Primary and secondary prevention of cardiovascular pathology in injured with combat trauma

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Ukrainian Military Medical Academy, Kyiv

National Military Medical Clinical Center “Main Military Clinical Hospital”, Kyiv

Primary and secondary prevention of cardiovascular pathology in injured with combat trauma

N.M. Sydorova

O.V. Druz

V.L. Savytskyi

I.A. Chernenko

L.L. Sydorova

Abstract

The purpose of the study was to develop and implement measures for primary and secondary prevention of cardiovascular pathology in injured with combat trauma. The data of 448 injured with combat trauma who were admitted to the National Military Medical Clinical Center «Main Military Clinical Hospital» were analyzed. Analysis of the average values of biochemical blood parameters showed the presence among injured with combat trauma and signs of cardiovascular disease more pronounced metabolic disorders, cytolysis and inflammation compared with injured without such complication: high levels of fibrinogen (by 11.1 %, p=0.0294), glucose (by 11.1 %, p=0.0004), asparagine transaminase (by 74.6 %, p=0.0005), alanine transaminase (by 58.4 %, p=0.0013), and lower levels of total protein (by 7.1 %, p=0.0008). The obtained results allowed us to offer hypermetabolism syndrome as one of the mechanisms of cardiovascular pathology development in injured with combat trauma, as well as to develop and implement approaches for prevention of this syndrome associated with the secondary pathology of the cardiovascular system.

Key words: metabolism, psychological support, military medicine, cardiology.

Н.М. Сидорова, О.В. Друзь, В.Л. Савицький, I.A. Черненко, Л.Л. Сидорова

Первинна та вторинна профілактика серцево-судинної патології у постраждалих, які отримали бойову травму

Анотація

hypermetabolism syndrome combat trauma

Метою роботи було розробити та запровадити заходи первинної та вторинної профілактики ураження серцево-судинної системи у постраждалих, які перенесли бойову травму. Були проаналізовані дані 448 постраждалих з бойовою травмою, які поступали до Національного військово-медичного клінічного центру «Головний військовий клінічний госпіталь». Аналіз середніх величин біохімічних показників крові показав наявність у постраждалих з бойовою травмою та ознаками ураження серцево-судинної системи більш виражених метаболічних порушень, цитолізу та запалення порівняно з постраждалими, які не мали цього ускладнення травмування: вищі рівні фібриногену (на 11,1 %, р=0,0294), глюкози (також на 11,1 %, р=0,0004), аспарагінової трансамінази (на 74,6 %, р=0,0005) та аланінової трансамінази (на 58,4 %, р=0,0013), та нижчі - загального білку (на 7,1 %, р=0,0008). Отримані результати дозволили запропонувати в якості одного з механізмів розвитку ураження серцево-судинної системи у постраждалих з бойовою травмою синдрому гіперметаболізму, а також обґрунтувати, розробити та запровадити заходи профілактики цього синдрому, асоційованого з розвитком вторинної патології серцево-судинної системи у постраждалих, які перенесли бойову травму.

Ключові слова: метаболізм, психологічна підтримка, військова медицина, кардіологія.

Studies of the last 7 years show that people who have suffered a combat trauma in the area of the Anti-Terrorist Operation (ATO)/Joint Forces Operation (JFO), in addition to health problems directly related to the injury, may experience secondary pathology of internal organs. The frequency of such complications according to various data can reach 40 % [8]. Most often in the first 2 weeks after injury, there are signs of the pathology of the cardiovascular system (15.4 %) and hepatopathy (9.9 %) [8]. Moreover, the incidence of secondary pathology of the cardiovascular system reaches 92.5 % among patients who were treated for combat trauma in the intensive care units [4].

Secondary pathology of the cardiovascular system as a consequence of combat trauma is defined as cardiovascular abnormalities in the wounded outside the area of injury, due to impaired neuroendocrine regulation, hypoxia, systemic and local response to injury, dysregulation of the autonomic nervous system, stress - a set of effects of the damage and compensatory reactions to injury, as well as nature, location and severity of trauma. A special role in the development of secondary pathology of the cardiovascular system after combat trauma is given to metabolic disorders, anaemia and hypoproteinemia [4], post-traumatic stress disorder and mental trauma. It should be noted that post-traumatic stress disorder and mental trauma are also accompanied by increased metabolism, activation of lipid peroxidation, slowing down the recombination of free radicals in the body [12-14].

It is known that secondary pathology of the cardiovascular system as a consequence of combat trauma can adversely affect the prognosis of patients due to the development of both organic (myocardial necrosis, acute myocarditis, dilated cardiomyopathy, etc.) and functional signs of the lesion (systolic and/or diastolic dysfunction of the left ventricle, congestive heart failure, heart rhythm and conduction disorders, including fatal arrhythmias) [9, 14], and lead to disability of patients [7]. Timely detection of a group of injured with combat trauma who are at high risk of secondary pathology of the cardiovascular system as well as the implementation of measures to prevent this complication at the stage of providing qualified medical care will significantly improve the prognosis of such patients and reduce the cost of their treatment.

However, despite the urgency of the problem of secondary pathology of the cardiovascular system, the genesis of this pathological condition is insufficiently studied, as verification of the nature of heart disease is almost impossible without a myocardial biopsy, whereas laboratory and instrumental changes are usually nonspecific.

Recently, methods of probabilistic-statistical modelling and multidimensional statistical analysis are increasingly used in medical and biological research to predict various processes. The advantage of such methods is the ability to identify the nature and interdependence between the features that describe the process under study. Multidimensional methods of regression, discriminant analysis, Bayesian classification methods, etc. are most often used for this purpose [2, 10].

The purpose of the study was to develop and implement measures of primary and secondary prevention of secondary pathology of the cardiovascular system as a consequence of combat trauma on the basis of substantiation of the genesis of its development in injured with combat trauma, using mathematical methods of processing routine biochemical blood parameters in the first three days after injury.

Materials and methods

The data of the injured in the area of Anti-Terrorist Operation/Joint Forces Operation (ATO/JFO), who were admitted to the specialized (fourth) level of medical care - to the National Military Medical Clinical Center “Main Military Clinical Hospital” (NMMCC “MMCH”) were analyzed.

The inclusion of injured in the analysis was based on a study protocol approved according to the Helsinki Declaration by the Ethics Committee of the NMMCC “MMCH”, which is sufficient for retrospective analysis of patient data from the Data Registry.

In order to determine the characteristics of biochemical blood parameters in servicemen with combat trauma, the data of 448 injured who were admitted to the NMMCC “MMCH” in 2014-2016 were analyzed. According to the chosen design and purpose of the study, injured with combat trauma were allocated to two groups depending on the presence of signs of secondary pathology of the cardiovascular system, which appeared in the first two weeks after receiving combat trauma.

Group I included 260 injured (58.0 % of subjects), in whom the examination on the 10th-14th day after receiving combat trauma did not show any signs of secondary pathology of the cardiovascular system (mean age 31.72±0.53). Group II included 188 patients (42.0 % of subjects, mean age 31.77±0.69), in whom signs of secondary pathology of the cardiovascular system were diagnosed. According to the main clinical characteristics, patients of both groups did not differ.

The laboratory tests were performed by the Clinic of Laboratory Diagnostics of NMMCC “MMCH”. The results of the study were processed on IBM-compatible computers using Excel computer software.

For each sample of indicators studied, we calculated and analyzed the average value (M), the standard error of the average value (m), the variance (a) [1].

According to the values of the coefficients of asymmetry (As) and excess (Ex), all samples had a normal distribution (As and Ex <2) [6]. Analysis and verification of the equality of the mean populations analyzed in this study confirmed that the samples had a normal distribution and were independent, the variances of the samples differed (a12 Ф a22, pa in all cases <0.025). In this regard, parametric methods were used for samples with different variances [6]. The statistical significance of the difference between the mean sample values of groups studied was determined by the results of a two-sample t-test with different variances [6]. Differences at p-value <0.05 were considered statistically significant.

Results of the study and their discussion

According to the results of our analysis, patients from Group II more often had gunshot wounds (29.8 % compared to 21.5 % of those from Group I, p <0.05) and less often - closed injuries (10.6 and 23.1 %, respectively, p <0.001). Patients from Group II had multiple or combined injuries more often (35.1 and 25.5 %, respectively) compared with the frequency of these indicators in Group I (28.1 and 16.2 %, respectively, p for both cases <0.05). Patients in both groups had a moderate injury in almost half of the cases, however, patients from Group II have diagnosed a severe injury more often than in Group I, (42.6 vs. 23.1 %, p<0.001) and less often - minor injury (13.83 vs. 28.08 %, p<0.001).

Analysis of the average values of blood parameters of injured with signs of secondary pathology of the cardiovascular system showed the presence of more severe metabolic disorders, cytolysis and inflammation in the early period after combat trauma compared with parameters in injured who did not have signs of secondary pathology of the cardiovascular system (Table 1).

Table 1. Biochemical blood parameters (M±m) of injured in the area of ATO/JFO

Patients in Group II had higher blood levels of fibrinogen (by 11.1 %, p=0.0294), glucose (also by 11.1 %, p=0.0004), asparagine transaminase (AST, by 74.6 %, p=0.0005), alanine transaminase (ALT, by 58.4 %, p=0.0013), and lower - total protein (by 7.1 %, p=0.0008) compared with such parameters in Group I.

Our new data on the development of hypermetabolism syndrome in injured with combat trauma, and further clinical observation of this contingent allowed us to justify and develop measures for the prevention of this syndrome associated with the development of secondary pathology of the cardiovascular system in injured with combat trauma (table 2).

We earlier using the methods of mathematical modeling [8] proved the role of metabolic disorders in the genesis of secondary pathology of the cardiovascular system. According to the proposed binomial logistic regression, the model of the impact of laboratory blood parameters determined in the first three days after injury, on the risk of developing secondary pathology of the cardiovascular system had the form [8]: y=0.71-0.013 total protein (g/L)+0.099 glucose (mmol/L).

The prognosis of the event development (secondary pathology of the cardiovascular system in this case) is positive at y>0.5 and negative at y <0.5 (0=<y>=1).

This model suggests that combatants, who have lower blood levels of total protein and higher serum levels of glucose in the first three days after combat trauma are at high risk of secondary pathology of the cardiovascular system. This finding also supports our previous concept of hypermetabolism syndrome as a main cause of secondary pathology of the cardiovascular system.

Thus, in the series of our studies, we have confirmed the role of metabolic disorders in the development of secondary pathology of the cardiovascular system as a consequence of combat trauma, which revealed one of the possible mechanisms of myocardial damage in injured with combat trauma and justify measures for its prevention.

Classical studies of the early century have shown that systemic inflammation, the presence of which in patients with combat trauma is essential, is accompanied by secondary toxic damage due to absorption of tissue breakdown products, both neuroendocrine and metabolic response - the so-called hypermetabolism syndrome [3, 5, 8].

Because of hypermetabolic energy consumption and activation of catabolic processes (proteolysis, protein oxidation, activation of acute protein synthesis) due to hypermetabolism syndrome, there is a decrease in reparative processes and increased secondary immunodeficiency. Energy deficiency, which is formed as a result of these disorders, leads to the dysfunction of membrane cell pumps with the replacement of intracellular K + to Na +, followed by intracellular hyperhydration [3].

Table 2 Measures of primary and secondary prevention of secondary pathology of the cardiovascular system in injured with combat trauma

When developing measures for primary and secondary prevention of secondary pathology of the cardiovascular system in injured with combat trauma, we considered the high frequency of post-traumatic stress disorder in this group of patients (25-35 % of cases among persons with psychological trauma) [15]. The presence of this syndrome has an additional contribution to the development of secondary pathology of the cardiovascular system, as it can play a significant role in the formation of myocardial and vascular damage in injured with combat trauma. Some adverse effects on the myocardium and blood vessels have been described in patients with post-traumatic stress disorder [8, 9, 11-14]:

increased levels of adrenaline and noradrenaline (increased activity of the sympathetic nervous system);

increase in blood pressure and heart rate;

increase in platelet aggregation capacity;

disorders of lipid metabolism.

The presented above measures were introduced as a clinical component to the new functional and organizational model of providing medical care to injured with combat trauma. They are implemented in the work of field hospitals, military hospitals and military medical clinical centres, in particular NMMCC “MMCH”, civilian institutions that provide medical care to the specified contingent (acts of implementation), and received a high expert assessment.

Conclusions

Secondary pathology of the cardiovascular system was detected in 42.0 % of patients, confirming the high frequency of such pathology, which is manifested usually on days 10-14 after injury.

Injured with combat trauma and secondary pathology of the cardiovascular system are characterized by greater severity of metabolic disorders, cytolysis and inflammation, namely, higher blood levels of fibrinogen (by 11.1 %, p=0.0294), glucose (by 11.1 %, p=0.0004), asparagine transaminase (by 74.6 %, p=0.0005), alanine transaminase (by 58.4 %, p=0.0013), and lower - total protein (by 7.1 %, p=0.0008).

The revealed changes of biochemical indicators allow us to offer hypermetabolism syndrome as one of the mechanisms of cardiovascular pathology development in injured with combat trauma. Our findings as well as results of further clinical monitoring allowed us to justify, develop and implement a comprehensive program of measures for the prevention of hypermetabolism syndrome associated with the development of secondary pathology of the cardiovascular system in injured with combat trauma.

The presence of metabolic disorders in injured with combat trauma requires preventive measures both in the early stages after injury (as the primary prevention of secondary pathology of the cardiovascular system), and subsequent medical and psychological support of such patients to minimize the effects of combat trauma on the cardiovascular system in the long-term perspective.

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