Utility of venous blood gases for the assessment of traumatic shock: a prospective observational study.

BACKGROUND: ABG samples are often obtained in trauma patients to assess shock severity. Venous blood gas (VBG) sampling, which is less invasive, has been widely used to assess other forms of shock. The study aim was to determine the agreement between VBG and ABG measurements in trauma. METHODS: Patients were enrolled at an Australian trauma centre between October 2016 and October 2018. Bland-Altman limits of agreement (LOA) between paired blood gas samples taken <30 min apart were used to quantify the extent of agreement. The impact of using only VBG measurements was considered using an a priori plan. Cases where venous sampling failed to detect 'concerning levels' were flagged using evidence-based cut-offs: pH ≤7.2, base deficit (BD) ≤-6, bicarbonate <21 and lactate ≥4. Case summaries of these patients were assessed by independent trauma clinicians as to whether an ABG would change expected management. RESULTS: During the study period 176 major trauma patients had valid paired blood gas samples available for analysis. The median time difference between paired measurements was 11 min (IQR 6-17). There was a predominance of men (81.8%) and blunt trauma (92.0%). Median Injury Severity Score was 13 (range 1-75) and inpatient mortality was 6.3%. Mean difference (ABG-VBG) and LOA between paired arterial and venous measurements were 0.036 (LOA -0.048 to 0.120) for pH, -1.27 mmol/L (LOA -4.35 to 1.81) for BD, -0.64 mmol/L (LOA -1.86 to 0.57) for lactate and -1.97 mmol/L (LOA -5.49 to 1.55) for bicarbonate. Independent assessment of the VBG 'false negative' cases (n=20) suggested an ABG would change circulatory management in two cases. CONCLUSIONS: In trauma patients VBG and ABG parameters displayed suboptimal agreement. However, in cases flagged as VBG 'false negative' independent review indicated that the availability of an ABG was unlikely to change management.

Circulating sFasL Levels Predict the Severity and Outcome of Burn Injury: A Prospective Observational Study.

BACKGROUND: Severe burn injury activates shock, inflammation, and blood cell system, but inappropriate reactions may lead to adverse outcomes. Soluble Fas ligand (sFasL) participates in apoptosis and inflammatory response. The circulating sFasL levels we investigated in association with the burn severity, shock, inflammation, blood cells, and mortality in patients with severe burns. METHODS: A total of 56 patients with severe burns were recruited. The levels of sFasL and the biomarkers reflecting shock, organ damage, inflammation, and blood cells at 48 h postburn were analyzed. We compared the practical situation of patients that stratified by median sFasL levels and investigated the predictive value of sFasL for mortality. RESULTS: High circulating sFasL levels were associated with the higher degrees of burn index, shock index, lactate, N-terminal probrain natriuretic peptide, total bilirubin, blood urea nitrogen, creatinine, tumor necrosis factor-α, interleukin-1ß, interleukin-8, intercellular adhesion molecule 1, and complement 3, and the lower degrees of oxygenation index, lymphocytes, and platelets. Multiple linear regression analysis showed that the higher tumor necrosis factor-α (P < 0.001) and the lower oxygenation index (P = 0.031) and lymphocytes (P = 0.043) were associated with the higher sFasL. High sFasL (a unit is 50 ng/L) (odds ratio [OR] 5.50 [95% CI 1.04-29.20], P = 0.045) was an independent predictor of increased mortality by multivariate logistic regression analysis. CONCLUSIONS: High circulating sFasL at 48 h postburn in patients with severe burns reflect shock, proinflammatory response, organ damage, and lymphocyte reductions and predict 30-day mortality.

Forgot calcium? Admission ionized-calcium in two civilian randomized controlled trials of prehospital plasma for traumatic hemorrhagic shock.

BACKGROUND: Randomized clinical trials (RCTs) support the use of prehospital plasma in traumatic hemorrhagic shock, especially in long transports. The citrate added to plasma binds with calcium, yet most prehospital trauma protocols have no guidelines for calcium replacement. We reviewed the experience of two recent prehospital plasma RCTs regarding admission ionized-calcium (i-Ca) blood levels and its impact on survival. We hypothesized that prehospital plasma is associated with hypocalcemia, which in turn is associated with lower survival. METHODS: We studied patients enrolled in two institutions participating in prehospital plasma RCTs (control, standard of care; experimental, plasma), with i-Ca collected before calcium supplementation. Adults with traumatic hemorrhagic shock (systolic blood pressure ≤70 mm Hg or 71-90 mm Hg + heart rate ≥108 bpm) were eligible. We use generalized linear mixed models with random intercepts and Cox proportional hazards models with robust standard errors to account for clustered data by institution. Hypocalcemia was defined as i-Ca of 1.0 mmol/L or less. RESULTS: Of 160 subjects (76% men), 48% received prehospital plasma (median age, 40 years [interquartile range, 28-53 years]) and 71% suffered blunt trauma (median Injury Severity Score [ISS], 22 [interquartile range, 17-34]). Prehospital plasma and control patients were similar regarding age, sex, ISS, blunt mechanism, and brain injury. Prehospital plasma recipients had significantly higher rates of hypocalcemia compared with controls (53% vs. 36%; adjusted relative risk, 1.48; 95% confidence interval [CI], 1.03-2.12; p = 0.03). Severe hypocalcemia was significantly associated with decreased survival (adjusted hazard ratio, 1.07; 95% CI, 1.02-1.13; p = 0.01) and massive transfusion (adjusted relative risk, 2.70; 95% CI, 1.13-6.46; p = 0.03), after adjustment for confounders (randomization group, age, ISS, and shock index). CONCLUSION: Prehospital plasma in civilian trauma is associated with hypocalcemia, which in turn predicts lower survival and massive transfusion. These data underscore the need for explicit calcium supplementation guidelines in prehospital hemotherapy. LEVEL OF EVIDENCE: Therapeutic, level II.

Organ-Specific Oxidative Events under Restrictive Versus Full Reperfusion Following Hemorrhagic Traumatic Shock in Rats.

Background aim: Reperfusion after hemorrhagic traumatic shock (HTS) is often associated with complications that are partly ascribed to the formation of reactive oxygen species (ROS). The aim of our study was to compare the effects of restrictive reperfusion (RR) to rapid full reperfusion (FR) on ROS formation and/or oxidative events. MATERIALS AND METHODS: Anesthetized male rats were randomly subjected to HTS followed by FR (75 mL/kg/h) or RR (30 mL/kg/h for 40 min, followed by 75 mL/kg/h) with Ringer's solution (n = 8/group). Compartment-specific ROS formation was determined by infusion of ROS scavenger 1-hydroxy-3-carboxy-2,2,5,5-tetramethyl-pyrrolidine hydrochloride (CP-H) during resuscitation, followed by electron paramagnetic resonance spectroscopy. Sham-operated animals (n = 8) served as controls. The experiment was terminated 100 min post-shock. RESULTS: Mean arterial pressure was significantly higher in the FR compared to the RR group during early reperfusion. Only RR animals, not FR animals, showed significantly higher ROS concentrations in erythrocytes (1951 ± 420 vs. 724 ± 75 AU) and in liver (474 ± 57 vs. 261 ± 21 AU) compared to sham controls. This was accompanied by elevated alanine aminotransferase and creatinine levels in RR animals compared to both shams and FR animals, while lipid peroxidation products (thiobarbituric acid reactive substances) were significantly increased only in the kidney in the FR group (p < 0.05). RR animals showed significantly higher plasma peroxiredoxin-4 values when compared to the FR group (20 ± 2 vs. 14 ± 0.5 RLU). CONCLUSION: Restrictive reperfusion after HTS is associated with increased ROS formation in erythrocytes and liver compared to sham controls. Moreover, the restrictive reperfusion is associated with a more pronounced injury to the liver and kidney, which is likely mediated by other than lipid peroxidation process and/or oxidative stress reactions.

Blood glucose concentrations in prehospital trauma patients with traumatic shock: A retrospective analysis.

BACKGROUND: 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. OBJECTIVES: 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. DESIGN: Retrospective analysis of the predefined, observational database of a nationwide Helicopter Emergency Medical Service (34 bases). SETTING: Emergency trauma patients treated by Helicopter Emergency Medical Service between 2005 and 2013 were investigated. PATIENTS: All adult trauma patients (≥18 years) with recorded blood glucose concentrations were enrolled. OUTCOMES: 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. RESULTS: 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). CONCLUSION: 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.

Comparison of compensatory reserve and arterial lactate as markers of shock and resuscitation.

BACKGROUND: During traumatic hemorrhage, the ability to identify shock and intervene before decompensation is paramount to survival. Lactate is extremely sensitive to shock, and its clearance has been demonstrated a useful gauge of shock and resuscitation status. Though lactate can be measured in the field, logistical constraints render it impractical in certain environments. The compensatory reserve represents a new clinical measurement reflecting the remaining capacity to compensate for hypoperfusion. We hypothesized the compensatory reserve index (CRI) would be an effective surrogate marker of shock and resuscitation compared to lactate. METHODS: The CRI device was placed on consecutive patients meeting trauma center activation criteria and remained on the patient until discharge, admission, or transport to operating suite. All subjects had a lactate level measured as part of their routine admission metabolic analysis. Time-corresponding CRI and lactate values were matched in regards to initial and subsequent lactate levels. Mean time from lactate sample collection to data availability in the electronic medical record was calculated. Predictive capacity of CRI and lactate in predicting hemorrhage was determined by receiver-operator characteristic curve analysis. Correlation analysis was performed to determine if any association existed between changing CRI and lactate values. RESULTS: Receiver-operator characteristic (ROC) curves were generated and area under the curve was 0.8052 and 0.8246 for CRI and lactate, respectively. There was no significant difference in each parameter's ability to predict hemorrhage (p = 0.8015). The mean duration from lactate sample collection to clinical availability was 44 minutes whereas CRI values were available immediately. Analysis of the concomitant change in serial CRI and lactate levels revealed a Spearman's correlation coefficient of -0.73 (p < 0.01). CONCLUSION: CRI performed with equivalent predictive capacity to lactate with respect to identifying initial perfusion status associated with hemorrhage and subsequent resuscitation. LEVEL OF EVIDENCE: Diagnostic, Level II.

Can venous base excess replace arterial base excess as a marker of early shock and a predictor of survival in trauma?

INTRODUCTION: Arterial base excess is an established marker of shock and predictor of survival in trauma patients. However, venous blood is more quickly and easily obtained. This study aimed to determine if venous base excess could replace arterial base excess as a marker in trauma patients at presentation and if venous base excess is predictive of survival at 24 hours and one week. METHODS: This was a prospective study of 394 trauma patients presenting to the emergency department of a tertiary hospital over a 17-month period. Data on base excess at presentation, vital signs, shock index (SI), injury severity score (ISS), and mortality at 24 hours and one week was collected and analysed. RESULTS: Arterial and venous blood gas tests were performed on 260 and 134 patients, respectively. Patients were stratified into groups based on their SI and ISS for analysis. There was no statistical difference between mean venous blood gas and arterial blood gas levels at presentation when SI > 0.7, regardless of ISS (p > 0.05). The mortality rate was 4.57%. Both venous and arterial base excess was lower in nonsurvivors compared to survivors (p < 0.05). However, at 24 hours and one week, the difference in base excess values at presentation between survivors and nonsurvivors was greater when using venous base excess compared to arterial base excess (11.53 vs. 4.28 and 11.41 vs. 2.66, respectively). CONCLUSION: In conclusion, venous base excess can replace arterial base excess in trauma patients as a means of identifying and prognosticating early shock.

The tissue factor pathway mediates both activation of coagulation and coagulopathy after injury.

BACKGROUND: The initiation of coagulation in trauma is thought to originate from exposed tissue factor (TF); recent data have led to the alternative hypothesis that damage-associated molecular patterns may contribute to postinjury coagulation. In acute traumatic coagulopathy, aberrant coagulation is mediated via the activated protein C (aPC) pathway; the upstream regulators of this process and its relation to TF remain uncharacterized. To examine the role of the TF pathway in mediating acute traumatic coagulopathy, we used specific antibody blockades in an established murine model of traumatic hemorrhagic shock, hypothesizing that both coagulation activation after injury and aPC-mediated coagulopathy are driven by TF via thrombin. METHODS: Mice underwent an established model of trauma and hemorrhage and were subjected to either sham (vascular cannulation) or trauma-hemorrhage (cannulation, laparotomy, shock to mean arterial pressure of 35 mm Hg); they were monitored for 60 minutes before sacrifice. Mice in each group were pretreated with either targeted anti-TF antibody to block the TF pathway or hirudin for specific blockade of thrombin. Plasma was assayed for thrombin-antithrombin (TAT) and aPC by enzyme-linked immunosorbent assay. RESULTS: Compared with controls, trauma-hemorrhage mice treated with anti-TF antibody had significantly reduced levels of TAT (2.3 ng/mL vs. 5.7 ng/mL, p = 0.016) and corresponding decreases in aPC (16.3 ng/mL vs. 31.6 ng/mL, p = 0.034), with reductions to levels seen in sham mice. Direct inhibition of thrombin yielded similar results, with reduction in aPC to levels below those seen in sham mice. CONCLUSION: In this study, blockade of the TF pathway led to the attenuation of both thrombin production and aPC activation observed in traumatic shock. Specific thrombin inhibition achieved similar results, indicating that aPC-related coagulopathy is mediated via thrombin activated by the TF pathway. The near-complete blockade of TAT and aPC observed in this model argues for a dominant role of the TF-thrombin pathway in both coagulation activation after injury and traumatic coagulopathy.

Determining the utility of metabolic acidosis for trauma patients in the emergency department.

BACKGROUND: Metabolic acidosis has been proposed as the gold standard to define shock in trauma patients. Other studies determine the presence of shock by use of serum lactate. However, not all medical centers have the ability to utilize point-of-care lactate at bedside. OBJECTIVE: This study seeks to determine the relationship between serum lactate and metabolic acidemia in trauma patients, and if metabolic acidemia can be used to guide therapy. We hypothesized that acidemia would be strongly correlated with lactate levels and would be associated with activation of massive transfusion (MT) in the presence of shock in trauma. METHODS: This was a prospective observational cohort study, level II evidence; this study aids in decision-making. Setting was a Level I academic, urban trauma center. The study took place from July 1, 2012 to March 1, 2013 and included patients who were ≥18 years old and required trauma team activation. Observations included baseline demographics (age, gender, type of injury), vital signs, point-of-care arterial blood gas, lactate, and need for MT. RESULTS: One hundred patients were enrolled over the study period. The average age was 34 years, and 82% were male. Forty patients were acidemic (pH < 7.35), and there was a significant difference in lactate levels between the acidemic and non-acidemic groups (p < 0.002). We found a strong correlation between pH and lactate: rs = -0.38, t = -4.03, p < 0.001. In addition, using a logistic regression, we show that pH was associated with activation of MT (p = 0.002). CONCLUSION: This is a prospective observational cohort study with level II evidence. This study demonstrates that acidemia was strongly correlated to serum lactate, lactate levels were higher in the acidemic group, and metabolic acidemia was associated with the activation of MT for trauma patients at our institution.

Noble-Collip Drum Trauma Induces Disseminated Intravascular Coagulation But Not Acute Coagulopathy of Trauma-Shock.

BACKGROUND: There are two opposing possibilities for the main pathogenesis of trauma-induced coagulopathy: an acute coagulopathy of trauma shock and disseminated intravascular coagulation with the fibrinolytic phenotype. OBJECTIVE: The objective of this study was to clarify the main pathogenesis of trauma-induced coagulopathy using a rat model of Noble-Collip drum trauma. METHODS: Eighteen rats were divided into the control, trauma 0, and trauma 30 groups. The trauma 0 and 30 groups were exposed to Noble-Collip drum trauma. Blood samples were drawn without, immediately after, and 30 min after Noble-Collip drum trauma in the control, trauma 0, and trauma 30 groups, respectively. Coagulation and fibrinolysis markers were measured. Thrombin generation was assessed according to a calibrated automated thrombogram. RESULTS: Spontaneous thrombin bursts resulting from circulating procoagulants were observed in the nonstimulated thrombin generation assay immediately after trauma. Soluble fibrin levels (a marker of thrombin generation in the systemic circulation) were 50-fold greater in the trauma groups than in the control group. The resultant coagulation activation consumed platelets, coagulation factors, and antithrombin. Endogenous thrombin potential and factor II ratio were significantly negatively correlated with antithrombin levels, suggesting insufficient control of thrombin generation by antithrombin. High levels of active tissue-type plasminogen activator induced hyperfibrin(ogen)olysis. Soluble thrombomodulin increased significantly. However, activated protein C levels did not change. CONCLUSIONS: The systemic thrombin generation accelerated by insufficient antithrombin control leads to the consumption of platelets and coagulation factors associated with hyperfibrin(ogen)olysis. These changes are collectively termed disseminated intravascular coagulation with the fibrinolytic phenotype.

Pre-hospital emergency values of hypertonic-hyperonconic limited resuscitation for traumatic shock.

Traumatic shock is a serious threat to life and health. The aim of this study is to investigate the effect of different resuscitation fluid compositions on the emergency resuscitation for patients with traumatic shock. Sixty patients were enrolled and divided into two groups, Group A and Group B. The patients in Group A were treated with resuscitation fluid, with 2:1 ratio of crystal (0.9% sodium chloride injection) and colloid (hydroxyethyl starch 40 injection). The patients in Group B were treated with hypertonic sodium chloride hydroxyethyl starch 40 injection (HSH40). Both vital signs and fluid dosage were monitored and recorded. At the beginning of resuscitation (T0) and 30 min (T1), 60 min (T2) and 120 min (T3) after resuscitation, indicator parameters including hemoglobin (HB), hematocrit (HCT), prothrombin time (PT), arterial blood lacic acid (LA) and C-reactive protein (CRP) were monitored and recorded. Tissue oxygenation and hemodynamic profile were also analyzed. At T1, T2and T3after fluid resuscitation, the heart rates of the patients in Group B were lower than those in Group A, whereas the average arterial pressure in Group B was significantly higher than that in Group A. Notably, significant decreases of HB and HCT were detected at T1, T2and T3compared with T0 in Group A. In contrast, no significant difference was shown in detected HCT at T2and T3compared with T0 in Group B, while the detected HB value was smaller. a statistically significant decrease of LA was detected at T1, T2and T3in Group A and Group B compared with that at T0. At T2and T3in Group A and Group B, a statistically significant increase of PT was detected compared with the beginning of resuscitation. At T2and T3after resuscitation, CRP in both Group A and Group B was significantly increased compared with that upon admission to hospital, and was lower in Group B than in Group A.

Coagulopathy following major trauma hemorrhage: lytic, lethal and a lack of fibrinogen.

Trauma-induced coagulopathy (TIC) is present soon after injury and is associated with increased transfusion requirements and worse outcomes. The pathophysiological mechanisms, which result in the widespread derangements of hemostasis following major trauma hemorrhage, are as yet not fully defined. Profound activation of fibrinolytic pathways and fibrinogen depletion appear to be fundamental processes in the development of TIC and offer potential therapeutic targets. Collaborative and multi-disciplinary scientific study is thus a research priority in order to characterize the primary drivers of TIC and develop targeted and efficacious treatment strategies.

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.

Hemostasis during the early stages of trauma: comparison with disseminated intravascular coagulation.

INTRODUCTION: We tested two hypotheses that disseminated intravascular coagulation (DIC) and acute coagulopathy of trauma-shock (ACOTS) in the early phase of trauma are similar disease entities and that the DIC score on admission can be used to predict the prognosis of patients with coagulopathy of trauma. METHODS: We conducted a retrospective study of 562 trauma patients, including 338 patients whose data were obtained immediately after admission to the emergency department. We collected serial data for the platelet counts, global markers of coagulation and fibrinolysis, and antithrombin levels. DIC was diagnosed according to the Japanese Association for Acute Medicine (JAAM) DIC scoring system, and ACOTS was defined as a prothrombin-time ratio of >1.2. RESULTS: The higher levels of fibrin/fibrinogen degradation products (FDP) and D-dimer and greater FDP/D-dimer ratios in the DIC patients suggested DIC with the fibrinolytic phenotype. The DIC patients with the fibrinolytic phenotype exhibited persistently lower platelet counts and fibrinogen levels, increased prothrombin time ratios, higher FDP and D-dimer levels, and lower antithrombin levels compared with the non-DIC patients on arrival to the emergency department and during the early stage of trauma. Almost all ACOTS patients met the criteria for a diagnosis of DIC; therefore, the same changes were observed in the platelet counts, global markers of coagulation and fibrinolysis, and antithrombin levels as noted in the DIC patients. The JAAM DIC score obtained immediately after arrival to the emergency department was an independent predictor of massive transfusion and death due to trauma and correlated with the amount of blood transfused. CONCLUSIONS: Patients who develop DIC with the fibrinolytic phenotype during the early stage of trauma exhibit consumption coagulopathy associated with increased fibrin(ogen)olysis and lower levels of antithrombin. The same is true in patients with ACOTS. The JAAM DIC score can be used to predict the prognosis of patients with coagulopathy of trauma.

[Protective effect of necrostatin-1 on the liver of rats with trauma induced hemorrhagic shock].

OBJECTIVE: To investigate the effects of necrostatin-1( Nec-1) on the liver of rats with trauma induced hemorrhagic shock. METHODS: Trauma induced hemorrhagic shock model was produced by adopting the left femur, tibia fracture and soft tissue injury, bleeding and reperfusion in male Sprague-Dawley (SD) rats. A total of 22 rats were divided into model group and Nec-1 group with 11 rats in each group by randomized digital number method and the 72-hour mortality was observed. In addition, 72 rats were randomly divided into sham group, model group, Nec-1 group with 24 rats in each group. Rats in sham group were only received anesthesia, separating a nd ligating blood vessels, without trauma induced hemorrhagic and reperfusion, and the rats in Nec-1 group were received 1 mg/kg Nec-1 through femoral vein 5 minutes before reperfusion, and the rats in Nec-1 group were received the same amount of solvent. The serum and liver tissues of each group were collected at 2, 4, 8 hours after reperfusion. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected by automatic biochemistry analyzer. The pathology changes in liver were observed by hematoxylin-eosin (HE) staining. The mRNA expressions of tumor necrosis factor-α (TNF-α) and interleukin -1ß (IL-1ß) in the liver were determined by reverse transcription-polymerase chain reaction (RT-PCR). The protein expressions of receptor interaction of protease 1/3( RIP1/RIP3) were also assessed by Western blot analysis. RESULTS: Compared to the model group, Nec-1 significantly reduced the 72 hour mortality [18.18% (2/11) vs. 63.64% (7/11), P = 0.040]. Two hours after trauma induced hemorrhagic shock and reperfusion, the expressions of ALT and AST in model group were significantly increased compared with those in sham group. [ ALT (U/L): 110.21 ± 22.32 vs. 80.98 ± 19.94, AST (U/L): 364.29 ± 64.83 vs. 279.76 ± 70.64, both P<0.05], and reached the peak at 8 hours [ALT (U/L): 387.41± 47.11 vs. 82.76 ±22.44, AST ( U/L): 973.35 ±77.51 vs.261.49 ± 52.03, both P <0.01]. Levels of serum ALT and AST in NEc-1 group were significantly decreased compared with model group [ALT (U/L) 4 hours: 144.64 ± 33.79 vs. 213.96 ± 36.21, 8 hours: 159.48 ± 43.57 vs. 387.41>11; AST (U/L): 4 hours: 398.78 ± 59.48 vs. 630.61 ± 59.93, 8 hours: 427.38 ± 80.75 vs. 973.35 ± 77.51, all P < 0.01] Under light microscopy, it was noted that the hepatic sinus expansion, liver cells degeneration, necrosis, as well as infiltration of abundant inflammatory cells were observed. But the pathology changes in hepatic tissues were significantly mitigated in Nec-1 group. Along with the time extension, the mRNA expressions of TNF-α and IL-ß and the protein expressions of RIP1 and RIP3 were markedly up-regulated. Compared with model group, difference in the mRNA expressions of TNF-α and IL-ß in hepatic tissues in Nec-1 group were statistically significant, and the most obvious difference was at 8 hours [TNF-α mRNA: 1.457 ± 0.081 vs. 2.317 ± 0.062, IL-ß mRNA: 0.690 ± 0.087 vs. 1.812 ± 0.112, both P<0.01]. But there was no statistically significant difference in RIP1 and RIP3 between Nec-1 group and model group [RIP1 protein 8 hours: 0.561 ± 0.033 vs. 0.587 ± 0.036, RIP3 protein 8 hours: 0.976 ± 0.040 vs. 1.044 ± 0.115, both P > 0.05]. CONCLUSION: Nec-1 may be remarkable protect effect on the liver of rats with trauma induced hemorrhage shock and reperfusion, and the intrinsic mechanisms need further investigation.

Normal prothrombinase activity, increased systemic thrombin activity, and lower antithrombin levels in patients with disseminated intravascular coagulation at an early phase of trauma: comparison with acute coagulopathy of trauma-shock.

BACKGROUND: We tested the hypotheses that an increase in systemic thrombin activity occurs in both disseminated intravascular coagulation (DIC) with the fibrinolytic phenotype and in acute coagulopathy of trauma shock (ACoTS), and that the patients diagnosed as having ACoTS overlap or are identical with those diagnosed as having DIC. METHODS: We made a prospective study of 57 trauma patients, including 30 patients with DIC and 27 patients without DIC. Patients with ACoTS, defined as a prothrombin time ratio >1.2, were also investigated. We included 12 healthy volunteers as controls. The levels of soluble fibrin, antithrombin, prothrombinase activity, soluble thrombomodulin, and markers of fibrin(ogen)olysis were measured on days 1 and 3 after the trauma. The systemic inflammatory response syndrome and the Sequential Organ Failure Assessment were scored to evaluate the extent of inflammation and organ dysfunction. RESULTS: Patients with DIC showed more systemic inflammation and greater Sequential Organ Failure Assessment scores and were transfused with more blood products than the patients without DIC. On day 1, normal prothrombinase activity, increased soluble fibrin, lesser levels of antithrombin, and increased soluble thrombomodulin were observed in patients with DIC in comparison with controls and non-DIC patients. These changes were more prominent in patients with DIC who met the overt criteria for DIC established by the International Society on Thrombosis and Haemostasis. Multiple regression analysis showed that antithrombin is an independent predictor of high soluble fibrin in DIC patients. Greater levels of fibrin and fibrinogen degradation products, D-dimer, and the fibrin and fibrinogen degradation products/D-dimer ratio indicated increased fibrin(ogen)olysis in DIC patients. Almost all ACoTS patients overlapped with the DIC patients. The changes in the measured variables in ACoTS patients coincided with those in DIC patients. CONCLUSION: Normal prothrombinase activity and insufficient control of coagulation give rise to systemic increase in thrombin generation and its activity in patients with DIC with the fibrinolytic phenotype at an early phase of trauma. The same is true in patients with ACoTS, and shutoff of thrombin generation was not observed.

[Erythrocytes and microvascular tone during acute traumatic haemorrhagic shock]. / Érythrocytes et tonus microvasculaire au cours du choc hémorragique traumatique.

Haemorrhagic shock remains a leading cause of death in trauma patients. The concept of haematologic damage control is gradually taking place in the management of traumatic haemorrhagic shock. It is based primarily on the early implementation of a quality blood transfusion involving erythrocytes, plasmas and platelets transfusion. Red blood cell transfusion is mainly supported by the oxygen carrier properties of erythrocytes. However, it appears that erythrocytes ability to modulate the bioavailability of nitric oxide (NO) plays a major role in capillary opening and perfusion. Erythrocytes are also actively involved in the processes of hemostasis and coagulation. In this context, it seems difficult to define a threshold of hemoglobin concentration to determine the implementation of a blood transfusion in traumatic haemorrhagic shock.

Venous and arterial base deficits: do these agree in occult shock and in the elderly? A Bland-Altman analysis.

BACKGROUND: Trauma centers are increasingly advocating the replacement of arterial blood gas measurements with venous blood gas measurements for simplification of base deficit (BD) determination. These values have never been demonstrated to agree in important trauma populations, such as for patients in occult shock (OS) or the elderly. The goal of this study was to investigate the level of agreement between venous and arterial BDs from blood gases in critically ill or injured patients, specifically in OS and the elderly. METHODS: This is a retrospective, consecutive, cohort study using matched pairs of venous and arterial blood gases from patients admitted to the Trauma and Neurosurgery Intensive Care Unit in a Level I trauma center in Toronto, Ontario, Canada. Agreement between near simultaneous arterial and venous BD was calculated using the Bland-Altman method. McNemar's test was used for differences in BDs in the presence or absence of OS and in elderly patients. RESULTS: BDs for 466 arterial and venous samples from 72 patients were compared pairwise. There was no significant difference between samples (p = 0.88). Ninety-eight percent of samples were within 3.0 mmol/L of each other. No significant differences were detected between venous and arterial BD in the presence of OS or in the elderly (p = 0.72 and p = 0.25, respectively). CONCLUSION: Arterial and venous BDs agree, including in the presence of OS and in the elderly. Consideration may be given to venous sampling both in the intensive care unit or in other areas of care, such as the trauma bay. LEVEL OF EVIDENCE: Diagnostic study, level III.