Translational Research in Enteral and Parenteral Nutrition Support for Patients with Severe Head Injury
LIN Fa-liang1, CHI Nan2, LI Wei1, XIE Lin1, WANG Xue-xin1,*
1. Department of Rehabilitation Medicine, Yantai Yuhuangding Hospital, Yantai, Shandong, 264000, China
2. Department of Neurosurgery, Yantai Yuhuangding Hospital, Yantai, Shandong, 264000, China.
*Corresponding Author: WANG Xue-xin, E-mail: 18905356189@163.com
Abstract

Objective: To explore the key points of the translational research in enteral and pareenteral nutrition support for patients with severe head injury (SHI), and to analyze the influence of different nutritional support routes on the prognosis of SHI patients.

Methods: Totally 141 patients with severe craniocerebral injury were selected as study subjects, 47 cases for each group, and were given early enteral nutrition (EEN), delayed enteral nutrition (DEN), and parenteral nutrition (PN), respectively. The effect of different nutritional support routes on SHI patients was observed.

Results: After 14 d of treatment, Glasgow coma scale (GCS) scores of 3 groups were higher than treatment before ( P<0.01), and with statistical differences among groups ( P<0.05, or P<0.01). The levels of serum albumin, total serum protein and hemoglobin were higher in EEN group than the other groups ( P<0.01). The level of serum albumin was lower in PN group than in DEN group ( P<0.05). There were statistical differences in the incidence of complications among three groups (χ2=9.2487, P=0.0098).

Conclusion: EEN support is more conductive to the improvement of the nutrition status, reduction of the incidence of complications, and promotion of the prognosis of SHI patients than DEN and PN.

Keyword: Translational medicine; Severe head injury; Enteral nutrition; Parenteral nutrition; Prognosis
Introduction

With the development of national economy and increase of traffic accident, accidental falls and violent crimes, the occurrence, disability and mortality rate of head injury still remain high, and severe head injury (SHI) accounts for 20% of all head injury in large and medium-sized transport developed city[1]. After head injury occurs, the body requires much energy because it is in a high catabolism state, mainly manifesting with hypermetabolism, carbohydrate intolerance and negative nitrogen balance, especially more energy is required due to operative wound and postoperative tissue repair. If the nutritional status is not timely offered, severe malnutrition may result in immune hypofunction of the body, the increase of complications, aggravation of secondary brain injury, even organ failures in respiratory and circulatory systems[2]. SHI patients have different degrees of consciousness disturbance after injury and are unable to eat, so it is of importance for the favorable prognosis of patients to improve the nutritional status, enhance the immune function, reduce the occurrence of complications, promote the recovery of nerve function and lower the disability and fatality rate of the patients.

Translational medicine is a new concept in the field of scientific research at home and abroad which creates a direct link between basic research and clinical practice to realize the two-way rapid transformation. Clinical enteral and parenteral nutrition science is one active field of international medical research, and the translational research on it establishes a bridge between laboratory science and clinical care. Moreover, the important progress has been made in such field such the establishment and application of total parenteral nutrition[3], protection of gastrointestinal barrier function[4], development and use of immune nutrient[5], practice and development of rapid fast-track surgery (FTS), etc.. That translational study focused on key points of enteral and parenteral nutrition is further conducted, being favorable to improve the prognosis of patients. At present, the main nutrition support routes for SHI patients include total enteral nutrition, total parenteral nutrition, and enteral and parenteral nutrition. In this paper, the purpose of this paper is to explore the influence of early enteral nutrition (EEN), delayed enteral nutrition (DEN) and parenteral nutrition (PN) on the prognosis of SHI patients, analyze the difference of nutritive indicators and complications of different nutritional support routes so as to provide the reference of nutritional strategies for SHI patients.

Materials and Methods
General data

Totally 141 patients with SHI patients admitted in Yantai Yuhuangding Hospital from May 2013 to May 2014 were selected, in which 77 patients were males and 64 patients were females, aged 22-67 years old with the median age of (41.45± 3.61). Inclusion criteria: (1) Patients confirmed as SHI by clinical manifestations and CT, (2) Admitted within 12 h after injury, (3) Glasgow coma scale (GCS) scores ≤ 8 points, (4) Severe disturbance of consciousness and unable to eat, (5) Survival time ≥ 14 d, (6) Patients and family member signed the informed form. Exclusion criteria: (1) SHI patients complicated with abdominal trauma or severe complications of other organs, (2) Patients with heart, liver, and kidney dysfunction, (3) Patients with diabetes mellitus, hematopathy and other endocrine diseases of influencing nutrition and metabolism of the body, (4) Patients with the history of digestive tract diseases and organic gastrointestinal diseases, (5) Pregnant or cancer patients. 141 patients were randomly divided into EEN group, DEN group and PN group, 47 cases in each group. The difference in gender, age, GCS score showing no significant difference among three groups (P> 0.05) was comparable. The study was approved by the Ethnic Committee of Yantai Yuhuangding Hospital.

Treatment

Three groups of patients after admission were given intensive care. According to the actual conditions of illness, patients undergone surgery, and were given conventional treatment such as dehydration, hemostasis and infection prevention. Additionally, all patients were given neurotrophic drugs, consciousness-promoted drug and glucose control.

Nutrition support

EEN group: After 24 h of treatment, patients were given nasogastric enteral nutrition. The specific operation was done as follows: Patients were implanted with nose-jejunum nutrition tube which was inserted into duodenum or jejunum and given continuous drip of 500 mL/d Ruidai (Enteral Nutritional Emulsion, Sino-Swed Pharmaceutical Corp. Ltd, J20040074) by nasogastric tube at a dripping speed of 50 mL/h for 3 d. Afterwards, according to patients’ tolerance, Ruidai was increased to 1 500-2 000 mL/d by enteral feeding pump at a dripping speed of 100 mL/d at temperature of 35-40℃.

PN group: After 24 h of treatment, patients were given PN via central vein. The operation was as follows: Energy, which was given 146.4 KJ/(kg· d) in the first three days, afterwards, changed to 121.33 KJ/(kg· d), came from glucose and lipid emulsion, with the ratio being (1-1.2): 1. Protein was provided by 8.5% of Novamin (Sino-Swed Pharmaceutical Corp. Ltd, H10980028). Besides, microelement, vitamin, water, electrolyte were added properly for preparing 3 L of total nutrient admixture which was dripped via vein.

DEN group: After 24 h of treatment, patients were conducted with total parenteral nutrition. The energy source and infusion method were the same as PN group. When borborygmus and cacation occurred after 6-7 d, nasogastric enteral nutrition was given for patients, and the nutrient solution, dosage, infusion method were the same as EEN group.

Observational indicators

(1) The GCS score of 3 groups was recorded on admission and after 14 d of treatment. (2) The changes of the levels of serum albumin, total serum protein, hemoglobin and peripheral blood lymphocyte count (PBLC) after 14 d of treatment were observed. (3) The occurrence of complications of 3 groups was observed.

Statistical analysis

SAS 9.3 software package was applied for data analysis. The measurement data was presented as ( ), and analyzed by t test. The enumeration data was conducted using χ 2 test. A value of P< 0.05 was considered statistically significant.

Results
Comparison of GCS score of 3 groups on admission and after treatment

There was no statistical difference in GCS score among 3 groups (P> 0.05). After 14 d of treatment, the GCS score of 3 groups were obviously higher than that on admission (P< 0.01). The GCS score of EEN group was higher than in the other groups after 14 d of treatment, with significant difference (P< 0.05, or P< 0.01). (Table 1).

Table 1 Comparison of GCS Score of 3 Groups on Admission and After Treatment (, Points)
Comparison of nutritional status of 3 groups

After 14 d of treatment, the levels of serum albumin, total serum protein and hemoglobin were higher in EEN group than the other groups (P< 0.01). The level of serum albumin was lower in PN group than in DEN group (P< 0.05).

Table 2 Comparison of Nutritional Status of 3 Groups ()
Comparison of the occurrence of complications among 3 groups

During the course of nutrition support, upper gastrointestinal hemorrhage, pulmonary infection, diarrhea and stress ulcer occurred in 3 groups. The occurrence of complications was 31.91% (15/47) in EEN group, 55.32% (26/47) in DEN group and 61.70% (29/47), with the statistical difference among groups (χ 2=9.2487, P=0.0098).

Discussion

SHI patients are in a stress state, so adrenocortical hormone, catecholamine and glucagon are secreted increasingly and the function of hypothalamus-hypophysis system is damaged, which make the body in a state of hypermetabolism, a high state of decomposition and an increased consumption of energy. Additionally, due to inadequate energy intake caused by disturbance of consciousness and dysphagia, patients are prone to negative nitrogen balance for most patients are in a state of malnutrition which makes immune function of the body decline and leads to multiple organ failure, thus affecting the prognosis of patients[6]. The nutrition support within 5 d after injury for SHI patients is related to fatality rate. If the daily intake of energy reduce by 10 kacal/kg, the fatality rate increases by 30%-40%[7]. Therefore, improving the status of nutrition is important for the prognosis of patients, so is the selection of nutrition support route. Moreover, demand of patients during the course of treatment is the motive force for the development of translational research in nutrition support, so with the coming of the era of 4P (Personalized, Predictive, Preventive, Participatory) medical model, translational research in enteral and parenteral nutrition support has a new developing opportunity. Facing the challenge of new medical mode, realization of translational medicine on integration of nutrition disciplines of enteral and parenteral nutrition should be strengthened thoroughly, which makes every link of translational research form into an organic whole, thus realizing the rapid development of nutrition support associated discipline based on translational medicine dual mode[9].

Nutrition support routes include enteral and parenteral nutrition. Marcus et al.[9] summarized the nutrition support routes for SHI patients in clinical practice and the results showed that enteral and parenteral nutrition could provide enough heat energy and protein for patients, strengthen the immune function of the body, improve the nitrogen balance, better the recovery of wound tissue and neural function, reduce the death rate and disability rate as well as enhance the quality of life of patients. However, nutritional ingredients are digested and absorbed by normal physiological channel, so enteral nutrition support is more in accord with human body physiological needs, for it can improve the release of digestion and gastrointestinal hormone, increase gastrointestinal motility, help remove intestinal contents, maintain the intestinal mucosal barrier function and reduce the intestinal bacteria translocation. In addition, enteral nutrition can prevent the occurrence of stress ulcer by neutralizing stomach acid and recovering intestinal mucosal blood flow[10]. Many studies have shown that enteral nutrition can provide the nutrient for the body, maintain and improve the immune as well as reduce the occurrence of complications[11, 12].

However, how to keep enough intake of nutrition for patients with SHI is still controversial. In 2009, nutrition support guideline for ASPEN critically ill patients pointed out that enteral nutrition given within 24-72 h could decrease the permeability of enteric mucosa, release and activity of inflammatory cytokines, and the occurrence of pyaemia and toxaemia[13, 14]. Meirelles et al.[15] pointed out that due to a serious stress state, limited gastrointestinal digestion and absorption function, reduced tolerance and intracranial hypertension complicated with vomiting of SHI patients, pure enteral nutrition support was difficult to meet energy demand of patients. Vizzini et al.[16] reported in their study that parenteral nutrition could promptly offer the overall nutrition for patients with head injury, reduce the stimulation of food to gastrointestinal tract, avoid gastric retention, as well as prevent vomiting, food reflux and aspiration. In present research, the effect of EEN, DEN and PN on the prognosis of SHI patients was observed, and the results showed that the GCS score of patients were improved significantly after 14 d of nutrition support compared with patients on admission, while DEN and PN groups were inferior to EEN group. Because of most SHI patients accompanied with disturbance of consciousness and coma, so the GCS score can directly influence the prognosis of head injury[3]. Therefore, the improvement of GCS score of 3 groups in present study showed that the reasonable nutrition support had positive effect on the prognosis of patients, and EEN group were the most obvious one.

SHI patients has poor prognosis because the metabolic ability of their organs slows down, with low general immunity and high risk of various complications[18]. The levels of serum albumin, prealbumin, hemoglobin and lymphocyte are common indicators of monitoring the status of nutrition and immune function of the body. In present study, the above indicators of 3 groups were in normal condition, the levels of serum albumin, total serum protein and hemoglobin of EEN group improved more significantly than the other groups, and the levels of the above indicators of DEN group were higher than those in PN group, showing that those three nutrition support routes could improve the protein metabolism, reduce negative nitrogen balance, better the recovery the neurological function and the synthesis of skeletal muscle, and improve the body's nutritional status, consequently enhancing the immune function and anti-infectious ability. Moreover, in three groups, the levels of the above indicators in EEN group were best recovered. However, the level of lymphocyte was similar among three groups might because patients were critically ill with low level of lymphocyte. Besides, the occurrence of complications was the lowest for EEN group and the highest for PN group, which may associated with the fact that EEN support could maintain gastrointestinal barrier, reduce intestinal infection and prevent the stress ulcer by neutralizing stomach acid and recovering intestinal mucosal blood flow, accordingly reducing gastrointestinal bleeding, perforation, etc., which indicated that the good nutrition support could reduce the occurrence of complications and provide the favorable conditions for the body rehabilitation of patients.

In conclusion, it is necessary for SHI patients to employ the early, standard and reasonable nutrition for it can improve the status of nutrition significantly, reduce the occurrence of complications, so EEN can be considered as the first choice for SHI patients.

Declaration

The authors of this manuscript declare that they have no conflict of interest.

Reference
1 Cadotte DW, Vachhrajani S, Pirouzmand F. The epidemiological trends of head injury in the largest Canadian adult trauma center from 1986 to 2007. J Neurosurg, 2011, 114(6): 1502-9. [本文引用:1]
2 Lee-anne SC, Lithand er FE, Gruen RL, et al. Nutrition therapy in the optimisation of health outcomes in adult patients with moderate to severe traumatic brain injury: Findings from a scoping review. Injury, 2014, 45(12): 1834-41. [本文引用:1]
3 Sepehripour S, Papagrigoriadis S. A systematic review of the benefit of total parenteral nutrition in the management of enterocutaneous fistulas. Minerva Chir, 2010, 65(5): 577-85. [本文引用:2]
4 Dodge ME, Bertolo RF, Brunton JA. Enteral feeding induces early intestinal adaptation in a parenterally fed neonatal piglet model of short bowel syndrome. JPEN J Parenter Enteral Nutr, 2012, 36(2): 205-12. [本文引用:1]
5 de Aguilar-Nascimento JE, Dock-Nascimento DB, Bragagnolo R. Role of enteral nutrition and pharmaconutrients in conditions of splanchnic hypoperfusion. Nutrition, 2010, 26(4): 354-8. [本文引用:1]
6 Curtis L, Epstein P. Nutritional treatment for acute and chronic traumatic brain injury patients. J Neurosurg Sci, 2014, 58(3): 151-60. [本文引用:1]
7 Casaer MP, Van den Berghe G. Nutrition in the acute phase of critical illness. N Engl J Med, 2014, 370(25): 2450-1. [本文引用:1]
8 Zhou L, Li Y, Bosworth HB, et al. Challenges facing translational research organizations in China: a qualitative multiple case study. J Transl Med, 2013, 11: 256. [本文引用:1]
9 Marcus HE, Spöhr FA, Böttiger BW, et al. Nutritional therapy in traumatic brain injury : Update 2012. Anaesthesist, 2012, 61(8): 696-702. [本文引用:2]
10 Chiang YH, Chao DP, Chu SF, et al. Early enteral nutrition and clinical outcomes of severe traumatic brain injury patients in acute stage: a multi-center cohort study. J Neurotrauma, 2012, 29(1): 75-80. [本文引用:1]
11 Chourdakis M, Kraus MM, Tzellos T, et al. Effect of Early Compared With Delayed Enteral Nutrition on Endocrine Function in Patients With Traumatic Brain Injury An Open-Labeled Rand omized Trial. JPEN J Parenter Enteral Nutr, 2012, 36(1): 108-16. [本文引用:1]
12 Scrimgeour AG, Condlin ML. Nutritional treatment for traumatic brain injury. J Neurotrauma. 2014, 31(11): 989-99. [本文引用:1]
13 Lu CY, Shih YL, Sun LC, et al. The inflammatory modulation effect of glutamine-enriched total parenteral nutrition in postoperative gastrointestinal cancer patients. Am Surg, 2011, 77(1): 59-64. [本文引用:1]
14 Khorana J, Rerkasem K, Apichartpiyakul C, et al. Immunonutrition and cytokine response in patients with head injury. J Med Assoc Thai, 2009, 92(2): 188-94. [本文引用:1]
15 Meirelles CMJ, de Aguilar-Nascimento JE. Enteral or parental nutrition in traumatic brain injury: a prospective rand omised trial. Nutrición hospitalaria: Organo oficial de la Sociedad española de nutrición parenteral y enteral, 2011, 26(5): 1120-4. [本文引用:1]
16 Vizzini A, Arand a-Michel J. Nutritional support in head injury. Nutrition, 2011, 27(2): 129-32. [本文引用:1]
17 Tohme S, Delhumeau C, Zuercher M, et al. Prehospital risk factors of mortality and impaired consciousness after severe traumatic brain injury: an epidemiological study. Scand J Trauma Resusc Emerg Med, 2014, 22: 1. [本文引用:1]
18 Lazaridis C, Andrews CM. Brain tissue oxygenation, lactate-pyruvate ratio, and cerebrovascular pressure reactivity monitoring in severe traumatic brain injury: systematic review and viewpoint. Neurocrit Care, 2014, 21(2): 345-55. [本文引用:1]