INFLUENCE OF INTESTINAL FAILURE SYNDROME ON THE CLINICAL COURSE OF TRAUMATIC DISEASE IN PATIENTS WITH THORACIC AND ABDOMINAL TRAUMA Ponomarev S.V., Sorokin E.P., Leyderman I.N., Shilyaeva E.V.
Izhevsk State Medical Academy,
City Clinical Hospital No. 9, Izhevsk, Russia
Almazov National Medical Research Centre, Saint Petersburg, Russia
The rate of injuries presents one of the actual medical problems of the modern world. It is associated with high economic and demographic consequences: high disability and mortality in working age population, high costs for medical care, losses of working potential of society [1, 2].
The human intestine is responsible not only for digestion and clearance of metabolites. The non-digestive functions of the intestine include endocrine (synthesis of multiple hormones of local and systemic action) and protective (60-70 % of lymphoid tissue is located in the intestinal wall) ones [3].
The important features of gastrointestinal tract (GIT) functioning are:
1) enterocytes of intestinal mucosa – quickly proliferating cells with life about 5 days [4];
2) perfusion of the erythrocyte depends on presence of big molecular nutrients in the bowel lumen;
3) up to 3 kg of microorganisms are in the bowel lumen [5].
Any injury is accompanied by development of clinical signs of traumatic, hemorrhagic shock or their combination. It leads to redistribution of systemic blood flow and priority perfusion of important organs and systems. One of experimental studies of pigs with modeling of cardiac output decrease from 2.3 to 1.7 l/min/m2 showed an evident decrease in blood flow in the small intestine wall and pancreas in preserved perfusion of central nervous system (CNS) and kidneys [3, 6].
Hypoperfusion and hypoxemia of intestinal wall lead to apoptosis of enterocytes, with intestinal barrier disruption, and increasing intestinal permeability [7, 8]. The role of TNK1 (Thirty-eight-negative kinase 1) as a clinical mediator of intestinal apoptosis with subsequent development of organ insufficiency is described in a recent experimental study [9, 10]. It promotes the translocation of toxins and microorganisms from intestinal lumen into regional lymph nodes and systemic blood flow. As result, systemic inflammatory response (SIRS) is maintained, multiple organ failure progresses, and sepsis develops [9-14]. Removal of TNK1 from intestinal epithelium can be a promising therapeutic approach for situations with disorder of intestinal homeostasis [9, 10]. Plasma citrulline [3], I-FABP (intestinal fatty acid-binding protein), intestinal type of protein, binding fatty acids [3, 14, 15], glutathione S-transferase (GSTs) and its subgroup αGST can present the biomarkers of preservation of epithelial intestinal barrier. Their increase in plasma supposes mesenterial ischemia [3].
Development of intestinal failure influences on management strategy for patients with traumatic disease. For disorder of motor and evacuation function of the intestine, the nutrition program should include the agents for parenteral nutrition. Total parenteral nutrition (TPN) is indicated in presence of absolute contraindications for enteral nutrition. TPN is not physiological and can promote more intense disorder of GIT function and intestinal barrier damage.
Objective − to analyze the course of traumatic disease in thoracic and abdominal injured patients with intestinal failure syndrome.
MATERIALS AND METHODS
The medical records of 86 patients of the intensive care unit of Izhevsk City Clinical Hospital No. 9 were analyzed. The patients were admitted with thoracoabdominal injuries. The study was prospective and controlled.
The inclusion criteria were duration of stay in ICU > 48 hours, and the age of 18-75.
The exclusion criteria were traumatic brain injury, primary and secondary immune deficiency (also in oncologic pathology and chemotherapy), concurrent sub- or decompensated chronic pathology of the kidneys, liver and heart, severe basic nutrition insufficiency or obesity (body mass index < 19 or > 35), blood system disease, condition severity with APACHE II > 25. The severity of intestinal failure syndrome (IFS) was estimated with GIF [16]. If GIF was 2 and more points in the early period of traumatic disease, then agents for parenteral nutrition were prescribed. If a patient could not receive > 60 % of daily energy on the days 3-4 in ICU, additional parenteral nutrition was prescribed.
The criteria of efficiency of intensive care were duration of stay in the hospital and in ICU, changes in time course of main values of nutritive status (total protein, albumin, blood lymphocytes), development of nosocomial infectious complications.
All patients were distributed into 2 groups. The group 1 (IFS) included patients with intense manifestations of IFS (GIF ≥ 2). In this group, the nutritive support included both various combinations of enteral and parenteral nutrition, as well as full parenteral nutrition (n = 26). The group 2 (EN) included patients with good tolerance of early enteral nutrition (n = 60). The nutritive support was initiated within the first 24-48 hours after condition stabilization.
A degree of GIT lesion according to GIF showed some statistically significant differences in the first day in ICU (in the IFS group, this value was 1.7 [1.2-2.2] points, in EN group – 0.8 [0.5-1.1], p < 0.01) and on the day 3 – 1.1 [0.7-1.5] and 0.3 [0.1-0.5] points, correspondingly (p = 0.03). Subsequently, intestinal failure was not diagnosed in the EN group. In the group 2, the GIT disorders were observed up to 7th day of treatment in ICU (average GIF was 0.7 on the day 5 and 0.9 on the day 7 in ICU). The differences were not statistically significant (Fig. 1).
Dynamics of severity of gastrointestinal insufficiency on the GIF scale in the compared groups
Note: GIF – Gastrointestinal Failure, IFS – Intestinal Failure Syndrome, EN – Enteral Nutrition.
Also the groups were compared according to anthropometric values (body mass, body mass index, body mass deficiency), transportation time and surgical care time, duration of stay in ICU and hospital, artificial lung ventilation (ALV) duration). Severity of patients’ condition in both groups was estimated with ISS, SOFA and APACHE II. Moreover, the analysis of amount of introduced parenteral and enteral nutrition was conducted, and then the nutrition status was studied according to changes in total level of protein, albumin and absolute amount of lymphocytes in the blood on the days 1, 3, 5 and 7 in ICU. Estimation of intensity of catabolic response was conducted with estimation of daily urine losses of nitrogen on the days 1, 3, 5 and 7 in ICU. Sheldon’s formula was used for calculation of daily energy requirements. Development of nosocomial infectious complications was registered for the whole period of inhospital treatment with use of the Federal clinical recommendations “Epidemiological observation of infections relating to arrangement of medical care” (2014). The values of cumulative incidence were used for estimation of intensity of manifestations of the epidemic process.
The groups were comparable according to severity of injuries (ISS), age, BMI and time before realization of surgical care (the table 1).
Table 1
Anthropometric data, severity of injury, time of medical care
|
Parameters/group |
IFS group (n = 26) M (95% CI) |
EN group (n = 60) Ì (95% CI) |
Significance level p |
|
ISS, points |
19.3 (15.9–22.7) |
20.4 (18.4–22.5) |
0.68 |
|
Age, years |
36.2 (31.4–40.9) |
36.7 (33.6–39.8) |
0.93 |
|
BMI, kg/m2 |
24.3 (22.9–25.8) |
23.2 (22.2–24.1) |
0.13 |
|
Transportation time, min |
61 (44–77) |
67 (59–74) |
0.14 |
|
Time before surgery, min |
59 (34–83) |
46 (39–53) |
0.85 |
Statistica 6.0 was used for data analysis. Non-parametrical methods were used: Mann-Whitney’s test, Fisher’s exact test, chi-square test with Yates correction, odds ratio. The differences were reliable with p ≤ 0.05.
The study corresponds to biomedical ethical principles (the approval from the biomedical ethical committee of Izhevsk State Medical Academy (application number No. 498, June 30, 2016)).
RESULTS AND DISCUSSION
The indices of condition severity for all estimated parameters were identical at the moment of admission and for the whole period of treatment in ICU. There were not any significant differences (the table 2).
Table 2
Assessment of the severity of patients’ condition on the APACHE II, SOFA, and the number of SIRS sings in dynamics
|
Scores |
Group |
Stages of study |
|||
|
day 1 M (95% CI) |
day 3 M (95% CI) |
day 5 M (95% CI) |
day 7 M (95% CI) |
||
|
Apache II, points |
IFS |
10.8 |
6.5 |
7.2 |
6 |
|
(8.5–13.1) |
(4.7–8.3) |
(4.6–9.8) |
(3.3–8.7) |
||
|
EN |
10.2 |
5.2 |
5.3 |
5.7 |
|
|
(8.9–11.4) |
(4.2–6.2) |
(3.9–6.6) |
(-8.5–19.8) |
||
|
SOFA, points |
IFS |
4.5 |
2.3 |
2.7 |
2.4 |
|
(3.3–5.6) |
(1.3–3.2) |
(1.0–4.4) |
(0.4–4.5) |
||
|
EN |
3.4 |
1.8 |
1.7 |
1.3 |
|
|
(2.8–3.9) |
(1.4–2.2) |
(0.9–2.4) |
(-0.1–2.8) |
||
|
SIRS, number of signs |
IFS |
2.5 |
1.5 |
1.7 |
1.9 |
|
(2.2–2.8) |
(1.2–1.8) |
(1.0–2.4) |
(1.0–2.7) |
||
|
EN |
2.5 |
1.2 |
1.4 |
2.0 |
|
|
(2.3–2.7) |
(1.0–1.5) |
(0.8–2.0) |
(-3.0–7.0) |
||
The markers of hepatic and renal dysfunctions did not exceed the reference values. Oxygenation index (OI) and serum lactate level did not show any statistical differences. High values of CRP at all stages in the IFS group showed intensity of SIR as compared to the EN group. Some statistical differences were identified in the first day in the hospital: 57 [25-88] mg/l and 26 [17-34] mg/l, correspondingly (p = 0.021) (the table 3).
Table 3
Some markers of systemic inflammation and organ dysfunction in the study groups in dynamics
|
Scores |
Groups |
Stages of study |
|||
|
day 1 M (95% CI) |
day 3 M (95% CI) |
day 5 M (95% CI) |
day 7 M (95% CI) |
||
|
CRP, mg/l |
IFS |
57* |
101 |
97 |
106 |
|
(25–88) |
(62–140) |
(3–190) |
(40–171) |
||
|
EN |
26 |
81 |
62 |
24 (24–24) |
|
|
(17–34) |
(64–97) |
(32–92) |
|||
|
OI |
IFS |
348 |
358 |
251 |
266 |
|
(267–429) |
(272–444) |
(32–470) |
(-1132–1664) |
||
|
EN |
354 |
380 |
303 |
336 |
|
|
(329–378) |
(340–420) |
(261–345) |
(6–666) |
||
|
Bilirubin, mmol/l |
IFS |
11.1 |
10.2 |
11.4 |
10.8 |
|
(9.2–13.1) |
(8.9–11.5) |
(7.2–15.7) |
(6.1–15.4) |
||
|
EN |
10.5 |
12.3 |
11.8 |
9.5 |
|
|
(9.3–11.8) |
(10.9–13.7) |
(10.2–13.3) |
(2.5–16.5) |
||
|
Creatinine, mmol/l |
IFS |
113 |
92 |
95* |
94 |
|
(101–125) |
(82–101) |
(84–106) |
(82–106) |
||
|
EN |
114 |
92 |
79 |
91 |
|
|
(103–125) |
(84–100) |
(70–88) |
(57–125) |
||
|
Lactate level, mmol/l |
IFS |
4 |
2,6 |
2,5 |
3,4 |
|
(1.9–6.2) |
(2.1–3.1) |
(0.5–4.5) |
(-5.3–12.0) |
||
|
EN |
4.9 |
2.2 |
2.4 |
2.9 |
|
|
(4.0–5.7) |
(1.8–2.5) |
(1.0–3.8) |
(-0.7–6.5) |
||
The result of formation of organ dysfunction (SOFA) and SIR, persistent signs of intestinal failure (according to GIF), and development of nosocomial infections was an increasing ICU stay for patients of the IFS group (Fig. 2).
Figure 2
Average duration of ICU stay
The duration of stay in ICU and in the hospital differed significantly (Fig. 2 and 3). The patients of the IFS groups were treated in ICU within 116 [86-143] hours on average, the EN group – 76 [67-85] hours (p = 0.05). However, there were not any statistically significant differences in ALV duration in the groups. The hospital treatment for patients of the EN group took 3.4 bed-days less than for the IFS group: 15.5 [13.9-17.0] and 18.9 [16.3-21.5] bed-days, correspondingly (p = 0.009).
Figure 3
Average duration of hospital stay
The metabolism in both groups was characterized by single-type manifestations of hypermetabolism-hypercatabolism syndrome. Protein and energy requirements were at the highest level on the seventh day of traumatic disease. The changes in time course of main metabolic values did not show statistical significance (the table 4).
Table 4
Daily nitrogen excretion, protein and energy requirements, the amount of protein and energy delivered in dynamics
|
Values |
Group |
Stages of study |
|||
|
day 1 M (95% CI) |
day 3 M (95% CI) |
day 5 M (95% CI) |
day 7 M (95% CI) |
||
|
Nitrogen excretion, g/day |
IFS |
17.8 (14.6–21.1) |
20.4 (16.1–24.6) |
20.1 (13.3–26.9) |
26.0 (11.8–40.2) |
|
EN |
16.8 (15.2–18.5) |
17.3 (13.6–21.1) |
21.0 (-8.5–50.4) |
35.0 (35.0–35.0) |
|
|
Protein requirement, g/day |
IFS |
114.8 (101.9–127.8) |
126.9 (106.1–147.7) |
127.0 (91.3–162.6) |
158.2 (90.2–226.2) |
|
EN |
107.2 (99.0–115.4) |
108.9 (90.7–127.0) |
128.0 (62.3–193.7) |
218.8 (218.8–218.8) |
|
|
Delivered protein, g/day |
IFS |
22.4 (12.5–32.2) |
69.5 (52.1–86.9) |
61.7 (43.7–79.7) |
117.6 (83.2–152.1) |
|
EN |
18.2 (14.2–22.1) |
70.6 (56.4–84.7) |
83.1 (38.2–128.0) |
134.0 (134.0–134.0) |
|
|
Energy requirements, kcal/day |
IFS |
2389 (2120–2658) |
2642 (2210–3074) |
2643 (1902–3384) |
3292 (1879–4705) |
|
EN |
2229 (2058–2399) |
2264 (1888–2640) |
2662 (1297–4028) |
4550 (4550–4550) |
|
|
Delivered energy, kcal/day |
IFS |
624 (457–792) |
1645 (1271–2020) |
1696 (1311–2081) |
2644 (1922–3366) |
|
EN |
632 (542–722) |
1727 (1469–1985) |
2004 (1264–2744) |
2920 (2920–2920) |
|
Protein and energy balance, as well as the time course of nutrition status (levels of general protein and albumin in the blood) during nutrition support did not show any statistically significant changes (the table 5).
Table 5
Dynamics of changes in the balance of protein and energy, total protein, albumin and blood lymphocytes
|
Scores |
Group |
Stages of study |
|||
|
day 1 M (95% CI) |
day 3 M (95% CI) |
day 5 M (95% CI) |
day 7 M (95% CI) |
||
|
Protein balance, g/day |
IFS |
-92.5 |
-57.4 |
-65.3 |
-40.6 |
|
(-108.3 – -76.6) |
(-87.4 – -27.5) |
(-104.2 – -26.3) |
(-99.2 – 18.0) |
||
|
EN |
-89 |
-37.8 |
-44.9 |
-84.4 (-84.4 – -84.4) |
|
|
(-98.1 – -79.9) |
(-56.5 – -19.0) |
(-116.7 – 26.9) |
|||
|
Energy balance, g/day |
IFS |
-1764 |
-997 |
-947 |
-649 |
|
(-2113 – -1416) |
(-1669 – -324) |
(-1703 – -190) |
(-2019 – 722) |
||
|
EN |
-1596 |
-537 |
-658 |
1630 (-1630– -1630) |
|
|
(-1785 – -1407) |
(-929 – -145) |
(-1940 – 623) |
|||
|
Total protein, g/l |
IFS |
60.6 |
58.2 |
59.4 |
60.7 |
|
(57.3 – 63.9) |
(55.3 – 61.0) |
(53.3 – 65.5) |
(51.6 – 69.7) |
||
|
EN |
58.9 |
59.9 |
60.4 |
65.9 |
|
|
(56.8 – 61.1) |
(58.4 – 61.5) |
(56.8 – 64.0) |
(50.4 – 81.4) |
||
|
Albumin, g/l |
IFS |
34 |
33.2 |
32.5 |
31.6 |
|
(30.8 – 37.2) |
(31.0 – 35.4) |
(27.8 – 37.2) |
(26.6 – 36.6) |
||
|
EN |
33.8 |
34.7 |
34.8 |
37.2 (21.5 – 52.8) |
|
|
(32.2 – 35.5) |
(33.5 – 35.9) |
(32.3 – 37.3) |
|||
|
Lymphocytes, 109/l |
IFS |
1.0 |
1.3* |
1.5 |
2.8 |
|
(0.8 – 1.2) |
(1.1 – 1.5) |
(0.9 – 2.0) |
(0.9 – 4.8) |
||
|
EN |
1.2 |
1.7 |
1.7 |
1.8 |
|
|
(1.1 – 1.4) |
(1.5 – 1.9) |
(1.4 – 2.1) |
(1.1 – 2.6) |
||
The level of lymphocytes was higher in the EN group within five days of ICU stay as compared to the IFS group. Some statistically significant differences were found on the 3rd day: 1.7 [1.5-1.9] * 109/l, correspondingly (p = 0.018) (Fig. 4). On the seventh day, the changes were associated with small size of the sample.
Figure 4
Dynamics of lymphocytes level in compared groups
Nosocomial infectious complications were identified in both IFS and EN groups: 9 (35 %) and 7 (12 %), correspondingly (χ2 with Yates correction = 4.88, p = 0.027). The risk of nosocomial infectious complications was 3 times higher in development of intestinal failure syndrome (RR = 3 [1.13-9.24], p = 0.029).
The most important changes included development of surgical site infection (SSI) (Fig. 5). In the EN group, the incidence of infections complications in the surgical site was 6.4 per 100 operations, in the IFS group – 14.8 per 100 operations (χ2 with Yates correction = 3.79, p = 0.05). The risk of SSI increased 3.2 times in case of intestinal failure syndrome (RR = 3.2 [1.13-9.24], p = 0.029).
Figure 5
Infections of the area of surgical intervention in the compared groups per 100 operations performed
CONCLUSION
Development of intestinal failure syndrome makes significant influence on the course of traumatic disease. Patients with IFS demonstrate more severe SIR and multiple organ dysfunction. Patients with IFS and full parenteral nutrition show 3-fold increase in the risk of infectious complications as compared to patients with enteral nutrition. Higher incidence of nosocomial infections in patients with IFS causes a natural increase in stay in ICU and hospital.
Information on financing and conflict of interests
The study was conducted without sponsorship. The authors declare the absence of any potential conflicts of interests relating to publication of this article.