Review of machine learning for optical imaging of burn wound severity assessment.

Significance: Over the past decade, machine learning (ML) algorithms have rapidly become much more widespread for numerous biomedical applications, including the diagnosis and categorization of disease and injury. Aim: Here, we seek to characterize the recent growth of ML techniques that use imaging data to classify burn wound severity and report on the accuracies of different approaches. Approach: To this end, we present a comprehensive literature review of preclinical and clinical studies using ML techniques to classify the severity of burn wounds. Results: The majority of these reports used digital color photographs as input data to the classification algorithms, but recently there has been an increasing prevalence of the use of ML approaches using input data from more advanced optical imaging modalities (e.g., multispectral and hyperspectral imaging, optical coherence tomography), in addition to multimodal techniques. The classification accuracy of the different methods is reported; it typically ranges from ∼70% to 90% relative to the current gold standard of clinical judgment. Conclusions: The field would benefit from systematic analysis of the effects of different input data modalities, training/testing sets, and ML classifiers on the reported accuracy. Despite this current limitation, ML-based algorithms show significant promise for assisting in objectively classifying burn wound severity.

Engaging Underrepresented Youth: Remote Transition of the Health Career Collaborative Program.

INTRODUCTION: Pipeline programs can help increase diversity in health care by engaging underrepresented minority groups to pursue higher education and training in medical fields. Here we describe the implementation of Health Career Collaborative, a pipeline program designed to connect high school students with health care professionals, and the transition to remote delivery of the curriculum. METHODS: This study is a retrospective, descriptive observational study where the baseline characteristics of participating students were evaluated via preparticipation surveys. This study took place in a community with an area deprivation index of 6 at a high school in southern California in conjunction with an academic medical center and level I trauma center. Due to the coronavirus disease 2019 pandemic, the program transitioned to a virtual setting in the second half of the academic year. RESULTS: A total of 37 high school student participants enrolled in the 2019-2020 Health Career Collaborative program, with over 97% identifying as Hispanic, 89% female, and 92% between the ages of 15 and 17. Ninety-five percent of students indicated plans to graduate from high school and attend college, and 89% agreed with having a mentor to help plan for their future. While high school students had exposure to several health topics prior to the program, students reported a preference to learn about health topics from doctors compared to other sources. CONCLUSIONS: An online platform helped facilitate more interaction with health care professionals and could improve feasibility of implementing pipeline programs because physical space and transportation are not required.

The Effects of the COVID-19 Pandemic on Burn Clinic.

The COVID-19 pandemic has led to anxiety and fears for the general public. It is unclear how the behavior of people with acute burns and the services available to them has changed during the pandemic. The aim of our observational study was to evaluate our clinic's experience with patients presenting with burns during the first 10 months of the COVID-19 pandemic and determine if delays in presentation and healthcare delivery exist within our burn population. Patients referred to our clinic from March 1, 2020 to December 15, 2020 were reviewed for time of presentation after injury. We defined a true delay in presentation of >5 days from date of injury to date of referral for patients who were not inpatients at our facility or received initial care elsewhere prior to referral. Of the 246 patients who were referred to our clinic, during this time period, 199 patients (80.89%) attended their appointments. Our in-person clinic volume from referrals increased in July 2020 with a sharp decrease in August 2020. Our total clinic volume decreased in 2020 from 2019 by about 14%. Referrals to our clinic decreased in 2020 from 2019 by about 34%. Video telehealth visits did not account for the decrease in visits. There was low incidence of delays in presentation to our clinic during the pandemic. Additional investigation is necessary to see if the incidence of burn injury decreased. Despite the pandemic, our clinic remained ready and open to serve the burn population.

Blunt Trauma Mortality: Does Trauma Center Level Matter?

INTRODUCTION: Trauma centers have improved outcomes compared to nontrauma centers when caring for injured patients. A multicenter report found blunt trauma patients treated at American College of Surgeons' Level I trauma centers have improved survival compared to Level II centers. In a subsequent multicenter study, Level II centers had improved survival in all trauma patients. We sought to provide a more granular analysis by stratifying blunt mechanisms-to determine if there was a difference in mortality between Level I and Level II centers. METHODS: The Trauma Quality Improvement Program (2010-2016) was queried for patients presenting to an American College of Surgeons' Level I or II trauma center after blunt trauma. A multivariable logistic regression analysis was performed controlling for comorbidities and Trauma and Injury Severity Score. RESULTS: From 734,473 patients with blunt trauma, 507,715 (69.1%) were treated at a Level I center and 226,758 (30.9%) at a Level II center. The Level I cohort was younger (median age, 53 versus 58, P = 0.01), with a higher median injury severity score (13 versus 10, P < 0.001) and with more patients presenting after a motor vehicle accident (MVA) (27.9% versus 22.4%, P < 0.001) and lower rates of falls (46.6% versus 54.5%, P < 0.001). After adjusting for covariates, there was no difference in mortality between Level I and Level II centers (P > 0.05). When stratifying by mechanisms, Level I centers had a decreased associated mortality for MVA (odds ratio = 0.94, CI: 0.88-0.99, P = 0.04) and bicycle accidents (odds ratio = 0.77, CI: 0.74-0.03, P = 0.01) but no difference in falls or pedestrians struck (P > 0.05). CONCLUSIONS: Overall, blunt trauma patients presenting to a Level I center have no difference in mortality compared to a Level II center. However, when stratified by mechanism, those involved in MVA or bicycle accidents have a decreased associated risk of mortality. Future prospective studies examining variations in practice to account for these differences are warranted.

Coaching for impact: successful implementation of a multi-national, multi-institutional synchronous research course in Ethiopia.

Purpose: Under the American College of Surgeons' Operation Giving Back, several US institutions collaborated with a teaching and regional referral hospital in Ethiopia to develop a surgical research curriculum. Methods: A virtual, interactive, introductory research course which utilized a web-based classroom platform and live educational sessions via an online teleconferencing application was implemented. Surgical and public health faculty from the US and Ethiopia taught webinars and led breakout coaching sessions to facilitate participants' project development. Both a pre-course needs assessment survey and a post-course participation survey were used to examine the impact of the course. Results: Twenty participants were invited to participate in the course. Despite the majority of participants having connection issues (88%), 11 participants completed the course with an 83% average attendance rate. Ten participants successfully developed structured research proposals based on their local clinical needs. Conclusion: This novel multi-institutional and multi-national research course design was successfully implemented and could serve as a template for greater development of research capacity building in the low- and middle-income country (LMIC) setting.

Injury and Mortality Profiles in Level II and III Trauma Centers.

BACKGROUND: While the benefit of admission to trauma centers compared to non-trauma centers is well-documented and differences in outcomes between Level-I and Level-II trauma centers are well-studied, data on the differences in outcomes between Level-II trauma centers (L2TCs) and Level-III trauma centers (L3TCs) are scarce. OBJECTIVES: We sought to compare mortality risk between patients admitted to L2TCs and L3TCs, hypothesizing no difference in mortality risk for patients treated at L3TCs compared to L2TCs. METHODS: A retrospective analysis of the 2016 Trauma Quality Improvement Program (TQIP) database was performed. Patients aged 18+ years were divided into 2 groups, those treated at American College of Surgeons (ACS) verified L2TCs and L3TCs. RESULTS: From 74,486 patients included in this study, 74,187 (99.6%) were treated at L2TCs and 299 (.4%) at L3TCs. Both groups had similar median injury severity scores (ISSs) (10 vs 10, P < .001); however, L2TCs had a higher mean ISS (14.6 vs 11.9). There was a higher mortality rate for L2TC patients (6.0% vs 1.7%, P = .002) but no difference in associated risk of mortality between the 2 groups (OR .46, CI .14-1.50, P = .199) after adjusting predictors of mortality. L2TC patients had a longer median length of stay (5.0 vs 3.5 days, P < .001). There was no difference in other outcomes including myocardial infarction (MI) and cerebrovascular accident (CVA) (P > .05). DISCUSSION: Patients treated at L2TCs had a longer LOS compared to L3TCs. However, after controlling for covariates, there was no difference in associated mortality risk between L2TC and L3TC patients.

No Difference in Morbidity or Mortality Between Octogenarians and Other Geriatric Burn Trauma Patients.

BACKGROUND: Geriatric burn trauma patients (age ≥65 years) have a 5-fold higher mortality rate than younger adults. With the population of the US aging, the number of elderly burn and trauma patients is expected to increase. A past study using the National Burn Repository revealed a linear increase in mortality for those >65 years old. We hypothesized that octogenarians with burn and trauma injuries would have a higher rate of in-hospital complications and mortality, than patients aged 65-79 years old. METHODS: The Trauma Quality Improvement Program (2010-2016) was queried for burn trauma patients. To detect mortality risk a multivariable logistic regression model was used. RESULTS: From 282 patients, there were 73 (25.9%) octogenarians and 209 (74.1%) aged 65-79 years old. The two cohorts had similar median injury severity scores (16 vs. 15 in octogenarians, P = .81), total body surface area burned (P = .30), and comorbidities apart from an increased smoking (12.9% vs. 4.1%, P = .04) and decreased hypertension (52.2% vs. 65.8%, P = .04) in the younger cohort. Octogenarians had similar complications, including acute respiratory distress syndrome, pulmonary embolism, deep vein thrombosis (P > .05), and mortality (15.1% vs. 10.5%, P = .30), compared to the younger cohort. Octogenarians were not associated with an increased mortality risk (odds ratio 1.51, confidence interval 0.24-9.56, P = .67). DISCUSSION: Among burn trauma patients ≥65 years, age should not be a sole predictor for mortality risk. Continued research is necessary in order to determine more accurate approaches to prognosticate mortality in geriatric burn trauma patients, such as the validation and refinement of a burn-trauma-related frailty index.

Alcohol is not associated with increased mortality in adolescent traumatic brain injury patients.

PURPOSE: Compared to adults, there is a paucity of data regarding the association of a positive alcohol screen (PAS) and outcomes in adolescent patients with traumatic brain injury (TBI). We hypothesize adolescent TBI patients with a PAS on admission to have increased mortality compared to patients with a negative alcohol screen. METHODS: The 2017 Trauma Quality Improvement Program database was queried for patients aged 13-17 years presenting with a TBI and serum alcohol screen. Patients with missing information regarding midline shift on imaging and Glasgow Coma Scale (GCS) score were excluded. A multivariable logistic regression analysis for mortality was performed. RESULTS: From 2553 adolescent TBI patients with an alcohol screen, 220 (8.6%) had a PAS. Median injury severity scores and rates of penetrating trauma (all p > 0.05) were similar between alcohol positive and negative patients. Patients with a PAS had a similar mortality rate (13.2% vs. 12.1%, p = 0.64) compared to patients with a negative screen. Multivariate logistic regression controlling for risk factors associated with mortality revealed a PAS to confer a similar risk of mortality compared to alcohol negative patients (p = 0.40). CONCLUSION: Adolescent TBI patients with a PAS had similar associated risk of mortality compared to patients with a negative alcohol screen.

Octogenarians with blunt splenic injury: not all geriatrics are the same.

Geriatric trauma patients (GTP) (age ≥ 65 years) with blunt splenic injury (BSI) have up to a 6% failure rate of non-operative management (NOM). GTPs failing NOM have a similar mortality rate compared to GTPs managed successfully with NOM. However, it is unclear if this remains true in octogenarians (aged 80-89 years). We hypothesized that the failure rate for NOM in octogenarians would be similar to their younger geriatric cohort, patients aged 65-79 years; however risk of mortality in octogenarians who fail NOM would be higher than that of octogenarians managed successfully with NOM. The Trauma Quality Improvement Program (2010-2016) was queried for patients with BSI. Those undergoing splenectomy within 6 h were excluded to select for patients undergoing NOM. Patients aged 65-79 years (young GTPs) were compared to octogenarians. A multivariable logistic regression model was used to determine the risk for failed NOM and mortality. From 43,041 BSI patients undergoing NOM, 3660 (8.5%) were aged 65-79 years and 1236 (2.9%) were octogenarians. Both groups had a similar median Injury Severity Score (ISS) (p = 0.10) and failure rate of NOM (6.6% young GTPs vs. 6.8% octogenarians p = 0.82). From those failing NOM, octogenarians had similar units of blood products transfused (p > 0.05) and a higher mortality rate (40.5% vs. 18.2%, p < 0.001), compared to young GTPs. Independent risk factors for failing NOM in octogenarians included ≥ 1 unit of packed red blood cells (PRBC) (p = 0.039) within 24 h of admission. Octogenarians who failed NOM had a higher mortality rate compared to octogenarians managed successfully with NOM (40.5% vs 23.6% p = 0.001), which persisted in a multivariable logistic regression analysis (OR 2.25, CI 1.37-3.70, p < 0.001). Late failure of NOM ≥ 24 h (vs. early failure) was not associated with increased risk of mortality (p = 0.88), but ≥ 1 unit of PRBC transfused had higher risk (OR 1.88, CI 1.20-2.95, p = 0.006). Compared to young GTPs with BSI, octogenarians have a similar rate of failed NOM. Octogenarians with BSI who fail NOM have over a twofold higher risk of mortality compared to those managed successfully with NOM. PRBC transfusion increases risk for mortality. Therefore, clinicians should consider failure of NOM earlier in the octogenarian population to mitigate the risk of increased mortality.

Ground-Level Falls at Skilled Nursing Facilities Are Associated With More Serious Lower Extremity Injuries Compared With Home.

Ground-level falls (GLFs) are the number one cause of injury and death in the older adult population. We compared injury profiles of GLFs at SNFs to those at homes, hypothesizing that GLFs at SNFs would lead to higher risks for serious (AIS ≥ 3) traumatic brain injury (TBI) and lower extremity (LE) injuries compared to GLFs at home. The 2015-2016 Trauma Quality Improvement Program was used to compare patients sustaining GLFs at home and SNFs. From 15,873 patients sustaining GLFs, 14,306 (90.1%) occurred at home while 1,567 (9.9%) at SNFs. More patients with GLFs at SNFs were female, older, and had greater incidence of congestive heart failure, end-stage renal disease, and dementia (p < 0.001) compared to those at home. Although, GLF SNF patients had lower injury severity scores (9 vs. 10, p < 0.001) and incidence for TBI (28.0% vs 33.4%, p < 0.001), they had a higher rate of femur fractures (55.1% vs. 38.9%, p < 0.001). After controlling for female, end stage renal disease, smoking, dementia, diabetes mellitus, chronic obstructive pulmonary disease, congestive heart failure, and stroke, patients falling at SNFs had an increased risk of sustaining serious LE injury AIS (OR 1.64, p < 0.001), but not serious TBI AIS (OR 0.89, p = 0.073). In conclusion, compared to GLFs at home, those at SNFs have a higher risk for serious LE injury, with femur fractures being the most common. However, GLFs at SNFs and homes had no significant difference in risk for serious TBI. Future studies are warranted to evaluate preventative measures to reduce LE injuries at SNFs.

Sternotomy for Hemorrhage Control in Trauma.

BACKGROUND: Little is known about the injuries, mechanisms, and outcomes in trauma patients undergoing sternotomy for hemorrhage control (SHC). The purpose of this study was to identify predictors of mortality for SHC and provide a descriptive analysis of the use of SHC in trauma. We hypothesize blunt trauma is associated with higher mortality compared with penetrating trauma among trauma patients requiring SHC. METHODS: The Trauma Quality Improvement Program (2013-2016) database was queried for adult patients undergoing SHC within 24 h of admission. Patients with blunt and penetrating trauma were compared using chi-square and Mann-Whitney U-test. A multivariable logistic regression model was used to determine the risk of mortality. RESULTS: Of 584 patients undergoing SHC, 322 (55.1%) were involved in penetrating trauma, and 69 (11.8%) were involved in blunt. The blunt trauma group had a higher median injury severity score (31.5 versus 25.0; P < 0.001) compared with the penetrating group. The median time to hemorrhage control was longer in those with blunt compared with penetrating trauma (84.6 versus 49.8 min; P < 0.001). The mortality rate was higher in patients with blunt compared with penetrating trauma (29.0% versus 12.7%; P < 0.001). However, after adjusting for covariates, there was no difference in risk of mortality between blunt and penetrating trauma (P = 0.06). CONCLUSIONS: Trauma patients requiring SHC after blunt trauma had a higher mortality rate than those in penetrating trauma. After adjusting for predictors of mortality, there was no difference in risk of mortality despite nearly double the time to hemorrhage control in patients presenting after blunt trauma.

Trends 10 years after burn injury: A Burn Model System National Database study.

BACKGROUND: The Burn Specific Health Scale-Brief (BSHS-B) evaluates 9 aspects of health and has been validated globally. Existing reports typically focus on outcomes shortly after injury. The purpose of this study is to determine whether quality of life remains a concern for burn survivors ten years after-injury. METHODS: Cross sectional data of survivors admitted from 1994 to 2006 to four US burn centers were collected in the Burn Model System National Database 10 years after injury. Responses to the items in the nine BSHS-B domains range from 0 to 4. Lower scores indicating poorer quality of life. Median scores are reported and differences were compared using Wilcoxon-Mann-Whitney test. RESULTS: Ten-year survivor injury characteristics suggest a moderate severity of injury. Survivors scored lower in heat sensitivity, affect, body image, and work (median=3.2, 3.6, 2.8, and 3.6, respectively). Affect, body image, and interpersonal scores were significantly lower for females (median=3.1, 2.8, 3.8, respectively) than males [median=3.6, 3.3, 4, respectively (p=0.008, 0.004, 0.022, respectively)]. CONCLUSIONS: Our results suggest certain domains of burn specific health benefit from support at 10 years after injury, and select populations such as females may necessitate additional treatment to restore burn-specific health. These results support that burn injuries represent a chronic condition and long-term medical and psychosocial support may benefit burn survivor recovery.

Goal-directed Hemostatic Resuscitation of Trauma-induced Coagulopathy: A Pragmatic Randomized Clinical Trial Comparing a Viscoelastic Assay to Conventional Coagulation Assays.

BACKGROUND: Massive transfusion protocols (MTPs) have become standard of care in the management of bleeding injured patients, yet strategies to guide them vary widely. We conducted a pragmatic, randomized clinical trial (RCT) to test the hypothesis that an MTP goal directed by the viscoelastic assay thrombelastography (TEG) improves survival compared with an MTP guided by conventional coagulation assays (CCA). METHODS: This RCT enrolled injured patients from an academic level-1 trauma center meeting criteria for MTP activation. Upon MTP activation, patients were randomized to be managed either by an MTP goal directed by TEG or by CCA (ie, international normalized ratio, fibrinogen, platelet count). Primary outcome was 28-day survival. RESULTS: One hundred eleven patients were included in an intent-to-treat analysis (TEG = 56, CCA = 55). Survival in the TEG group was significantly higher than the CCA group (log-rank P = 0.032, Wilcoxon P = 0.027); 20 deaths in the CCA group (36.4%) compared with 11 in the TEG group (19.6%) (P = 0.049). Most deaths occurred within the first 6 hours from arrival (21.8% CCA group vs 7.1% TEG group) (P = 0.032). CCA patients required similar number of red blood cell units as the TEG patients [CCA: 5.0 (2-11), TEG: 4.5 (2-8)] (P = 0.317), but more plasma units [CCA: 2.0 (0-4), TEG: 0.0 (0-3)] (P = 0.022), and more platelets units [CCA: 0.0 (0-1), TEG: 0.0 (0-0)] (P = 0.041) in the first 2 hours of resuscitation. CONCLUSIONS: Utilization of a goal-directed, TEG-guided MTP to resuscitate severely injured patients improves survival compared with an MTP guided by CCA and utilizes less plasma and platelet transfusions during the early phase of resuscitation.

Overwhelming tPA release, not PAI-1 degradation, is responsible for hyperfibrinolysis in severely injured trauma patients.

BACKGROUND: Trauma-induced coagulopathy (TIC) is associated with a fourfold increased risk of mortality. Hyperfibrinolysis is a component of TIC, but its mechanism is poorly understood. Plasminogen activation inhibitor (PAI-1) degradation by activated protein C has been proposed as a mechanism for deregulation of the plasmin system in hemorrhagic shock, but in other settings of ischemia, tissue plasminogen activator (tPA) has been shown to be elevated. We hypothesized that the hyperfibrinolysis in TIC is not the result of PAI-1 degradation but is driven by an increase in tPA, with resultant loss of PAI-1 activity through complexation with tPA. METHODS: Eighty-six consecutive trauma activation patients had blood collected at the earliest time after injury and were screened for hyperfibrinolysis using thrombelastography (TEG). Twenty-five hyperfibrinolytic patients were compared with 14 healthy controls using enzyme-linked immunosorbent assays for active tPA, active PAI-1, and PAI-1/tPA complex. Blood was also subjected to TEG with exogenous tPA challenge as a functional assay for PAI-1 reserve. RESULTS: Total levels of PAI-1 (the sum of the active PAI-1 species and its covalent complex with tPA) are not significantly different between hyperfibrinolytic trauma patients and healthy controls: median, 104 pM (interquartile range [IQR], 48-201 pM) versus 115 pM (IQR, 54-202 pM). The ratio of active to complexed PAI-1, however, was two orders of magnitude lower in hyperfibrinolytic patients than in controls. Conversely, total tPA levels (active + complex) were significantly higher in hyperfibrinolytic patients than in controls: 139 pM (IQR, 68-237 pM) versus 32 pM (IQR, 16-37 pM). Hyperfibrinolytic trauma patients displayed increased sensitivity to exogenous challenge with tPA (median LY30 of 66.8% compared with 9.6% for controls). CONCLUSION: Depletion of PAI-1 in TIC is driven by an increase in tPA, not PAI-1 degradation. The tPA-challenged TEG, based on this principle, is a functional test for PAI-1 reserves. Exploration of the mechanism of up-regulation of tPA is critical to an understanding of hyperfibrinolysis in trauma. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level II.

Combat: Initial Experience with a Randomized Clinical Trial of Plasma-Based Resuscitation in the Field for Traumatic Hemorrhagic Shock.

The existing evidence shows great promise for plasma as the first resuscitation fluid in both civilian and military trauma. We embarked on the Control of Major Bleeding After Trauma (COMBAT) trial with the support of the Department of Defense to determine if plasma-first resuscitation yields hemostatic and survival benefits. The methodology of the COMBAT study represents not only 3 years of development work but also the integration of nearly two decades of technical experience with the design and implementation of other clinical trials and studies. Herein, we describe the key features of the study design, critical personnel and infrastructural elements, and key innovations. We will also briefly outline the systems engineering challenges entailed by this study. The COMBAT trial is a randomized, placebo-controlled, semiblinded, prospective, phase IIB clinical trial conducted in a ground ambulance fleet based at a level I trauma center and part of a multicenter collaboration. The primary objective of the COMBAT trial is to determine the efficacy of field resuscitation with plasma first compared with standard of care (normal saline). To date, we have enrolled 30 subjects in the COMBAT study. The ability to achieve intervention with a hemostatic resuscitation agent in the closest possible temporal proximity to injury is critical and represents an opportunity to forestall the evolution of the "bloody vicious cycle." Thus, the COMBAT model for deploying plasma in first-response units should serve as a model for randomized clinical trials of other hemostatic resuscitative agents.

Exploring ethical conflicts in emergency trauma research: the COMBAT (Control of Major Bleeding after Trauma) study experience.

BACKGROUND: Up to 25% of severely injured patients develop trauma-induced coagulopathy. To study interventions for this vulnerable population for whom consent cannot be obtained easily, the Food and Drug Administration issued regulations for emergency research with an exception from informed consent (ER-EIC). We describe the community consultation and public disclosure (CC/PD) process in preparation for an ER-EIC study, namely the Control Of Major Bleeding After Trauma (COMBAT) study. METHODS: The CC/PD was guided by the four bioethical principles. We used a multimedia approach, including one-way communications (newspaper ads, brochures, television, radio, and web) and two-way communications (interactive in-person presentations at community meetings, printed and online feedback forms) to reach the trials catchment area (Denver County's population: 643,000 and the Denver larger metro area where commuters reside: 2.9 million). Particular attention was given to special-interests groups (eg, Jehovah Witnesses, homeless) and to Spanish-speaking communities (brochures and presentations in Spanish). Opt-out materials were available during on-site presentations or via the COMBAT study website. RESULTS: A total of 227 community organizations were contacted. Brochures were distributed to 11 medical clinics and 3 homeless shelters. The multimedia campaign had the potential to reach an estimated audience of 1.5 million individuals in large metro Denver area, the majority via one-way communication and 1900 in two-way communications. This resource intensive process cost more than $84,000. CONCLUSION: The CC/PD process is resource-intensive, costly, and complex. Although the multimedia CC/PD reached a large audience, the effectiveness of this process remains elusive. The templates can be helpful to similar ER-EIC studies.

Hyperfibrinolysis, physiologic fibrinolysis, and fibrinolysis shutdown: the spectrum of postinjury fibrinolysis and relevance to antifibrinolytic therapy.

BACKGROUND: Fibrinolysis is a physiologic process maintaining patency of the microvasculature. Maladaptive overactivation of this essential function (hyperfibrinolysis) is proposed as a pathologic mechanism of trauma-induced coagulopathy. Conversely, the shutdown of fibrinolysis has also been observed as a pathologic phenomenon. We hypothesize that there is a level of fibrinolysis between these two extremes that have a survival benefit for the severely injured patients. METHODS: Thrombelastography and clinical data were prospectively collected on trauma patients admitted to our Level I trauma center from 2010 to 2013. Patients with an Injury Severity Score (ISS) of 15 or greater were evaluated. The percentage of fibrinolysis at 30 minutes by thrombelastography was used to stratify three groups as follows: hyperfibrinolysis (≥3%), physiologic (0.081-2.9%), and shutdown (0-0.08%). The threshold for hyperfibrinolysis was based on existing literature. The remaining groups were established on a cutoff of 0.8%, determined by the highest point of specificity and sensitivity for mortality on a receiver operating characteristic curve. RESULTS: One hundred eighty patients were included in the study. The median age was 42 years (interquartile range [IQR], 28-55 years), 70% were male, and 21% had penetrating injuries. The median ISS was 29 (IQR, 22-36), and the median base deficit was 9 mEq/L (IQR, 6-13 mEq/L). Distribution of fibrinolysis was as follows: shutdown, 64% (115 of 180); physiologic, 18% (32 of 180); and hyperfibrinolysis, 18% (33 of 180). Mortality rates were lower for the physiologic group (3%) compared with the hyperfibrinolysis (44%) and shutdown (17%) groups (p = 0.001). CONCLUSION: We have identified a U-shaped distribution of death related to the fibrinolysis system in response to major trauma, with a nadir in mortality, with level of fibrinolysis after 30 minutes between 0.81% and 2.9%. Exogenous inhibition of the fibrinolysis system in severely injured patients requires careful selection, as it may have an adverse affect on survival. LEVEL OF EVIDENCE: Prognostic study, level III.

Activated clotting time of thrombelastography (T-ACT) predicts early postinjury blood component transfusion beyond plasma.

INTRODUCTION: Rapid thrombelastography (rTEG) has been advocated as a point-of-care test to manage trauma-induced coagulopathy. rTEG activated clotting time (T-ACT) results become available much sooner than other rTEG values, thus offering an attractive tool to guide blood component transfusion in a hemorrhagic shock. We hypothesize that patients with a prolonged T-ACT require replacement of platelets (Plts) and cryoprecipitate (Cryo) in addition to plasma to correct trauma-induced coagulopathy. METHODS: A prospective trauma registry was reviewed for patients with an r-TEG available within 3 hours of injury. Blood was collected via a standardized protocol for rTEG. Patients were stratified into quartiles: low (T-ACT <113 seconds), mild (T-ACT 113-120 seconds), moderate (T-ACT 121-140 seconds), and severe (T-ACT >140 seconds). Transfusion requirements were evaluated during the first 6 hours after injury. RESULTS: A total of 114 patients were included. Median age was 39 years, injury severity score 20, base-deficit 10, and mortality rate 13%. T-ACT cohorts had similar age (P = .11), injury severity score (P = .55), and base deficit (P = .38). An T-ACT >140 seconds predicted a lower angle (median 57 vs 70, P < .000) and maximum amplitude (46 vs 60, P = .002), and patients received more Cryo (0.5 vs 0, P ≤ .000) and Plts (1 vs 0, P = .006). CONCLUSION: Injured patients requiring resuscitation with blood transfusion that have a T-ACT >140 seconds are polycoagulopathic and may benefit from early Cryo and Plts.

A principal component analysis of postinjury viscoelastic assays: clotting factor depletion versus fibrinolysis.

INTRODUCTION: The mechanisms driving trauma-induced coagulopathy (TIC) remain to be defined, and its therapy demands an orchestrated replacement of specific blood products. Thrombelastography (TEG) is a tool to guide the TIC multicomponent therapy. Principal component analysis (PCA) is a statistical approach that identifies variable clusters; thus, we hypothesize that PCA can identify specific combinations of TEG-generated values that reflect TIC mechanisms. METHODS: Adult trauma patients admitted from September 2010 to October 2013 for whom a massive transfusion protocol was activated were included. Rapid TEG values obtained within the first 6 hours after injury were included in the PCA. PCA components with an eigenvalue >1 were retained, and, within components, variable loadings (equivalent to correlation coefficients) >|60| were considered significant. Component scorings for each patient were calculated and clinical characteristics of patients with high and low scores were compared. RESULTS: Of 98 enrolled patients, 67% were male and 70% suffered blunt trauma. Median age was 41 years (interquartile range 28-55) and median Injury Severity Score was 31.5 (interquartile range 24-43). PCA identified three principal components (PCs) that together explained 93% of the overall variance. PC1 reflected global coagulopathy with depletion of platelets and fibrinogen whereas PC3 indicated hyperfibrinolysis. PC2 may represent endogenous anticoagulants such as the activation of protein C. CONCLUSION: PCA suggests depletion coagulopathy is independent from fibrinolytic coagulopathy. Furthermore, the distribution of mortality suggests that low levels of fibrinolysis may be beneficial in a select group of injured patients. These data underscore the potential of risk for concurrent presumptive treatment for preserved depletion coagulopathy and possible fibrinolysis.