The Syndrome of Traumatic Shock

BackgroundClot strength by Thrombelastography (TEG) is associated with mortality during trauma and has been linked to severity of tissue hypoperfusion. However, the optimal method for monitoring this important relationship remains undefined. We hypothesize that oxygen transport measurements will be associated with clot strength during traumatic shock, and test this hypothesis using a swine model of controlled traumatic shock.MethodsN = 33 swine were subjected to femur fracture and hemorrhagic shock by controlled arterial bleeding to a predetermined level of oxygen debt measured by continuous indirect calorimetry. Hemodynamics, oxygen consumption, systemic central venous oxygenation (ScvO2), base excess, lactate, and clot maximal amplitude by TEG (TEG-MA) as clot strength were measured at baseline and again when oxygen debt = 80 ml/kg during shock. Oxygen transport and metabolic markers of tissue perfusion were then evaluated for significant associations with TEG-MA. Forward stepwise selection was then used to create regression models identifying the strongest associations between oxygen transport and TEG-MA independent of other known determinants of clot strength.ResultsMultiple markers of tissue perfusion, oxygen transport, and TEG-MA were all significantly altered during shock compared to baseline measurements (p < 0.05). However, only ScvO2 demonstrated a strong bivariate association with TEG-MA measured during shock (R = 0.7, p < 0.001). ScvO2 measured during shock was also selected by forward stepwise selection as an important covariate in linear regression models of TEG-MA after adjusting for the covariates fibrinogen, pH, platelet count, and hematocrit (Whole model R2 = 0.99, p ≤ 0.032).ConclusionsAmong multiple measurements of oxygen transport, only ScvO2 was found to retain a significant association with TEG-MA during shock after adjusting for multiple covariates. ScvO2 should be further studied for its utility as a clinical marker of both tissue hypoxia and clot formation during traumatic shock.

In a prospective investigation of 19 patients with traumatic (n = 11) and septic (n = 8) shock admitted to the Intensive Care Unit of the University Hospital of Uppsala, differences in coagulation and fibrinolysis between the two conditions were evaluated. It was found that plasma coagulation variables such as thrombotest, normotest and antithrombin III were significantly lower in the septic patients, thus indicating a more intense and/or altered intravascular coagulation. Significantly higher levels of the von Willerbrand factor were found in septic patients, indicating a greater release from endothelial cells and platelets. The plasminogen activator inhibitor and the plasminogen-binding form of alpha 2-antiplasmin showed significantly higher values in septic patients, indicating a greater fibrinolysis inhibition in these patients. The greater disturbance in the protease-inhibitor balance in septicaemia was also verified by significantly lower levels of plasminogen and alpha 2-macroglobulin than after traumatic shock. Two out of 11 patients in traumatic shock developed the adult respiratory distress syndrome with a slow onset and benign course, whereas six out of eight septic shock patients developed a similar syndrome with a rapid onset and malignant course. These laboratory and clinical results lend further support to the hypothesis that the differences in coagulation and fibrinolysis systems reflect partly different pathogenic mechanisms underlying septic- and traumatic-induced adult respiratory distress syndrome.

Deranged glucose metabolism after moderate to severe trauma with either high or low concentrations of blood glucose is associated with poorer outcome. Data on prehospital blood glucose concentrations and trauma are scarce. The primary aim was to describe the relationship between traumatic shock and prehospital blood glucose concentrations. The secondary aim was to determine the additional predictive value of prehospital blood glucose concentration for traumatic shock when compared with vital parameters alone. Retrospective analysis of the predefined, observational database of a nationwide Helicopter Emergency Medical Service (34 bases). Emergency trauma patients treated by Helicopter Emergency Medical Service between 2005 and 2013 were investigated. All adult trauma patients (≥18 years) with recorded blood glucose concentrations were enrolled. Primary outcome: upper and lower thresholds of blood glucose concentration more commonly associated with traumatic shock. Secondary outcome: additional predictive value of prehospital blood glucose concentrations when compared with vital parameters alone. Of 51 936 trauma patients, 20 177 were included. In total, 220 (1.1%) patients died on scene. Hypoglycaemia (blood glucose concentration 2.8 mmol l or less) was observed in 132 (0.7%) patients, hyperglycaemia (blood glucose concentration exceeding 15 mmol l) was observed in 265 patients (1.3%). Blood glucose concentrations more than 10 mmol l (n = 1308 (6.5%)) and 2.8 mmol l or less were more common in patients with traumatic shock (P < 0.0001). The Youden index for traumatic shock ((sensitivity + specificity) - 1) was highest when blood glucose concentration was 3.35 mmol l (P < 0.001) for patients with low blood glucose concentrations and 7.75 mmol l (P < 0.001) for those with high blood glucose concentrations. In logistic regression analysis of patients with spontaneous circulation on scene, prehospital blood glucose concentrations (together with common vital parameters: Glasgow Coma Scale, heart rate, blood pressure, breathing frequency) significantly improved the prediction of traumatic shock in comparison with prediction by common vital parameters alone (P < 0.0001). In adult trauma patients, low and high blood glucose concentrations were more common in patients with traumatic shock. Prehospital blood glucose concentration measurements in addition to common vital parameters may help identify patients at risk of traumatic shock.

BACKGROUND: Combined pelvic trauma in men in 10%–24% of cases is accompanied by damage to the posterior urethra, and no consensus on the treatment tactics has been established for such patients. AIM: This study aimed to evaluate the results of treatment of patients with closed injury of the posterior urethra and traumatic shock. MATERIALS AND METHODS: A retrospective analysis of the results of treatment of 46 patients with closed injury of the posterior urethra caused by a fracture of the pelvic bones and traumatic shock was performed. The average age of patients was 42.1 ± 9.9 years. The severity of urethral injuries was assessed according to the American Association for the Surgery of Trauma (AAST) classification. RESULTS: The choice of treatment techniques depended on the degree of damage to the urethra and severity of traumatic shock. Upon hospital admission, 15 (32.6%) patients were diagnosed with grade I, 21 (45.6%) with grade II, and 10 (21.7%) with grade III traumatic shock. In grade I–II traumatic shock patients with incomplete urethral rupture, a urethral catheter was inserted, followed by conservative therapy. If a catheter insertion was possible, a retropubic revision of the urethra was performed. Patients with grade III–V urethral injury according to AAST and grade I–II traumatic shock underwent primary or delayed urethroplasty, such as urethral suturing and urethra-urethral anastomosis. Patients with grade III traumatic shock had a urethral catheter or cystostomy. In the long-term, 6 of 17 (36.9%) patients who underwent primary or delayed urethroplasty had short-term (up to 5 mm) urethral strictures, for which optical urethrotomy was performed. All patients with complete urethral avulsion who did not undergo early urethroplasty developed 10–20 mm strictures, requiring reconstructive surgery. CONCLUSIONS: The choice of treatment techniques for patients with concomitant damage to the posterior urethra depends on the degree of damage to the urethra and severity of traumatic shock. The scope of treatment in the acute period may include urethral or suprapubic drainage of the bladder or reconstructive surgery.

Myocardial injury increases major adverse cardiovascular events and mortality in patients with traumatic hemorrhagic shock, but its prevalence and risk factors remain unclear. This study aimed to assess the prevalence and risk factors of myocardial injury after traumatic hemorrhagic shock. This was an observational, retrospective cohort study of patients with traumatic hemorrhagic shock at a tertiary university hospital from November 2012 to July 2021. Patient characteristics and clinical variables were recorded in 314 patients. The outcome was the occurrence of myocardial injury after traumatic hemorrhagic shock. Risk factors for myocardial injury were identified using logistic regression. The incidence of myocardial injury after the traumatic hemorrhagic shock was 42.4%, and 95.5% of myocardial injuries occurred within the first three days after trauma. In the multivariate analysis, the independent risk factors for myocardial injury after traumatic hemorrhagic shock included heart rate of >100 beats/min (OR [odds ratio], 3.33; 95% confidence interval [CI], 1.56–7.09; p = 0.002), hemoglobin level of <70 g/L (OR, 3.50; 95% CI, 1.15–10.60; p = 0.027), prothrombin time of >15 s (OR, 2.39; 95% CI, 1.12–5.10; p = 0.024), acute kidney injury (OR, 2.75; 95% CI, 1.27–5.93; p = 0.01), and a higher APACHE II score (OR, 1.08; 95% CI, 1.01–1.15; p = 0.018). The area under the receiver operating characteristic curve for the prediction of myocardial injury after a traumatic hemorrhagic shock was 0.67 (95% CI, 0.68–0.79) for a heart rate of >100 beats/min, 0.67 (95% CI, 0.61–0.73) for hemoglobin level of <70 g/L, 0.66 (95% CI, 0.60–0.73) for prothrombin time of >15 s, 0.70 (95% CI, 0.64–0.76) for acute kidney injury, and 0.78 (95% CI, 0.73–0.83) for APACHE II scores. The incidence rate of myocardial injury in traumatic hemorrhagic shock is high, and heart rates of >100 beats/min, hemoglobin levels of <70 g/L, prothrombin times of >15 s, AKI and higher APACHE II scores are independent risk factors for myocardial injury after traumatic hemorrhagic shock. These findings may help clinicians to identify myocardial injury after traumatic hemorrhagic shock early and initiate appropriate treatment.

The clinical state of shock constitutes a relative or absolute deficiency of circulating volume for adequate oxygen delivery to meet the metabolic demands.1 Although shock states differ in epidemiology, etiology, and pathophysiologic pathways, a common denominator of shock is endothelial barrier dysfunction.2, 3 Different kinds of shock states, such as occurring after major surgery, trauma, and in sepsis, can result in strong pro‐inflammatory host responses with ensuing endothelial hyperpermeability.4, 5, 6 Loss of endothelial barrier results in leakage of fluid into surrounding tissue, contributing to edema, tissue hypoxia, and organ failure.6 This loss of fluids further aggravates the intravascular circulatory volume deficiency during shock. Obviously, septic and traumatic shock are different entities, with different etiologies and differences in initiation of host response and coagulation response. However, endothelial activation with loss of endothelial barrier integrity is a common finding in both shock states. In trauma‐induced shock, current resuscitation strategies consist of the early transfusion of whole blood or a balanced ratio of plasma, platelets, and red blood cells.7, 8 The aim of resuscitation is to ensure adequate oxygen delivery and to correct coagulopathy. Plasma transfusion may play a key role, as trials point toward improved survival with high dose or early use of plasma transfusion compared to standard care.9, 10, 11 Upon reaching surgical hemostasis, it is general practice to stop transfusion. However, as a result of ongoing inflammation and endothelial activation, patients can continue to be fluid dependent, which is often responded to with crystalloids. However, liberal use of crystalloids in traumatic hemorrhagic shock is associated with increased mortality and increased endothelial permeability, inflammation, and reduced perfusion of vital organs.12, 13, 14 In septic shock, the primary treatment of shock is volume resuscitation with crystalloid or colloids, as advocated in guidelines.15 However, comparable to traumatic hemorrhagic shock, use of a restrictive fluid balance reduces the occurrence of organ failure as well as mortality in sepsis.16, 17, 18 most likely, the association between the amount of infused volume and adverse outcome in shock states is related to increased shedding of the glycocalix, breakdown of adherent junctions, and tight junctions resulting in an increased gradient of leakage over the hyper permeable endothelium.19 Taken together, due to a relative or absolute deficiency of intravascular volume, patients with shock are likely to need volume expansion to maintain perfusion pressure. This poses a challenge to the treatment of shock, as fluid therapy is both a cornerstone of therapy as well as a foe. Different fluids may have differential effects on endothelial integrity. Low‐protein‐content fluids seem to aggravate shedding of glycocalix,20 whereas protein‐rich fluids such as plasma may be superior to normal saline in protecting the glycocalix and endothelial barrier function.21 Transfusion with plasma as a volume expander in shock may seem controversial at first, but one needs to consider that despite the fact that plasma is transfused in millions of patients annually, there currently is limited understanding of its mechanisms of action. In traumatic blood loss, transfusion of plasma may improve survival by decreasing exsanguination.7, 10 The common perception is that plasma is a pro‐coagulant blood product, by replenishing coagulation factors. However, as plasma contains coagulation factors but also anticoagulant proteins, the net effect of plasma on coagulation may be neutral. In line with this, plasma transfusion increases the amount of coagulation factors as well as levels of anti‐coagulant proteins,22 resulting in unchanged thrombin generation, at least in non‐bleeding critically ill patients with an inflammatory‐driven consumption coagulopathy. In patients with traumatic hemorrhagic shock, it is not apparent whether the mechanism of effect of plasma is directly related to the correction of coagulopathy.23 In rats with hemorrhagic shock, deranged thrombin formation was somewhat restored with resuscitation with plasma but not with crystalloids, but whether this relates to prevention of dilutional coagulopathy or to a specific pro‐coagulant effect of plasma is not clear.24, 25 Other mechanisms of the protective effect of plasma may be at hand. These may include preservation of the glycocalix, decreasing inflammation and decreasing endothelial leak. This review aims to discuss the potential of plasma as a resuscitation fluid in shock, with an emphasis on possible mechanisms of benefit on the activated endothelium. Studies comparing plasma with other fluids on (markers of) endothelial integrity have found effects both in (models of) trauma‐induced shock and in septic shock. As loss of endothelial integrity may be a common denominator of shock, we will discuss both these shock states.

Efficacy of a combination thromboxane receptor antagonist and lipoxygenase inhibitor in traumatic shock.

We studied the effects of CP-0127, a novel bradykinin receptor antagonist, in a rat model of traumatic shock. Pentobarbital-anesthetized rats subjected to Noble-Collip drum trauma developed a shock state characterized by marked hypotension, significant increases in plasma-free amino-nitrogen (8.6 +/- 0.97 vs. 2.3 +/- 0.15 U/ml in control rats) and intestinal myeloperoxidase (MPO) activity (2.7 +/- 0.33 vs. 0.08 +/- 0.03 U/100 mg control rats, intestinal tissue), and a survival time of only 110 +/- 9 min. Moreover, superior mesenteric artery (SMA) rings isolated from rats subjected to traumatic shock relaxed to the endothelium-dependent vasodilator acetylcholine (ACh) significantly less than rings isolated from control rats (21 +/- 4 vs. 92 +/- 4%, P < 0.001). Administration of CP-0127 at a dose of 10 mg/kg subcutaneously completely blocked the hypotensive response to 2.5 micrograms/kg bradykinin injected intravenously in sham traumatic shock rats. CP-0127 given immediately posttrauma prolonged survival time to 219 +/- 27 min (P < 0.01) and attenuated the increases in plasma-free amino-nitrogen (3.7 +/- 0.41 U/ml, P < 0.01) and tissue MPO activities (1.2 +/- 0.71 U/100 mg intestinal tissue, P < 0.05). Furthermore, SMA endothelial function was significantly preserved (relaxation to ACh: 57 +/- 6%, P < 0.01) in CP-0127-treated traumatic shock rats. These results indicate that bradykinin plays an important role in tissue injury associated with traumatic shock and that CP-0127 affords significant protection, which may be achieved through inhibition of neutrophil-endothelial interaction and protection of vascular endothelial function.

We have investigated the role of platelet activating factor (PAF) in the pathogenesis of a murine model of traumatic shock using CV-6209, a specific antagonist of PAF. CV-6209, at a dose of 1 mg/kg (i.v.) given after trauma, significantly improved survival rate at 150 min and overall survival time. Furthermore, the plasma accumulation of the lysosomal hydrolase, cathepsin D, and a cardiotoxic peptide, myocardial depressant factor (MDF), were also attenuated by CV-6209 in traumatic shock. Combined treatment employing low doses of CV-6209 [0.2 mg/kg, i.v. and prostaglandin (PG) E1, 0.8 microgram/kg/min] in this shock model was also examined. CV-6209 (0.2 mg/kg) or PGE1 (0.8 microgram/kg/min) alone at these doses showed only minimal effects on survival, or plasma cathepsin D or MDF activities. However, combined treatment with CV-6209 (0.2 mg/kg, i.v.) and PGE1 (0.8 microgram/kg/min) significantly improved survival rate at 150 min, overall survival time, and decreased the accumulation of plasma MDF. These results suggest that PAF may play an important pathophysiologic role in traumatic shock in rats. Moreover, combination therapy using a PAF antagonist and PGE1 may be useful for the treatment of traumatic shock.

Procalcitonin (PCT), C-reactive protein (CRP) and interleukin-6 (IL-6) were detected to explore the value of these inflammatory markers in the assessment of traumatic shock patients. The clinical data of 80 patients with traumatic shock and infections in Zhangzhou Municipal Hospital of Fujian Province from January 2014 to December 2017 were collected as the experimental group. During the same period, 80 acute trauma patients who did not suffer from traumatic shock were regarded as the control group. According to the prognosis outcomes, the experimental group was divided into 56 patients with good prognosis and 24 patients with poor prognosis. Also the PCT, CRP and IL-6 levels in serum of patients at admission (T1), 12 h after admission (T2), three days after admission (T3) and on day 7 (T4) were detected. The differences between the three inflammatory indicators, the pre-admission injury severity score (ISS score), the acute physiology and chronic psychological score (APACHE II score) were compared between the good prognosis and the poor prognosis group. The serum CRP at the T4 time period was significantly lower than both the T1 and T2 time periods (P<0.05). There were differences in serum PCT, CRP and IL-6 between the good prognosis and the poor prognosis group at the time of T1-T4 (P<0.05). The expression levels of PCT, CRP and IL-6 in the serum of patients with poor prognosis were higher than those with good prognosis (P<0.05). Pre-admission ISS scores and APACHE II scores in patients with good prognosis were lower than those with poor prognosis (P<0.05). Detection of PCT, CRP and IL-6 expression levels in serum of the patients has an important reference value for assessing the condition of patients with traumatic shock.

Protective effects f CG-4203, a novel stable prostacyclin analog, in traumatic shock

Inhibitors of lipoxygenase products improve survival in traumatic shock

Polytrauma: Acute acquired mitochondrial disease

: Specific Aim 1: Examine the ability of androstenetriol to improve survival in a rodent model of combined hemorrhage and tissue injury (traumatic shock). Hypothesis 1: The use of androstenetriol shortly after the onset of traumatic shock will improve survival in a rodent model of combined hemorrhage and tissue injury (traumatic shock). Specific Aim 2: Examine the ability of androstenetriol to modulate the immune and inflammatory response systemically and in multiple organ systems in response to traumatic shock. Hypothesis 2: The administration of androstenetriol shortly after the onset of traumatic shock will result in changes in the immune and inflammatory response systemically and in individual organ systems which will assist in understanding the mechanisms by which androstenetriol may improve outcome. Specific Aim 3: Examine the ability of androstenetriol to preserve microcirculatory flow and tissue oxygenation during the early stages of traumatic shock Hypothesis 3: The use of androstenetriol shortly after the onset of traumatic shock will be associated with improvements in microcirculatory flow and tissue oxygenation.

Traumatic shock is associated with microcirculatory dysfunction. Plasma resuscitation for traumatic shock outside the context of bleeding may exert benefit by augmenting intravascular volume and inhibiting endotheliopathy. However, its effects on microcirculatory perfusion and tissue oxygenation in trauma remain poorly understood. Following polytraumatic injury and shock induction with controlled bleeding, rats (n = 11) received crystalloids or plasma until mean arterial pressure (MAP) was 65 mmHg for 2 h, after resuscitation was stopped. Total vessel density (TVD), functional capillary density (FCD), proportion of perfused vessel density (PPV), and tissue red blood cell perfusion (tRBCp) were evaluated. Microcirculatory oxygen availability (μHbO2sat) was measured by tissue spectroscopy. Plasma hyaluronan and sVCAM were assessed for endothelial integrity. After resuscitation, MAP was restored in both groups. However, TVD, FCD, and tRBCp were impaired in the crystalloid group as compared to the sham (p < 0.05), which did not occur in the plasma group. tRBCp was significantly improved by plasma resuscitation compared to crystalloid (p < 0.05). After resuscitation had stopped, TVD, FCD, and tRBCp remained significantly higher in the plasma group compared to the crystalloid group (p < 0.05). sVCAM decreased significantly by plasma compared to crystalloid (p < 0.05). There was no significant change in hyaluronan and μHbO2sat levels. Plasma, but not crystalloids, preserved microcirculatory diffusion and perfusion, which was associated with correction of endothelial functionality in rats requiring fluids following traumatic shock. Results suggest that plasma may be used in traumatic shock patients with persistent need of volume after bleeding has been contained.