Beneficial effect of cyclosporine A on traumatic hemorrhagic shock.

BACKGROUND: Vascular hyporeactivity plays an important role in severe trauma and shock. We investigated the beneficial effect of cyclosporine A (CsA) on traumatic shock and its relationship to vascular reactivity improvement and mitochondrial permeability transition pore (MPTP). MATERIALS AND METHODS: Sodium pentobarbital-anesthetized rats were used to induce traumatic hemorrhagic shock by left femur fracture and hemorrhage, the beneficial effects of CsA (1, 5, and 10 mg/kg, intravenously) on animal survival, cardiovascular function, tissue blood perfusion, and mitochondrial function of vital organs were observed. In addition, hypoxia-treated vascular smooth muscle cells from normal rats were used to investigate the relationship of this beneficial effect of CsA to Rho-associated serine/threonine kinase (ROCK) and protein kinase C. RESULTS: CsA prolonged the survival time and increased the 24-h survival rate of traumatic hemorrhagic shock (31%, 56%, and 56% in 1, 5, and 10 mg/kg CsA group versus 25% in lactated Ringer solution group). Five milligrams per kilogram of CsA had the best effect, which stabilized and improved the hemodynamics, increased the tissue blood flow, and improved the liver and kidney function including its mitochondrial function in shock rats. CsA had no significant influences on the production of inflammatory mediators and cardiac output after traumatic hemorrhagic shock. Further results indicated that CsA significantly improved the vascular constriction and dilation reactivity of superior mesenteric artery to norepinephrine and acetylcholine, which was antagonized by ROCK inhibitor, Y27632, but not by protein kinase C inhibitor, staurosporine. Further studies showed that CsA restored hypoxia-induced decrease of ROCK activity and inhibited the opening of MPTP in hypoxia-treated vascular smooth muscle cells. CONCLUSIONS: CsA is beneficial for the treatment of traumatic hemorrhagic shock. The mechanism is mainly through improving the vascular reactivity, stabilizing the hemodynamics, and increasing tissue perfusion. This beneficial effect of CsA is related to the inhibitory effect of CsA on MPTP opening. ROCK is an important regulator molecule in this process.

Resuscitation strategies with different arterial pressure targets after surgical management of traumatic shock.

INTRODUCTION: Hypotensive fluid resuscitation has a better effect before and during surgical intervention for multiple trauma patients with haemorrhagic shock. However, it is questionable whether hypotensive fluid resuscitation is suitable after surgical intervention for these patients, and whether resuscitation with different mean arterial pressure (MAP) targets after surgical intervention can obtain different results. The aim of this study was to investigate these questions and to explore the underlying mechanisms. METHODS: A total of 30 anesthetized piglets were randomly divided into 3 groups (n = 10 per group): low MAP, middle MAP, and high MAP, which had MAP targets of 60, 80, and 100 mmHg, respectively. All animals underwent femur fracture, intestine and liver injury, haemorrhagic shock, early hypotensive resuscitation, and surgical intervention. Then, the animals received fluid resuscitation with different MAP targets as mentioned above for 24 hours. Hemodynamic parameters and vital organ functions were evaluated. RESULTS: Fluid resuscitation in the 80 mmHg MAP group maintained haemodynamic stability, tissue perfusion, and organ function better than that in the other groups. The 60 mmHg MAP group presented with profound metabolic acidosis and organ histopathologic damage. In addition, animals in the 100 mmHg MAP group exhibited severe tissue oedema, organ function failure, and histopathologic damage. CONCLUSIONS: In our porcine model of resuscitation, targeting high MAP by fluid administration alone resulted in a huge increase in the infusion volume, severe tissue oedema, and organ dysfunction. Meanwhile, targeting low MAP resulted in persistent tissue hypoperfusion and metabolic stress. Hence, a resuscitation strategy of targeting appropriate MAP might be compatible with maintaining haemodynamic stability, tissue perfusion, and organ function.

Local hemostasis, immunothrombosis, and systemic disseminated intravascular coagulation in trauma and traumatic shock.

Knowing the pathophysiology of trauma-induced coagulopathy is important for the management of severely injured trauma patients. The aims of this review are to provide a summary of the recent advances in our understanding of thrombosis and hemostasis following trauma and to discuss the pathogenesis of disseminated intravascular coagulation (DIC) at an early stage of trauma. Local hemostasis and thrombosis respectively act to induce physiological wound healing of injuries and innate immune responses to damaged-self following trauma. However, if overwhelmed by systemic inflammation caused by extensive tissue damage and tissue hypoperfusion, both of these processes foster systemic DIC associated with pathological fibrin(ogen)olysis. This is called DIC with the fibrinolytic phenotype, which is characterized by the activation of coagulation, consumption coagulopathy, insufficient control of coagulation, and increased fibrin(ogen)olysis. Irrespective of microvascular thrombosis, the condition shows systemic thrombin generation as well as its activation in the circulation and extensive damage to the microvasculature endothelium. DIC with the fibrinolytic phenotype gives rise to oozing-type non-surgical bleeding and greatly affects the prognosis of trauma patients. The coexistences of hypothermia, acidosis, and dilution aggravate DIC and lead to so-called trauma-induced coagulopathy. He that would know what shall be must consider what has been. The Analects of Confucius.

Trauma-hemorrhagic shock induces a CD36-dependent RBC endothelial-adhesive phenotype.

OBJECTIVE: Microvascular dysfunction is a key element in the development of the multiple organ dysfunction syndrome. Although the mechanisms for this response are unclear, RBC adhesion to endothelium may initiate intravascular occlusion leading to ischemic tissue injury. Thus, we tested the hypothesis that trauma-hemorrhage induces RBC-endothelial cell adhesion. DESIGN: Prospective in vivo and in vitro animal study and analysis of patient blood samples. SETTING: University research laboratory and hospital emergency and trauma units. INTERVENTION: We initially assayed RBC adhesion to endothelial cells in vitro using RBCs obtained from rats subjected to trauma-hemorrhagic shock or sham shock as well as from severely injured trauma patients. Subsequently, we measured the role of putative RBCs and endothelial cell receptors in the increased RBC-endothelial cell adhesive response. MAIN RESULTS: In both rats and humans, trauma-hemorrhagic shock increased RBC adhesion to endothelium as well as increasing several putative RBC surface adhesion molecules including CD36. The critical factor leading to RBC-endothelial cell adhesion was increased surface RBC CD36 expression. Adhesion of trauma-hemorrhagic shock RBCs was mediated, at least in part, by the binding of RBC CD36 to its cognate endothelial receptors (αVß3 and VCAM-1). Gut-derived factors carried in the intestinal lymphatics triggered these trauma-hemorrhagic shock-induced RBC changes because 1) preventing trauma-hemorrhagic shock intestinal lymph from reaching the systemic circulation abrogated the RBC effects, 2) in vitro incubation of naïve whole blood with trauma-hemorrhagic shock lymph replicated the in vivo trauma-hemorrhagic shock-induced RBC changes while 3) injection of trauma-hemorrhagic shock lymph into naïve animals recreated the RBC changes observed after actual trauma-hemorrhagic shock. CONCLUSIONS: 1) Trauma-hemorrhagic shock induces rapid RBC adhesion to endothelial cells in patients and animals. 2) Increased RBC CD36 expression characterizes the RBC-adhesive phenotype. 3) The RBC phenotypic and functional changes were induced by gut-derived humoral factors. These novel findings may explain the microvascular dysfunction occurring after trauma-hemorrhagic shock, sepsis, and other stress states.

Hypertonic saline in the traumatic hypovolemic shock: meta-analysis.

BACKGROUND: A wealth of evidence from animal experiments has indicated that hypertonic saline (HS) maybe a better choice for fluid resuscitation in traumatic hypovolemic shock in comparison with conventional isotonic saline. However, the results of several clinical trials raised controversies on the superiority of fluid resuscitation with HS. This meta-analysis was performed to better understand the efficacy of HS in patients with traumatic hypovolemic shock comparing with isotonic saline. MATERIALS AND METHODS: According to the search strategy, we searched the PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, which was completed on October 2013. After literature searching, two investigators independently performed the literature screening, assessment of quality of the included trials, and data extraction. Disagreements were resolved by consensus or by a third investigator if needed. The outcomes included mortality, blood pressure, fluid requirement, and serum sodium. RESULTS: Six randomized controlled trials were included in the meta-analysis. The pooled risk ratio for mortality at discharge was 0.96 (95% confidence interval [CI], 0.82-1.14), whereas the pooled mean difference for the change in systolic blood pressure from baseline and the level of serum sodium after infusion was 6.47 (95% CI, 1.31-11.63) and 7.94 (95% CI, 7.38-8.51), respectively. Current data were insufficient to evaluate the effect of HS on the fluid requirement for the resuscitation. CONCLUSIONS: The present meta-analysis was unable to demonstrate a clinically important improvement in mortality after the HS administration. Moreover, we observed HS administration maybe accompanied with significant increase in blood pressure and serum sodium.

A 10-second fluid challenge guided by transthoracic echocardiography can predict fluid responsiveness.

INTRODUCTION: The accurate assessment of intravascular volume status for the therapy of severe hypovolemia and shock is difficult and critical to critically ill patients. Non-invasive evaluation of fluid responsiveness by the rapid infusion of a very limited amount of volume is an important clinical goal. This study aimed to test whether echocardiographic parameters could predict fluid responsiveness in critically ill patients following a low-volume (50-ml crystalloid solution) infusion over 10 seconds. METHODS: We prospectively studied 55 mechanically ventilated patients. Echocardiography was performed during a 50-ml infusion of crystalloid solution over 10 seconds and a further 450 ml over 15 minutes. Cardiac output (CO), stroke volume (SV), aortic velocity time index (VTI), and left ventricular ejection fraction (LVEF) were recorded. Patients were classified as responders (Rs) if CO increased by at least 15% following the 500-ml volume expansion or were classified as non-responders (NRs) if CO increased by less than 15%. Area under the receiver operating characteristic curves (AUC) compared CO variations after 50 ml over 10 seconds (∆CO50) and 500 ml over 15 minutes (∆CO500) and the variation of VTI after infusion of 50 ml of fluid over 10 seconds (∆VTI50). RESULTS: In total, 50 patients were enrolled, and 27 (54%) of them were Rs. General characteristics, LVEF, heart rate, and central venous pressure were similar between Rs and NRs. In the Rs group, the AUC for ∆CO50 was 0.95 ± 0.03 (P <0.01; best cutoff value, 6%; sensitivity, 93%; specificity, 91%). Moreover, ∆CO50 and ∆CO500 were strongly correlated (r = 0.87; P <0.01). The AUC for ∆VTI50 was 0.91 ± 0.04 (P <0.01; best cutoff value, 9%; sensitivity, 74%; specificity, 95%). ∆VTI50 and ∆CO500 were positively correlated (r = 0.72; P <0.01). CONCLUSION: In critically ill patients, the variation of CO and VTI after the administration of 50-ml crystalloid solution over 10 seconds (∆CO50 and ∆VTI50) can accurately predict fluid responsiveness. TRIAL REGISTRATION: Current Controlled Trials ISRCTN10524328. Registered 12 December 2013.

Tissue ischemia microdialysis assessments following severe traumatic haemorrhagic shock: lactate/pyruvate ratio as a new resuscitation end point?

BACKGROUND: Intensive care of severe trauma patients focuses on the treatment of haemorrhagic shock. Tissues should be perfused sufficiently with blood and with sufficient oxygen content to ensure adequate tissue oxygen delivery. Tissue metabolism can be monitored by microdialysis, and the lactate/pyruvate ratio (LPR) may be used as a tissue ischemia marker. The aim of this study was to determine the adequate cardiac output and haemoglobin levels that avoid tissue ischemia. METHODS: Adult patients with serious traumatic haemorrhagic shock were enrolled in this prospective observational study. The primary observed parameters included haemoglobin, cardiac output, central venous saturation, arterial lactate and the tissue lactate/pyruvate ratio. RESULTS: Forty-eight patients were analysed. The average age of the patients was 39.8 ± 16.7, and the average ISS was 43.4 ± 12.2. Hb < 70 g/l was associated with pathologic arterial lactate, ScvO2 and LPR. Tissue ischemia (i.e., LPR over 25) developed when CI ≤ 3.2 l/min/m(2) and Hb between 70 and 90 g/l were observed. Severe tissue ischemia events were recorded when the Hb dropped below 70 g/l and CI was 3.2-4.8 l/min/m(2). CI ≥ 4.8 l/min/m(2) was not found to be connected with tissue ischemia, even when Hb ≤ 70 g/l. CONCLUSION: LPR could be a useful marker to manage traumatic haemorrhagic shock therapies. In initial traumatic haemorrhagic shock treatments, it may be better to maintain CI ≥ 3.2 l/min/m(2) and Hb ≥ 70 g/l to avoid tissue ischemia. LPR could also be a useful transfusion trigger when it may demonstrate ischemia onset due to low local DO2 and early reveal low/no tissue perfusion.

[Surgical strategy in bullet wound of the thorax accompanied by shock].

The article analyzes the experience of treatment of bullet penetrating wounds of the thorax accompanied by shock in 131 armed forces personnel of internal army and officers of the Ministry of Home Affairs of Russia during contra-terrorist operations on the North Caucasus at the period from 2000 to 2011. The postoperative lethality was reduced from 22.7% to 10.8% due to usage of the strategy which was directed to decrease of surgical aggression in 65 patients.

Temporary rapid bowel ligation as a damage control adjunct improves survival in a hypothermic traumatic shock swine model with multiple bowel perforations.

BACKGROUND: Primary intestinal anastomosis is not the right choice for multiple bowel perforations under hemodynamically stable conditions. Our group has employed temporary rapid bowel ligation as a damage control procedure in a hypothermic traumatic shock swine model with multiple bowel perforations and hypothesized that damage control treatment would improve survival in the setting of a damage control surgery. MATERIALS AND METHODS: The abdomen was shot one time with an experimental modified gun while pigs were hemorrhaged to a mean arterial pressure of 40 mm Hg and maintained in shock for 40 min. Cold lactated Ringer solution was gradually infused to induce hypothermia. Animals were randomized to control (no resuscitation), primary anastomosis (PA), or temporary rapid bowel ligation (damage control group, DC). Animals were resuscitated for 12 h with the shed blood and lactated Ringer solution. Delayed anastomosis was performed in DC animals after resuscitation. Surviving animals were humanely killed 24 h after operation. Systemic hemodynamic parameters were recorded and blood samples were obtained for biochemical assays. The lung and ileum was harvested at the end of the experiment for pathologic evaluation and test of wet/dry weight ratio, TNF-α level, and nuclear factor-κB activations. RESULTS: All animals suffered extreme physiologic conditions: hypothermia, severe acidosis, hypotension, and depressed cardiac output. Control animals suffered 100% mortality. Compared with the PA group, DC animals required less resuscitation fluid, normalized lactate levels faster, had lower serum creatine kinase, aspartate amino transferase levels and tissue TNF-α level and nuclear factor-κB activations, suffered less severe histopathology, had greater early survival. CONCLUSIONS: Multiple bowel perforations under hemodynamically stable conditions seem better managed with DC than with PA. Temporary rapid bowel ligation as a damage control adjunct is important to rapid control of multiple bowel perforations instead of a prolonged operative time.

Traumatic shock: the fifth shock.

Although, historically, shock associated with traumatic injury has been evaluated through knowledge of the 4 recognized shock patterns--cardiogenic, obstructive, distributive, and hypovolemic--many trauma practitioners view traumatic shock as a unique fifth shock pattern. Although secondary to a systemic inflammatory response syndrome triggered by endogenous danger signals, traumatic shock represents a unique pathological condition that begins with multiple, usually blunt, trauma and may conclude with multiple organ dysfunction syndrome and death. While varying mechanisms of injury may lead to different presentations of shock and cardiovascular decompensation, a unifying theme of traumatic shock is an overwhelming inflammatory response driven by proinflammatory cytokines, and the downstream results of this cytokine storm including, but not limited to, acute respiratory distress syndrome, coagulopathy, sepsis, and multiple organ dysfunction syndrome. Treatment is primarily supportive; however, research into novel therapeutics for traumatic shock is ongoing and promises some direction for future care.

[Risk factors of gastroduodenal bleeding in patients with severe burns].

An experience of treatment of 133 patients with severe bums was analyzed. Bleedings from the upper parts of the gastrointestinal tract were diagnosed in 16 patients in different terms since their admission to the hospital. At the moment of carrying out of the endoscopic research all bleedings were considered as taking place. Statistically significant risk factors of the development of gastroduodenal bleedings were considered to be an alcoholic intoxication at the moment of injury and insufficient fluid therapy during the pre-admission stage and young age of the patients. The antisecretory therapy showed that the detection of risk factors in question should be regarded as an indication to the reinforced regime of preventive measures for gastroduodenal injuries.

[Pharmacological prophylaxis of reperfusion syndrome in patients with severe polytrauma accompanied by shock].

A comparative assessment of buffer activity of reamberin and polyoxyfumaren was made. Their influence on systemic consumption of oxygen, content of lactate in blood, parameters of central hemodynamics were followed. The research includes 44 victims (aged 25-70 years) with severe shockogenic injuries. Reamberin was included in composition of fluid therapy of I group (n=30)and polyoxyfumaren was used in 11 group (n=14). Parameters of acid-base balance of arterial blood, VO2, VCO,, contents of lactate in mixed venous blood, parameters of central hemodynamics were measured in monitor regimen before the infusion. It was proved, that the intravenous infusion of reamberin and polyoxyfumaren accompanied by reliable rise of minute consumption of oxygen (27 and 18% respectively). The drugs decrease the lactate level in blood, reliably increase buffer capacity of blood, correct the metabolic acidosis. Both antihy-poxanthines allow the increase of minute volume of circulation: reamberin on 15%, polyoxyfumaren on 34,9%. The volemic effect of polyoxyfumaren resulted in the increase of circular plasma volume after finishing the infusion on 49,5%, in the case of reamberin - on 16%.

Adaptation of motor function after spinal cord injury: novel insights into spinal shock.

The mechanisms underlying spinal shock have not been clearly defined. At present, clinical assessment remains the mainstay to describe progression through spinal shock following traumatic spinal cord injury. However, nerve excitability studies in combination with conventional nerve conduction and clinical assessments have the potential to investigate spinal shock at the level of the peripheral axon. Therefore, peripheral motor axon excitability was prospectively and systematically evaluated in more than 400 studies of 11 patients admitted to hospital after traumatic spinal cord injury, with cord lesions above T9 (nine cervical, two thoracic). Recordings commenced within 15 days of admission from the median nerve to abductor pollicis brevis in the upper limb and the common peroneal nerve to tibialis anterior in both lower limbs, and were continued until patient discharge from hospital. Excitability was assessed using threshold tracking techniques and recordings were compared with data from healthy controls. In addition, concurrent clinical measures of strength, serum electrolytes and nerve conduction were collected. High threshold stimulus-response relationships were apparent from the early phase of spinal shock that coincided with depolarization-like features that reached a peak on Day 16.9 (± 2.7 standard error) for the common peroneal nerve and Day 11.8 (± 2.0 standard error) for the median nerve. Overall, changes in the common peroneal nerve were of greater magnitude than for the median nerve. For both nerves, the most significant changes were in threshold electrotonus, which was 'fanned in', and during the recovery cycle superexcitability was reduced (P < 0.001). However, refractoriness was increased only for the common peroneal nerve (P < 0.05). Changes in the spinal injured cohort could not be explained on the basis of an isolated common peroneal nerve palsy. By the time patients with spinal injury were discharged from hospital between Days 68 and 215, excitability for upper and lower limbs had returned towards normative values, but not for all parameters. Electrolyte levels and results for nerve conduction studies remained within normal limits throughout the period of admission. Contrary to prevailing opinion, these data demonstrate that significant changes in peripheral motor axonal excitability occur early during spinal shock, with subsequent further deterioration in axonal function, before recovery ensues.

Comparisons of three surgical procedures on intestine ischemia reperfusion injury in a superior mesenteric artery injury model.

BACKGROUND: Temporary ligation, primary anastomosis, and temporary shunt have been reported to deal with superior mesenteric artery (SMA) injuries. We aimed to investigate which brought minimal ischemia reperfusion injury in a hypothermic traumatic shock swine model. METHODS: SMA was completely clamped while pigs were hemorrhaged to a mean arterial pressure (MAP) of 40 mm Hg. Animals were then randomized into temporary ligation (A, n=8), primary anastomosis (B, n=8), temporary shunt (C, n=8), and control groups (n=4). Animals in group A remained SMA interrupted for additional 1h while the other groups underwent the corresponding procedures immediately. Intestine injury was assessed by histologic examination and measurement of lipid peroxidations at the end of ischemia and experiment. RESULTS: Overall mortality rate was 50%, 25%, and 0% in groups A, B, and C, respectively (P<0.05). The total intestine ischemia time was predominantly shorter in group C in the other groups. Remarkable elevations of malonaldehyde (MDA) in small intestine were noted after reperfusion in group A. Animals in other groups, however, did not exacerbate during the 6-h reperfusion (resuscitation period). Group C showed the lowest MDA level at the end of experiment. Myeloperoxidase (MPO) levels showed no significant elevations during the ischemia or early reperfusion period; nevertheless, it reached approximately 3- to 6-fold in groups A and B (compared with baseline, P<0.01), and remained unchanged in group C at the end of experiment. CONCLUSION: Our study suggests that temporary shunt insertion might be preferred as it shortens ischemia time, alleviates intestinal ischemia/reperfusion injury, and thus decreases early mortality in this animal model.

The anatomic sites of disruption of the mucus layer directly correlate with areas of trauma/hemorrhagic shock-induced gut injury.

BACKGROUND: The intestinal mucus layer is an important but understudied component of the intestinal barrier. Consequently, we tested the hypothesis that the anatomic sites of loss of the mucus layer would directly correlate with sites of intestinal villous injury after trauma-hemorrhagic shock (T/HS) and may, therefore, serve as loci of gut barrier failure. Consequently, to investigate this hypothesis, we used Carnoy's fixative solution to prepare fixed tissue blocks where both the gut morphology and the mucus layer could be assessed on the same tissues slides. METHODS: Male Sprague-Dawley rats were subjected to a laparotomy (trauma) and 90 minutes of sham shock (T/SS) or 35 mm Hg × 90 minutes of actual shock (T/HS). Three hours after resuscitation, the rats were killed, and samples of the terminal ileum were processed by fixation in Carnoy's solution. Gut injury was evaluated by determining the percentage of villi injured. The status of the intestinal mucus layer was quantified by determining the percentage of the villi covered by the mucus and the mucus thickness. RESULTS: Histologic analysis of gut injury showed that the incidence of gut injury was ∼10-fold higher in the T/HS than the T/SS rats (T/SS=2.5% ± 0.5% vs. T/HS=22.4% ± 0.5% of injured villi; p<0.01). The T/SS rats had 98% of their ileal mucosa covered with a mucus layer, and this was decreased after T/HS to 63% ± 3% (T/HS vs. T/SS; p<0.001). Furthermore, loss of the mucus layer was found to directly correlate with villous injury with a regression coefficient of r=0.94 (p<0.001). CONCLUSION: This study shows that T/HS significantly reduces the intestinal mucus layer and causes villous injury and that a correlation exists between specific anatomic sites of T/HS-induced loss of the mucus layer and gut injury.

Discrepancy between heart rate and makers of hypoperfusion is a predictor of mortality in trauma patients.

BACKGROUND: Tachycardia is an important early sign of shock in trauma. Although the base deficit (BD) and lactate are indicative of hypoperfusion and known to predict mortality, some cases show a discrepancy between heart rate (HR) and BD or lactate; such cases have poor prognosis. The objective of this study was to examine whether lack of tachycardia after hypoperfusion is associated with increased mortality. METHODS: Retrospective data were collected on 1,742 adult trauma patients. Mortality was compared with different levels of BD, lactate, and HR on admission. Multivariate logistic regression was used to identify significant risk factors for mortality. RESULTS: Significantly increased mortality was observed in patients with hypoperfusion (BD less than -5 mmol/L or lactate more than 5 mmol/L). Among these patients, those with a normal HR (<80 bpm) were associated with a higher mortality rate than those with tachycardia (HR, 80-100 or>100 bpm). However, systolic blood pressure (SBP) was not significantly different between the different HR groups. Logistic regression analysis revealed that discrepancy between HR and indicators of hypoperfusion (Dis BD: BD less than -5 mmol/L and HR less than 80 bpm; or Dis lac: lactate more than 5 mmol/L and HR less than 80 bpm) are independent predictors of mortality after controlling for age, SBP, Injury Severity Score, head Abbreviated Injury Scale, HR, and BD or lactate (Dis BD: odds ratio, 2.67; 95% confidence interval, 1.07-6.61; p<0.05 and Dis lac: odds ratio, 4.11; 95% confidence interval, 1.57-10.74; p<0.01, respectively). CONCLUSIONS: The lack of tachycardia in the presence of hypoperfusion is associated with poor prognosis independent of injury severity, SBP, and head injury. A discrepancy between HR and indicators of hypoperfusion could be considered as a predictor of mortality in trauma patients.

Association of shock, coagulopathy, and initial vital signs with massive transfusion in combat casualties.

BACKGROUND: Timely initiation of a massive transfusion (MT) protocol is associated with improved survival and reduced transfusion for patients requiring MT; however, a priori identification of this population is difficult. The objective of this study was to compare the results of an MT prediction model and actual MT incidence in combat casualties. METHODS: We performed a retrospective review of the Joint Theater Trauma Registry transfusion database for all US service personnel injured in combat during overseas contingency operations who received at least 1 unit of blood. Systolic blood pressure at the time of admission, heart rate, hemoglobin, international normalized ratio, and base deficit were used in a previously developed prediction model for MT. RESULTS: Casualties (n = 1124) were identified who had received at least 1 unit of blood and had all data points. Of these patients, 420 patients (37%) received an MT. Subjects presenting with any two of four possible variables (heart rate >110, systolic blood pressure <110 mm Hg, base deficit < or = -6, and hemoglobin <11) had a 54% incidence of MT with a model sensitivity of 69%. Patients predicted but not observed to receive an MT had earlier time of death and an increased incidence of head injuries compared with those predicted and observed to receive an MT. Patients not predicted but observed to receive an MT had increased chest, abdominal, and extremity injuries than those neither predicted nor observed to receive an MT. CONCLUSION: The decision to implement an MT seems to rely heavily on clinical evaluation of severity of abdominal and extremity injury rather than physiologic derangement. Using a model based on the physiologic parameters--a more objective measure--may decrease mortality in combat casualties.

Estrogenic hormone modulation abrogates changes in red blood cell deformability and neutrophil activation in trauma hemorrhagic shock.

BACKGROUND: Decreased red blood cell (RBC) deformability and activation of neutrophils (polymorphonuclear leukocytes [PMN]) after trauma-hemorrhagic shock (T/HS) have been implicated in the development of multiple organ dysfunction. Experimentally, female animals seemed to be protected from the effects of T/HS, at least in part, because of elevated estrogen levels. Thus, we examined the relative role of estrogen receptor (ER)-alpha and -beta in this protective response. METHODS: To accomplish this goal, RBC deformability and neutrophil respiratory burst activity were measured in several groups of hormonally intact or ovariectomized (OVX) female rats subjected to T/HS (laparotomy plus hemorrhage to an MAP of 30 mm Hg to 35 mm Hg for 90 minutes) or trauma-sham shock (T/SS) and 3 hours of reperfusion. These groups included rats receiving vehicle, estradiol, or either an ER-alpha agonist or an ER-beta agonist administered at the end of the shock period just before volume resuscitation. RESULTS: RBC deformability and neutrophil activation were similar among all the T/SS groups and were not different from that observed in the non-OVX female rats subjected to T/HS. In contrast, RBC deformability was reduced and neutrophil activation was increased in the OVX, T/HS female rats as compared with the T/SS groups or the non-OVX, T/HS rats. The administration of estrogen to the T/HS, OVX rats returned RBC and neutrophil function to normal. Both the ER-alpha and -beta agonist partially, but not completely, protected the OVX rats from T/HS-induced loss of RBC deformability, whereas only the ER-beta agonist prevented the increase in neutrophil activation. CONCLUSIONS: The protective effects of estrogen on T/HS-induced RBC deformability are mediated, at least in part, via activation of both ER-alpha and -beta, whereas ER-beta activation is involved in limiting T/HS-induced neutrophil activation.

Evidence of hormonal basis for improved survival among females with trauma-associated shock: an analysis of the National Trauma Data Bank.

BACKGROUND: Basic science research suggests that sex hormones affect survival after traumatic shock. This study sought to determine the independent effect of gender on mortality among trauma patients in different hormone-related age groups. METHODS: Review of severely injured trauma patients with shock included in the National Trauma Databank. Patients were stratified into three groups on the basis of likely hormonal status: prehormonal (age, 0-12 years), hormonal (age,13-64 years), and posthormonal (age, ≥ 65 years). Multiple logistic regression was used to analyze the independent effect of gender on mortality in each group, adjusting for anatomic and physiologic injury severity. RESULTS: A total of 48,394 patients met our inclusion criteria (Injury Severity Score ≥ 16 and systolic blood pressure <90 mm Hg). Crude mortality was higher (p < 0.05) for males in all categories: prehormonal = 29% for males (n = 3,553) versus 24% for females (n = 1,831); hormonal = 34% for males (n = 26,778) versus 30% for females (n = 8,677) and posthormonal = 36% for males (n = 4,280) versus 31% for females (n = 3,275). After adjusting for covariates, women in the hormonally active group had a 14% decreased odds of death (0.86 [95% CI, 0.76-0.93]) compared with men. Females did not exhibit this survival advantage in the prehormonal (odds of death = 0.92 [0.74-1.14]) or posthormonal (odds of death = 0.90 [0.76-1.05]) groups. CONCLUSIONS: Females aged between 13 and 64 years exhibit significantly lower mortality than males after trauma-associated shock. This outcome difference is lost at the extremes of age (preadolescent children and individuals aged ≥ 65 years) where the effects of sex hormones are absent or diminished. These findings suggest that hormonal differences play a role in the gender-based outcome disparities after traumatic shock.