The major pathological change in the gastrointestinal tract following TBI is gastrointestinal mucosal ischemia, which usually manifests as stress ulcers and gastrointestinal bleeding. The incidence of stress ulcers in adult TBI patients is as high as 41-75%, and 17% of stress ulcers gradually develop into severe gastrointestinal bleeding in patients with severe TBI [8]. In this study, the incidence of stress ulcers in children with TBI was 48.5%. With the increase in TBI severity, the incidence of stress ulcers gradually increased, and the incidence in severe cases was 85.9%, suggesting that gastrointestinal mucosal ischemia is a common clinical complication of TBI children, a result similar to previous reports. After major trauma, the nervous, endocrine, and immune systems are fully mobilized to activate numerous adaptive responses, and blood distribution can be readjusted to ensure the perfusion of vital organs, such as the heart and brain. Therefore, the gastrointestinal mucosa is in a state of hypoperfusion, and secondary ischemia, anoxia, acidosis, reperfusion injury, and accumulation of inflammatory mediators aggravate the structural damage to the gastrointestinal mucosa, resulting in the spread of focal small ulcers and further aggravation of gastrointestinal dysfunction, directly triggering the development of a series of intestinal events such as FI [9]. Based on whether FI was present, children were divided into two groups: GIF score <2 and GIF score ≥2. GSC scores, SOFA scores, PCIS, and mortality were significantly different between the two groups. Although the application of SOFA scores to children still has not reached a consensus [10], compared with the PCIS scoring system, which is widely accepted in the field of pediatrics, the two methods are consistent in assessing TBI severity. These results suggested that children with GIF scores ≥2 had poorer systemic pathological conditions and higher mortality. The causes of these findings were analyzed. It was found that the intestinal mucosa morphology had changed within a short time after trauma, including epithelial cell detachment and apoptosis, rupture of the villi, edema of interstitial tissue and the lamina propria, interruption of tight junctions, etc., and that the mucosal barrier had lost its protective function [11]. Additionally, the intestinal flora was completely disordered within a few hours after injury, and the microbial composition and relative abundance changed significantly. The number of beneficial microbiota decreased, the pathogenic flora, with relatively increased invasiveness and virulence, dominated the intestinal tract, and the diversity and stability of the microbial ecological system were destroyed. This dysbacteriosis also greatly affected gastrointestinal function. The infection risk and the mortality rate of pediatric patients were greatly increased [12].
Second, the main manifestations of gastrointestinal dysfunction after TBI are inadequate motility and impaired digestion and absorption of water and nutrients, leading to a negative N balance and malnutrition. The clinical manifestations are usually gastric retention, abdominal distension and high intra-abdominal pressure [13]. However, it is hard to provide an objective evaluation of gastrointestinal dysfunction in clinical practice because there is still a lack of quantitative standards to classify severity although there are numerous relevant research reports and many scholars have defined gastrointestinal dysfunction and continuously improved and unified the definition [14-15]. GIF scores provide a quantification evaluation for the varying degrees of gastrointestinal dysfunction and objectively and accurately reflect gastrointestinal functional status. In this study, 135 children with TBI (78.8%) had gastrointestinal dysfunction on the first day of admission, including 34 cases of insufficient feeding (20.6%), 60 cases of FI (36.4%), and 36 cases of IAH or ACS (21.8%), suggesting that gastrointestinal dysfunction in children with TBI is very common in clinical practice and should receive increased attention. Furthermore, according to GCS score, children were divided into severe, moderate and mild groups. The incidence of secondary gastrointestinal dysfunction increased with injury severity, and GIF score on the first day and the mean GIF score for the first three days were significantly different among the three groups, suggesting that TBI severity is directly related to GIF score, indicating that TBI causes gastrointestinal dysfunction. Because the children included in this study did not have primary gastrointestinal injury, the complex neuroendocrine network named brain-gut axis played an important role in regulating gastrointestinal function. When the gastrointestinal tract is stimulated, such as with food and nutrients, children with TBI are unable to receive all types of information normally, due to direct impairment of the central nervous system. After misintegration, the autonomic nerves and the endocrine system transmit regulatory information to effector cells in the gastrointestinal tract, thereby resulting in regulatory dysfunction of the gastrointestinal mucosa, smooth muscle, blood vessels and glands [16-17]. Meanwhile, after damage to the central nervous system, many brain-gut peptides are secreted abnormally. They cannot function as neurotransmitters to exert normal information transmission and transfer effects between the brain and enteric nerves and effector cells, protect gastrointestinal tissues and the nerve plexus, and stimulate gastrointestinal motility. Various pathways in the brain-gut axis are blocked, and the important targets do not bind with brain-gut peptides, resulting in abnormal sphincter tone and smooth muscle contraction and slow gastric emptying and intestinal motility [18]. In addition, patients are in a state of stress after trauma, and emotions fluctuate greatly. The patients are affected by changes in the biopsychology and neuroendocrine systems. Gastrointestinal hormone levels and secretion are disordered, visceral sensitivity and epithelial permeability are increased, endotoxin is translocated, and intestinal flora are imbalanced [19-20]. Therefore, feedback from the gastrointestinal tract to the central nervous system is abnormal, causing gastrointestinal dysfunction.
In this study, the main indicator for evaluating the prognosis of children was mortality. Univariate analysis of the group of patients who died and the group of patients who survived showed that the clinical indicators GCS score, leucocyte count, Hb, Glu, lactate, ALB, PT, and APTT were significantly different between the two groups (P <0.05), suggesting that the degree of brain injury, hematology, internal environment, and coagulation in the children who died were all worse than those in the children who survived; furthermore, the SOFA scores and PCIS for the children who died were higher than those for the children who survived. Meanwhile, the GIF score on the first day and mean GIF score for the first three days for the children who died were significantly higher than those for the children who survived, suggesting that the children who died had a worse gastrointestinal functional status than that of the children who survived. Although the GIF score can be used as an independent risk factor in the prediction of the risk of death in critically ill patients [21], it focuses on gastrointestinal function at the time of injury. However, the condition of a child develops and changes during hospitalization. The GIF score cannot be limited only on the first day. Therefore, the role of the GIF score on the first day in predicting death during the entire ICU stay is limited [22]. The mean GIF score for the first three days can be used to dynamically observe and assess changes in gastrointestinal dysfunction during peak disease development, providing better continuity. Researchers such as Reintam et al. [3] found that GIF scores had higher application value in the assessment of gastrointestinal function in critically ill patients; the mean GIF score for the first three days was more important in predicting death than was the GIF score on the first day. In this study, the GIF score on the first day, the mean GIF score for the first three days, the SOFA score, and the PCIS were used as test factors, and multivariate regression analysis was included to assess the predictive value of the four factors. The mean GIF score for the first three days was considered an independent risk factor. The reliability of the GIF score on the first day was relatively low, suggesting that although the GIF score can be used as an objective indicator, the effectiveness and accuracy of dynamic observation and scoring are even higher; therefore, the mean GIF score for the first three days is better than the GIF score on the first day for evaluating the gastrointestinal function of children with TBI. One limitation of this study is that the SOFA score may be inapplicable to low-age infants and toddlers in terms of the items assessed [23-25], and it is easy to evaluate the normal or nonquiet state as the pathological state by mistake, leading to an increase in the SOFA score. In terms of predicting the risk of death, the accuracy and reliability of the SOFA score are not ideal. PCIS, as a recognized and commonly used effective means in the field of pediatric critical care, fully integrates the physiological and morbidity characteristics of children at different ages, more accurately, objectively and comprehensively reflects the disease condition, can be used to predict the risk of death and provides a reliable basis for the implementation of a rational clinical treatment plan [26-27]. In this study, the PCIS scoring system was also included in the death prediction equation. As two independent risk factors for the death prediction equation, the mean GIF score for the first three days had a predictive ability of death comparable to that for the PCIS, and when survival curves of the two score systems were generated, the areas under the curve were 0.795 and 0.819, respectively. They both had good predictive ability for risk of death, once again confirming the clinical significance of the GIF score in diagnosing gastrointestinal dysfunction in children with TBI and further emphasizing the importance of continuous monitoring and dynamic observation of the gastrointestinal status of children at different time points. Organ dysfunction in critically ill patients should be scored dynamically [28].
In summary, gastrointestinal dysfunction has a high incidence rate in children with TBI. The GIF score can accurately classify and objectively assess gastrointestinal status. A high GIF score is significantly correlated with ICU mortality. As an independent risk factor, the mean GIF score for the first three days has a higher predictive value for the prediction of ICU mortality; this result can provide guidance for the clinical evaluation and treatment of gastrointestinal dysfunction in children with TBI.