesised de novo. However, during stress and catabolic conditions such as multiple trauma and critical illness, the demand for glutamine increases and its concentration in plasma and muscle falls dramatically. Therefore, glutamine has been re-classified as an essential amino acid under such conditions.
The purpose of this thesis is to elucidate the importance of glutamine supplementation in multiple trauma patients. To do this, the thesis attempts to answer the following questions: “What is the effect of intravenous alanyl-glutamine (Ala-Gln) supplementation in multiple trauma patients receiving enteral nutrition?” and “Does introducing Ala-Gln supplementation as routine practice in critically ill patients affect the current practice of intravenous drug and fluid continuous infusion administration?”. In addition, there are currently limited compatibility studies of Ala-Gln with different drugs and continuous infusions. To address these issues, a narrative review and three studies were conducted.
The narrative review (first objective) was conducted to appraise previous trials that have been conducted specifically to investigate the effect of glutamine supplementation in adult multiple trauma patients, including patients with head injury. The review also developed recommendations for future investigations of glutamine supplementation in this homogenous group of patients.
A prospective observational study (second objective) was conducted to describe the types of central venous access, the use of this access and to evaluate the practice of administering drug and fluid continuous infusions through central venous catheters (CVCs). In this study, which involved 39 critically ill patients, more patients had three-lumen CVCs than four-lumen or peripherally-inserted CVCs (67%, 28%, 5% respectively). All the patients received at least three continuous drug or fluid infusions via the CVC. Only 10% of patients had one unused lumen available for an additional infusion. Fifteen per cent of patients had co-administration of continuous infusions with no information on compatibility. The use of four-lumen catheters is suggested in patients who are expected to receive numerous drug and fluid continuous infusions. However, this should be balanced against the potential risk of infection. More compatibility studies are required for different drug combinations used in the ICU.
The third objective was to investigate the physical and chemical compatibility of Ala-Gln with select antibiotics and drug continuous infusions used in the ICU during simulated Y-site injection. To simulate the Y-site administration of infusions, a 50:50 mix of each drug with Ala-Gln was used. The physical compatibility was investigated by a visual method, and the chemical compatibility by high-performance liquid chromatography during the 60 minutes after mixing. Ala-Gln was found to be physically and chemically compatible with meropenem, cephalothin, doripenem, piperacillin, ciprofloxacin, ceftriaxone, fluconazole, frusemide, propofol, adrenaline, noradrenaline and midazolam (1 mg/mL) for at least 60 minutes at room temperature. Ala-Gln was physically incompatible with midazolam (2 mg/mL and 5 mg/mL). The chemical incompatibility of midazolam (5 mg/mL) with Ala-Gln was confirmed. Midazolam at concentrations of 2 and 5 mg/mL should not be administered simultaneously with Ala-Gln through the same lumen.
The fourth objective was to conduct a triple-blinded, randomised, controlled clinical trial of the effect of intravenous Ala-Gln supplementation on organ failure, infectious complications and body composition in multiple trauma patients receiving enteral nutrition. Participants were randomly allocated (block-randomisation) to receive either intravenous Ala-Gln (0.5 g/kg body weight; n = 14) or intravenous placebo (n = 14). The primary outcome, which was the pattern of change in total Sequential Organ Failure Assessment (SOFA) score from day 2 to day 11 (over 10 days), was not significantly different between groups (intention-to-treat: regression coefficient 0.4938, 95% CI = −0.8113 – 1.7988, p = 0.46; per protocol: regression coefficient 0.7220, 95% CI = −0.9758 – 2.4197, p = 0.41). Although there was no significant difference reported in infectious complications with Ala-Gln supplementation, there was a slight reduction in ventilator-associated pneumonia (VAP) cases (2 vs. 6; p = 0.21). Similarly, there were no significant differences in other secondary outcome measures (number of days of antibiotic use, number of ventilator-free days, ICU and hospital length of stay, protein levels, albumin levels and lymphocyte count). However, there was a significant increase in urea (p = 0.001) and creatinine (p = 0.01) levels in the Ala-Gln group. There was no significant difference in fat-free mass percentage (p = 0.12) or fat mass percentage (p = 0.12) between groups. Although there was a significant overall decrease in fat-free mass percentage over time in both groups (p = 0.002), the rate of decline in the Ala-Gln group was slower, suggesting a beneficial effect. Overall, the beneficial effect of intravenous Ala-Gln was not confirmed in this trial possibly due to a type II error. A rigorous, multicentre trial is needed to confirm the efficacy of intravenous Ala-Gln supplementation in preserving lean body mass, and reducing VAP and infectious complications in multiple trauma patients receiving enteral nutrition. Furthermore, the significant increase in urea and creatinine levels suggests further investigation about the safety of glutamine supplementation on renal function.