Abstract Background Fibrinolysis is a physiologic process to maintain microvascular patency by breaking down excessive fibrin clot. Hyperfibrinolysis (HF) is associated with a doubling of mortality. ...Fibrinolysis shutdown (SD), an acute impairment of fibrinolysis, has been recognized as a risk factor for increased mortality. The purpose of this study was to assess the incidence and outcomes of fibrinolysis phenotypes in two urban trauma centers. Study Design Injured patients admitted 2010-2013, who were ≥18 years of age, had an injury severity score (ISS) >15 were included in the analysis. Admission fibrinolysis phenotypes were determined by the clot lysis at 30 minutes (LY30): SD ≤0.8%, physiologic 0.9-2.9%, HF ≥3%. Logistic regression was used to adjust for age, arrival blood pressure, ISS, mechanism, and facility. Results 2540 patients met inclusion. Median age was 39(IQR 26-55) and median ISS was 25(IQR 20-33) with a mortality rate of 21%. Fibrinolysis shutdown was the most common phenotype (46%) followed by physiologic (36%) and hyperfibrinolysis(18%). HF was associated with the highest death rate (34%), followed by SD(22%), and physiologic (14%, p<0.001). The risk of mortality remained increased for HF(OR=3.3, 95%C: 2.4-4.6, p<0.0001) and SD(OR 1.6 95%CI 1.3-2.1, p=0.0003) compared to physiologic when adjusting for age, ISS, mechanism, head injury, and blood pressure (AUROC=0.82, 95% CI 0.80-0.84). Conclusions Fibrinolysis SD is the most common phenotype upon admission and is associated with increased mortality. Moreover, these data provide additional evidence of distinct phenotypes of coagulation impairment and that individualized hemostatic therapy may be required.
The resuscitation of traumatic hemorrhagic shock has undergone a paradigm shift in the last 20 years with the advent of damage control resuscitation (DCR). Major principles of DCR include ...minimization of crystalloid, permissive hypotension, transfusion of a balanced ratio of blood products, and goal-directed correction of coagulopathy. In particular, plasma has replaced crystalloid as the primary means for volume expansion for traumatic hemorrhagic shock. Predicting which patient will require DCR by prompt and accurate activation of a massive transfusion protocol, however, remains a challenge.
Abstract Background Endothelial glycocalyx breakdown elicits syndecan-1 shedding, and traumatic endotheliopathy (EoT). We hypothesized that a cutoff syndecan-1 level can identify patients with ...endothelial dysfunction who would have poorer outcomes. Study Design Prospective observational study; trauma patients with the highest level of activation admitted during July 2011-September 2013 were eligible. We recorded demographics, injury type/severity (ISS), physiology and outcome data, and quantified syndecan-1 and soluble thrombomodulin from plasma with ELISAs. With receiver operating characteristic curve (ROC) analysis, we defined EoT+ as the syndecan-1 cutoff level that maximized the sum of sensitivity and specificity (Youden index) in predicting 24-hour in-hospital mortality. We stratified by this cutoff, and compared both groups. Factors associated with 30-day in-hospital mortality were assessed with multivariable logistic regression (adjusted odds ratios (ORs) and 95% confidence intervals (CIs) reported). Results From ROC analysis (area under the curve=0.71, 95%CI 0.58-0.84), we defined EoT+ as syndecan-1 level ≥ 40 ng/ml (sensitivity= 0.62, specificity= 0.73). Of the 410 patients evaluated, 34% (n=138) were EoT+ patients, who presented with higher ISS ( p <0.001) and blunt trauma frequency ( p =0.016) than EoT- patients. While EoT+ patients had lower systolic blood pressure (median 119 vs. 128 mmHg; p <0.001), base excess and hemoglobin were similar between groups. The proportion of transfused (EoT+ 71.7% vs. EoT- 36.4%; p<0.001), and deceased EoT+ patients (EoT+ 24.6% vs. EoT- 12.1%; p <0.001) was higher. EoT+ was significantly associated with 30-day in-hospital mortality (adjusted OR 2.23, 95%CI 1.22-4.04). Conclusions A syndecan-1 level ≥40 ng/ml identified patients with significantly worse outcomes, despite similar admission physiology to those without the condition.
Background For trauma patients requiring massive blood transfusion, aggressive plasma usage has been demonstrated to confer a survival advantage. The aim of this study was to evaluate the impact of ...plasma administration in nonmassively transfused patients. Study Design Trauma patients admitted to a Level I trauma center (2000–2005) requiring a nonmassive transfusion (<10 U packed RBC PRBC within 12 hours of admission) were identified retrospectively. Propensity scores were calculated to match and compare patients receiving plasma in the first 12 hours with those who did not. Results The 1,716 patients (86.1% of 1,933 who received PRBC transfusion) received a nonmassive transfusion. After exclusion of 31 (1.8%) early deaths, 284 patients receiving plasma were matched to patients who did not. There was no improvement in survival with plasma transfusion (17.3% versus 14.1%; p = 0.30) irrespective of the plasma-to-PRBC ratio achieved. However, the overall complication rate was significantly higher for patients receiving plasma (26.8% versus 18.3%, odds ratio OR = 1.7; 95% CI, 1.1–2.4; p = 0.016). As the volume of plasma increased, an increase in complications was seen, reaching 37.5% for patients receiving >6 U. The ARDS rate specifically was also significantly higher in patients receiving plasma (9.9% versus 3.5%, OR = 3.0; 95% CI, 1.4–6.2; p = 0.004. Patients receiving >6 U plasma had a 12-fold increase in ARDS, a 6-fold increase in multiple organ dysfunction syndrome, and a 4-fold increase in pneumonia and sepsis. Conclusions For nonmassively transfused trauma patients, plasma administration was associated with a substantial increase in complications, in particular ARDS, with no improvement in survival. An increase in multiple organ dysfunction, pneumonia, and sepsis was likewise seen as increasing volumes of plasma were transfused. The optimal trigger for initiation of a protocol for aggressive plasma infusion warrants prospective evaluation.
Background Progressive hemorrhagic injury (PHI) in traumatic brain injury (TBI) patients is associated with poor outcomes. Early prediction of PHI is difficult yet vital. We hypothesize that TBI ...subtype and coagulation would be predictors of PHI. Methods This was a retrospective analysis of highest level activation adult trauma patients with evidence of TBI (head Abbreviated Injury Scale ≥3). Coagulopathy was determined using rapid thrombelastography (r-TEG), complete blood counts, and conventional coagulation tests obtained on arrival. Patients were dichotomized into PHI and stable groups based on head computerized CT. Subtypes of TBI included subdural hematoma, intraparenchymal contusions (IPC), subarachnoid hemorrhage, epidural hematoma, and combined. Data are reported as median values with interquartile range (IQR). Multivariate logistic regression was used to assess the effect of subtype and coagulation on PHI. Results We included 279 isolated TBI patients who met study criteria. There were 157 patients (56%) who experienced PHI; 122 (44%) were stable on repeat CT. Patients with PHI were older, had fewer hospital-free days, and higher mortality (all P < .001). No differences were noted in r-TEG parameters between groups; however, coagulopathy and age were independent predictors of progression in all subtypes (odds ratio OR, 1.81; 95% CI, 1.09–3.01 P = .021; OR, 1.02, 95% CI, 1.01–1.04 P = .006). Controlling for age, Glasgow Coma Scale score, and coagulopathy, patients with IPC were more likely to experience PHI (OR, 4.49; 95% CI, 2.24–8.98; P < .0001). Conclusion This study demonstrates that older patients with coagulation abnormalities and IPC on admission are more likely to experience PHI, identifying a target population for earlier therapies.
Background The impact of platelet transfusion in trauma patients undergoing a massive transfusion (MT) was evaluated. Study Design The Institutional Trauma Registry and Blood Bank Database at a Level ...I trauma center was used to identify all patients requiring an MT (≥10 packed red blood cells PRBC within 24 hours of admission). Mortality was evaluated according to 4 apheresis platelet (aPLT):PRBC ratios: Low ratio (<1:18), medium ratio (≥1:18 and <1:12), high ratio (≥1:12 and <1:6), and highest ratio (≥1:6). Results Of 32,289 trauma patients, a total of 657 (2.0%) required an MT. At 24 hours, 171 patients (26.0%) received a low ratio, 77 (11.7%) a medium ratio, 249 (37.9%) a high ratio, and 160 (24.4%) the highest ratio of aPLT:PRBC. After correcting for differences between groups, the mortality at 24 hours increased in a stepwise fashion with decreasing aPLT:PRBC ratio. Using the highest ratio group as a reference, the adjusted relative risk of death was 1.67 (adjusted p = 0.054) for the high ratio group, 2.28 (adjusted p = 0.013) for the medium ratio group, and 5.51 (adjusted p < 0.001) for the low ratio group. A similar stepwise increase in mortality with decreasing platelet ratio was observed at 12 hours after admission and for overall survival to discharge. After stepwise logistic regression, a high aPLT:PRBC ratio (adjusted p < 0.001) was independently associated with improved survival at 24 hours. Conclusions For injured patients requiring a massive transfusion, as the apheresis platelet-to-red cell ratio increased, a stepwise improvement in survival was seen. Prospective evaluation of the role of platelet transfusion in massively transfused patients is warranted.
Background Our institution has published damage control laparotomy (DCL) rates of 30% and documented the substantial morbidity associated with the open abdomen. The purpose of this quality ...improvement (QI) project was to decrease the rate of DCL at a busy, Level I trauma center in the US. Study Design A prospective cohort of all emergent trauma laparotomies from November 2013 to October 2015 (QI group) was followed. The QI intervention was multifaceted and included audit and feedback for every DCL case. Morbidity and mortality of the QI patients were compared with those from a published control (control group: emergent laparotomy from January 2011 to October 2013). Results A significant decrease was observed immediately on beginning the QI project, from a 39% DCL rate in the control period to 23% in the QI group (p < 0.001). This decrease was sustained over the 2-year study period. There were no differences in demographics, Injury Severity Score, or transfusions between the groups. No differences organ/space infection (control 16% vs QI 12%; p = 0.15), fascial dehiscence (6% vs 8%; p = 0.20), unplanned relaparotomy (11% vs 10%; p = 0.58), or mortality (9% vs 10%; p = 0.69) were observed. The reduction in use resulted in a decrease of 68 DCLs over the 2-year period. There was a further reduction in the rate of DCL to 17% after completion of the QI project. Conclusions A QI initiative rapidly changed the use of DCL and improved quality of care by decreasing resource use without an increase morbidity or mortality. This decrease was sustained during the QI period and further improved upon after its completion.
Background An early predictive model for massive transfusion (MT) is critical for management of combat casualties because of limited blood product availability, component preparation, and the time ...necessary to mobilize fresh whole blood donors. The purpose of this study was to determine which variables, available early after injury, are associated with MT. We hypothesized that International Normalized Ratio and penetrating mechanism would be predictive. Study Design We performed a retrospective cohort analysis in two combat support hospitals in Iraq. Patients who required MT were compared with patients who did not. Eight potentially predictive variables were subjected to univariate analysis. Variables associated with need for MT were then subjected to stepwise logistic regression. Results Two hundred forty-seven patients required MT and 311 did not. Mean Injury Severity Score was 22 in the MT group and 5 in the non-MT group (p < 0.001). Patients in the MT group received 17.9 U stored RBCs and 2.0 U fresh whole blood, versus 1.1 U RBCs and 0.2 U whole blood in the non-MT group (p < 0.001). Mortality was 39% in the MT group and 1% in the non-MT group (p < 0.001). Variables that independently predicted the need for MT were: hemoglobin ≤ 11 g/dL, International Normalized Ratio > 1.5, and a penetrating mechanism. The area under the receiver operator characteristic curve was 0.804 and Hosmer-Lemeshow goodness-of-fit test was 0.98. Conclusion MT after combat injury is associated with high mortality. Simple variables available early after admission allow accurate prediction of MT.
Background Failure to achieve primary fascial closure (PFC) after damage control laparotomy is costly and carries great morbidity. We hypothesized that time from the initial laparotomy to the first ...take-back operation would be predictive of successful PFC. Methods Trauma patients managed with open abdominal techniques after damage control laparotomy were prospectively followed at 14 Level 1 trauma centers during a 2-year period. Time to the first take-back was evaluated as a predictor of PFC using hierarchical multivariate logistic regression analysis. Results A total of 499 patients underwent damage control laparotomy and were included in this analysis. PFC was achieved in 327 (65.5%) patients. Median time to the first take-back operation was 36 hours (interquartile range 24–48). After we adjusted for patient demographics, resuscitation volumes, and operative characteristics, increasing time to the first take-back was associated with a decreased likelihood of PFC. Specifically, each hour delay in return to the operating room (24 hours after initial laparotomy) was associated with a 1.1% decrease in the odds of PFC (odds ratio 0.989; 95% confidence interval 0.978–0.999; P = .045). In addition, there was a trend towards increased intra-abdominal complications in patients returning after 48 hours (odds ratio 1.80; 95% confidence interval 1.00–3.25; P = .05). Conclusion Data from this prospective, multicenter study demonstrate that delays in returning to the operating room after damage control laparotomy are associated with reductions in PFC. These findings suggest that emphasis should be placed on returning to the operating room within 24 hours after the initial laparotomy if possible (and no later than 48 hours).
Background Plasma-based resuscitation improves outcomes in trauma patients with hemorrhagic shock, while large-animal and limited clinical data suggest that it also improves outcomes and is ...neuroprotective in the setting of combined hemorrhage and traumatic brain injury. However, the choice of initial resuscitation fluid, including the role of plasma, is unclear for patients after isolated traumatic brain injury. Methods We reviewed adult trauma patients admitted from January 2011 to July 2015 with isolated traumatic brain injury. “Early plasma” was defined as transfusion of plasma within 4 hours. Purposeful multiple logistic regression modeling was performed to analyze the relationship of early plasma and inhospital survival. After testing for interaction, subgroup analysis was performed based on the pattern of brain injury on initial head computed tomography: epidural hematoma, intraparenchymal contusion, subarachnoid hemorrhage, subdural hematoma, or multifocal intracranial hemorrhage. Results Of the 633 isolated traumatic brain injury patients included, 178 (28%) who received early plasma were injured more severely coagulopathic, hypoperfused, and hypotensive on admission. Survival was similar in the early plasma versus no early plasma groups (78% vs 84%, P = .08). After adjustment for covariates, early plasma was not associated with improved survival (odds ratio 1.18, 95% confidence interval 0.71–1.96). On subgroup analysis, multifocal intracranial hemorrhage was the largest subgroup with 242 patients. Of these, 61 (25%) received plasma within 4 hours. Within-group logistic regression analysis with adjustment for covariates found that early plasma was associated with improved survival (odds ratio 3.34, 95% confidence interval 1.20–9.35). Conclusion Although early plasma transfusion was not associated with improved in-hospital survival for all isolated traumatic brain injury patients, early plasma was associated with increased in-hospital survival in those with multifocal intracranial hemorrhage.
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