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Parenteral glutamine supplementation improves serum albumin levels in cancer surgery patients

Parenteral glutamine supplementation improves serum albumin levels in cancer surgery patients. The study showed that perioperative parenteral supplementation of glutamine is dose-dependent on the recovery of serum albumin levels in patients after gastrectomy, which means postoperative nutritional suppression and improvement of stress-related inflammation.

Foreword:

Patients with gastric adenocarcinoma often suffer from malnutrition. Surgery can aggravate the deterioration of nutritional status and adversely affect the prognosis. Glutamine is the most abundant non-essential amino acid in plasma and tissues. It participates in various biological processes such as nitrogen balance, immune system regulation and nitrogen metabolism. It is the preferred energy source for rapidly proliferating cells (such as immune cells and mucosal cells).

However, in critically ill or hypermetabolized patients, glutamine is significantly depleted, resulting in intestinal barrier dysfunction, wound healing disorders and negative nitrogen balance. Jin-Ming Wu from National Taiwan University Hospital and others studied whether parenteral supplementation of glutamine can improve the nutritional status and prognosis of patients. The results were published in Clinical Nutrition in 2020.

Methods:

This retrospective single-center cohort study included patients with gastric adenocarcinoma who underwent gastrectomy at National Taiwan University Hospital from January 2007 to June 2019. Patients were divided into non-glutamine group or glutamine group. Use propensity score matching to minimize patient demographic bias.

The average parenteral glutamine dose from the day of surgery to the fourth day after surgery was calculated in g/kg/day. The adjusted model was used to compare the surgical results (length of hospitalization, major complications, and mortality) between the two groups, as well as the changes in lymphocyte count and serum albumin levels 7 days after surgery.

Results:

A total of 1950 patients were retrospectively analyzed, of which 522 (26.8%) received parenteral glutamine supplementation (glutamine dose was 0.05～0.49g/kg/day). Males accounted for 57.2% of the included patients, and the median age was 64.9 years. After matching, there were 478 cases in each group. There was no significant difference in surgical results and lymphocyte counts between the two groups.

Compared with the non-glutamine group, the serum albumin level decreased slightly in the glutamine group (-0.6 vs -1.1 g/dl; P<0.001). The adjusted matching model showed that the dose of glutamine can significantly increase the serum albumin level (coefficient=0.08/glutamine every 0.1g/day/kg; 95% confidence interval: 0.04~0.10; P<0.001).

Parenteral glutamine supplementation improves serum albumin levels in cancer surgery patients

Conclusion:

Perioperative parenteral glutamine supplementation has a dose-dependent effect on the recovery of serum albumin levels in patients after gastrectomy, suggesting that glutamine can improve postoperative nutritional suppression and reduce stress-related inflammation. Although supplementation of glutamine has nothing to do with the results of surgery, further research should be done to evaluate the clinical significance of serum albumin levels.

Expert Reviews

Glutamine is involved in metabolism, signal transduction and tissue repair, and is considered to be an important cell signaling molecule in the process of diseases and stress. The results of this study indicate that parenteral supplementation of glutamine in patients with gastric adenocarcinoma undergoing gastrectomy does not significantly affect the results of surgery, such as hospital stay, major complications, and mortality. However, the authors observed that glutamine had a dose-related effect on the recovery of postoperative serum albumin levels, but did not affect lymphocyte counts.

Large-scale gastrointestinal surgery causes high inflammation burden and impairs liver protein metabolism. In terms of albumin metabolism, serum albumin is affected by different physiological effects such as liver albumin synthesis, vascular permeability and interstitial volume. It has been found in most in vivo studies that albumin synthesis is increased after surgery. Therefore, leakage through capillaries and reduction of decomposition appear to be the main reason for parenteral glutamine supplementation to improve postoperative albumin reduction.

The improvement of liver function not only regulates synthetic processes, such as glycogen, fat and protein synthesis, but also reduces proteolysis mediated by the P38 mitogen-activated protein kinase signaling pathway. Supplementing glutamine in the rat model not only stimulates protein synthesis in skeletal muscle, but also inhibits protein degradation and related signaling pathways in this tissue.

In addition, it stimulates the synthesis of secreted and non-secreted proteins in the small bowel cells. In summary, these studies indicate that glutamine may play an important role in protein synthesis. It is worth noting that patients with advanced gastric adenocarcinoma have a higher incidence of malnutrition due to cancer cachexia, gastric obstruction and cancer-related bleeding. Another reason for supplementing glutamine to relieve the decrease in serum albumin levels after surgery may be related to the restoration of protein synthesis in malnourished gastric adenocarcinoma patients.

Although supplementation with glutamine can reverse hypoalbuminemia, it has no effect on the outcome of the surgery in this study. Changes in albumin levels during the perioperative period depend on the interaction between transcapillary escape rate (TER) and albumin synthesis. However, two recent studies have shown that plasma albumin concentration has little relationship with changes in albumin TER and synthesis, and provide different results in terms of postoperative time, operation type and changes in plasma volume. The underlying mechanism still needs further study .

A recent Meta analysis found that patients were stratified according to the type of elective surgery. Among patients undergoing low gastrointestinal surgery, supplementation with glutamine had better surgical outcomes (infection incidence and Length of hospitalization). This phenomenon still needs further research to clarify.

The study has several notable limitations. First of all, this is a retrospective study and is only conducted in a single institution. The results of the study may not be universal. Therefore, large-scale, prospective, randomized clinical trials are necessary to verify the relevance proposed in this article. Second, the preoperative serum glutamine level of the study population has not been obtained. Studies have suggested that glutamine deficiency is an independent predictor of mortality in intensive care unit patients.

In summary, this study shows that perioperative parenteral supplementation of glutamine is dose-dependent on the recovery of serum albumin levels in patients after gastrectomy, which means postoperative nutritional suppression and improvement of stress-related inflammation. Although glutamine supplementation is not significantly associated with surgical results, further studies are still needed to evaluate the clinical significance of serum albumin recovery.