THE INDICATORS ASSOCIATED WITH LETHAL OUTCOMES IN PATIENTS WITH TRAUMATIC SHOCK
Omsk First Aid Station,
Omsk City Clinical Hospital named after A.N. Kabanov,
Omsk State Medical Academy, Omsk, Russia
At the present stage of critical care medicine the actuality of the problem of traumatic shock is associated not only with progressive increase in the number of patients of working age, the features of rendering emergency care, but also with absence of generally accepted protocols for diagnostics and treatment [1] for improving clinical outcomes [2, 3, 4, 5]. Therefore, the objective of the present study was identifying and defining the information significant clinical laboratory values associated with lethal outcomes in patients with traumatic shock at hospital stage.
MATERIALS AND METHODS
The study presents the results of the simple blinded prospective clinical cohort randomized (envelope method) study covering 75 patients (the mean age of 29.5 ± 3.8) with traumatic shock of degree 3 and distribution into 3 groups depending on the type of infusion therapy at prehospital and hospital stages. The cause of traumatic shock was road traffic accidents, and the cause of acute blood loss – closed and opened fractures of the femoral and/or tibial and fibular bones in combination with pelvic fractures and closed abdominal trauma with injuries to the internal organs. The inclusion criteria were: 1) the age of 18-40; 2) acute initiation of the disease; 3) admission to the medical prophylactic facility within 2 hours after initiation of the disease. The exclusion criteria were: 1) concurrent sub- and decompensated chronical pathology of the kidneys, the liver, the heart and the lungs; 2) history of oncologic pathologies; 3) history of hormonal and chemical therapy; 4) diabetes mellitus of the types 1 and 2; 5) terminal state; 6) participation in other study; 7) allergic responses to colloid solutions of hemodynamic type on the basis of 6 % HES and 4 % MG. Traumatic shock of degree 3 was diagnosed at prehospital stage of treatment (before infusion therapy) in the presence of previous injuries and on the basis of the following signs: the level of consciousness of 9 points and less according to Glasgow Coma Scale, paleness and coldness of skin surface, the mean arterial pressure < 35 mm Hg and shock index ≥ 2.9. At prehospital stage all patients received multimodal anesthesia (narcotic and non-narcotic analgetics), infusion therapy through the catheter in the central (subclavicular or jugular) vein and inotropic and vascular support with dopamine in the dosage of 5 mkg/1 kg/1 min. After tracheal intubation all patients received artificial lung ventilation with Chirolog Paravent PAT (Chirana, Slovakia). Infusion therapy in the group I (25 patients) was realized with non-balanced saline crystalloid solution of 0.9 % sodium chloride and the colloid solution of 6 % hydroxyethyl starch (HES) 200/0.5, in the group II (25 patients) – crystalloid solution of 4 % modified gelatin (MG), and in the patients of the group III (25 persons) – saline balanced (identical to electrolyte composition of the human blood plasma) – with crystalloid solution of isotonic sterofundine and colloid solution of 4 % MG. The ratio between crystalloid and colloid solutions was 1:1 in the patients of the group I, and 1:3 for the patients of the groups II and III. The inequivalence in the ratios of crystalloids/colloids was associated with different therapeutic range of action for the used colloid solutions, because the maximal daily dosage of 6 % HES 200/0.5 is 33 ml per a kilogram of body mass, and 150 ml/kg for 4 % MG [1]. At prehospital and hospital stages the volume of blood loss was defined on the basis of shock index, clinical symptoms and evaluation of external blood loss [1]. The total volume of blood loss was 3,396.5 ± 212.5 ml in the group I, 3,447.7 ± 231.1 in the group II, 3,431.6 ± 212 ml in the group III. The total volume of transfused infusion-transfusion media was 9,906.5 ± 117.4 ml in the first days in the group I, 9,987.4 ± 111.5 ml in the group II and 9,979.6 ± 109. 5 ml in the group III. The volume of infused colloid solutions was 2,465.35 ± 99.7 in the group I, 3,246.3 ± 97.1 ml in the group II and 3,301.2 ± 92.8 ml in the group III. The volume of infused crystalloid solutions was 2,398.3 ± 56.8 in the group I, 1,265.2 ± 48.6 ml in the group II and 1,245.4 ± 56.7 ml in the group III. Within the first 24 hours for all patients the relative therapy for anemia and consumption coagulopathy was realized with the general criteria with use of transfusion of fresh frozen single-group plasma and red blood cells [6]. During the following two days infusion therapy was carried out according to the results of the parameters of coagulation hemostasis, hemoglobin and hematocrit. The time from the moment of initiating the anti-shock measures to admission to the hospital was 57.1 ± 0.2 min in the group I, 56.9 ± 0.4 and 38.9 ± 0.4 min in the group II, 56.7 ± 0.5384 ± 0.3 in the group III. At hospital stage all patients with traumatic shock were immediately admitted to the operating room for carrying out acute surgical treatment, with continuation of anti-shock therapy initiated at prehospital stage, and diagnostic examinations (plain X-ray for thoracic and abdominal organs, cranium, the pelvis and injured extremities, abdominal ultrasound, laparoscopy, biochemical data, hemostasis parameters, total blood and urine analysis, blood group and Rh determination). Surgical treatment was realized with total intravenous (fentanyl + ketamine + seduxen) anesthesia with muscle relaxants in conditions of artificial lung ventilation with air-oxygen mixture. All patients received surgical treatment (n = 75, 100 %), and its volume depended on location and severity of injuries. Surgical treatment was initiated after 8.6 ± 1.1 min in the group I, 8.6 ± 1.1 min in the group II, and 8.8 min ± 1.3 min in the group III. After that they were admitted to the intensive care unit (ICU) for infusion, antibacterial, respiratory and symptomatic therapy. At hospital stage the patients were evaluated for parameters of cardiovascular system (stroke output, circulation rate, total peripheral vascular resistance, total blood volume) by means of non-invasive tetrapolar rheography and impedancemetry. The monitor ICARD (Chirana, Slovakia) was used for systemic AP, diastolic AP, MAP, HR and body temperature (Ò,ᵒ Ñ). The parameters of vascular thrombocytic (amount of platelets) and coagulation (activated partial thromboplastin time, APTT), soluble fibrin complexes (SFC), thrombin clotting time (TCT), fibrinogen and hemostasis were examined [7]. The uniform methods were used for estimating hematocrit, amount of white and red blood cells, hemoglobin, lactate, endotheline-1 (E-1) and von Willebrand factor (VWF) in the serum of venous blood, the values of electrolytic (ions of kalium - Ê+, natrium - Nà+, chloride - Cl-, calcium - Ca++) and acid-base (pH) composition of arterial (a) and venous (v) blood. Gas exchange function of the lungs was estimated according to the level of oxygen partial pressure (ÐÎ2) in arterial (a) and venous (v) blood with use of gas analyzer Radiometr-2 (Denmark) and the following calculation of oxygenation index (OI = PaO2/percent content of oxygen in inspired mixture [FiO2]). The intensity of multiple organ dysfunction syndrome (MODS) and efficiency of therapeutic interventions were estimated with SOFA [1]. The examination was carried out at the moment of admission to ICU, 12 hours after ICU admission, and within the following 3 days. Systemic statistical analysis of the results of clinical, laboratory and instrumental studies was performed in several stages with use of analysis of variance and Statistica 6 (StatSoft, USA, 1999), with obligatory estimation of statistical significance for an identified relationship (p < 0.05) [8]. The study included the analysis of curves (ROC-analysis) which allow estimating the quality of binary classification reflecting the relationship between the proportion of true positive classification from the general amount of positive values with proportion of false positive classifications from the general amount of negative values in variation of the value of decision rule for all studied parameters of homeostasis. The study included odds ratio (OR) for mortality which demonstrates the relation of probability (odds) for appearance of specific dichotomized variable (deceased-survived) in the groups of the patients [8]. The study was carried out after approval from the bioethical committee of Kabanov City Clinical Hospital #1 and Omsk First Aid Station #1 and it corresponded to Helsinki Declaration – Ethical Principles for Medical Research with Human Subjects 2000 and the rules for Clinical Practice in Russian Federation confirmed by the order of Russian Ministry of Health from 19.06.2003, #266.
RESULTS
ROC-analysis of all examined values of homeostasis was performed for identification of statistically significant clinical laboratory parameters associated with lethal outcomes in the patients with traumatic shock. The table 1 demonstrates that lethal outcomes were registered in all patients of all groups within the whole period of observation (3 days). At the same time, realized anti-shock treatment was not uniform for the patients of the groups I, II and III, because it influenced on clinical outcomes with varying degrees (table 1). Moreover, in comparison with the patients of the groups II and III the patients of the group I demonstrated different number of lethal outcomes (table 1) which were caused by early multiple organ dysfunction and coagulopathic bleeding [3, 9]. In its turn, despite of different amount of unsatisfactory outcomes in the examined groups, OR for mortality did not find any statistically significant difference in this parameter (table 1). In view of insignificant mortality (table 1) the patients of the groups II and III did not show any reliable predictors. Therefore, the values associated with mortality were calculated in the patients of the group I which demonstrated the highest mortality (table 1). The performed ROC-analysis (table 2) found the following statistically significant parameters of lethal outcomes in the patients with traumatic shock of degree III at hospital stage: body temperature (Fig. 1), venous blood pH (Fig. 2), level of ionized calcium (Fig. 3) and lactate in venous blood (Fig. 4), and APTT (Fig. 5).
| Table 1 | ||||||||
| Lethal outcomes and odds ratio in the examined patient groups during disease period (3 days) | ||||||||
| Note: there are no statistically significant intergroup differences in the table (p > 0.05).
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| Table 2 | |||
| ROC-analysis of the values in the group I | |||
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Figure 1 ROC-analysis of body temperature in the patients in the group 1 |
Figure 2 ROC-analysis of venous blood pH in the patients in the group I |
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Figure 3 ROC-analysis of ionized calcium levels in the patients in the group I |
Figure 4 ROC-analysis of venous blood lactate in the patients in the group I |
Figure 5
ROC-analysis of APTT in the patients in the group I
DISCUSSION
The detailed analysis of the values which are associated with mortality found the specific direction in pathogenesis of critical state in the patients of the group I. In good faith, at the moment of admission to ICU and at the background of anti-shock therapy the following events were noted: hypothermia (up to 35.80Ñ), increased lactate (up to 4.1 mmol/L) in venous blood, low venous blood pH (7.19); these states supposed severe circulatory disorders conditioned by significant hypovolemia as result of massive blood loss [2, 9]. Besides, hypovolemia, metabolic acidosis and deficiency of clotting factors after acute blood loss conditioned significant disorders in hemostasis [3, 6, 10, 11], which took place within the whole follow-up period in the patients with unsatisfactory outcomes, despite of replacement therapy. That’s why these patients demonstrated the high values of APTT (up to 59 sec.) and extremely low levels of ionized calcium (up to 0.32 mmol/L). Increase in APTT was observed in view of deficiency of such internal clotting factors as XII, XI, IX, VIII high-molecular-weight kininogen, and the factors of extrinsic pathway – Õ, V, II and I, that are common for patients with acute blood loss [7, 10] and during infusion therapy with 6 % HES 200/0.5 [9, 12]. The important fact was that increase in calcium ions in plasma was registered in the same time interval with disorders of plasma hemostasis. It is possible that it was associated with increased consumption of calcium ions in processes of clotting in the patients with massive blood loss and changed hemostasis [7]. The correlation analysis supported the role of calcium ions for clotting processes. It found statistically significant negative relationship between the levels of calcium ions and APTT (r = -0.48; p = 0.04). In its turn, regarding the patients with traumatic shock of degree III it allowed discussing appropriateness of crystalloid solutions containing different electrolytes, particularly, calcium ions for pathogenetically- feasible correction [9, 12]. Infusion-transfusion therapy was important in relation to clinical outcomes during complex emergency medical assistance for the patients with traumatic shock of degree III at prehospital and hospital stages [9]. In the examined groups such therapy was virtually the same according to the strategy and tactics of realization and nearly the same according to its volume, but different in terms of qualitative composition (crystalloids/colloids) at prehospital and hospital stages. Moreover, infusion-transfusion therapy for the patients of the groups II and III allowed stopping inotropic and vascular support by the end of the second day (after 48.1 ± 2.4 and 47.3 ± 2.1 hours correspondingly), but for the patients of the group I – only by the end of the third day (74.2 ± 2.3 hours). Surely, this fact significantly influenced on the clinical outcomes that was supported by the values of lethal outcomes in the patients of the groups I, II and III during the whole period of observation (table 1). In its turn, it indicated that the program of infusion-transfusion therapy for the patients of the groups II and III (in comparison with the variant of volemic replacement in the patients of the group I) was more effective in relation to correction of circulatory disorders in the patients with traumatic shock of degree III.
CONCLUSION
1. For the patients with traumatic shock of degree 3 the values associated with lethal outcomes are: decreasing body temperature (up to 35.7ᵒ Ñ), decreasing venous blood pH (up to 7.19), the level of ionized calcium on venous blood (up to 0.3 mmol/L), increasing level of lactate in venous blood (up to 4.1 mmol/L) and increasing activated partial thromboplastin time (up to 59 sec.).
2. It is appropriate to use 4 % MG and balanced crystalloid solution in the program of infusion therapy.