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.

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.

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.

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.

Mesenteric lymph diversion abrogates 5-lipoxygenase activation in the kidney following trauma and hemorrhagic shock.

BACKGROUND: Early acute kidney injury (AKI) following trauma is associated with multiorgan failure and mortality. Leukotrienes have been implicated both in AKI and in acute lung injury. Activated 5-lipoxygenase (5-LO) colocalizes with 5-LO-activating protein (FLAP) in the first step of leukotriene production following trauma and hemorrhagic shock (T/HS). Diversion of postshock mesenteric lymph, which is rich in the 5-LO substrate of arachidonate, attenuates lung injury and decreases 5-LO/FLAP associations in the lung after T/HS. We hypothesized that mesenteric lymph diversion (MLD) will also attenuate postshock 5-LO-mediated AKI. METHODS: Rats underwent T/HS (laparotomy, hemorrhagic shock to a mean arterial pressure of 30 mm Hg for 45 minutes, and resuscitation), and MLD was accomplished via cannulation of the mesenteric duct. Extent of kidney injury was determined via histology score and verified by urinary neutrophil gelatinase-associated lipocalin assay. Kidney sections were immunostained for 5-LO and FLAP, and colocalization was determined by fluorescence resonance energy transfer signal intensity. The end leukotriene products of 5-LO were determined in urine. RESULTS: AKI was evident in the T/HS group by derangement in kidney tubule architecture and confirmed by neutrophil gelatinase-associated lipocalin assay, whereas MLD during T/HS preserved renal tubule morphology at a sham level. MLD during T/HS decreased the associations between 5-LO and FLAP demonstrated by fluorescence resonance energy transfer microscopy and decreased leukotriene production in urine. CONCLUSION: 5-LO and FLAP colocalize in the interstitium of the renal medulla following T/HS. MLD attenuates this phenomenon, which coincides with pathologic changes seen in tubules during kidney injury and biochemical evidence of AKI. These data suggest that gut-derived leukotriene substrate predisposes the kidney and the lung to subsequent injury.

Temporal trends of postinjury multiple-organ failure: still resource intensive, morbid, and lethal.

BACKGROUND: While the incidence of postinjury multiple-organ failure (MOF) has declined during the past decade, temporal trends of its morbidity, mortality, presentation patterns, and health care resources use have been inconsistent. The purpose of this study was to describe the evolving epidemiology of postinjury MOF from 2003 to 2010 in multiple trauma centers sharing standard treatment protocols. METHODS: "Inflammation and Host Response to Injury Collaborative Program" institutions that enrolled more than 20 eligible patients per biennial during the 2003 to 2010 study period were included. The patients were aged 16 years to 90 years, sustained blunt torso trauma with hemorrhagic shock (systolic blood pressure < 90 mm Hg, base deficit ≥ 6 mEq/L, blood transfusion within the first 12 hours), but without severe head injury (motor Glasgow Coma Scale [GCS] score < 4). MOF temporal trends (Denver MOF score > 3) were adjusted for admission risk factors (age, sex, body max index, Injury Severity Score [ISS], systolic blood pressure, and base deficit) using survival analysis. RESULTS: A total of 1,643 patients from four institutions were evaluated. MOF incidence decreased over time (from 17% in 2003-2004 to 9.8% in 2009-2010). MOF-related death rate (33% in 2003-2004 to 36% in 2009-2010), intensive care unit stay, and mechanical ventilation duration did not change over the study period. Adjustment for admission risk factors confirmed the crude trends. MOF patients required much longer ventilation and intensive care unit stay, compared with non-MOF patients. Most of the MOF-related deaths occurred within 2 days of the MOF diagnosis. Lung and cardiac dysfunctions became less frequent (57.6% to 50.8%, 20.9% to 12.5%, respectively), but kidney and liver failure rates did not change (10.1% to 12.5%, 15.2% to 14.1%). CONCLUSION: Postinjury MOF remains a resource-intensive, morbid, and lethal condition. Lung injury is an enduring challenge and should be a research priority. The lack of outcome improvements suggests that reversing MOF is difficult and prevention is still the best strategy. LEVEL OF EVIDENCE: Epidemiologic study, level III.

Fibrinolysis greater than 3% is the critical value for initiation of antifibrinolytic therapy.

BACKGROUND: The acute coagulopathy of trauma is present in up to one third of patients by the time of admission, and the recent CRASH-2 and MATTERs trials have focused worldwide attention on hyperfibrinolysis as a component of acute coagulopathy of trauma. Thromboelastography (TEG) is a powerful tool for analyzing fibrinolyis, but a clinically relevant threshold for defining hyperfibrinolysis has yet to be determined. Recent data suggest that the accepted normal upper bound of 7.5% for 30-minute fibrinolysis (LY30) by TEG is inappropriate in severe trauma, as the risk of death rises at much lower levels of clot lysis. We wished to determine the validity of this hypothesis and establish a threshold value to treat fibrinolysis, based on prediction of massive transfusion requirement and risk of mortality. METHODS: Patients with uncontrolled hemorrhage, meeting the massive transfusion protocol (MTP) criteria at admission (n = 73), represent the most severely injured trauma population at our center (median Injury Severity Score [ISS], 30; interquartile range, 20-38). Citrated kaolin TEG was performed at admission blood samples from this population, stratified by LY30, and evaluated for transfusion requirement and 28-day mortality. The same analysis was conducted on available field blood samples from all non-MTP trauma patients (n = 216) in the same period. These represent the general trauma population. RESULTS: Within the MTP-activating population, the cohort of patients with LY30 of 3% or greater was shown to be at much higher risk for requiring a massive transfusion (90.9% vs. 30.5%, p = 0.0008) and dying of hemorrhage (45.5% vs. 4.8%, p = 0.0014) than those with LY30 less than 3%. Similar trends were seen in the general trauma population. CONCLUSION: LY30 of 3% or greater defines clinically relevant hyperfibrinolysis and strongly predicts the requirement for massive transfusion and an increased risk of mortality in trauma patients presenting with uncontrolled hemorrhage. This threshold value for LY30 represents a critical indication for the treatment of fibrinolysis. LEVEL OF EVIDENCE: Prognostic study, level III.

Platelets are dominant contributors to hypercoagulability after injury.

BACKGROUND: Venous thromboembolic (VTE) disease has a high incidence following trauma, but debate remains regarding optimal prophylaxis. Thrombelastography (TEG) has been suggested to be optimal in guiding prophylaxis. Thus, we designed a phase II randomized controlled trial to test the hypothesis that TEG-guided prophylaxis with escalating low-molecular weight heparin (LMWH), followed by antiplatelet therapy would reduce VTE incidence. METHODS: Surgical intensive care unit trauma patients (n = 50) were randomized to receive 5,000 IU of LMWH daily (control) or to TEG-guided prophylaxis, up to 5,000 IU twice daily with the addition of aspirin, and were followed up for 5 days. In vitro studies were also conducted in which apheresis platelets were added to blood from healthy volunteers (n = 10). RESULTS: Control (n = 25) and TEG-guided prophylaxis (n = 25) groups were similar in age, body mass index, Injury Severity Score, and male sex. Fibrinogen levels and platelet counts did not differ, and increased LMWH did not affect clot strength between the control and study groups. The correlation of clot strength (G value) with fibrinogen was stronger on Days 1 and 2 but was superseded by platelet count on Days 3, 4, and 5. There was also a trend in increased platelet contribution to clot strength in patients receiving increased LMWH. In vitro studies demonstrated apheresis platelets significantly increased clot strength (7.19 ± 0.35 to 10.34 ± 0.29), as well as thrombus generation (713.86 ± 12.19 to 814.42 ± 7.97) and fibrin production (274.03 ± 15.82 to 427.95 ± 16.58). CONCLUSION: Increased LMWH seemed to increase platelet contribution to clot strength early in the study but failed to affect the overall rise clot strength. Over time, platelet count had the strongest correlation with clot strength, and in vitro studies demonstrated that increased platelet counts increase fibrin production and thrombus generation. In sum, these data suggest an important role for antiplatelet therapy in VTE prophylaxis following trauma, particularly after 48 hours. LEVEL OF EVIDENCE: Therapeutic study, level III.

Elderly patients may benefit from tight glucose control.

BACKGROUND: While minimizing hyperglycemia in critically injured patients improves outcomes, it is debatable whether postinjury glucose control should aim for conventional glucose control levels (≤180 mg/dL) or tight glucose control levels (81-108 mg/dL). We queried our 17-year prospective database of patients at risk for postinjury multiple organ failure to examine the association between glucose levels and adverse outcomes. METHODS: Acutely injured patients admitted to a Level I trauma center intensive care unit from 1992 to 2008 who were more than 15 years of age, had Injury Severity Scores >15, and who survived >48 hours were eligible for the study. Multiple logistic regression was used to determine the independent association of glucose control with adverse outcomes (death, ventilator-free days, intensive care unit-free days, and major infections), adjusted for Injury Severity Score, age, and red blood cell transfusion in the first 12 hours. RESULTS: Overall, 2,231 patients were eligible, of whom 153 (6.9%) died. The mean age was 37.8 ± 0.4 years, and the median Injury Severity Score was 27 (interquartile range, 21-35). The majority (77%) of these patients maintained mean glucose within conventional glucose control levels and only 10% achieved mean glucose levels within tight glucose control levels. Nonsurvivors required greater doses of insulin to control glucose levels and had greater mean insulin to glucose ratios (t test; P = .025). After adjusting for confounders, mean glucose remained significantly associated with the studied adverse outcomes. Age significantly modified all these associations with older patients seeming to benefit more from tight glucose control levels than their younger counterparts. CONCLUSION: Age is an effect modifier of the association between glucose levels and adverse outcomes. Future studies including larger samples of elderly trauma patients are needed to determine the ideal levels for glucose control in this growing population.