Clarissa Sumanting

NFS 2000

12 March 2018

Parenteral Nutrition Glutamine Supplementation

The American Society of Parenteral and Enteral Nutrition (A.S.P.E.N.) upholds the position that

parenteral nutrition of glutamine supplementation can benefit specific patient populations.1 A.S.P.E.N.

also states their opinion of supporting an FDA-approved commercial solutions of parenteral glutamine

dipeptides to be used clinically and prescribed with professional judgement.1

Vanek et al1, collectively known as the Parenteral Glutamine Working Group, had formed this

position paper to be presented and approved by the A.S.P.E.N Board of Directors. This paper consists of

information about parenteral glutamine supplementation from published meta-analyses, clinical

guidelines, review articles and original articles that were found using a PubMed search of parenteral

glutamine.

Vanek et al1 presents several studies of the outcomes and effects of parenteral glutamine

supplementation in the following six groups: (1) critically ill patients, (2) surgical patients, (3) bone

marrow transplant patients, (4) infants, (5) acute pancreatitis patients, and (6) other patient

populations. In addition to these studies, the Parenteral Glutamine Working Group also briefly explains

the difficulty of the US obtaining an FDA approved commercially available parenteral free L-glutamine

solution.

The first group of studies that are reviewed for the effectiveness of PN glutamine

supplementation are that of critically ill patients. Three published meta-analyses have contributed to

this group. The first meta-analysis consisted of a combination of both surgical and critically ill patients.

Although the evidence of improved mortality and infectious incidences were not statistically significant,
the meta-analysis did exhibit a significantly shorter length of stay in the hospital in patients that

received PN glutamine supplementation. 1

Critically ill patients illustrated, in subgroup analysis, a reduction in mortality and infections but

no significant change in hospital length of stay. The route used and dose amounts of glutamine

supplementation were also studied in subgroup analysis, showing a significant decrease in mortality and

hospital LOS when glutamine was taken parenterally compared to an enteral route. A reduction in

infectious complications, hospital LOS and mortality was apparent in patients who had received a higher

dose of glutamine supplementation of more than 0.2 g/kg/day.2 Patients who received a low dose of

glutamine supplementation of less than 0.2g/kg/day had insignificant differences in LOS, infectious

complications and mortality.2 The second meta-analysis separated the studies into surgical patients,

critically ill patients, and a combination of both. The study involving critically ill patients showed no

important differences in regards to occurrences of infections or mortality. The last meta-analysis

involved critically ill patients on mechanical ventilation that did display a major decrease in infections,

hospital mortality and hospital LOS and no influence of mortality for those who received

supplementation through enteral means.1

The second group in which the usefulness of PN glutamine supplementation was reviewed is

surgical patients. The literature consisted of five meta-analyses that had several positive outcomes to

receiving glutamine parenterally. According to Vanek et al1, there was a significant decline in infections

in all five meta-analyses, a significantly shorter length of stay in the hospital in four meta-analyses, and a

notable cut in hospital costs in one meta-analysis.

Parenteral glutamine supplementation in bone marrow transplant patients was the next group

studied. Although Vanek et al1 stated that a Cochrane Review specified that there was no substantial

clinical evidence that bone marrow transplant patients can benefit from PN glutamine supplementation,
A.S.P.E.N. and ESPEN, European Society for Clinical Nutrition and Metabolism, both state that these

patients may benefit from supplementation. A meta-analysis study did demonstrate a shorter hospital

LOS and a smaller number of positive blood cultures. The remaining studies that the A.S.P.E.N. and

ESPEN guidelines based their recommendation on revealed conflicting outcomes. For example, one

study illustrated a decrease in morbidity, hospital LOS and an improvement in one’s nitrogen balance,

resulting in A.S.P.E.N.’s supportive recommendation of PN glutamine supplementation. These positive

results differ from a study that showed an increase in mortality, narcotics use, relapses, and severity of

mucositis.3

The review of PN glutamine supplementation in infants was based upon only two meta-

analyses. Each of these studies showed no significant difference in infections, hospital mortality, hospital

LOS, or necrotizing enterocolitis incidences. This resulted in a lack of clinical guidelines for PN glutamine

supplementation in pediatric and neonatal patients.

The influence of PN glutamine supplementation in patients with acute pancreatitis was

demonstrated in one meta-analysis that comprised of only three small studies. Each of these studies

displayed a decrease of general complications from receiving glutamine supplementation parenterally.

All three studies had a reduction in hospital LOS but this result was considered statistically insignificant

because of the very few patients in the study. A study did exhibit a notable decline in total

complications, from 20% (4/20) vs. 52% (11/21), and pancreatic infection, from 0% (0/20) vs. 24%

(5/21).4 Another study separated and randomized 80 patients that had severe acute pancreatitis. Each

group was intravenously given 20 g of alanyl-glutamine dipeptide but either on the day the patient was

admitted or five days after admission. The group that was treated early showed a reduction in infection

rate, hospital stay, operation rate and mortality.5 In addition to these results, the early treatment group

also displayed a shorter duration of renal failure, acute respiratory distress syndrome, acute hepatitis,

shock and encephalopathy.5

 The last group in which PN glutamine supplementation was observed consisted of a group of

varying patient populations, such as burn patients and patients with gastrointestinal diseases. Vanek et

al1 states that both of these patient groups do not have published clinical guidelines due to a lack of

sufficient data that states any benefits PN glutamine supplementation may have for either of these

patients. Though this is true, a selection of randomized controlled trials of burn patients receiving PN

supplementation was reviewed and concluded that an improvement in mortality, morbidity and hospital

LOS was possible with this supplementation.

The Parenteral Glutamine Working Group briefly described the inability of the US procuring a

commercially available parenteral free L-glutamine due to the specific procedures one must follow.

Vanek et al1 explained that compounded glutamine solutions need to be cold sterilized and must be

compounded in an ISO Class 5 environment to reduce any possible bacterial contamination. A certificate

of analysis and a micron filter of 0.22 is also used. Despite the commercially available parenteral

glutamine dipeptide products outside of the US, licensed pharmacies do have the ability to compound

free L-glutamine as either part of a solution containing amino acids or a its own IV solution.1

Based upon the collection of literature that was reviewed and put together by Vanek et al1,

RDNs may be able to use this information to better serve critically ill patients who are under metabolic

stress and could benefit from PN glutamine supplementation. Specifically, Vanek et al1 had stressed that

research had shown that 0.5 g/kg/day of glutamine supplementation may be an ideal dose for patients

in order to see a decrease of complications. With this presented information, I agree with the position

paper in that parenteral nutrition of glutamine supplementation can benefit specific patient

populations, especially critically ill and surgical patients. I do believe that more studies and randomized

controlled trials are needed to understand more about PN glutamine supplementation specifically in

pediatric patients.
 References

1. Vanek VW, Matarese LE, Robinson M, Sacks GS, Young LS, Kochevar M. Parenteral Nutrition
Glutamine Supplementation. Nutrition in Clinical Practice. 2011;26(4):479-494.
2. Novak F, Heyland DK, Avenell A, Drover JW, Su X. Glutamine supplementation in serious illness:
a systematic review of the evidence. Crit Care Med. 2002;30(9):2022-2029.
3. Pytlik R, Benes P, Patorkova M, et al. Standardized parenteral alanyl-glutamine dipeptide
supplementation is not beneficial in autologous transplant patients: a randomized, double-blind,
placebo controlled study. Bone Marrow Transplantation. 2002;30: 953-961.

4. Xian-li H, Qing-jiu M, Jian-guo L, Yan-kui C, Xi-lin D. Effect of total parenteral nutrition (TPN) with
and without glutamine dipeptide supplementation on outcome in severe acute pancreatitis (SAP).
Clin Nutr Suppl. 2004;1:43-47.
5. Xue P, Deng LH, Xia Q, et al. Impact of alanylglutamine dipeptide on severe acute pancreatitis in
early stage. World J Gastroenterol. 2008;14:474-478.