Kabanov City Clinical Hospital #1,

Omsk State Medical Academy,

Omsk, Russia

 

Hypovolemia is one of the leading pathogenetic factors of traumatic shock [1]. It causes negative changes in hemostasis system [2, 3], systemic inflammatory response and [4] and endothelial dysfunction [5, 6, 7] which act the part in development of multiple organ failure syndrome (MOFS) [8], which is one of the causes of lethal outcome in such patients [9]. The aim of the study was identification of chronology and structure of systemic and organ dysfunctions in patients with traumatic shock, as well as comparative estimation of regression during different types of infusion therapy.

 

MATERIALS AND METHODS

The simple blind prospective cohort randomized (envelope method) study included 75 patients (mean age of 29.5 ± 3.8) with traumatic shock of degree 3. The patients were distributed into 3 groups depending on the type of infusion therapy at prehospital and hospital stages of treatment. The cause of traumatic shock was road traffic accident in all patients, the cause of acute blood loss ‒ open and closed fractures of femoral or/and splint bones in combination with pelvic fractures and closed abdominal trauma with injuries to abdominal organs. Traumatic shock was defined at prehospital stage (before infusion therapy) in the presence  of trauma in disease history or on the basis of the clinical signs: consciousness level, skin pallor and chilliness, systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP = 0.42 SAP + 0.58 DAP), hear rate (HR) and shock index (HR/SAP ratio). At prehospital stage all patients received multimodal anesthesia (narcotic and non-narcotic analgetics), infusion therapy through the central vein (subclavicular or jugular) catheter, and also inotropic and vascular support with dopamine, 5 ug/kg of body weight per minute. After trachea intubation all patients received artificial lung ventilation with Chirolog Paravent PAT (Chirana, Slovakia). In the group I (25 patients) infusion therapy was performed with non-balanced 0.9 % sodium chloride saline crystalloid solution and 6 % hydroxyethyl starch (HES) colloid solution 200/0.5. The group II (25 patients) received 0.9 % sodium chloride crystalloid solution and 4 % modified gelatin (MG), the group III (25 patients) ‒ saline balanced (similar with electrolyte composition of human blood plasma) crystalloid solution (isotonic sterofundine) and 4 % MG colloid solution. The colloid/crystalloid solutions ratio was 1:1 in the group I, and 1:3 in the groups II and III. Nonequivalence in the ratios of crystalloids/colloids was associated with different therapeutic effect range of the colloid solutions, because the maximal 24 hour dose is 33 ml/kg of body mass for 6 % HES 200/0.5, and 150 ml/kg of body mass for 4 % MG [10, 11].

At prehospital and hospital stages the blood loss volume was assessed with shock index, clinical symptoms and external blood loss [4]. During the first 24 hours the total blood loss was 3396.5 ± 212.5 ml in the group I, 3447.7 ± 231.1 ml in the group II, 3431.6 ± 212.3 ml in the group III. During the first 24 hours the total volume of infusion transfusion agents was 9906.5 ± 117.4 ml in the group I, 9987.4 ± 111.5 ml in the group II, 9979.6 ± 109.5 ml in the group III. The total infusion of colloid solutions was 2465.35 ± 99.7 ml in the group I, 3246.3 ± 97.1 ml in the group II, 3301.2 ± 92.8 ml in the group III. The total infusion of crystalloid solutions was 2398.3 ± 56.8 ml in the group I, 1265.2 ± 48.6 ml in the group II, 1245.4 ± 56.7 ml in the group III. During the first 24 hours, replacement therapy of anemia and consumption coagulopathy was performed according to the generally accepted criteria using transfusion of fresh frozen single group plasma and red blood cells with the 3:1 ratio [12]. During the subsequent 2 days transfusion therapy was carried out according to the results of coagulation hemostasis, hemoglobin and hematocrit [12]. The time from the moment of initiation of anti-shock measures to hospital admission was 57.1 ± 0.2 min. in the group I, 56.9 ± 0.4 38.9 ± 0.4 min. in the group II, 56.7 ± 0.538.4 ± 0.3 in the group III.

At hospital stage all patients with traumatic shock were transferred to the operating room for emergency surgical treatment, with continuation of anti-chock treatment, which was initiated at prehospital stage, and with diagnostic measures (plain X-ray for chest, abdominal organs, skull, pelvis and extremities, ultrasound examination of abdominal organs, laparoscopy, biochemical data, hemostasis parameters, total urine and blood analysis, blood group and Rh determination) [13]. For surgical treatment the total intravenous (fentanyl + ketamine + seduxen) anesthesia with muscle relaxants during ALV with air-oxygen mixture was performed. The surgical treatment was performed for all patients (n = 75, 100 %). Its volume depended on localization and severity of an injury. Surgical treatment was initiated after 86 ± 1.1 min. in the group I, 8.6 ± 1.1 min. in the group II, 8.8 ± 1.3 min. in the group III. Then the patients were transferred to ICU for infusion, antibacterial, respiratory and symptomatic therapy.

At hospital stage the assessment of the cardiovascular system parameters was performed (stroke volume (SV), circulation minute volume (CMV), total peripheral vascular resistance (TPVR), circulating blood volume (CBV)) through non-invasive tetrapolar rheography and impedancemetry [4]. The parameters of vascular thrombocytic (thrombocyte count) and coagulative (activated partial thromboplastin time (APTT), soluble fibrin monomeric complexes (SFMC), thrombin time (TT) and fibrinogen) hemostasis were evaluated [14]. The standardized methods were used for evaluation of hematocrit, leukocyte and erythrocyte count, hemoglobin level, lactate, endothelin-1 and von Willebrand factor in the venous blood serum, as well as for the values of electrolyte (kalium ‒ Ê⁺, natrium – Nà⁺, chloride – Cl⁺) and acid-base (pH) composition of arterial (a) and venous (v) blood. Gas exchange lung function was assessed with the level of PO₂ in arterial and venous blood using Radiometr-2 gas analyzer (Denmark), with subsequent calculation of oxygenation index (OI = PaO₂/percent O₂ contents in inspired mixture (FiO₂)). The severity of general state, MOFS expression and efficiency of therapeutic measures were estimated with SOFA [4]. The studies were performed on admission to ICU, 12 hours later and during 3 days.

The systemic statistic analysis of clinical, laboratory and instrumental studies was performed with Statistica 6. The difference was statistically significant with p < 0.05 [15]. The inclusion criteria were 1) the age of 18-40, 2) acute initiation of disease, 3) admission to medical prophylactic facility during 2 hours after disease initiation. The exclusion criteria were 1) concurrent sub- and decompensated chronic pathology of kidneys, liver, heart and lungs, 2) oncologic pathology in the anamnesis, 3) previous history of hormonal therapy and chemotherapy, 4) diabetes mellitus of type I and II, 5) terminal state, 6) participation in other study, 7) allergic reactions to introduction of colloid solutions of hemodynamic type based on 6 % HES and 4 % MG.

The study was performed with permission of the bioethics committee of Kabanov City Clinical Hospital #1. It corresponded to Helsinki Declaration – Ethic Principles for Scientific Medical Research Involving Human Subjects 2000 and the Rules for Clinical Practice in Russian Federation confirmed by the Order of the Health Ministry of Russian Federation from 19.06.2003, #266.

 

RESULTS

On admission to ICU the systemic hemodynamics values were associated with statistically significant differences from the control indices in the patients of all groups (table 1). It testified severe circulatory disorders which were supported by lactate level in the venous blood (table 1). The comparison of parameters of volemic status in the controls and in the patients of all groups showed that in the control group CBV was 56.1 %, 56.5 % and 56.3 % compared to the patients of groups I, II and III correspondingly, even with consideration of infusion therapy (at prehospital stage and during surgery). It conditioned statistically significant increase in HR and peripheral resistance and statistically significant decrease in stroke volume and MBV in all patients (table 1) compared to the controls, and it testified the dominating role of hypovolemia in development of acute cardiovascular insufficiency (ACVI). One of the factors of persistent hypovolemia was endothelial dysfunction, which was supported by high levels of von Willebrand factor and endothelin-1 in the blood serum (table 1). Infusion-transfusion therapy supported significance of hypovolemia as a leading pathogenetic factor. It favored increase in CBV, SV, CMV and SAD, and decrease in peripheral resistance and lactate in all patients (table 1).

Table 1
The comparative analysis of system hemodynamics, hemostasis, tissue perfusion and endothelial dysfunction in patients with traumatic shock of degree 3, Me (QL; QA) - median (upper and lower quartiles)

Table 2
The results of paired comparative analysis of SOFA and its components in patients with traumatic shock of degree 3, Me (QL; QA) - median (upper and lower quartiles)

On admission to ICU all patients demonstrated absent urination, which had tendency to gradual hour increase (< 0.2 ml/kg of body mass) after 12 hours at the background of anti-shock treatment. In its turn, it conditioned increase in creatinine level in the serum blood at the end of the first day (table 2). In all patients the central nervous inefficiency was registered as lately as at prehospital stage (according to GCS, consciousness level was 7.9 ± 0.3 in the group I, 7.8 ± 0.2 in the groups II and III). Also on admission all patients demonstrated disorders in hemostasis system (table 1 and 2). Already at the end of the first day (table 3) ARDS was registered in all patients. It was conditioned by disorders in gas exchange functions of the lungs, because of evident circulatory and hemodynamic disorders (table 1), DIC (table 1, 2) and systemic inflammatory response that required ALV up to full regression of this pathologic process (table 3). Also at the end of the first day all patients had disordered liver function (table 2) because of persistent ischemia and apparent hypoxia. The infusion-transfusion therapy conditioned faster correction of ACVI and tissue perfusion in the groups II and III compared to the group I (table 1). It determined thee statistically significant expressiveness of MOFS in the group I compared to the groups III and III (table II). Also it testified higher efficiency of infusion-transfusion therapy for ACVI regression in the patients of the groups II and III compared to volemic load in the patients of the group I (table 3).

Table 3
System hemodynamics stabilization, ARDS rate, ALV duration, MODS, bed-days in ICU, mortality in patients with traumatic shock of degree 3

 

DISCUSSION

Predominance of hypodynamic type of circulation was conditioned by deficiency in venous return and was associated with significant CBV loss, but not with myocardial contraction disorders, which developed later [1, 3]. The severe circulation disorders conditioned disorders of transcapillary exchange and development of endothelial insufficiency [5]. Actually, increased levels of von Willebrand factor and its activity are accelerators for thrombocyte adhesion to subendothelium through glycoprotein Ib surface thrombocyte receptor binding and stimulation of platelet-thrombocytic interactions through glycoprotein IIb/IIIa binding [6], but also the indicator of endothelial injury in critically ill patients [7]. Platelet adhesion is most intensive in the macro- and microcirculation vessels. It determines development of disorders in hemostasis system and non-respiratory lung functions [7]. Increased levels of endothelin-1 in the blood serum in the patients with severe traumatic shock were conditioned by immediate mechanical injury and acute cardiovascular insufficiency as result of blood loss, because the main activators of endothelin-1 synthesis are activation of sympathoadrenal system, ischemia and hypoxia [6]. Furthermore, endothelin-1 can induce immediate vascular constriction [7], as shown by high peripheral resistance (table 1), but also deteriorate the course and induce development of cardiac insufficiency by means of immediate toxic influence on the cardiac muscle, cause lung hypertension and produce prothrombogenic activity [7]. Besides, traumatic shock, which is characterized with injury, systemic hypoperfusion and hypoxia in tissues and in organs, and release of significant amount of inflammatory mediators [7], can condition severe metabolic disorders [2] and favor formation and preservation of endothelial function [6], which, in its turn, by means of activation of rennin-angiotensine system and oxidant stress can condition development of unprogrammed cell apoptosis and favor injuries to organs and systems [7].

Decrease in systemic arterial pressure, as result of hypovolemia, conditions decrease in renal perfusion pressure and is accompanied by release of noradrenaline, angiotensine II, antidiuretic hormone and endothelin that result in local vasoconstrictor effect favoring capillary stasis, increase in resistance to blood flow, development of endothelial dysfunction and excessive accumulation of fluid in renal interstitial space that favored development of renal insufficiency in the patients [10]. Furthermore, severe volemic and hemodynamic disorders do not favor adequate brain perfusion that causes insufficient CNS [4]. In patients with traumatic shock after massive blood loss the severe hypovolemia conditions apparent disorders in vascular thrombocytic and plasma links of hemostasis [2]. It is associated with the fact that hemostasis system responses quickly to non-arrested bleeding with hypercoagulation and favors subsequent decrease in clotting factors and platelet count at the background of preexisting deficiency of factors (platelet loss and loss of plasma clotting factors during blood loss) that determines DIC development with increasing bleeding [14]. Furthermore, infusion therapy can save coagulopathy events [10, 11]. During the whole ICU period all patients demonstrated ARDS as manifestation of pulmonary dysfunction and main moving force for MOFS (tables 2, 3). As the table 3 shows, the ALV duration (which was carried out because of ARDS) was similar in all groups, as well as MOFS duration. Besides, MOFS (table 3) was the main cause of lethal outcomes in the patients of all groups during both the whole period of the follow-up (days 2-3) and in the long term period (days 12-13). Liver insufficiency (table 2) in traumatic shock was associated with undergone critical state [1] and high levels of the products of natural, disordered and pathologic metabolism which extensively transfer to systemic flow during infusion-transfusion therapy and improvement of peripheric circulation [4]. Actually, the realized intensive care favored regression of liver insufficiency at the beginning of the days 3 in all groups (table 3).

 

CONCLUSION

1. In patients with traumatic shock of degree 3 the following chronology and the structure of development of organ and systemic dysfunctions are registered: peripheral resistance, renal, cerebral, hemostasiological, respiratory and liver insufficiency.

2. In patients with traumatic shock of degree 3 SOFA allows assessing expressiveness of systemic and organ dysfunctions, except for plasma hemostasis system.

3. For patients with traumatic shock of degree 3 it is appropriate to evaluate and to monitor plasma hemostasis using APPT during surgery and in postsurgical period.

4. For patients with traumatic shock of degree 3                                      infusion therapy can include 4 % modified gelatin, which effectively corrects volemic and circulatory disorders and also has minimal influence on hemostasis.

5. For patients with traumatic shock of degree 3 infusion therapy with 4 % MG (contrary to 6 % HES 200/0.5) favors earlier regression of dysfunction of cardiovascular system.