Temporal expression of circulating miRNA after severe injury.

BACKGROUND: Severe injury can lead to immune dysfunction and predispose patients to infection and death. Micro-RNAs regulate gene expression and may act as biomarkers for susceptibility to infection. The aim of this study was to examine the temporal and differential expression of previously identified dysregulated micro-RNAs in patients with severe injury. METHODS: Fourteen severely injured patients requiring transfusion were enrolled prospectively in this study approved by our institutional review board. Inclusion criteria consisted of adult patients deemed clinically to be in hemorrhagic shock necessitating transfusion in the acute phase of their injury care. Peripheral blood samples were obtained after admission to the surgical intensive care unit and again at 6, 12, 24, and 48 hours after admission. The samples obtained at arrival to the intensive care unit and 24 and 48 hours later were analyzed in this data set. Fourteen healthy volunteers served as controls. The 10 dysregulated micro-RNAs identified in a prior study at the 12-hour time point and important genes in innate immunity were measured using quantitative reverse transcription-polymerase chain reaction. RESULTS: The participants were 21-77 years old (median, 42), 78% were male, and their Injury Severity Score ranged from 11 to 43 (median, 27); 11 had blunt and 3 had penetrating injuries. Three were intubated and 5 had received blood products before arrival at the hospital. Base deficit on hospital admission was 3-20 (median, 9). All patients required blood transfusion secondary to blood loss sustained during injury. Eleven of the 14 patients went directly to the operating room from the emergency department for control of the source of hemorrhage. Survival to discharge was 93%. Seven patients developed infection. Compared with healthy controls, miR-106a was downregulated at all time points compared with controls (P < .05). miR-618 was upregulated in initial blood draws (P < .05) and at 24 and 48 hours (P < .06). Tumor necrosis factor α and human leukocyte antigen-DR (HLA-DR) were downregulated, and interleukin-10 and PD-L1 were upregulated (P < .05). In patients who developed infection, miR-106a levels appeared more downregulated than those who did not develop infection. CONCLUSION: miR-106a was downregulated in trauma patients after major injury for up to 48 hours after intensive care unit admission. Tumor necrosis factor α and interleukin-10 are targeted by miR-106a, which are regulators of the immune response. Manipulation of micro-RNA expression may be a therapeutic target for immune dysfunction.

Acute haemolysis, DIC and renal failure after transfusion of uncross-matched blood during trauma resuscitation: illustrative case and literature review.

AIMS/OBJECTIVES: The aims of this study were to report a patient with acute haemolytic transfusion reaction (HTR) after transfusing uncross-matched red blood cell (RBC) units and to identify the frequency of this complication. BACKGROUND: Uncross-matched RBC units are commonly transfused in emergencies, but the frequency of acute HTR is unknown. METHODS: We describe a male stabbing victim who received three units of uncross-matched RBC units complicated by acute intravascular HTR, disseminated intravascular coagulation (DIC) and renal failure. We identified 14 studies evaluating the frequency of acute HTR post-emergency transfusion of uncross-matched RBC units. RESULTS: Acute HTR was shown by haemoglobinuria, free-plasma haemoglobin and methemalbumin, with anti-K and anti-Fya eluted from recipient red cells; acute DIC featured severe hypofibrinogenemia, thrombocytopenia, elevated fibrin D-dimer and multiple bilateral renal infarcts. Two of the three transfused units reacted with pre-existing RBC alloantibodies [anti-K (titre, 128), anti-Fya (titre, 512)], explained by transfusion 25 years earlier. Our literature review found the frequency of acute HTR following emergency transfusion of uncross-matched RBC units to be 2/3998 [0·06% (95% CI, 0·01-0·21%)]. CONCLUSIONS: Although emergency transfusion of uncross-matched blood is commonly practiced at trauma centres worldwide, with low risk of acute HTR (<1/1000), our well-documented patient case demonstrates the potential for acute HTR with severe complications.

A BRIEF OVERVIEW OF COMPARTMENTAL MODELING FOR INTAKE OF PLUTONIUM VIA WOUNDS.

The aim of this study is to present several approaches that have been used to model the behavior of radioactive materials (specifically Pu) in contaminated wounds. We also review some attempts by the health physics community to validate and revise the National Council on Radiation Protection and Measurements (NCRP) 156 biokinetic model for wounds, and present some general recommendations based on the review. Modeling of intake via the wound pathway is complicated because of a large array of wound characteristics (e.g. solubility and chemistry of the material, type and depth of the tissue injury, anatomical location of injury). Moreover, because a majority of the documented wound cases in humans are medically treated (excised or treated with chelation), the data to develop biokinetic models for unperturbed wound exposures are limited. Since the NCRP wound model was largely developed from animal data, it is important to continue to validate and improve the model using human data whenever plausible.

The percutaneous toxicokinetics of VX in a damaged skin porcine model and the evaluation of WoundStat™ as a topical decontaminant.

This study used a damaged skin, porcine model to evaluate the in vivo efficacy of WoundStat™ for the decontamination of superficial, nerve agent-contaminated wounds. Anaesthetized animals were randomly assigned to either control (n = 7), no decontamination (n = 12) or WoundStat™ (n = 12) treatment groups. Pigs were exposed to a 5× LD50 dose of neat, radiolabelled S-[2-(diisopropylamino)ethyl]-O-ethyl methyl-phosphonothioate (VX; or equivalent volume of sterile saline for the control group) via an area of superficially damaged skin on the ear. WoundStat™ was applied at 30 seconds post-exposure to assigned animals. The VX contaminant (or saline) and decontaminant remained in place for the duration of the study (up to 6 hours). Physiological parameters and signs of intoxication were recorded during the exposure period. Skin and organ samples were taken post mortem for 14 C-VX distribution analyses. Blood samples were taken periodically for toxicokinetic and whole-blood acetylcholinesterase (AChE) activity analyses. VX exposure was accompanied by a rapid decrease in AChE activity in all animals, regardless of decontamination. However, decontamination significantly improved survival rate and time and reduced the severity of signs of intoxication. In addition, the distribution of 14 C-VX in key internal organs and post mortem blood samples was significantly lower in the WoundStat™ treatment group. This study demonstrates that WoundStat™ may be a suitable medical countermeasure for increasing both survival rate and time following VX exposure. The results also suggest that AChE activity is not a useful prognostic indicator.

[Possibilities of correction rheological blood svoytv at chipped and cut wounds of the breast ].

The purpose: research objective: to study influence of electromagnetic oscillations of millimetric range on rheological properties of blood at patients with chipped and cut wounds of a breast for the purpose of their correction. Methods. For the solution of a research objective we have carried out studying of changes of rheological properties of blood at the 22nd patient with the getting chipped and cut wounds of a breast without internal injury during the next postoperative period. All patient has executed primary surgical processing and drainage of a pleural cavity. At all patients the volume of blood loss has made 200-500 ml. Criteria of inclusion were: existence of the getting wound of a thorax, existence of a small gemotoraks. Criteria of an exception: blood loss existence more than 500 ml, existence of the combined and multiple damages. The main group is divided into two subgroups, in the first 12 patients with application of electromagnetic oscillations of millimetric range, have entered the second 10 people without application of electromagnetic oscillations of millimetric range. The group of comparison was made by 15 rather healthy donor volunteers of the same age and a floor. To all patients the hemotransfusion wasn't carried out, the volume of infusional therapy was comparable in both groups. Changes of a rheology of blood came to light by means of the accounting of viscosity of blood, change of an index of deformation and aggregation of erythrocytes. Conclusion. As a result of the conducted research it is established that application of electromagnetic oscillation of millimetric range for patients with chipped and cut wounds of a breast prevents development of changes of rheological properties of blood, at the same time patients well transfer this procedure that is shown by lack of side effects.

A comparison of base deficit and vital signs in the early assessment of patients with penetrating trauma in a high burden setting.

INTRODUCTION: An assessment of physiological status is a key step in the early assessment of trauma patients with implications for triage, investigation and management. This has traditionally been done using vital signs. Previous work from large European trauma datasets has suggested that base deficit (BD) predicts clinically important outcomes better than vital signs (VS). A BD derived classification of haemorrhagic shock appeared superior to one based on VS derived from ATLS criteria in a population of predominantly blunt trauma patients. The initial aim of this study was to see if this observation would be reproduced in penetrating trauma patients. The power of each individual variable (BD, heart rate (HR), systolic blood pressure (SBP), shock index(SI) (HR/SBP) and Glasgow Coma Score (GCS)) to predict mortality was then also compared. METHODS: A retrospective analysis of adult trauma patients presenting to the Pietermaritzburg Metropolitan Trauma Service was performed. Patients were classified into four "shock" groups using VS or BD and the outcomes compared. Receiver Operator Characteristic (ROC) curves were then generated to compare the predictive power for mortality of each individual variable. RESULTS: 1863 patients were identified. The overall mortality rate was 2.1%. When classified by BD, HR rose and SBP fell as the "shock class" increased but not to the degree suggested by the ATLS classification. The BD classification of haemorrhagic shock appeared to predict mortality better than that based on the ATLS criteria. Mortality increased from 0.2% (Class 1) to 19.7% (Class 4) based on the 4 level BD classification. Mortality increased from 0.3% (Class 1) to 12.6% (Class 4) when classified based by VS. Area under the receiver operator characteristic (AUROC) curve analysis of the individual variables demonstrated that BD predicted mortality significantly better than HR, GCS, SBP and SI. AUROC curve (95% Confidence Interval (CI)) for BD was 0.90 (0.85-0.95) compared to HR 0.67(0.56-0.77), GCS 0.70(0.62-0.79), SBP 0.75(0.65-0.85) and SI 0.77(0.68-0.86). CONCLUSION: BD appears superior to vital signs in the immediate physiological assessment of penetrating trauma patients. The use of BD to assess physiological status may help refine their early triage, investigation and management.

Course of serum amyloid A (SAA) plasma concentrations in horses undergoing surgery for injuries penetrating synovial structures, an observational clinical study.

BACKGROUND: Injuries penetrating synovial structures are common in equine practice and often result in septic synovitis. Significantly increased plasma levels of serum amyloid A (SAA) have been found in various infectious conditions in horses including wounds and septic arthritis. Plasma SAA levels were found to decrease rapidly once the infectious stimulus was eliminated. The purpose of the current study was to investigate the usefulness of serial measurements of plasma SAA as a monitoring tool for the response to treatment of horses presented with injuries penetrating synovial structures. In the current study plasma SAA concentrations were measured every 48 hours (h) during the course of treatment. RESULTS: A total of 19 horses with a wound penetrating a synovial structure were included in the current study. Horses in Group 1 (n = 12) (injuries older than 24 h) only needed one surgical intervention. Patients in this group had significantly lower median plasma SAA levels (P = 0.001) between 48 h (median 776 mg/L) and 96 h (median 202 mg/L) after surgery. A significant decrease (P = 0.004) in plasma SAA levels was also observed between 96 h after surgery (median 270 mg/L) and 6 days (d) after surgery (median 3 mg/L). Four horses (Group 2) required more than one surgical intervention. In contrast to Group 1 patients in Group 2 had either very high initial plasma concentrations (3378 mg/L), an increase or persistently high concentrations of plasma SAA after the first surgery (median 2525 mg/L). A small group of patients (n = 3) (Group 3) were admitted less than 24 h after sustaining a wound. In this group low SAA values at admission (median 23 mg/L) and peak concentrations at 48 h after surgery (median 1016 mg/L) were observed followed by a decrease in plasma SAA concentration over time. CONCLUSIONS: A decrease in plasma SAA concentrations between two consecutive time points could be associated with positive response to treatment in the current study. Therefore, serial measurements of plasma SAA could potentially be used as an additional inexpensive, quick and easy tool for monitoring the treatment response in otherwise healthy horses presented with injuries penetrating synovial structures. However further studies will be necessary to ascertain its clinical utility.

Peak creatinine kinase level is a key adjunct in the evaluation of critically ill trauma patients.

BACKGROUND: Elevated creatinine kinase (CK) can indicate rhabdomyolysis, a risk factor for acute kidney injury (AKI). We investigated risk factors and clinical significance of peak CK levels. METHODS: Retrospective analysis, adult trauma patients. Logistic regression was used to identify risk factors for elevated CK and AKI. RESULTS: 3240 trauma patients were analyzed; median time to peak CK was 17 h and 347 patients had peak CK > 5000. On multivariable analysis, younger males with severe injury were more likely to have peak CK > 5000 and peak CK > 5000 was an independent risk factor for AKI (AOR 3.79). Although peak CK levels were significantly lower in older patients (1,637U/L vs 2,604U/L), older patients were more likely to develop AKI at lower CK levels. CONCLUSIONS: CK levels commonly peak within 1-2 days after admission. Despite lower peak CK levels, older patients are more likely to develop AKI. These data may support more rigorous CK monitoring and lower intervention threshold in older patients.

Fatores associados ao óbito e à reposição volêmica em pacientes com trauma por lesões penetrantes / Factors associated with death or volume replacement in patients with trauma due to penetrating injuries

Objective: to evaluate the prognostic factors of volume replacement in patients with trauma due to penetrating injuries. Methods: retrospective cohort study whose data were obtained by analyzing medical records of 544 patients who were admitted to the emergency unit, victims of penetrating trauma. Results: among the victims, 282 (51.9%) suffered stab wound, 262 (48.2%) injury by firearms, 486 (89.3%) were male, 382 (70.2%) were aged between 14 and 30 years. Most who received volume greater than 2000ml, systolic blood pressure ≤90mmHg and mean arterial pressure ≤65mmHg presented more mortality, with p <0.05, p <0.002 and p <0.003, respectively. Conclusion: the limited volume replacement can help in the good prognosis of victims of penetrating trauma.

Avaliar os fatores prognósticos da reposição volêmica em pacientes com trauma por lesões penetrantes. Métodos: estudo de coorte retrospectiva cujos dados foram obtidos através da análise de prontuários de 544 pacientes que deram entrada no serviço de emergência, vítimas de traumatismo penetrante. Resultados: dentre as vítimas, 282 (51,9%) sofreram ferimento por arma branca, 262 (48,2%) ferimento por arma de fogo, 486 (89,3%) eram do sexo masculino, com idade entre 14 e 30 anos 382 (70,2%). A maioria que recebeu fluído maior que 2000ml, pressão arterial sistólica ≤90mmHg e pressão arterial média ≤65mmHg, apresentou mais mortalidade, com valor de p<0,05, p<0,002 e p<0,003, respectivamente. Conclusão: a reposição volêmica limitada pode auxiliar no bom prognóstico do paciente vítima de trauma penetrante.

[PROGNOSTIC SIGNIFICANCE OF CHANGES OF BLOOD GLUCOSE LEVEL IN PATIENTS WITH THORACOABDOMINAL INJURIES.]

Background Currently, one of the causes of high morbidity and mortality is injuries. Predict the outcome of injuries - it is an important task of the treating physician. Trauma is a stress factor so to predict the outcome, you can use markers of stress, the most accessible ofwhich is blood glucose. THE AIM: to reveal the dynamics of the relationship between blood glucose levels and the outlook for the life ofpatients with thoracoabdominal injuries. MATERIALS AND METHODS: A retrospective analysis of medical records of hospitalized patients were divided into two groups, depending on the outlook for the life of (favorable or unfavorable), and each of the groups - into two subgroups according to the presence or absence of signs of intoxication at admission. The subgroups were calculated and compared the mean blood glucose levels at different hours of hospital treatment. RESULTS: It was found that the average blood glucose levels at various hours of hospital stay were significantly higher in patients with poor outcome. The most noticeable was the difference in the first days of hospital treatment. Signs of intoxication was associated with lower values of glucose and a tendency to hypoglycaemia. In addition, among patients with high blood glucose ( 8 mg / dL) was observed over deaths in the first day of hospital stay. CONCLUSION: High blood glucose levels ( 8,0 mmol / L) in the first day of hospital treatment is a predictor ofpoor outcome in patients with thoracoabdominal injuries.

Effect of platelet-rich plasma on the healing of cutaneous defects exposed to acute to chronic wounds: a clinico-histopathologic study in rabbits.

BACKGROUND: Platelet-rich plasma (PRP) contains numerous growth factors to promote wound healing and angiogenesis. The aim of this study was to gain further information about the benefits of platelet-rich-plasma for healing cutaneous acute to chronic wounds. METHODS: A total of 30 New Zealand albino rabbits (n = 15/group) were randomly assigned to two experimental groups: control group, and PRP group. Bilateral resection defects measuring 3 cm were surgically created on the dorsolateral of the cutaneous in animals and the defects were randomly divided into two mentioned groups. Wound area, neovascularization, size and epithelialization were compared on days 7, 14 and 21 post-wounding. Histopathological analyses were conducted on 15 specimens from each group after sacrifice by the cellular aspects of the regeneration of the tissue. RESULTS: Our results were indicated that the wound area of PRP was smaller than that in the non-treated group on days 7, 14 and 21. Furthermore, a significant decrease of the wound size was observed in PRP groups that were significantly greater than that in the control group. A significant increase of the mean vascular density was noted in the PRP treated groups compared to the control groups at day 14 and especially day 21. This results indicated that PRP treated group' enhanced angiogenesis at the wound beds as compared to no treatment group. CONCLUSION: These results could be useful for researchers in the growing fields of tissue repair and experimental wound healing. Further studies will be essential to determine the role of PRP in clinical practice.

Initial venous lactate levels in patients with isolated penetrating extremity trauma: a retrospective cohort study.

INTRODUCTION: Elevated initial lactate levels have been shown to be associated with severe injury in trauma patients, but some patients who do not appear to be in shock also presented with elevated lactate levels. We hypothesized that in hemodynamically stable patients with isolated penetrating extremity trauma, initial lactate level does not predict clinically significant bleeding. METHODS: A 5-year institutional database review was performed. Hemodynamically stable patients (HR < 101, SBP > 90) with isolated penetrating extremity trauma with an initial lactate sent were included. The exposure of interest was captured as a dichotomous variable by initial lactate level normal (N ≤ 2.2 mEq/L), elevated (E > 2.2 mEq/L). The primary outcome measurement was clinically significant bleeding, defined by need for intervention (operation, angioembolization, or transfusion) or laboratory evidence of bleeding (presenting Hg < 7 g/dL, or Hg decrease by >2 g/dL/24 h). Chi-squared and Mann-Whitney tests were used to compare variables. RESULTS: A total of 132 patients were identified. There were no differences in demographics or mechanism of injury between the N (n = 43, 7%) and E (n = 89, 14%) groups. Median lactate levels were 1.6 (IQR 1.2-1.9) mEq/dL vs. 3.8 (IQR 2.8-5.2) in the N and E groups, p < 0.001. Lactate was elevated in 89 (67%) patients but was not associated with clinically significant bleeding (37% elevated vs. 39 % not elevated p = 0.82). CONCLUSIONS: In hemodynamically stable patients with isolated penetrating trauma to the extremity, elevated initial venous lactate levels (>2.2 mEq/L) are not associated with bleeding or need for interventions. Clinical judgment remains the gold standard for evaluation and management of these patients.

Use of a Novel Abdominal Aortic and Junctional Tourniquet to Reduce or Eliminate Flow in the Brachial and Popliteal Arteries in Human Subjects.

BACKGROUND: Penetrating injuries of the proximal large arteries are a common cause of death on the battlefield due to rapid exsanguination. Applying an effective tourniquet to stop bleeding at the axillary and proximal femoral arteries (junctional sites) is difficult. Prior studies have shown that the Abdominal Aortic and Junctional Tourniquet (AAJT) effectively reduced blood flow in the common femoral artery with application of the device around the lower abdomen. Our objective was to determine the effectiveness of the AAJT to stop blood flow in the proximal femoral artery (PFA), and the axillary artery (AA). METHOD: This was a prospective observational trial using human volunteers. The AAJT consists of a wedge-shaped bladder and integrated strap. The bladder has an integrated manometer, which is used to measure the pressure in the bladder. For the AA, the AAJT was placed over the axillary junction at the anterior axillary line with the strap placed across the contralateral shoulder. For the PFA, the AAJT bladder was placed over the right groin with the strap positioned across both femoral trochanters. Spectral Doppler measurements were taken of the PFA and AA at baseline and as the bladder was inflated. Collected data included pressure of the AAJT.

Tranexamic acid administration to pediatric trauma patients in a combat setting: the pediatric trauma and tranexamic acid study (PED-TRAX).

BACKGROUND: Early administration of tranexamic acid (TXA) has been associated with a reduction in mortality and blood product requirements in severely injured adults. It has also shown significantly reduced blood loss and transfusion requirements in major elective pediatric surgery, but no published data have examined the use of TXA in pediatric trauma. METHODS: This is a retrospective review of all pediatric trauma admissions to the North Atlantic Treaty Organization Role 3 hospital, Camp Bastion, Afghanistan, from 2008 to 2012. Univariate and logistic regression analyses of all patients and select subgroups were performed to identify factors associated with TXA use and mortality. Standard adult dosing of TXA was used in all patients. RESULTS: There were 766 injured patients 18 years or younger (mean [SD] age, 11 [5] years; 88% male; 73% penetrating injury; mean [SD], Injury Severity Score [ISS], 10 [9]; mean [SD] Glasgow Coma Scale [GCS] score, 12 [4]). Of these patients, 35% required transfusion in the first 24 hours, 10% received massive transfusion, and 76% required surgery. Overall mortality was 9%. Of the 766 patients, 66 (9%) received TXA. The only independent predictors of TXA use were severe abdominal or extremity injury (Abbreviated Injury Scale [AIS] score ≥ 3) and a base deficit of greater than 5 (all p < 0.05). Patients who received TXA had greater injury severity, hypotension, acidosis, and coagulopathy versus the patients in the no-TXA group. After correction for demographics, injury type and severity, vitals, and laboratory parameters, TXA use was independently associated with decreased mortality among all patients (odds ratio, 0.3; p = 0.03) and showed similar trends for subgroups of severely injured (ISS > 15) and transfused patients. There was no significant difference in thromboembolic complications or other cardiovascular events. Propensity analysis confirmed the TXA-associated survival advantage and suggested significant improvements in discharge neurologic status as well as decreased ventilator dependence. CONCLUSION: TXA was used in approximately 10% of pediatric combat trauma patients, typically in the setting of severe abdominal or extremity trauma and metabolic acidosis. TXA administration was independently associated with decreased mortality. There were no adverse safety- or medication-related complications identified. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Tissue pharmacokinetics of cefazolin in patients with lower limb infections.

Cefazolin, a first-generation cephalosporin with activity against methicillin-susceptible Staphylococcus aureus and streptococci, is often used to treat lower limb infections caused by these pathogens. Antimicrobial penetration is often limited in these patients due to compromised vasculature. Therefore, we sought to evaluate the exposure profile of cefazolin in serum and tissue in patients with lower limb infections. An in vivo microdialysis catheter was inserted into the tissue near the margin of the wound and constantly perfused with lactated Ringer's solution. Steady-state serum and tissue samples were simultaneously collected over a dosing interval. Serum protein binding was also assessed. Serum concentrations were analyzed by noncompartmental analysis. Tissue concentrations were corrected for percent in vivo recovery by using the retrodialysis technique. Seven patients with a mean weight of 95.45 ± 18.51 kg and a mean age of 54 ± 19 years were enrolled. Six patients received 1 g every 8 h, and one patient received 2 g every 24 h due to acute kidney injury. The free area under the curve from 0 to 8 h (fAUC0-8) values for serum and wound were 48.0 ± 18.66 and 56.35 ± 41.17 µg · h/ml, respectively, for the patients receiving 1 g every 8 h. The fAUC0-24 values for serum and wound were 1,326.1 and 253.9 µg · h/ml, respectively, for the single patient receiving 2 g every 24 h. The mean tissue penetration ratio (tissue/serum fAUC ratio) was 1.06. These data suggest that the amount of time that free-drug concentrations remain above the MIC (fT>MIC) for cefazolin in wound tissue is adequate to treat patients with lower limb infections.

Impact of hormonal protection in blunt and penetrating trauma: a retrospective analysis of the National Trauma Data Bank.

Over the last decade, gender and age-related hormonal status of trauma patients have been increasingly recognized as outcome factors. In the present study, we examine a large cohort of trauma patients to better appraise the effects of gender and age on patient outcome after blunt and penetrating trauma. We hypothesize that adult females are at lower risk for complications and mortality relative to adult males after both blunt and penetrating trauma. A retrospective analysis was conducted of the National Trauma Data Bank examining hormonally active females for advantages in survival and outcome after blunt and/or penetrating trauma. Over 1.4 million incident trauma cases were identified between 2002 and 2006. Multiple logistic regressions were calculated for associations between gender and outcome, stratified by injury type, age, comorbidity, Injury Severity Score (ISS), and complications. Risk factors associated with mortality in our multiple logistic regression analyses included: penetrating trauma (odds ratio [OR, 2.31; 95% confidence interval [CI], 2.27 to 2.36); adult male (OR, 1.45; 95% CI, 1.41 to 1.49); and ISS 15 or greater (OR, 14.68; 95% CI, 14.38 to 14.98). Adult females demonstrated a survival advantage over adult males (OR, 0.69; 95% CI, 0.67 to 0.71). Adult females with ISS less than 15 demonstrated a distinct survival advantage compared with adult males after both blunt and penetrating trauma. These results warrant further investigation into the role of sex hormones in trauma.

A principal component analysis of coagulation after trauma.

BACKGROUND: Clotting factor abnormalities underlying acute traumatic coagulopathy are poorly understood, with application of traditional regression techniques confounded by colinearity. We hypothesized that principal components analysis (PCA), a pattern-finding and data reduction technique, would identify clinically predictive patterns in the complex clotting factor milieu after trauma. METHODS: Plasma was prospectively collected from 163 critically injured trauma patients. Prothrombin; factors V, VII, VIII, IX, X; D-dimer; activated and native protein C; and antithrombin III levels were assayed and subjected to nonlinear PCA to identify principal components (PCs). RESULTS: Of 163 patients, 19.0% were coagulopathic on admission. PCA identified 3 significant PCs, accounting for 67.5% of overall variance. PC1 identified global clotting factor depletion; PC2 the activation of protein C and fibrinolysis; and PC3 factor VII elevation and VIII depletion. PC1 score correlated with penetrating injury and injury severity, predicting coagulopathy (odds ratio [OR], 4.67; p < 0.001) and mortality (OR, 1.47; p = 0.032). PC2 score correlated with injury severity, acidosis, and shock, and significantly predicted ventilator-associated pneumonia (OR, 1.59; p = 0.008), acute lung injury (OR, 2.24; p < 0.001), multiorgan failure (OR, 1.83; p = 0.002), and mortality (OR, 1.62; p = 0.006) but was not associated with international normalized ratio (INR)-based or partial thromboplastin time (PTT)-based coagulopathy (p > 0.200). PC3 did not significantly predict outcomes. CONCLUSION: PCA identifies distinct patterns of coagulopathy: depletion coagulopathy predicts mortality and INR/PTT elevation, while fibrinolytic coagulopathy predicts infection, end-organ failure, and mortality, without detectable differences in INR or PTT. While depletion coagulopathy is intuitive, fibrinolytic coagulopathy may be a distinct but often overlapping entity with differential effects on outcomes.

Increased apoptosis of peripheral blood neutrophils is associated with reduced incidence of infection in trauma patients with hemorrhagic shock.

OBJECTIVE: We aimed to describe the relationship between early peripheral leukocyte apoptosis and incidence of subsequent infection in trauma patients with hemorrhagic shock (T/HS). METHODS: T/HS patients requiring emergency surgery were prospectively enrolled. Nucleosome ELISA and TUNEL staining were performed on peripheral blood drawn pre-operatively, post-operatively and at 24 h. Subjects were followed for 30 days or until death or hospital discharge to record all episodes of infection. RESULTS: Forty-one subjects were enrolled. Six died within 24 h of surgery and were not included in the analysis. Nucleosome levels peaked post-operatively and dropped to baseline levels at 24 h (p = 0.03). TUNEL analysis revealed that polymorphonuclear neutrophils (PMNs) accounted for 72% of apoptotic leukocytes; the remaining apoptotic cells were mainly lymphocytes. Increased post-operative leukocyte apoptosis was associated with decreased systemic inflammatory response syndrome (SIRS) severity. Seventeen of the 35 survivors (48.6%) developed infections, while 18 (51.4%) did not. Pre-operative and post-operative nucleosome levels were 2.5 and 3 times higher, respectively, in T/HS patients who did not develop infection compared to those who did. Increased nucleosome levels were associated in particular with protection against sepsis (p=0.03) and multiple infections (p = 0.01). CONCLUSION: Peripheral blood PMN apoptosis in the early resuscitative period is associated with decreased incidence of subsequent infection in T/HS patients.

Triage vital signs do not correlate with serum lactate or base deficit, and are less predictive of operative intervention in penetrating trauma patients: a prospective cohort study.

BACKGROUND: Triage vital signs are often used to help determine a trauma patient's haemodynamic status. Recent studies have demonstrated that these may not be very specific in determining major injury. The purpose of this study was to determine if there is any correlation between triage vital signs, base deficit (BD) and lactate, and to determine the odds of operative intervention in penetrating trauma patients. METHODS: A prospective observational cohort study was undertaken. Baseline vital signs, BD and lactate were recorded in all patients for whom the trauma team was activated. Pearson correlation and coefficient (ρ) were calculated. ORs were calculated. RESULTS: 75 patients were enrolled. Pearson correlations and coefficients calculated for lactate to systolic blood pressure were: -0.052 (ρ=0.0011, 95% CI -0.225 to 0.228); lactate and HR: 0.23 (ρ=0.0166, 95% CI -0.211 to 0.242); lactate and RR: 0.23 (ρ=0.054, 95% CI -0.174 to 0.277). BD to systolic blood pressure were: 0.003 (ρ=0.00001, 95% CI -0.229 to 0.224); BD and HR: -0.19 (ρ=0.038, 95% CI -0.399 to 0.038); BD and RR: -0.019 (ρ=0.0004, 95% CI -0.244 to 0.208). Odds of operative intervention were greater in patients with abnormally high lactate, OR 4.17 (95% CI 1.57 to 11), but not for BD, OR 2.53 (95% CI 0.99 to 6.45), or any of the vital signs. CONCLUSIONS: Triage vital signs have no correlation to lactate or BD levels in penetrating trauma patients. Odds of operative intervention are greater in patients with abnormally high serum lactate levels, but not in those with abnormal triage vital signs or BD.

Temporal changes in ROTEM®-measured coagulability of citrated blood samples from coagulopathic trauma patients.

BACKGROUND: Rotational thromboelastometry (ROTEM(®)) relies on citrated blood samples, which are regarded as biologically stable for up to 4 h after venepuncture. However, this recommendation is based on data from normal volunteers. The aim of this study was to evaluate possible temporal changes in the coagulability of blood samples from coagulopathic trauma patients. PATIENTS AND METHODS: This is a prospective series of 10 coagulopathic (maximum clot firmness, MCF<40 mm) trauma patients. ROTEM(®) EXTEM (tissue factor activated) and FIBTEM (tissue factor activated, cytochalasin D inhibited) analyses were performed on samples obtained on admission, and after approximately 60 min of storage in an incubator, at 37°C. RESULTS: There were statistically significant differences between the median EXTEM MCF (22 mm vs 54 mm, p<0.001) and α angle (30.5 vs 59.5°, p=0.004) of the analyses performed immediately after sampling, and 51 min (median) subsequently, but not coagulation time (CT, p=0.133), clot formation time (p=0.0625) or maximum lysis (ML, p=0.154). There were also no differences in median FIBTEM MCF (p=1.00) or CT (p=0.877) between the immediate and delayed analyses. CONCLUSIONS: Repeated ROTEM(®) EXTEM analysis of citrated samples from coagulopathic trauma patients shows a spontaneous improvement in coagulability with time. The absence of parallel changes on FIBTEM analysis suggests that this effect may be due to a change in platelet function.