Effect Of Early Enteral Nutrition Supplemented With Probiotics On Immune Function In Patients With Severe Head Injury

Objective: patients with severe head injury (SHI) are in systemic stress and immune dysfunction. It shows that excessive inflammatory response, suppressed cellular and humoral immunity. This is very likely infection or sepsis and directly affect the prognosis.Therefore, improving the immune dysfunction of SHI has been an important subject of clinical studies. In recent years, enteral nutrition supplemented with probiotics has been shown can improve animal intestinal flora, reduce the release of intestinal pro-inflammatory mediators, upregulate intestinal local immunity, promote the recovery of cellular and humoral immune function. In clinical, it has been shown to reduce infection rate in patients with trauma, burns and liver transplantation. But its ability to improve immune dysfunction and reduce infection rates of patients with SHI need to be proved. In this study, the intestinal flora, fecal SIgA, TNF-α, IL-6 , CD3+, CD4+, CD8+, CD4+/CD8+ , IgA, IgG, IgM were observed to investgate the effect of early enteral nutrition supplemented with probiotics on immune dysfunction of patients with SHI. In addition, clinical infection were observed during the study. All the above we did were for providing experimental evidence to improve immune dysfunction and optimize nutritional support program of patients with SHI.Methods: A single blind, prospective, randomized control clinical trial was carried out. Research program was approved by the Hospital Ethics Committee and registed on the Chinese Clinical Trail Registry (Registration No. ChiCTR-TRC-00000804). 52 patients with SHI were included strictly in accordance with inclusion and exclusion criteria. Patients were randomly divided into two groups (group EEN & group EENP), 3 cases were lost during the study, 49 patients completed. Meanwhile, 30 cases of healthy adults constituted the normal control group (group C). Group EEN(n=24) started receiving continuous enteral nutrition (RuiSu,30kca1/kg.d) by nasogastric tube infusion with enteral nutrition pump within 24 to 48 hours after injury, group EENP (n=25) received a enteral nutritional support which as well as control group, but added probiotics (Golden Bifid, 6g / d). On day0, day4, day8, day15 of enteral nutrition support, Stool were collected for observation of intestinal flora and fecal SIgA to investgate the effects of early enteral nutrition supplemented with probiotics on intestinal flora disturbance and intestinal local immune, peripheral blood were collected for dynamic observation of TNF-α, IL-6 , CD3+, CD4+, CD8+, CD4+/CD8+ and IgA, IgG, IgM to investigate inflammatory response, cellular and humoral immune function of early enteral nutrition supplemented with probiotics on patients with SHI. In addition, to analyze the clinical efficacy, infectious complications were observed whenever necessary and GCS were recorded on day 0, day 4, day 8, day 15 of nutritional support. In group C, Only stool and blood samples were collected to do the normal reference values and without any intervention. The data were shown as mean plus standard deviation ( x±s) and analyzed with Chi-square test, independent t test and ANOVA by SPSS13.0 statistical software. P <0.05 for the difference significant, P <0.01 for the difference is very significant.Results:1. Effect of early enteral nutrition supplemented with probiotics on intestinal floraOn nutritional support day 0, intestinal flora disturbance occurred in group EEN and group EENP. Compared with group C (P<0.01), escherichia coli increased, bifidobacterium and lactobacillus decreased (P<0.01, P<0.01), there was no difference between two groups (P>0.05). On nutritional support day 8, bifidobacterium and lactobacillus in group EENP were significantly higher than group EEN (P<0.05, P<0.01). On nutritional support day 15, bifidobacterium and lactobacillus in group EENP were significantly higher than group EEN (P<0.01, P<0.05), escherichia coli were significantly lower than group EEN (P<0.01), but escherichia coli, bifidobacterium and lactobacillus in group EENP still did not recover to normal level (P<0.01).2. Effect of early enteral nutrition supplemented with probiotics on intestinal SIgAOn nutritional support day 0, fecal SIgA in group EEN and group EENP were lower than group C (P<0.01) and there was no difference between two groups (P>0.05). On nutritional support day 8 and day 15, fecal SIgA in group EENP were significantly higher than group EEN (P<0.05) and no difference compared with group C on day15 (P> 0.05).3. Effect of early enteral nutrition supplemented with probiotics on inflammatory cytokinesOn nutritional support day 0, peripheral blood pro-inflammatory cytokines TNF-αand IL-6 in group EEN and group EENP were significant higher than group C (P<0.01), there was no difference between two groups (P>0.05). On nutritional support day 8, TNF-αin group EENP was significant lower than the group EEN (P<0.05). On nutritional support day 15, TNF-αand IL-6 in group EENP were significant lower than group EEN (P<0.05), but TNF-αand IL-6 in group EENP still did not recover to normal level (P<0.01).4. Effect of early enteral nutrition supplemented with probiotics on cellular immunityOn nutritional support day 0, CD3+, CD4+, CD4+/ CD8+ in group EEN and group EENP were significant lower than group C (P<0.01) and there was no difference between two groups (P>0.05). On nutritional support day 8 and day 15, CD3+, CD4+, CD4+/ CD8+ in group EENP were significant higher than group EEN (P<0.01, P<0.01, P<0.05) and no significant difference compared with the group C (P>0.05).5. Effect of early enteral nutrition supplemented with probiotics on humoral immuneOn nutritional support day 0, IgA IgG IgM in group EEN and group EENP were significantly lower than group C (P<0.01). On nutritional support day 15, IgA, IgG, IgM were restored to normal. During the study period, IgA, IgG, IgM expressions were no difference between group EEN and group EENP (P>0.05).6. Effect of early enteral nutrition supplemented with probiotics on clinical efficacyInfection rate in group EENP was lower than group EEN (33.33% vs. 50.00%), but no significant difference (P>0.05).Also there were no significant difference in infectous sites between two groups. For the study period, Glasgow coma scale in group EEN and group EENP were no significant difference (P>0.05).Conclusion:1.Patients with SHI exist intestinal flora disturbance, early enteral nutrition supplemented with probiotics can improve it. 2.Pro-inflammatory cytokines TNF-αand IL-6 release excessively in patients with SHI , early enteral nutrition supplemented with probiotics can some extent reduce it.3.Patients with SHI exist lower intestinal local immunity and suppressed cellular and humoral immunity, early enteral nutrition supplemented with probiotics can upregulate the intestinal local immunity, promote the recovery of cellular immune function, but no obvious effect on the humoral immunity.4.Early enteral nutrition supplemented with probiotics can improve the immune dysfunction of patients with SHI, but in continuous use of 7 days or more had better curative effect.