THE EFFECT OF ENTERAL NUTRITIONAL SUPPORT ENRICHED WITH GLUTAMINE ON THE DEVELOPMENT OF NOSOCOMIAL INFECTIOUS COMPLICATIONS IN PATIENTS WITH TRAUMA OF THE CHEST AND ABDOMEN

City Clinical Hospital No.9,

Izhevsk State Medical Academy, 

Izhevsk, Russia,

Ural State Medical University, 

Ekaterinburg, Russia

The beginning of the 20th century with its industrial growth and implementation of the new technologies did not eliminate, but intensified the existing problems [1]. The increasing vehicle-to-population ratio with its road traffic injuries, terrorism and war conflicts, urbanization and technogenic disasters make the direct influence on the problems of injuries [1, 2]. Besides the incidence, the injury rate makes the significant influence on economical and medicosocial problems of the society (high rates of disability and mortality, high costs of medical aid, significant direct and indirect losses as result of lost working capacity of the society) [3].

The main pathogenetic factors of severe associated injury forms the mutual burdening syndrome with changing adaptation mechanisms in response to an injury that leads to increasing severity and resistance of traumatic shock, increasing volume and degree of blood loss, infectious complications, multiple organ dysfunction (MODS) and severe metabolic disorders such as syndrome of hypermetabolism-hypercatabolism [2].

The intensity of responses of natural and acquired immunity in associated injury is determined by variability and degree of manifestations of etiological and pathogenetic factors of trauma and shock considering the important component of pathogenesis of the traumatic disease and immune system [4, 5]. At the first stage, immune system response to damaging factors is characterized by activation of migration of various cell populations towards the inflammation site, but activation of neutrophilic granulocytes of the blood as the main cells of non-specific resistance provides the first line of protection from endogenic and exogenous infection and development of acute phase of inflammation. Therefore, disorders in development of inflammation and various stages of phagocytosis in associated mechanical injury is often  considered as one of the most important causes of infectious complications [6].

Patients with severe associated injury demonstrate high rates (86.1 %) of visceral infectious complications. The most common visceral infectious complications of severe associated injuries are bronchial and pulmonary ones:  tracheobronchitis and pneumonia (52 %), pleuritis (12.3 %), urinary tract infections (24.1 %), abdominal cavity infections (9.2 %), meningitis (3.4 %) [7, 8, 9]. Complex metabolic disorders (the syndrome of hypermetabolism-hypercatabolism) and protein-energy insufficiency, as well as concurrent complications and lethal outcomes are acknowledged as the important component of a traumatic injury [1].

Currently, the gold standard of estimation of real energetic requirements of the patient is the method of indirect calorimetry. Strict adherence to changed calorific capacity increases the survival as compared with the calculation techniques of daily requirements [10]. Strict 100 % compensation of energy losses decreases the rate of nosocomial infections, duration of artificial lung ventilation (ALV) and dosages of antibiotics [11].

One of the modern nutritional substances for enteral nutrition is immune nutrition. Immune nutrition is one of the methods of the new direction in clinical threpsology – pharmacological nutrition [4].

The glutamine conditionally essential amino acid [5, 12] is important and multifunctional for the body.           

Intense glutamine deficiency develops in hypercatabolism, which is associated with sepsis, surgical intervention and other critical states, because glutamine consumption is significantly increased and the synthesis becomes insufficient. For example, a patient with body mass of 70 kg and catabolic state demonstrates glutamine consumption by the cells of the gastrointestinal tract about 10-14 g per day, by immune system – 2-4 g per day, by kidneys – 4 g per day, but compensatory secretion by means of muscular proteolysis and increased synthesis is 8-10 g per day. Deficiency of this amino acid is 10-12 g per day and more [9, 13].

On the basis of the latest large-scale studies (2013), the Canadian society of nutrition publishes the new recommendations based on 275 randomized clinical studies. Intravenous dosages of glutamine remain the same, but with quite strict limitations in indications and prescriptions. It is not recommended to make such prescriptions for patients with MODS, acute renal insufficiency and hemodynamic instability [14].

The most important limitation of recommendations of multiple societies of nutrition is absence of clear dosages of glutamine administration for enteral introduction, because there are only limited findings for development of recommendations for prescription for critically ill patients, although there is a clear niche – patients with severe injury and burns (the level A) [3, 9]. Therefore, additional studies are necessary.                     

Objective – to conduct the analysis of development of nosocomial infectious complications in ICU patients with severe trauma of the chest and abdomen, to estimate the relationship with the tactics of nutritional support.

MATERIALS AND METHODS

The randomized prospective study included 90 medical charts by the inpatients with severe associated and single injuries to the chest and the abdomen. The patients were treated in the intensive care unit, City Clinical Hospital No.9, Izhevsk, during 2013-2016.

The inclusion criteria were patients with thoracic and abdominal injuries who were in the intensive care unit at least for 48 hours. The age of the patients was 18-75.

The exclusion criteria were severe traumatic brain injury, primary and secondary immune deficiency (oncologic pathology, chemotherapy), concurrent sub- and decompensated chronic pathology of kidneys, the liver and the heart, severe basic insufficiency of nutrition, obesity (body mass index < 17 or > 40), hematologic diseases, inadequate surgical correction, APACHE II > 25.

The patients were distributed into two groups: the main group and the controls (45 patients in each group). The main group received hypercaloric (1,360 kcal), hypernitrogenic (67 g of protein per 1 liter) and glutamine-enriched (20 g/l) nutrition. The control group received isocaloric (1,000 kcal/l), isonitrogenic (38 g of protein per 1 liter) enteral nutrition without glutamine (the table 1). The patients corresponded to the selection criteria and received nutritional support. Most patients mainly received enteral nutrition, but in some cases, if contraindications to enteral nutrition were found, the patients received full parenteral or mixed parenteral and enteral nutrition. Nutrition was introduced through the nasogastric tube and intravenous approach correspondingly. Nutritional support was initiated within 24-48 hours after stabilizing the condition.

Table 1

The groups were analyzed in terms of anthropometric data (body mass index [BMI]), demographic values (the age), time of transportation and arrangement of surgical management, duration of ICU and hospital stay, amount of ALV hours. The condition of the patients in both groups was estimated with ISS (Injury Severity Score), Glasgow Coma Scale (GCS), APACHE II (Acute Physiology and Chronic Health Evaluation II), SOFA (Sepsis-related Organ Failure Assessments Score). Also parenteral and enteral nutrition was analyzed, and nutrition status according to time course of total protein, albumin and absolute amount of lymphocytes were estimated on the days 1, 3, 5, 7 and 10 in the ICU. Estimation of intensity of catabolic response was conducted with assessment of daily urine losses of nitrogen on the days 1, 3, 5, 7 and 10 in the ICU. Daily energetic consumption was estimated with Sheldon’s equation. Extrapulmonary and pulmonary nosocomial infectious complications were registered for the whole period of hospital stay with use of the algorythms for epidemiological diagnostics of intrahospital infections developed by the Center for Disease Control and Prevention, CDC, USA. For objective diagnostics of nosocomial pneumonia we used CPIS (Clinical Pulmonary Infection Score). For characteristics of intensity of manifestations of the epidemiological process we used the values of cumulative incidence.

The study groups were comparable according to severity of injuries (ISS) and time before initiation of surgical management (the table 2). 

Table 2

The statistical analysis was conducted with Statistica 6.0. The comparison of the analyzed values was conducted with the non-parametrical methods. The reliability of the intergroup differences was estimated with Mann-Whitney test. The reliability of the qualitative signs was conducted with two-tailed Fisher’s test (< 5 observed cases) and chi-square with Yates' correction (5-10 observed cases), with odds ratio calculated. The critical level of reliability of the null statistic hypothesis was at the level of 0.05.

The study was conducted with the approval from the bioethical committee of Irkutsk State Medical Academy (the protocol #498, June 30, 2016). It corresponded to the ethical standards of Helsinki declare – the Ethical Principles for Medical Research with Human Subjects 2000 and the Rules for clinical practice in the Russian federation confirmed by the order of Health Ministry of the Russian federation, June 19, 2003, No.266. The written consent was received from all patients.

RESULTS AND DISCUSSION

At the moment of admission the patients of both groups showed the similar severity of condition with similar severity of the injuries (APACHE II, SOFA, GCS, lactate level). By the moment of the 7th day in the ICU the patients of both groups demonstrated the gradual decrease in severity of general condition (the table 3). There were no reliable differences.

Table 3

The severe catabolic response (nitrogen losses > 12 g/s) developed in the main group and in the controls within 24 hours in the ICU. Metabolic requirements were increasing in both groups, with reaching the maximal levels by the days 7-10 in the ICU (the table 4). There were no statistically significant differences. The daily protein and energy requirements were calculated for each group of the patients. The strategic objective of early nutrition support was achievement of delivered protein at least 1.1 g/kg per day. According to the results of the world-wide studies, it decreases the risk of nosocomial complications and lethal outcomes in such category of patients. Considering the various composition of the mixtures for enteral nutrition, it was possible to achieve such level of protein on the 3rd day in the ICU in the main group and only on the 7th day of the follow-up in the control group.

Table 4

The time course of the nutrition status in both groups demonstrates the efficiency of enteral nutrition enriched with glutamine. The levels of serum albumin were at the same level in both groups initially and on the 3rd day in the ICU. On the 5th day of the follow-up the patients of the main group demonstrated the higher level of albumin in comparison with the control group. Moreover, the control group showed a trend to decrease in albumin level as compared with the basic level (p = 0.001) (Fig. 1). The similar time course was observed in estimation of total protein: by the 5th day in the ICU the statistically significant increase in total protein level was found in the main group and a trend to decreasing in the control group (p = 0.030) (Fig. 2). No statistically significant differences were found in the absolute amount of lymphocytes in the peripheral blood. Despite of the similar level of lymphocytes, more rapid restoration of this value happened in both subgroups of the main group, which received glutamine-enriched nutrition (Fig. 3). First of all, it is associated with the fact that the control group demonstrated more intense negative protein balance. It is -31.2 (-45.9 – -16.5) in the main group, -64.8 (-91 – -38.5) on the 3rd day, -22.2 (-63.6 – -19.2) in the main group, -72.1 (-94.6 – -49.7) on the 5th day. The statistically significant differences were found on the days 3 and 5 in the ICU (p = 0.005, p = 0.02) (Fig. 4).

Figure 1

Dynamics of albumin in the patients 
in the groups of observation

Dynamics of the total protein levels in the patients 
in the groups of observation

1

2

Dynamics of the absolute number of lymphocytes 
in the groups of observation

The protein balance in the groups of observation

3

4

One of the unfavorable factors influencing on the outcome and the course of treatment of the posttraumatic period and, as result, on length of hospital stay and increasing costs of treatment, is development of secondary infectious complications. For the whole period of hospital stay only 27 cases of nosocomial infections were registered. 8 cases of infections were registered in the main group (29.6 % of all cases), as well as 19 (70.4 % from the total amount of developed infections) infectious processes in the control group (the table 5). Administration of enteral nutrition with glutamine decreases the frequency of infectious complications by 2.4 % in the posttraumatic period (chi-square with Yates correction – 3.94, degrees of freedom – 1, p = 0.047). The probability of development of infectious complications in the group of standard nutrition was 2.5 times higher than in the group with immune nutrition (OR = 2.5 [1.1-5.8], p = 0.034).

Table 5

In half of the cases (52 %) the development of nosocomial infections was associated with a region of surgical intervention – 14 cases including 3 incidents in the main group (37.5 % from the total number of infectious complications) and 11 cases in the control group – 58 % from the total amount of infections in the group. Administration of the enteral forms of glutamine results in 8.9 % decreasing in rate of infections in the region of surgical intervention (chi-square – 0.06, two-tailed exact Fisher’s test, p = 0.039). The probability of infectious complications in the region of surgical intervention was 4.5 higher in the control group than in the main group (OR – 4.5 [1.2-17.6], p = 0.029) (Fig. 5).      

Infections of the surgical area 
for 100 conducted operations in the groups

The incidence of nosocomial pneumonia 
for 1,000 bed-days in the groups

Nosocomial pneumonia (including ventilator-associated pneumonia) takes the second place among infectious complications. Total of 8 cases (29 %) were found: 2 cases of nosocomial pneumonia in the main group (25 % of all infections), 6 cases (43 % of all infections) in the control group (Fig. 6, 7).

18 % (5 cases) of all infectious complications were associated with infections: 3 cases of infected tracheobronchial tree (2 cases in the main group and 1 case in the control one), blood infection in 1 case in the control group. There were no statistically significant differences (the table 5).

The mean length of hospital stay was 15.8 (14.1-17.5) bed days in the main group, and 18.5 (16-21.1) in the control group (Fig. 8).

The incidence of ventilator-associated pneumonia 
for 1,000 ALV days in the groups

The average duration of hospital treatment

CONCLUSION

Administration of various mixtures for enteral nutrition for the group with hyper nitrogenic and hypercaloric composition provides the real protein and energy requirements by the moment of the third day in the ICU. Such requirements are achieved by the 7th day in the group with the standard composition of the mixture.

Also the values of the nutrition status (albumin, total protein, lymphocytes) were reliably different on the days 5 and 7 of the follow-up, i.e. the patients with immune nutrition showed the higher values as compared with the patients with the standard mixtures.

The targeted level of protein provision (1.1 g/kg per day and higher) is possible to achieve with enteral nutrition with hypercaloric and hypernitrogenic composition of the mixtures.

The patients with the standard nutritive mixtures showed 2.5 times higher risk of infectious complications as compared with the patients who received glutamine-enriched nutrition. Among the infectious complications, the leading place (52 %) was taken by the infectious complications relating to the region of surgical intervention, and the highest proportion of the complications developed in the group of standard enteral nutrition. The second significant complication was nosocomial pneumonia (29 %), which more often developed in the control group.