|Year : 2020 | Volume
| Issue : 1 | Page : 57-62
Effects of early enteral glutamine supplementation on the outcome of severe burns: A randomized control study
Savita Arora1, Chandni Shankar2
1 Department of Burns Plastic and Maxillofacial Surgery, VMMC and Safdarjung Hospital, New Delhi, India
2 Department of Plastic Surgery, Kasturba Medical College, Manipal, Karnataka, India
|Date of Submission||18-Dec-2019|
|Date of Acceptance||01-Jun-2020|
|Date of Web Publication||21-May-2021|
Dr. Chandni Shankar
Assistant Professor, Department of Plastic Surgery, Kasturba Medical College, Manipal - 576 104, Udupi, Karnataka
Source of Support: None, Conflict of Interest: None
Context: Burns is a condition associated with high mortality and morbidity. Nutrition plays an important role in the recovery of these patients. Amino acid glutamine is an important energy substrate for immune cells and for the intestinal epithelium. Glutamine is the preferred respiratory fuel for both lymphocytes and enterocytes. It stimulates the immune system and prevents catabolism.
Aim: This study is aimed at determining if oral supplementation of glutamine can improve the outcome in patients with severe burns.
Materials and Methods: It is a randomized controlled study. Patients of severe burns (30%–50%) were randomized into two groups. The first group was started on enteral nutrition but without glutamine supplementation. The second group received enteral nutrition with glutamine supplementation. All patients were followed up for a period of 1 month from the day of burns. Blood culture, wound culture, blood counts, and serum total proteins were done once every week for all patients.
Statistical Analysis: Student's t-test was used to analyze the quantitative and Chi-square test was used to measure the qualitative data.
Results: One hundred and two patients were included in the study, of which 49 were in Group 1 and 53 patients in Group 2. The mean percentage of burns in the two groups was comparable at 40.71% and 41.72%, respectively. Total leukocyte counts, mean duration of hospital stay, and mortality rates did not show any statistically significant difference between the two groups. However, serum protein levels showed a significant increase in the glutamine-supplemented group from the 3rd week onward. Wound infection rates were also lower in the glutamine-supplemented group, i.e., 19.5% vs. 2.1% by the 4th week.
Conclusion: Glutamine supplementation has shown to enhance serum protein levels and hence improve nutritional status of these patients. It is also useful for its immunomodulatory effects, thus reducing burn wound infection, as shown by lesser number of burn wound culture positivity rates.
Keywords: Early enteral nutrition, glutamine, severe burns
|How to cite this article:|
Arora S, Shankar C. Effects of early enteral glutamine supplementation on the outcome of severe burns: A randomized control study. Indian J Burns 2020;28:57-62
|How to cite this URL:|
Arora S, Shankar C. Effects of early enteral glutamine supplementation on the outcome of severe burns: A randomized control study. Indian J Burns [serial online] 2020 [cited 2021 Dec 5];28:57-62. Available from: https://www.ijburns.com/text.asp?2020/28/1/57/316577
| Introduction|| |
Burns is a condition associated with high mortality and morbidity, especially in severe cases where >30% burns have been sustained by the patient. Despite improvements in therapeutic strategies, infection remains a serious problem in severely burned patients. The postburn period is characterized by a hypermetabolic state, which, if not met, results in visceral protein loss, impaired antibacterial host defenses, and delayed wound healing. Infections are due to decreased immune function in the patient and translocation of Gram-negative bacteria from the gut. Therefore, any strategy to boost the immune system of these patients should, in theory, be helpful in improving outcomes.
Glutamine is an important energy substrate for immune cells and for the intestinal epithelium. Glutamine is the preferred respiratory fuel for both lymphocytes and enterocytes. It stimulates the immune system and prevents catabolism. Glutamine has traditionally been classified as a nonessential amino acid because it can be endogenously synthesized in nearly all tissues. However, glutamine is an amino acid which can actually be termed as “conditionally essential.” Because glutamine is an important energy source for the gut mucosa and it is a principal fuel substrate for enterocytes, 20%–30% of circulating glutamine is extracted by the small intestine. In metabolic stress, demand by the liver, kidney, and intestinal tract outstrips peripheral production and release, and therefore, plasma levels decrease rapidly. Due to severe catabolism, in burn injury, glutamine stores become depleted and biosynthetic pathways frequently cannot meet the increased demands of the glutamine metabolizing tissues. Glutamine thus becomes a conditionally essential amino acid. Burn injury is known to markedly deplete glutamine which may increase the incidence of gut atrophy and immune dysfunction and potentially increase the incidence of Gram-negative bacteremia.,
Because of glutamine's important roles in energy and protein metabolism and in nucleotide synthesis and its postulated protection against sepsis, our study is aimed at evaluating the improvements in outcomes, if any, by administering enteral glutamine supplementation in severe burn cases.
| Materials and Methods|| |
The study was conducted at a tertiary care burns referral unit. It was a randomized controlled study by design. Institutional ethics committee clearance was obtained before the commencement of the study (Serial No. IEC/VMMC/SIH/Thesis/Nov-13/32). Over a duration of 18 months, a total of 102 patients of severe burns were included in this study. These patients were managed as per the present standard of burn care along with initiating early enteral nutrition (within 24 h of burns) and were randomized by the envelope method into two study groups. The first group was started on enteral nutrition but without glutamine supplementation. The second group received enteral nutrition with glutamine supplementation. All patients were followed up for a period of 1 month from the day of burns.
Patients included in the study were aged between 18 and 60 years who had suffered thermal burns and/or electrical burns and the total surface area of burns was between 30% and 50%.
The mortality that occurred within 72 hours of sustaining burns (patients who expired within 72 hours of sustaining burns cannot be attributed to infections) were excluded from the study. Patients with comorbid illness including diabetes mellitus, renal disease, or cardiopulmonary disease which could adversely affect the outcome were excluded from the study. Pregnant women were also not included in the study. Any patient being admitted >24 h after sustaining burns (as primary admission or as a referral from other centers) was also excluded from the study.
Written informed consent was taken from all patients. Oral/enteral nutrition was started in all patients (both the groups) as early as possible (within 24 h of burns). Energy requirements were calculated using the modified Curreri formula: (25 × wt. [kg] + 20 × % of burns). The patients in Group 2 were given a glutamine supplementation of 0.5 g/kg/day (in powder form which was mixed in water or milk and given orally) over and above the energy requirement as calculated by the Curreri formula. This glutamine supplementation was continued for the whole duration of the patient follow-up.
Blood culture, wound culture, blood counts, and serum total proteins were done once every week for all patients included in the study. The data of each patient were pooled and tabulated using Microsoft excel. Developer SPSS Inc Chicago USA was used to analyze the data. Student's t-test was used to analyze the quantitative data, i.e., total leukocyte counts, serum total protein levels, and number of days of hospital stay. Moreover, Chi-square test was used to measure the qualitative data, i.e., number of positive blood cultures and positive wound cultures. Repeated measure analysis was used to analyze data over a 4-week follow-up.
| Results|| |
A total of 102 patients were included in the study, of which 49 were in Group 1, i.e., severe burn patients not given glutamine supplementation. Moreover, 53 patients were in Group 2, i.e., severe burn patients who were given glutamine supplementation.
The study participants included 51 males and 51 females. Most burns were due to fire i.e deep thermal burns (90.2%), 2 (2%) cases were due to electrical contact and flash burns, 5 (4.9%) cases were electric flash burns, and 3 (2.9%) were scalds [Table 1].
Gender and age distribution between the two groups were comparable. The patient distribution based on the cause of burns, however, showed that all 7 cases of electrical contact and/or flash burns were in Group 1. However, majority of the cases being thermal burns in nature, there was no statistically significant difference in distribution of cases between the groups [Table 1].
The mean percentage of burns in the two groups was comparable, i.e., in Group 1, it was 40.71%, and in Group 2, it was 41.72% [Table 2].
It was seen that the total leukocyte counts over the 4 weeks of the study, between the two groups, dropped steadily, with slightly lower corresponding values in Group 1 [Table 3]. The graphs were almost parallel between the two groups. The P value was not statistically significant in any of the 4 weeks [Figure 1].
|Table 3: Total leukocyte count (mean) over the 4 weeks in the two groups|
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The serum total protein levels in Group 1 showed a steady decrease in the levels, whereas in Group 2, the levels dropped slightly in the 2nd week, followed by a rise again in the 3rd week, the difference between the groups becoming statistically significant by the 4th week [Table 4] and [Figure 2]. The P value in the first 3 weeks was statistically insignificant but in the 4th week, P = 0.004, being statistically significant.
The mean duration of hospital stay between the two groups of patients was similar, being 18.8 and 18.96 days in Groups 1 and 2, respectively. The P value was 0.984, which is statistically insignificant.
There were 13 deaths in the study group: 8 out of 49 patients in Group 1 and 5 out of 53 patients in Group 2. The statistical analysis, however, did not show significance as P value was 0.297.
The wound cultures in weeks 1 and 2 showed no statistical difference between the groups, with positive wound culture seen in 40.8% and 39.6% in Groups 1 and 2, respectively, in week 1. 55.8% and 46.0% culture positive rates were seen in Groups 1 and 2, respectively, during week 2 [Table 5] and [Figure 3].
|Figure 3: Percentage of positive cultures among the two groups on weekly wound swab cultures|
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However, in weeks 3 and 4, they were statistically significant. There was a positive wound culture seen in 31.7% and 12.5% in Groups 1 and 2, respectively, in week 3 of the study, P value being 0.028. In week 4, positive wound cultures were seen in 19.5% and 2.1% in Groups 1 and 2, respectively. The P value was 0.007 and hence statistically significant [Table 5] and [Figure 3].
In this study, it was seen that the blood culture positivity rates between the two groups were comparable, with no statistically significant difference in the first 3 weeks of the study. There was no growth seen in the 4th week in either group. In week 1, there was a positive blood culture seen in 24.5% and 17% of patients in Groups 1 and 2, respectively. In week 2, it dropped to 16.3% and 10%, followed by a further drop to 4.9% and 2.1% of patients in Groups 1 and 2, respectively, in week 3. In week 4, none of the blood cultures were positive in either group [Table 6] and [Figure 4].
|Figure 4: Percentage of positive cultures among the two groups on weekly blood cultures|
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Out of the 21 patients with positive wound culture in Group 2, Acinetobacter was the predominant organism which was seen in 7 patients. In Group 1, out of 20 patients with positive wound culture, Acinetobacter was seen in only 1 patient. Pseudomonas was grown in 9 patients in Group 1, while it was seen in 8 patients in Group 2. During the 2nd week, Pseudomonas was the predominant organism grown in wound culture. In Group 1, out of 24 patients with positive wound culture, Pseudomonas was grown in 11 patients, while out of the 23 patients with positive wound culture in Group 2, it was seen in 9 patients.
By the 3rd week, Pseudomonas was grown in 9 out of 13 patients in Group 1 and 1 out of 6 positive cultures in Group 2.
By week 4, 8 out of 8 patients with positive wound culture in Group 1 were Pseudomonas, and in Group 2, only 1 patient showed positive wound culture and Acinetobacter was the organism grown [Table 7].
Pseudomonas was the predominant organism grown in blood culture during the 1st week. Seven out of 12 positive cultures in Group 1 and 4 out of 9 positive cultures in Group 2 was Pseudomonas. In week 2, again, Pseudomonas was the predominant organism grown. Six out of the 7 patients were in Group 1 and 1 out of 5 in Group 2. In week 3 of blood culture, out of the 2 patients showing blood culture positivity in Group 1, Pseudomonas alone was grown in one patient and mixture of organisms was grown in the other. In Group 2, only one patient's blood culture came positive and Klebsiella was the organism grown. By week 4, none of the blood cultures turned up positive [Table 8].
| Discussion|| |
Burn injury is known to markedly deplete glutamine, which may increase the incidence of gut atrophy and immune dysfunction and potentially increase the incidence of Gram-negative bacteremia.
In our study, we have supplemented our burn patients with glutamine of 0.5 g/kg body weight by oral route, as enteral route has become the preferred method of feeding in severe burn patients because there are fewer infections compared with parenteral feeding.
Patients were typically adult males and females who were in good health before their injury. As indicated by the average burn size (nearly 40%), these were severely burned patients. In our study, we found that the supplementation of glutamine in addition to standard nutrition reduced the wound culture positivity rate and improved serum protein levels in severely burned patients.
In our study, the serum total leukocyte count over the 4 weeks seemed to fall steadily in both the groups with slightly lower corresponding values in Group 2 but with no statistical significance. The P value was not significant in any of the 4 weeks, and the two graphs were parallel [Table 3].
Sheridan et al. did a stable isotope study to determine the effect of short-term enteral glutamine supplementation on protein accretion in burned children. The study showed that rapid protein accretion does not occur with short-term enteral glutamine supplementation. Several days of glutamine supplementation may be required to restore plasma glutamine levels and stimulate protein synthesis. In our study, the serum total proteins measured over the 4 weeks in Group 1 showed a steady decrease in the levels, whereas in Group 2, the levels seemed to drop slightly in the 2nd week with again a rise from the 3rd week. Although there was no statistically significant difference in the values in the first 3 weeks, the values in the 4th week in Group 2 were higher than that of Group 1 (P = 0.004), hence proving that the supplementation of glutamine is not of much value in immediate postburn period, but early and sustained supplementation does have an impact in the eventual outcome [Table 4].
In a study conducted by Peng et al. on the effect of enteral supplementation with glutamine granules on intestinal mucosal barrier function in severe burn patients, the average hospital stay days in the “glutamine” group were significantly shorter than that in the control group. The present study, however, did not show any such advantage with glutamine supplementation with respect to average hospitalization duration.
In the randomized study conducted by Pattanshetti et al., hospital stay days were significantly reduced in the glutamine-supplemented group (P = 0.003). It was observed in our study that the mean duration of hospital stay was about 18 days in both the groups, with no statistically significant difference (P = 0.984).
In the prospective, randomized clinical trial conducted by Garrel et al., the mortality rate was found to be significantly lower with glutamine supplementation. In our study, the mortality rates between Groups 1 and 2 were found to be 16.3% and 9.4%, respectively; though the glutamine-supplemented group did have a lower mortality rate, it was not statistically significant (P = 0.297).
In a study conducted by Pattanshetti et al., it was observed that enteral glutamine supplementation reduced the incidence of positive wound cultures (P = 0.001) and also the incidence of positive blood cultures (P = 0.065), thus reducing infectious morbidity. In our study, there was no significant difference in wound swab culture patterns between the two groups in weeks 1 and 2 (P = 0.902 and 0.345, respectively). However, in weeks 3 and 4, the number of positive wound cultures was higher in Group 1 as compared to Group 2, which was statistically significant (P = 0.028 and 0.007, respectively) [Table 5]. This can probably be attributed to the better immunological status of the glutamine-supplemented group.
In our study, it was seen that the predominant organism grown in the wound culture was Pseudomonas aeruginosa and that glutamine supplementation reduced the wound culture positivity, particularly with Pseudomonas, by week 4 of the study.
In a study conducted by Wischmeyer et al., there was a significant reduction in the incidence of Gram-negative infection in the treatment group compared with the control group (P < 0.04). Garrel et al. did a prospective, controlled, randomized clinical trial on effect of glutamine supplementation on mortality and infectious morbidity in adult burn patients, which showed that enteral glutamine reduces blood culture positivity, particularly with P. aeruginosa. In our study, the blood culture positivity rates between the two groups were comparable, with no statistically significant difference in the first 3 weeks of the study (P = 0.349, 0.368, and 0.467, respectively). There was no growth seen in the 4th week of the study in either group [Table 6]. In the study, it was seen that Pseudomonas was the predominant organism grown in the blood culture through the first 3 weeks of the study.
| Conclusion|| |
Oral supplementation has been a very feasible and effective method of glutamine supplementation in burn patients, which should be seriously considered in all cases of severe burns. Glutamine supplementation has shown to enhance serum protein levels, hence improve nutritional status of these patients. It is also useful for its immunomodulatory effects, thus reducing burn wound infection, as shown by lesser number of burn wound culture positivity rates in our study. Although the present study did not show any significant reduction in mortality or hospital stay duration with glutamine supplementation, it may have some positive impact on these parameters as well, as shown by other studies in literature.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]