Chitra N. Sambasivan

A high ratio of plasma and platelets to packed red blood cells in the first 6 hours of massive transfusion improves outcomes in a large multicenter study

BACKGROUNDnIn trauma, most hemorrhagic deaths occur within the first 6 hours. This study examined the effect on survival of high ratios of fresh frozen plasma (FFP) and platelets (PLTs) to packed red blood cells (PRBCs) in the first 6 hours.nnnMETHODSnRecords of 466 massive transfusion trauma patients (>or=10 U of PRBCs in 24 hours) at 16 level 1 trauma centers were reviewed. Transfusion ratios in the first 6 hours were correlated with outcome.nnnRESULTSnAll groups had similar baseline characteristics. Higher 6-hour ratios of FFP:PRBCs and PLTs:PRBCs lead to improved 6-hour mortality (from 37.3 [in the lowest ratio group] to 15.7 [in the middle ratio group] to 2.0% [in the highest ratio group] and 22.8% to 19.0% to 3.2%, respectively) and in-hospital mortality (from 54.9 to 41.1 to 25.5% and 43.7% to 46.8% to 27.4%, respectively). Initial higher ratios of FFP:PRBCs and PLTs:PRBCs decreased overall PRBC transfusion.nnnCONCLUSIONSnThe early administration of high ratios of FFP and platelets improves survival and decreases overall PRBC need in massively transfused patients. The largest difference in mortality occurs during the first 6 hours after admission, suggesting that the early administration of FFP and platelets is critical.

High ratios of plasma and platelets to packed red blood cells do not affect mortality in nonmassively transfused patients

BACKGROUNDnAdministration of high transfusion ratios in patients not requiring massive transfusion might be harmful. We aimed to determine the effect of high ratios of fresh frozen plasma (FFP) and platelets (PLT) to packed red blood cells (PRBC) in nonmassively transfused patients.nnnMETHODSnRecords of 1,788 transfused trauma patients who received <10 units of PRBC in 24 hours at 23 United States Level I trauma centers were reviewed. The relationship between ratio category (low and high) and in-hospital mortality was assessed with propensity-adjusted multivariate proportional hazards models.nnnRESULTSnAt baseline, patients transfused with a high FFP:PRBC ratio were younger, had a lower Glasgow Coma Scale score, and a higher Injury Severity Score. Those receiving a high PLT:PRBC ratio were older. The risk of in-hospital mortality did not vary significantly with FFP:PRBC ratio category. Intensive care unit (ICU)-free days, hospital-free days, and ventilator-free days did not vary significantly with FFP:PRBC ratio category. ICU-free days and ventilator-free days were significantly decreased among patients in the high (≥1:1) PLT:PRBC category, and hospital-free days did not vary significantly with PLT:PRBC ratio category. The analysis was repeated using 1:2 as the cutoff for high and low ratios. Using this cutoff, there was still no difference in mortality with either FFP:PRBC ratios or platelet:PRBC ratios. However, patients receiving a >1:2 ratio of FFP:PRBCs or a >1:2 ratio PLT:PRBCs had significantly decreased ICU-free days and ventilator-free days.nnnCONCLUSIONSnFFP:PRBC and PLT:PRBC ratios were not associated with in-hospital mortality. Depending on the threshold analyzed, a high ratio of FFP:PRBC and PLT:PRBC transfusion was associated with fewer ICU-free days and fewer ventilator-free days, suggesting that the damage control infusion of FFP and PLT may cause increased morbidity in nonmassively transfused patients and should be rapidly terminated when it becomes clear that a massive transfusion will not be required.

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

BACKGROUNDnAdvanced 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.nnnMETHODSnTwenty-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.nnnRESULTSnAll 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.nnnCONCLUSIONSnAdvanced hemostatic dressings do not perform better than conventional gauze in an injury and application model similar to a care under fire scenario.

Emerging therapies in traumatic hemorrhage control

Purpose of reviewCare of the injured patient is a dynamic process. Hemorrhage remains the primary cause of preventable death after trauma. Rapid and effective early care can improve survival and outcomes. Emerging therapies to address traumatic hemorrhage will be discussed. Recent findingsCurrent concepts in trauma care include damage control resuscitation with rapid surgical correction of bleeding; prevention of the development of the lethal triad; limitation of crystalloid administration and application of high ratios of plasma and platelets to packed red blood cells. Prehospital resuscitation strategies can effect care of the hemorrhaging trauma patient, as well. The goal should be to preserve vital functions without increasing the risk for further bleeding. The concept of hypotensive resuscitation has been formulated to address this issue. The type of resuscitation fluid also plays an important role, with novel fluids currently being studied for routine use. Compressible hemorrhage constitutes an important component of potentially survivable injury. Hemostatic dressings and tourniquets can prove essential to the management of combat and civilian wounds. SummaryGiven the potential to preserve life with appropriate attention applied to the bleeding trauma victim, it is vitally important to explore the options currently available and continue to make improvements in care.

A highly porous silica and chitosan-based hemostatic dressing is superior in controlling hemorrhage in a severe groin injury model in swine

BACKGROUNDnThis study compared the efficacy of 3 hemostatic dressings in a severe groin injury model in swine.nnnMETHODSnTwenty-three swine received TraumaStat (OreMedix, Lebanon, OR), Chitoflex (HemCon, Inc., Portland, OR), or standard gauze for hemostasis. Complete femoral vessel transections were followed by 30 seconds of uncontrolled hemorrhage. The groin was packed with the randomized dressing followed by 30 seconds of compression. Resuscitation with lactated Ringers solution commenced immediately postcompression to the preinjury mean arterial blood pressure. Hemostasis failure was defined as blood pooling outside the wound. Animals were monitored and maintained at the preinjury mean arterial pressure for 120 minutes, culminating with euthanization.nnnRESULTSnThere were no differences in baseline values between groups. TraumaStat resulted in less hemostasis failure (P < .05), decreased postcompression blood loss (P < .05), and decreased fluid requirement (P < .05). No significant difference in mortality was seen between groups. There were no differences between standard gauze and Chitoflex with respect to dressing failure, posttreatment blood loss, or fluid resuscitation.nnnCONCLUSIONSnTraumaStat performed significantly better than Chitoflex and standard gauze in controlling hemorrhage from a severe groin injury in swine.

Effects of Ethanol Intoxication and Gender on Blood Coagulation

BACKGROUNDnEthanol intoxication is a common contributor to traumatic injury. It is unknown whether ethanol consumption contributes to the coagulation differences seen between men and women after trauma. Our aim was to examine the combined effect of ethanol intoxication and gender on coagulation.nnnMETHODSnFifty-eight healthy subjects participated and chose to enter into a control group (CG; n = 20; 10 men and 10 women) or drinking group (DG; n = 38; 20 men and 18 women). Venous blood samples for thrombelastography, plasminogen activator inhibitor, thrombin-antithrombin complex, and tissue plasminogen activator were drawn at the beginning of the study. Subjects then interacted in a social atmosphere for at least 2 hours, eating and consuming alcoholic (DG) or nonalcoholic (CG) beverages. After 2 hours, blood alcohol level was determined and blood was drawn for a second set of coagulation studies.nnnRESULTSnDemographics were similar between groups except for age (36.7 years CG vs. 29.9 years DG; p = 0.009). All baseline thrombelastography measurements were similar between the CG and DG. Blood alcohol levels in the DG were similar between genders at the end of study. At the end of study, a decreased rate of fibrin formation, decreased clot strength, and a decreased rate of fibrin cross-linking was seen in men but not in women. Fibrinolysis was inhibited in drinkers compared with controls.nnnCONCLUSIONSnConsumption of commonly ingested quantities of alcohol correlated with the development of a hypocoagulable state in men but had no effect on coagulation status in women. This phenomenon may contribute to differences in post-trauma coagulation status previously noted between genders.

Lyophilized Plasma Reconstituted With Ascorbic Acid Suppresses Inflammation and Oxidative DNA Damage

BACKGROUNDnLyophilized plasma (LP) has been shown to be as effective as fresh frozen plasma (FFP) for resuscitation in polytrauma and hemorrhagic shock. LP reconstituted with ascorbic acid is associated with suppression of cytokines when compared with fresh frozen plasma. We aimed to determine the effect of using alternate LP reconstitution acids on physiologic parameters, blood loss, coagulation, oxidative DNA damage, and proinflammatory cytokines in a polytrauma and hemorrhagic shock model.nnnMETHODSnThirty swine were anesthetized, subjected to polytrauma, hemorrhagic shock, and randomized to resuscitation with LP-ascorbic acid (AA), LP-citric acid (CA), or LP-hydrochloric acid (HCL). Physiologic data were continuously monitored, blood loss measured, and serum collected at baseline, 2 hours, and 4 hours for enzyme-linked immunosorbent assays. Measured 8-OH-2-deoxyguanosine (8-OHdG) was a biomarker of oxidative DNA damage.nnnRESULTSnNo differences were observed in physiologic measures, blood loss, or coagulation parameters. Interleukin-6 increased over time for all groups, but at 2 hours, the concentration in AA (median [minimum, maximum]: 113 ng/mL [0, 244]) was lower compared with CA (181 ng/mL [69, 314], p = 0.01) and HCL (192 ng/mL [41, 310], p = 0.03). Comparing 4 hours to baseline, a significant increase in oxidative DNA damage was observed in CA (22.9 ng/mL [16.3, 34.3] vs. 15.6 ng/mL [13.6, 26.7], p = 0.03) and HCL (19.6 ng/mL [15.7, 56.7] vs. 15.8 ng/mL [11.6, 21.4], p = 0.01) but not in AA (17.9 ng/mL [12.6, 26.9] vs. 17.1 ng/mL [11.8, 18.4], p = 0.24).nnnCONCLUSIONSnResuscitation with AA results in decreased interleukin-6 expression and oxidative DNA damage compared with CA and HCL.

A predictive model for mortality in massively transfused trauma patients

BACKGROUNDnImprovements in trauma systems and resuscitation have increased survival in severely injured patients. Massive transfusion has been increasingly used in the civilian setting. Objective predictors of mortality have not been well described. This study examined data available in the early postinjury period to identify variables that are predictive of 24-hour- and 30-day mortality in massively transfused trauma patients.nnnMETHODSnMassively transfused trauma patients from 23 Level I centers were studied. Variables available on patient arrival that were predictive of mortality at 24 hours were entered into a logistic regression model. A second model was created adding data available 6 hours after injury. A third model evaluated mortality at 30 days. Receiver operating characteristic curves and the Hosmer-Lemeshow test were used to assess model quality.nnnRESULTSnSeven hundred four massively transfused patients were analyzed. The model best able to predict 24-hour mortality included pH, Glasgow Coma Scale score, and heart rate, with an area under the receiver operating characteristic curve (AUROC) of 0.747. Addition of the 6-hour red blood cell requirement increased the AUROC to 0.769. The model best able to predict 30-day mortality included the above variables plus age and Injury Severity Score with an AUROC of 0.828.nnnCONCLUSIONnGlasgow Coma Scale score, pH, heart rate, age, Injury Severity Score, and 6-hour red blood cell transfusion requirement independently predict mortality in massively transfused trauma patients. Models incorporating these data have only a modest ability to predict mortality and should not be used to justify withholding massive transfusion in individual cases.

Lyophilized Plasma With Ascorbic Acid Decreases Inflammation in Hemorrhagic Shock

BACKGROUNDnDelivery 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.nnnMETHODSnThirty 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.nnnRESULTSnNo 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.nnnCONCLUSIONnIn 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.

Comparison of abdominal damage control surgery in combat versus civilian trauma

BACKGROUNDnThe majority of individuals who perform damage control surgery in the military arena are trained in civilian venues. Therefore, it is important to compare and contrast damage control performed in civilian and military settings. In contrast to civilian trauma, which is primarily caused by blunt injury and addressed at one or two surgical facilities, combat casualties primarily sustain explosion-related injuries and undergo treatment at multiple levels of care across continents. We aimed to compare patients undergoing abdominal damage control surgery across these two very different settings.nnnMETHODSnParallel retrospective reviews were conducted over 2 years (2005-2006) in a combat setting and at a US Level I trauma center. Patients were examined during the first 7 days after injury.nnnRESULTSnThe civilian population (CP) was older (40 vs. 23; p < 0.01) with a higher injury severity score (35 vs. 27; p < 0.02). The CP experienced greater blunt injury than the military population (MP) (83 vs. 4%; p < 0.01). Explosion-related injury was only present in the MP (64%). At baseline, the CP presented with lower systolic blood pressure (108 vs. 126) and larger base deficit (9.8 vs. 6.5; p < 0.05). The MP underwent more surgeries (3.5 vs. 2.9; p = 0.02) with similar rates of fascial closure (48.7% vs. 70.0%; p = 0.11). Complication rates were similar between the CP and the MP (43% vs. 58%, respectively; p = 0.14).nnnCONCLUSIONSnMilitary and civilian trauma patients who undergo damage control surgery experience similar fascial closure rates despite differing demographics and widely disparate mechanisms of injury. The MP undergoes a greater number of procedures than the CP, but complication rates do not differ between the groups.