Jennifer M. Watters

Thrombelastography versus AntiFactor Xa levels in the assessment of prophylactic-dose enoxaparin in critically ill patients.

BACKGROUND A standard dose of enoxaparin is frequently used for deep venous thrombosis (DVT) prophylaxis. Evidence suggests inconsistent bioavailability in intensive care unit (ICU) patients. Antifactor Xa activity (anti-Xa) has been used to monitor enoxaparin dosing but its accuracy and availability are problematic. Thrombelastography (TEG) is used to evaluate coagulation in diverse settings. The purpose of this study was to analyze whether TEG could be used to predict which enoxaparin-treated patients would develop DVT. METHODS Two hundred sixty-one simultaneous enoxaparin-active (active) and enoxaparin-neutralized (neutral) TEGs were performed in 61 surgical ICU patients over four consecutive days. Patient characteristics and anti-Xa were collected. DVT screening was per ICU protocol. RESULTS Mean (+/-SEM) age was 54 (+/-2.3) years and Acute Physiology and Chronic Health Evaluation II score was 17 (+/-0.7). There were 30 trauma and 31 general surgery patients (69% men). The DVT rate was 28%. Time to clot formation (R) and percent lysis at 30 minutes were different between active versus neutralized blood (p < 0.001). R time was 1.5 minutes shorter in patients with DVT versus those without (p < 0.001) indicating hypercoagulability in DVT patients. Anti-Xa levels were similar in patients with (0.135 +/- 0.012) and without (0.135 +/- 0.007) DVT (p = 0.97). There were no differences in age, body mass index, injury severity score, Acute Physiology and Chronic Health Evaluation II score, or trauma status between DVT and non-DVT groups. CONCLUSIONS TEG demonstrates differences between enoxaparin-neutralized and enoxaparin-active blood in ICU patients that may be used to guide dosing. TEG differentiates enoxaparin-treated patients who subsequently develop DVT while anti-Xa levels do not. TEG demonstrates an enoxaparin-related increase in fibrinolysis.

Resuscitation of haemorrhagic shock with normal saline vs. lactated Ringer's: effects on oxygenation, extravascular lung water and haemodynamics

IntroductionPulmonary oedema and impairment of oxygenation are reported as common consequences of haemorrhagic shock and resuscitation (HSR). Surprisingly, there is little information in the literature examining differences in crystalloid type during the early phase of HSR regarding the development of pulmonary oedema, the impact on oxygenation and the haemodynamic response. These experiments were designed to determine if differences exist because of crystalloid fluid type in the development of oedema, the impact on oxygenation and the haemodynamic response to fluid administration in early HSR.MethodsTwenty anaesthetised swine underwent a grade V liver injury and bled without resuscitation for 30 minutes. The animals were randomised to receive, in a blinded fashion, either normal saline (NS; n = 10) or lactated Ringers solution (LR; n = 10). They were then resuscitated with study fluid to, and maintained at, the preinjury mean arterial pressure (MAP) for 90 minutes.ResultsExtravascular lung water index (EVLWI) began to increase immediately with resuscitation with both fluid types, increasing earlier and to a greater degree with NS. A 1 ml/kg increase in EVLWI from baseline occurred after administartion of (mean ± standard error of the mean) 68.6 ± 5.2 ml/kg of normal saline and 81.3 ± 8.7 ml/kg of LR (P = 0.027). After 150 ml/kg of fluid, EVLWI increased from 9.5 ± 0.3 ml/kg to 11.4 ± 0.3 ml/kg NS and from 9.3 ± 0.2 ml/kg to 10.8 ± 0.3 ml/kg LR (P = 0.035). Despite this, oxygenation was not significantly impacted (Delta partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) ≤ 100) until approximately 250 ml/kg of either fluid had been administered. Animals resuscitated with NS were more acidaemic (with lower lactates), pH 7.17 ± 0.03 NS vs. 7.41 ± 0.02 LR (P < 0.001).ConclusionsThis study suggests that early resuscitation of haemorrhagic shock with NS or LR has little impact on oxygenation when resuscitation volume is less than 250 ml/kg. LR has more favourable effects than NS on EVLWI, pH and blood pressure but not on oxygenation.

Correlation of Missed Doses of Enoxaparin With Increased Incidence of Deep Vein Thrombosis in Trauma and General Surgery Patients

IMPORTANCE Enoxaparin sodium is widely used for deep vein thrombosis (DVT) prophylaxis, yet DVT rates remain high in the trauma and general surgery populations. Missed doses during hospitalization are common. OBJECTIVE To determine if missed doses of enoxaparin correlate with DVT formation. DESIGN, SETTING, AND PARTICIPANTS Data were prospectively collected among 202 trauma and general surgery patients admitted to a level I trauma center. MAIN OUTCOMES AND MEASURES Deep vein thrombosis screening was performed using a rigorous standardized protocol. RESULTS The overall incidence of DVT was 15.8%. In total, 58.9% of patients missed at least 1 dose of enoxaparin. The DVTs occurred in 23.5% of patients who missed at least 1 dose and in 4.8% of patients who did not (P < .01). On univariate analysis, the need for mechanical ventilation (71.8% vs 44.1%), the performance of more than 1 operation (59.3% vs 40.0%), and male sex (75% vs 56%) were associated with DVT formation (P < .05 for all). A bivariate logistic regression was then performed, which revealed age 50 years or older and interrupted enoxaparin therapy as the only independent risk factors for DVT formation. The DVT rate did not differ between trauma and general surgery populations or in patients receiving once-daily vs twice-daily dosing regimens. CONCLUSIONS AND RELEVANCE Interrupted enoxaparin therapy and age 50 years or older are associated with DVT formation among trauma and general surgery patients. Missed doses occur commonly and are the only identified risk factor for DVT that can be ameliorated by physicians. Efforts to minimize interrupted enoxaparin prophylaxis in patients at risk for DVT should be optimized.

Resuscitation with lactated ringer's does not increase inflammatory response in a Swine model of uncontrolled hemorrhagic shock.

Lactated Ringer’s (LR) and normal saline (NS) are widely and interchangeably used for resuscitation of trauma victims. Studies show LR to be superior to NS in the physiologic response to resuscitation. Recent in vitro studies demonstrate equivalent effects of LR and NS on leukocytes. We aimed to determine whether LR resuscitation would produce an equivalent inflammatory response compared with normal saline (NS) resuscitation in a clinically relevant swine model of uncontrolled hemorrhagic shock. Thirty-two swine were randomized. Control animals (n = 6) were sacrificed following induction of anesthesia for baseline data. Sham animals (n = 6) underwent laparotomy and 2 h of anesthesia. Uncontrolled hemorrhagic shock animals (n = 10/group) underwent laparotomy, grade V liver injury, and blinded resuscitation with LR or NS to maintain baseline blood pressure for 1.5 h before sacrifice. Lung was harvested, and tissue mRNA levels of interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF), and tumor necrosis factor-alpha (TNF-α) were determined using quantitative reverse transcriptase polymerase chain reaction (Q-RT-PCR). Sections of lung were processed and examined for neutrophils sequestered within the alveolar walls. Cytokine analysis showed no difference in IL-6 gene transcription in any group (P = 0.99). Resuscitated swine had elevated G-CSF and TNF-α gene transcription, but LR and NS groups were not different from each other (P= 0.96 and 0.10, respectively). Both resuscitation groups had significantly more alveolar neutrophils present than controls (P < 0.01) and shams (P < 0.05) but were not different from one another (P= 0.83). LR and NS resuscitation have equivalent effects on indices of inflammation in the lungs in our model of uncontrolled hemorrhagic shock.

Evaluation and management of mild traumatic brain injury: An Eastern Association for the Surgery of Trauma practice management guideline

BACKGROUND An estimated 1.1 million people sustain a mild traumatic brain injury (MTBI) annually in the United States. The natural history of MTBI remains poorly characterized, and its optimal clinical management is unclear. The Eastern Association for the Surgery of Trauma had previously published a set of practice management guidelines for MTBI in 2001. The purpose of this review was to update these guidelines to reflect the literature published since that time. METHODS The PubMed and Cochrane Library databases were searched for articles related to MTBI published between 1998 and 2011. Selected older references were also examined. RESULTS A total of 112 articles were reviewed and used to construct a series of recommendations. CONCLUSION The previous recommendation that brain computed tomographic (CT) should be performed on patients that present acutely with suspected brain trauma remains unchanged. A number of additional recommendations were added. Standardized criteria that may be used to determine which patients receive a brain CT in resource-limited environments are described. Patients with an MTBI and negative brain CT result may be discharged from the emergency department if they have no other injuries or issues requiring admission. Patients taking warfarin who present with an MTBI should have their international normalized ratio (INR) level determined, and those with supratherapeutic INR values should be admitted for observation. Deficits in cognition and memory usually resolve within 1 month but may persist for longer periods in 20% to 40% of cases. Routine use of magnetic resonance imaging, positron emission tomography, nuclear magnetic resonance, or biochemical markers for the clinical management of MTBI is not supported at the present time.

Advanced hemostatic dressings are not superior to gauze for care under fire scenarios.

BACKGROUND Advanced hemostatic dressings perform superior to standard gauze (SG) in animal hemorrhage models but require 2 minutes to 5 minutes application time, which is not feasible on the battlefield. METHODS Twenty-four swine received a femoral artery injury, 30 seconds uncontrolled hemorrhage and randomization to packing with SG, Combat Gauze (CG), or Celox Gauze (XG) without external pressure. Animals were resuscitated to baseline mean arterial pressures with lactated Ringers and monitored for 120 minutes. Physiologic and coagulation parameters were collected throughout. Dressing failure was defined as overt bleeding outside the wound cavity. Tissues were collected for histologic and ultrastructural studies. RESULTS All animals survived to study end. There were no differences in baseline physiologic or coagulation parameters or in dressing success rate (SG: 8/8, CG: 4/8, XG: 6/8) or blood loss between groups (SG: 260 mL, CG: 374 mL, XG: 204 mL; p > 0.3). SG (40 seconds ± 0.9 seconds) packed significantly faster than either the CG (52 ± 2.0) or XG (59 ± 1.9). At 120 minutes, all groups had a significantly shorter time to clot formation compared with baseline (p < 0.01). At 30 minutes, the XG animals had shorter time to clot compared with SG and CG animals (p < 0.05). All histology sections had mild intimal and medial edema. No inflammation, necrosis, or deposition of dressing particles in vessel walls was observed. No histologic or ultrastructural differences were found between the study dressings. CONCLUSIONS Advanced hemostatic dressings do not perform better than conventional gauze in an injury and application model similar to a care under fire scenario.

A Clinical Tool for the Prediction of Venous Thromboembolism in Pediatric Trauma Patients

IMPORTANCE Although rare, the incidence of venous thromboembolism (VTE) in pediatric trauma patients is increasing, and the consequences of VTE in children are significant. Studies have demonstrated increasing VTE risk in older pediatric trauma patients and improved VTE rates with institutional interventions. While national evidence-based guidelines for VTE screening and prevention are in place for adults, none exist for pediatric patients, to our knowledge. OBJECTIVES To develop a risk prediction calculator for VTE in children admitted to the hospital after traumatic injury to assist efforts in developing screening and prophylaxis guidelines for this population. DESIGN, SETTING, AND PARTICIPANTS Retrospective review of 536,423 pediatric patients 0 to 17 years old using the National Trauma Data Bank from January 1, 2007, to December 31, 2012. Five mixed-effects logistic regression models of varying complexity were fit on a training data set. Model validity was determined by comparison of the area under the receiver operating characteristic curve (AUROC) for the training and validation data sets from the original model fit. A clinical tool to predict the risk of VTE based on individual patient clinical characteristics was developed from the optimal model. MAIN OUTCOME AND MEASURE Diagnosis of VTE during hospital admission. RESULTS Venous thromboembolism was diagnosed in 1141 of 536,423 children (overall rate, 0.2%). The AUROCs in the training data set were high (range, 0.873-0.946) for each model, with minimal AUROC attenuation in the validation data set. A prediction tool was developed from a model that achieved a balance of high performance (AUROCs, 0.945 and 0.932 in the training and validation data sets, respectively; P = .048) and parsimony. Points are assigned to each variable considered (Glasgow Coma Scale score, age, sex, intensive care unit admission, intubation, transfusion of blood products, central venous catheter placement, presence of pelvic or lower extremity fractures, and major surgery), and the points total is converted to a VTE risk score. The predicted risk of VTE ranged from 0.0% to 14.4%. CONCLUSIONS AND RELEVANCE We developed a simple clinical tool to predict the risk of developing VTE in pediatric trauma patients. It is based on a model created using a large national database and was internally validated. The clinical tool requires external validation but provides an initial step toward the development of the specific VTE protocols for pediatric trauma patients.

Cryopreserved red blood cells are superior to standard liquid red blood cells.

BACKGROUND Liquid preserved packed red blood cell (LPRBC) transfusions are used to treat anemia and increase end-organ perfusion. Throughout their storage duration, LPRBCs undergo biochemical and structural changes collectively known as the storage lesion. These changes adversely affect perfusion and oxygen off-loading. Cryopreserved RBCs (CPRBC) can be stored for up to 10 years and potentially minimize the associated storage lesion. We hypothesized that CPRBCs maintain a superior biochemical profile compared with LPRBCs. METHODS This was a prospective, randomized, double-blinded study. Adult trauma patients with an Injury Severity Score (ISS) greater than 4 and an anticipated 1-U to 2-U transfusion of PRBCs were eligible. Enrolled patients were randomized to receive either CPRBCs or LPRBCs. Serum proteins (haptoglobin, serum amyloid P, and C-reactive protein), proinflammatory and anti-inflammatory cytokines, d-dimer, nitric oxide, and 2,3-DPG concentrations were analyzed. Mann-Whitney U-test and Wilcoxon rank sum test were used to assess significance (p < 0.05). RESULTS Fifty-seven patients were enrolled (CPRBC, n = 22; LPRBC, n = 35). The LPRBC group’s final interleukin 8, tumor necrosis factor &agr;, and d-dimer concentrations were elevated compared with their pretransfusion values (p < 0.05). After the second transfused units, 2,3-DPG was higher in the patients receiving CPRBCs (p < 0.05); this difference persisted throughout the study. Finally, serum protein concentrations were decreased in the transfused CPRBC units compared with LPRBC (p < 0.01). CONCLUSION CPRBC transfusions have a superior biochemical profile: an absent inflammatory response, attenuated fibrinolytic state, and increased 2,3-DPG. A blood banking system using both storage techniques will offer the highest-quality products to critically injured patients virtually independent of periodic changes in donor availability and transfusion needs. LEVEL OF EVIDENCE Therapeutic study, level II.

Optimal timing of femur fracture stabilization in polytrauma patients: A practice management guideline from the Eastern Association for the Surgery of Trauma

BACKGROUND Femur fractures are common among trauma patients and are typically seen in patients with multiple injuries resulting from high-energy mechanisms. Internal fixation with intramedullary nailing is the ideal method of treatment; however, there is no consensus regarding the optimal timing for internal fixation. We critically evaluated the literature regarding the benefit of early (<24 hours) versus late (>24 hours) open reduction and internal fixation of open or closed femur fractures on mortality, infection, and venous thromboembolism (VTE) in trauma patients. METHODS A subcommittee of the Practice Management Guideline Committee of the Eastern Association for the Surgery of Trauma conducted a systematic review and meta-analysis for the earlier question. RevMan software was used to generate forest plots. Grading of Recommendations, Assessment, Development, and Evaluations methodology was used to rate the quality of the evidence, using GRADEpro software to create evidence tables. RESULTS No significant reduction in mortality was associated with early stabilization, with a risk ratio (RR) of 0.74 (95% confidence interval [CI], 0.50–1.08). The quality of evidence was rated as “low.” No significant reduction in infection (RR, 0.4; 95% CI, 0.10–1.6) or VTE (RR, 0.63; 95% CI, 0.37–1.07) was associated with early stabilization. The quality of evidence was rated “low.” CONCLUSION In trauma patients with open or closed femur fractures, we suggest early (<24 hours) open reduction and internal fracture fixation. This recommendation is conditional because the strength of the evidence is low. Early stabilization of femur fractures shows a trend (statistically insignificant) toward lower risk of infection, mortality, and VTE. Therefore, the panel concludes the desirable effects of early femur fracture stabilization probably outweigh the undesirable effects in most patients.

Lyophilized Plasma With Ascorbic Acid Decreases Inflammation in Hemorrhagic Shock

BACKGROUND Delivery of a high ratio of plasma to packed red blood cells to patients who require massive transfusion is associated with improved survival. Hemorrhagic shock causes increased production of pro-inflammatory cytokines. These are associated with late morbidity and mortality. The use of fresh frozen plasma makes high ratio resuscitation logistically difficult and does not address dysfunctional inflammation. Lyophilized plasma (LP) is a stable powdered form of plasma that is both safe and easily reconstituted. Previous work demonstrated that LP reconstituted with ascorbic acid (AA) decreased inflammation. Whether the reduction of inflammation was associated with LP or the AA is unknown. METHODS Thirty female swine were anesthetized and subjected to a multisystem combat relevant model consisting of femur fracture, controlled hemorrhage, and hypothermia. A standardized grade V liver injury was made and the animals were randomly assigned to receive LP reconstituted with AA, citric acid (CA), or hydrochloric acid (HCl). Blood was drawn at baseline and at 2 hours and 4 hours for interleukin (IL)-6, IL-8, and tumor necrosis factor-α serum concentrations measured by enzyme-linked immunosorbent assay. Lung tissue was harvested and processed for gene expression before euthanizing the animals. RESULTS No differences were observed in mortality, baseline cytokine serum concentration, or gene expression. Enzyme-linked immunosorbent assay demonstrated that IL-6 concentration increased over time for all groups (p < 0.05), but less so at 2 hours in the AA group compared with CA and HCl. CONCLUSION In this animal model of trauma, hemorrhage and resuscitation, AA decreases IL-6 expression relative to CA and HCl. These findings confirm previous work from our laboratory and suggest that AA is responsible for suppression of dysfunctional inflammation in this model.