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Главная > № 4 (2017) > Шестова

STATUS OF PATIENTS WITH HIGH RISK OF EMBOLIC COMPLICATIONS IN POLYTRAUMA

Shestova E.S., Vlasov S.V., Vlasova I.V., Ustyantseva I.M., Khokhlova O.I.

Regional Clinical Center of Miners’ Health Protection, Leninsk-Kuznetsky, Russia

Deep venousthrombosis in the lower extremities develops in 40-60 % of cases of polytrauma [1, 2]. In some cases, the course of the traumatic process can be complicated by instable fixation of a clot to the vascular wall and by development of its floating part, which, in some specific conditions, migrates with blood flow and becomes the cause of development of fatal pulmonary embolism (PE) in 2-5 % of patients [3, 4]. As compared to single injuries, the significantly higher percentage of polytrauma-related embolic complications determines the critical importance of the causes of the instable clot in such patients.
The flow of nociceptive impulsation appears and gradually increases owing to traumatic damage of tissues because of their alteration. It causes the increasing blood loss and tissue microcirculation disorder determining the body feedback to trauma, which is called the traumatic disease [5]. Polytrauma is characterized by specific severity of disorders of the compensatory processes: traumatic shock, hypocoagulation, massive blood loss, multiple organ insufficiency, fat embolia and thromboembolic complications.
There is a relationship between hemostasis disorders and development of systemic inflammatory response syndrome (SIRS). Its trigger factor is the relationship of leukocytes, activated platelets and injured endotheliocytes. Activation of platelets stimulates the release of various cytokines and the tissue factor with development of procoagulant state that is accompanied by migration of leukocytes to the region of injured endothelium and formation of a clot. Lymphopenia and cell immunity dysfunction can cause the disorders of the thrombotic process course, including the clot fixation to the vessel’s wall [6].
Besides coagulation stimulation, SIRS suppresses the fibrinolysis and causes the excessive production of acute phase proteins, intense leukocytosis and activation of B- and T-lymphocytes and adrenal hyperfunction. Dysregulation of inflammatory processes promotes the further injury to endothelial cells and pathologic fragmentation of clots and their migration with development of PE [7, 8].
High incidence of thromboembolic complications in patients with polytrauma, asymptomatic disease course, difficulties for treatment and high mortality determine the necessity for identification of factors predisposing to development of such complications.
The study objective – to identify the clinical and laboratory values relating to development of unstable thrombosis in patients with polytrauma.

MATERIALS AND METHODS

56 patients with polytrauma, the age of 18-66 (the mean age of 41.1 ± 9.4; 52 men (92.9 %), 4 women (7.1 %)) were examined in the intensive care unit of Regional Clinical Center of Miners’ Health Protection within the time interval from 40 minutes to 24 hours after trauma in January-December 2016. The table 1 shows the characteristics of the patients.

Table 1. The characteristics of patients

Values	Indicator values
Mean age, years	41.1 ± 9.4
Gender: men/women, abs. (%)	52 (92.9) / 4 (7.1)
Injury severity (ISS, points)	25.2 ± 6.40
Condition severity at admission (APACHE III, points)	78.1 ± 16.20
ICU stay, days	10.2 ± 4.20
ALV duration, days	4.1 ± 0.71
Blood loss, ml	1567 ± 578.0
Injury location:
TBI	29
Chest	29
Pelvis	14
Abdomen	21
Spine	9
Extremities	30

Traumatic shock of degree 1-3 with probable blood loss of 1,000-2,700 ml (20-50 % of circulating blood volume) was identified in all patients. The individual blood loss was estimated by summing the external and cavitary blood loss in fractures of bone structures.
The presence of the factors promoting the development of embolic complications was analyzed [9, 10]. The following clinical values were estimated: gender, age, systolic arterial pressure (SAP), diastolic arterial pressure (DAP), heart rate (HR), severity of the patients’ condition with APACHEIII, ISS, AIS, blood loss, time of stay in ICU, the number of SIRS criteria, the time course of leukocytes and lymphocytes in the peripheral blood, levels of glucose and lactate.
The main group (n = 26) included the patients with the verified venous thrombosis. This group was distributed into two subgroups: the subgroup A (n = 16) – the patients with venous thrombosis without signs of instability and flotation; the subgroup B (n = 10) – the patients with venous thrombosis in the basin of the superficial femoral vein (SFV) who had the instable clot (according to the data of the dynamic examinations) that required for surgical treatment for preventing PE. The comparison group (n = 30) included the patients without deep venous thrombosis in the lower extremities.
The veins of the lower extremities were examined with duplex scanning (DS) at the moment of admission and each 5 minutes with use of the ultrasonic scanner MyLab Class C (Esaote, Italy). The linear transducer (7-14 MHz) was used for scanning the veins from the posterior tibial veins (PTV) to the general femoral veins. The convex transducer of 3.5 MHz was used for examining the iliac vessels and inferior vena cava. The venous patency was estimated with the test with venous compression using the transducer with proximal and distal compression of the hip and leg muscles. The venous thrombosis was verified with the following criteria: extension and loss of venous compression, visualization of pathologic structures in the venous lumen, absence of blood flow or registration of parietal blood flow around thrombotic masses (Fig. 1) [11, 12].

Figure 1. Occlusive thrombus in the superficial femoral vein with signs of initiation of recanalization – insignificant mural blood flow

Embologenic threat was estimated if a moving top of a clot was identified. High possibility of embolia was associated with the clots with more than 2 cm length of the moving part, presence of spontaneous mobility in blood flow, the “spring” effect in Valsalva test or cough tests (if possible), active mural blood flow (circular blood flow in transverse scanning), with inhomogeneous structure of the clot (with hypoechogenic lumen and contour defects) (Fig. 2).

Figure 2. Floating thrombus with high possibility of embolism – on the narrow neck, with unhomogeneous structure

However non-stable clots were considered as embologenic owing to the feature of the study group (need for surgical intervention, long term defence attitude, condition severity etc.) and impossible (in most cases) tests for estimation of mobility degree: if a moving top was not more than 2 cm, in presence of point fixation to the venous wall and active rocking motions of the clot during vein compression with the transducer.
The most common location of the moving clot was the common femoral vein. Moreover, the clot originated from the superficial femoral vein (7 cases) or, rarer, from the entry of the deep femoral vein (2 cases). In one case, the clot located in the popliteal vein, beginning from the posterior tibial vein (Fig. 3).

Figure 3. Floating thrombus in the popliteal vein

The study of the cellular composition of the blood was carried out with the hematological analyzer Sysmex-XT 2000i (Japan). The lactate level in the venous blood was estimated with the critical states analyzer Roche Omni S (Germany), serum glucose – with the biochemical analyzer Cobas 501 c.
The statistical analysis of the results was conducted with IBM SPSS Statistics 20.0. Kolmogorov-Smirnov test was used for estimation of the character of distribution of the quantitative values. If the data distribution did not correspond to the normal distribution law, the results were presented as Me (LQ-UQ), where Me – the median and (LQ-UQ) – interquartile range (25%-75%). The qualitative signs were described as absolute (n) and relative values (%). Mann-Whitney non-parametric test was used for identification of differences in quantitative values between two groups, between three groups – with Kruskel-Wallis test with subsequent procedure of Dunnett’s multiple comparison test. The intergroup comparison of the categorical data was realized with consideration of the sample size with χ² test or Fisher’s exact test. The differences were statistically significant if p value was lower than 0.05. Two-tailed Pearson χ² test or Fisher’s exact test were used for estimating the relationships between the qualitative signs with indication of odds ratio (OR) and 95 % confidence interval (95 % CI).
The study was approved by the ethical committee of Regional Center of Miners’ Health Protection and corresponded to WMA Declaration of Helsinki - Ethical Principles for Medical Research Involving Human Subjects and the Rules for Clinical Practice in the Russian Federation confirmed by the Order of Russian Health Ministry, June 19, 2003, No.266.

RESULTS AND DISCUSSION

The analysis of the clinical symptoms and the laboratory values showed the presence of two-four SIRS criteria (tachypnea, tachycardia, hyperthermia, leukocytosis) in 64.3 % of the patients with polytrauma in the first three days of observation. Significant differences between the main group and the comparison group in relation to age, condition severity, injury severity and amount of surgical interventions were not identified. At the same time, it was found that polytrauma was more often complicated by thrombosis in the patients at the age of 36-45 (OR = 2.31 (95 % CI 1.009-5.278)), and was more often in the men than in the women (OR = 1.25 (95 % CI 1.045-1.425)). Also the statistically significant differences in location of injuries were found (the table 2). So if TBI, thoracic and abdominal injuries were the main damages in the patients with absent thrombosis, then injuries to the lower extremities prevailed in the patients with thrombosis (χ² = 16.547, p = 0.001; OR = 6.35 (95 % CI 2.512-16.035)). The pelvic injuries were commonly accompanied by embologenic thrombosis (OR = 4.8 (95 % CI 1.194-19.303)).

Table 2. Location of injuries in patients with polytrauma

Injury	Comparison group (n = 30)	Main group (n = 26)
Head (face)	17	12
Chest (ribs)	18	11
Pelvis	6	8
Abdomen	12	9
Spine	5	4
Extremities	8	22

The further analysis showed that the patients with floating thrombosis differed from the patients of two groups according to severity of their condition: APACHEIII was 24.8 % higher than in the comparison group (p = 0.004) and by 43.8 % – the patients with the uncomplicated course of thrombosis (p = 0.001) (the table 3). It was higher than 90 points in 75 % of the patients in the subgroup B as compared to only 14.3 % in the subgroup A (p = 0.008; OR = 5.25 (1.369-20.131)).

Table 3. Comparative clinical characteristics in patients with polytrauma

Criteria	Comparison group (n = 30)	Main group A (n = 16)	Main group В (n = 10)
Condition severity according to APACHE III, points	79 (56.0-104.0)	59 (47.0-86.0)	105 (85.7-113.0)*,**
Injury severity according to ISS, points	25 (23.0-27.0)	13 (9.0-34.0)	34 (18.2-35.7)**
Injury severity according to AIS	9 (8.0-11.0)	5 (3.0-10.0)	10 (5.7-11.2)**
Shock severity	1.0 (1.00-2.00)	1.0 (1.00-2.00)	2.0 (1.75-2.25)*,**
Heart rate	100 (100.0–115.0)	95 (90.0–110.0)	110 (105.5–128.7)
Systolic AP (mm Hg)	130.0 (115.0–145.0)	120.0 (115.0–140.0)	110.5 (105.25–115.0)
Diastolic AP (mm Hg)	80.0 (60.00–85.00)	75.0 (60.00–80.00)	79.5 (56.25–88.50)

Note: * – statistically significant differences as compared to the comparison group, p < 0.05; ** – statistically significant differences between the groups, p < 0.05.

This categoryof the patients showed the presence of at least three SIRS criteria, with higher incidence of leukocytosis as compared to other groups of the patients. So, the number of leukocytes in the peripheral blood was 27.3 % higher in the patients of the subgroup B in the first day after trauma as compared to the subgroup A (p = 0.028), and 21.2 % higher than in the comparison group (p = 0.042) (the table 4). The statistically significant differences relating to this value were observed between the groups during the following observation. In the first day after trauma, the subgroup B demonstrated the leukocytosis in combination with the increasing level of lymphocytes (2.2 times higher, p = 0.028). The inverse time trends were observed later: the increasing amount of lymphocytes in the subgroup B and the increase in the comparison group.

Table 4. Time course of hematological values in patients with polytrauma

Values	Day in ICU	Comparison group (n = 30)	Main subgroup A (n = 16)	Main subgroup B (n = 10)
Red blood cells х1012/л / х1012/l	1st	3.5 (3.40-3.67)	3.7 (3.26-4.37)	3.3 (2.65-3.97)
	3rd	3.5 (3.00-3.60)	3.6 (3.15-4.10)	3.1 (3.05-4.40)
	5th	3.6 (3.20-3.68)	3.4 (2.94-3.87)**	3.8 (3.65-4.10)
Platelets х109/л / х109/l	1st	169 (129.0-183.0)	190 (141.7-240.5)	138 (100.2-187.0)
	3rd	144 (140.0-152.0)	172 (111.0-203.2)	105 (73.0-231.2)
	5th	250 (215.0-344.0)	254 (145.5-379.2)	280 (272.5-340.7)
Leukocytes х109/л / х109/l	1st	10.4 (10.20-12.00)	9.6 (9.3-12.4)	13.2 (10.58-17.15)*,**
	3rd	10.9 (9.60-14.32)	9.70 (8.84-13.20)	11.5 (7.97-16.05)**
	5th	9.16 (6.00-15.00)	8.7 (6.50-10.30)	12.8 (11.60-14.45)*,**
Lymphocytes х109/л / х109/l	1st	0.84 (0.640-1.12)*	1.38 (0.832-4.332)	1.83 (0.880-2.960)
	3rd	1.77 (1.110-1.870)	1.37 (1.182-1.492)	1.17 (1.02-1.232)*
	5th	1.87 (1.50-2.70)	1.89 (1.050-2.337)	1.5 (1.122-2.167)

Note: * – statistically significant differences as compared to the comparison group, p < 0.05; ** – statistically significant differences between the groups, p < 0.05.

The mechanisms, which cause the migration of leukocytes to the injury region and development of immune and reparative processes there, include the adhesion reactions between activated platelets and leukocytes. The literature shows a relationship between reactions of hemostasis and inflammation in tissue alteration [5, 13]. This relationship, regulated by oxygen radicals, cytokines and growth factors, results in hypercoagulation and tissue injury. Also it can be important for vascular wall damage, and not also for clot formation, but also for the processes of adhesion to vascular endothelium [13, 14].
The high adhesion of leukocytes can produce the microvascular occlusions with subsequent tissue hypoperfusion and hypoxia. Lactate is considered as a parameter reflecting the degree of tissue hypoxia. No statistically significant intergroup differences were found in lactate examination in the first day, whereas the patients with developed floating thrombosis showed the significant increase (1.8 times on average, p = 0.03) in the lactate level on the third day as compared to other two groups. Along with lactate, the higher level of serum glucose was found on the third day in comparison with the comparison group and the subgroup A (by 26.8 % (p = 0.01) and 22.5 % (p = 0.01) correspondingly). One of the causes of blood glucose increase in hypoxia is associated with suppression of insulin activity and insufficient delivery of glucose to the cells, resulting in worsening patients’ condition. Correction of such non-diabetic increase in glycemia is possible only in normalizing oxygen provision.

Table 5. Time course of biochemical values in blood of patients with polytrauma

Values	Day in ICU	Comparison group (n = 30)	Main subgroup A (n = 16)	В Main subgroup B (n = 10)
Glucose (mmol/l)	1st	8.5 (6.40-10.20)	6.6 (4.87-9.95)	6.1 (5.39-7.50)*
	3rd	5.2 (5.00-5.40)	5.5 (5.30-5.80)	7.1 (6.12-8.07)*,**
Lactate (mmol/l)	1st	2.2 (0.72-4.27)	2.0 (1.77-2.77)	1.7 (1.50-1.90)
	3rd	2.0 (2.0-2.40)	2.2 (1.72-2.47)	3.8 (2.70–5.70)*,**
рН	1st	7.35 (7.330-7.350)	7.33 (7.280-7.40)	7.35 (7.150-7.385)
	3rd	7.34 (7.330-7.350)	7.35 (7.330-7.370)	7.36 (7.285-7.420)

Note: * – statistically significant differences as compared to the comparison group, p < 0.05; ** – statistically significant differences between the groups, p < 0.05.

The received results show more severe disorders of systemic hemodynamics, evident disorders of tissue capillary blood flow and gas exchange in the patients with embologenic thrombosis. Such disorders present the predictor of worsening condition that correlates with the presented values of patient’s condition severity according to APACHEIII. Blood lactate appears in glycolysis and presents the marker of tissue hypoxia. Hypoxia, influence of sympathomimetics on activity of the membrane enzymes, regionary blood flow disorder and liver dysfunction in development of multiple organ dysfunction can be a cause of lactatemia.
Therefore, the presented results show that severe course of the traumatic disease with events of systemic hemodynamics and capillary flow disorders, and systemic inflammatory response syndrome with vascular endothelial injury cause the clot formation, as well as a possibility of fragmentation of the clot head and increasing risk of PE. 

CONCLUSION

1. In patients with polytrauma, the development of venous thrombosis is associated with location of a main injury in the regions of the pelvis and the lower extremities. In pelvic injuries, the risk of floating clot is higher than stable one (OR = 4.8 (1.194-19.303)).
2. Development of unstable (floating) thrombosis in patients with polytrauma is associated with more severe condition (APACHE – 101.2 ± 11.3).
3. Development of embologenic thrombosis in patients with polytrauma was accompanied by systemic inflammatory response syndrome with leukocytosis and lymphopenia, as well as with hyperglycemia and hyperlactatemia.

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