Robert M. Van Haren

Do all trauma patients benefit from tranexamic acid

BACKGROUND This study tested the hypothesis that early routine use of tranexamic acid (TXA) reduces mortality in a subset of the most critically injured trauma intensive care unit patients. METHODS Consecutive trauma patients (n = 1,217) who required emergency surgery (OR) and/or transfusions from August 2009 to January 2013 were reviewed. At surgeon discretion, TXA was administered at a median of 97 minutes (1-g bolus then 1-g over 8 hours) to 150 patients deemed high risk for hemorrhagic death. With the use of propensity scores based on age, sex, traumatic brain injury (TBI), mechanism of injury, systolic blood pressure, transfusion requirements, and Injury Severity Score (ISS), these patients were matched to 150 non-TXA patients. RESULTS The study population was 43 years old, 86% male, 54% penetrating mechanism of injury, 25% TBI, 28 ISS, with 22% mortality. OR was required in 78% at 86 minutes, transfusion was required in 97% at 36 minutes, and 75% received both. For TXA versus no TXA, more packed red blood cells and total fluid were required, and mortality was 27% versus 17% (all p < 0.05). The effects of TXA were similar in those with or without TBI, although ISS, fluid, and mortality were all higher in the TBI group. Mortality associated with TXA was influenced by the timing of administration (p < 0.05), but any benefit was eliminated in those who required more than 2,000-mL packed red blood cells, who presented with systolic blood pressure of less than 120 mm Hg or who required OR (all p < 0.05). CONCLUSION For the highest injury acuity patients, TXA was associated with increased, rather than reduced, mortality, no matter what time it was administered. This lack of benefit can probably be attributed to the rapid availability of fluids and emergency OR at this trauma center. Prospective studies are needed to further identify conditions that may override the benefits from TXA. LEVEL OF EVIDENCE Therapeutic study, level IV.

An analysis of prehospital deaths: Who can we save?

BACKGROUND Since their inception in the late 1970s, trauma networks have saved thousands of lives in the prehospital setting. However, few recent works have been done to evaluate the patients who die in the field. Understanding the epidemiology of these deaths is crucial for trauma system performance evaluation and improvement. We hypothesized that specific patterns of injury could be identified and targeted for intervention. METHODS Medical examiner reports in a large, urban county were reviewed including all trauma deaths during 2011 that were not transported to a hospital (i.e., died at the scene) or dead on arrival. Age, sex, date of death, mechanism, and list of injuries were recorded. An expert panel reviewed each case to determine the primary cause of death, and if the patient’s death was caused by potentially survivable injuries or nonsurvivable injuries. RESULTS A total of 512 patients were included. Patients were 80% male, died mostly of blunt (53%) and penetrating (46%) causes, and included 21% documented suicides. The leading cause of death was neurotrauma (36%), followed by hemorrhage (34%), asphyxia (15%), and combined neurotrauma/hemorrhage (15%). The anatomic regions most frequently injured were the brain (59%), chest (54%), and abdomen (35%). Finally, 29% of the patient deaths were classified as a result of potentially survivable injuries given current treatment options, mostly from hemorrhage and chest injuries. CONCLUSION More than one of every five trauma deaths in our study population had potentially survivable injuries. In this group, chest injuries and death via hemorrhage were predominant and suggest targets for future research and implementation of novel prehospital interventions. In addition, efforts targeting suicide prevention remain of great importance. LEVEL OF EVIDENCE Epidemiologic study, level V.

Venous thromboembolism after trauma: A never event?

Objective:Rates of venous thromboembolism as high as 58% have been reported after trauma, but there is no widely accepted screening protocol. If Medicare adds venous thromboembolism to the list of “preventable complications,” they will no longer reimburse for treatment, which could have devastating effects on many urban centers. We hypothesized that prescreening with a risk assessment profile followed by routine surveillance with venous duplex ultrasound that could identify asymptomatic venous thromboembolism in trauma patients. Design:Prospective, observational trial with waiver of consent. Setting:Level I trauma center intensive care unit. Patients:At admission, 534 patients were prescreened with a risk assessment profile. Interventions:Patients (n = 106) with risk assessment profile scores >10 were considered high risk and received routine screening venous duplex ultrasound within 24 hrs and weekly thereafter. Results:In prescreened high-risk patients, 20 asymptomatic deep vein thrombosis were detected with venous duplex ultrasound (19%). An additional ten venous thromboembolisms occurred, including six symptomatic deep vein thrombosis and four pulmonary emboli, resulting in an overall venous thromboembolism rate of 28%. The most common risk factors discriminating venous thromboembolism vs. no venous thromboembolism were femoral central venous catheter (23% vs. 8%), operative intervention >2 hrs (77% vs. 46%), complex lower extremity fracture (53% vs. 32%), and pelvic fracture (70% vs. 47%), respectively (all p < .05). Risk assessment profile scores were higher in patients with venous thromboembolism (19 ± 6 vs. 14 ± 4, p = .001). Risk assessment profile score (odds ratio 1.14) and the combination of pelvic fracture requiring operative intervention >2 hrs (odds ratio 5.75) were independent predictors for development of venous thromboembolism. The rates of venous thromboembolism for no chemical prophylaxis (33%), unfractionated heparin (29%), dalteparin (40%), or inferior vena cava filters (20%) were not statistically different (p = .764). Conclusions:Medicare’s inclusion of venous thromboembolism after trauma as a “never event” should be questioned. In trauma patients, high-risk assessment profile score and pelvic fracture with prolonged operative intervention are independent predictors for venous thromboembolism development, despite thromboprophylaxis. Although routine venous duplex ultrasound screening may not be cost-effective for all trauma patients, prescreening using risk assessment profile yielded a cohort of patients with a high prevalence of venous thromboembolism. In such high-risk patients, routine venous duplex ultrasound and/or more aggressive prophylactic regimens may be beneficial.

Hypercoagulability and other risk factors in trauma intensive care unit patients with venous thromboembolism

BACKGROUND Thromboelastography (TEG) on hospital admission can identify hypercoagulable trauma patients at risk for venous thromboembolism (VTE), but the value of TEGs obtained after multiple interventions, including tranexamic acid (TXA), has not been defined. We test the following hypotheses. (1) TEG on intensive care unit (ICU) admission can help stratify patients screened with Greenfield’s risk assessment profile (RAP) for VTE. (2) TXA is a VTE risk factor, and its effect on fibrinolysis can be identified with TEG. METHODS Trauma patients who survived to the ICU with RAP ≥ 10 received serial venous duplex ultrasound examinations and blood samples for coagulation analysis at admission to the ICU and weekly thereafter. RESULTS Six hundred seventy-eight patients were screened and 121 were enrolled; 76% blunt injury, Injury Severity Score (ISS) 27, 13% mortality. Thromboprophylaxis was administered to 90% of the patients and was started a median of 2 days after hospital admission. VTE was detected in 28% (n = 34) of the patients (27 deep vein thrombosis and 7 pulmonary emboli) and occurred a median 10 days after admission. Twenty-nine percent (n = 10) of VTE occurred within 2 days of admission. Most variables were similar between those with and without VTE, but the VTE group received more operations (3 (2) vs. 2 (2), p = 0.044), had increased ICU days (25 (34) days vs. 15 (18) days, p = 0.004), and was more likely to have abdominal injury with Abbreviated Injury Scale (AIS) score > 2 (59% vs. 39%, p = 0.050). Upon ICU admission, standard coagulation markers were within normal limits, while TEG demonstrated hypercoagulability, but neither was associated with VTE. Repeat TEG one week after admission (n = 58) remained hypercoagulable but transitioned to a different pattern with increased clot strength. TXA was associated with reduced fibrinolysis on initial TEG (p < 0.05) but was not associated with VTE. CONCLUSION Trauma ICU patients with RAP ≥ 10 are hypercoagulable at admission to ICU and remain so during recovery. They have a ≥ 25% rate of VTE, despite thromboprophylaxis. TXA is associated with reduced fibrinolysis but does not increase VTE rates. Neither TEG nor standard coagulation markers (measured on ICU admission) stratify high-risk patients who develop VTE from those who do not. LEVEL OF EVIDENCE Prognostic study, level III.

Military trauma training at civilian centers: a decade of advancements.

Abstract In the late 1990s, a Department of Defense subcommittee screened more than 100 civilian trauma centers according to the number of admissions, percentage of penetrating trauma, and institutional interest in relation to the specific training missions of each of the three service branches. By the end of 2001, the Army started a program at University of Miami/Ryder Trauma Center, the Navy began a similar program at University of Southern California/Los Angeles County Medical Center, and the Air Force initiated three Centers for the Sustainment of Trauma and Readiness Skills (C-STARS) at busy academic medical centers: R. Adams Cowley Shock Trauma Center at the University of Maryland (C-STARS Baltimore), Saint Louis University (C-STARS St. Louis), and The University Hospital/University of Cincinnati (C-STARS Cincinnati). Each center focuses on three key areas, didactic training, state-of-the-art simulation and expeditionary equipment training, as well as actual clinical experience in the acute management of trauma patients. Each is integral to delivering lifesaving combat casualty care in theater. Initially, there were growing pains and the struggle to develop an effective curriculum in a short period. With the foresight of each trauma training center director and a dynamic exchange of information with civilian trauma leaders and frontline war fighters, there has been a continuous evolution and improvement of each center’s curriculum. Now, it is clear that the longest military conflict in US history and the first of the 21st century has led to numerous innovations in cutting edge trauma training on a comprehensive array of topics. This report provides an overview of the decade-long evolutionary process in providing the highest-quality medical care for our injured heroes.

Does hemopericardium after chest trauma mandate sternotomy

BACKGROUND Recently, three patients with hemopericardium after severe chest trauma were successfully managed nonoperatively at our institution. This prompted the question whether these were rare or common events. Therefore, we reviewed our experience with similar injuries to test the hypothesis that trauma-induced hemopericardium mandates sternotomy. METHOD Records were retrospectively reviewed for all patients at a Level I trauma center (December 1996 to November 2011) who sustained chest trauma with pericardial window (PCW, n = 377) and/or median sternotomy (n = 110). RESULTS Fifty-five (15%) patients with positive PCW proceeded to sternotomy. Penetrating injury was the dominant mechanism (n = 49, 89%). Nineteen (35%) were hypotensive on arrival or during initial resuscitation. Most received surgeon-performed focused cardiac ultrasound examinations (n = 43, 78%) with positive results (n = 25, 58%). Ventricular injuries were most common, with equivalent numbers occurring on the right (n = 16, 29%) and left (n = 15, 27%). Six (11%) with positive PCW had isolated pericardial lacerations, but 21 (38%) had no repairable cardiac or great vessel injury. Those with therapeutic versus nontherapeutic sternotomies were similar with respect to age, mechanisms of injury, injury severity scores, presenting laboratory values, resuscitation fluids, and vital signs. Multiple logistic regression revealed that penetrating trauma (odds ratio: 13.3) and hemodynamic instability (odds ratio: 7.8) were independent predictors of therapeutic sternotomy. CONCLUSION Hemopericardium per se may be overly sensitive for diagnosing cardiac or great vessel injuries after chest trauma. Some stable blunt or penetrating trauma patients without continuing intrapericardial bleeding had nontherapeutic sternotomies, suggesting that this intervention could be avoided in selected cases. LEVEL OF EVIDENCE Therapeutic study, level III.

Pre-existing hypercoagulability in patients undergoing potentially curative cancer resection

BACKGROUND Rotational thromboelastometry (ROTEM) is a new point-of-care test that allows a rapid and comprehensive evaluation of coagulation. We were among the first to show that ROTEM identifies baseline hypercoagulability in 40% of patients with intra-abdominal malignancies and that hypercoagulability persists for ≥1 month after resection. The purpose of this follow-up study was to confirm and extend these observations to a larger population in outpatient preoperative clinics. The hypothesis is that pre-existing hypercoagulability is present in patients undergoing surgery for malignant disease and that coagulation status varies by tumor type. METHODS After informed consent, preoperative blood samples were drawn from patients undergoing exploratory laparotomies for intra-abdominal malignancies and analyzed with ROTEM. RESULTS Eighty-two patients were enrolled, including 72 with a confirmed pathologic diagnosis and 10 age-matched controls with benign disease. The most common cancers involved the pancreas (n = 23; 32%), esophagus (n = 19; 26%), liver (n = 12; 17%), stomach (n = 7; 10%), and bile ducts (n = 5; 7%). Preoperative hypercoagulability was detected in 31% (n = 22); these patients were more likely to have lymphovascular invasion (88% vs 50%; P = .011), perineural invasion (77% vs 36%; P = .007), and stage III/IV disease (80% vs 62%; P = .039). More patients with pancreatic tumors (9/23, 39%) were hypercoagulable than with esophageal (3/19, 16%) or liver (2/13, 15%, P = .034) tumors. When only resectable malignancies were considered, clot formation was more rapid (low clot formation time, high alpha) with enhanced maximum clot strength (high maximum clot firmness) in pancreatic versus esophageal or liver cancers and in all cancers versus those with benign disease. CONCLUSION Preoperative hypercoagulability can be identified with ROTEM and is associated with lymphovascular/perineural invasion and advanced-staged disease in cancer. Compared with other tumor types, pancreatic adenocarcinomas have the greatest risk for hypercoagulability.

Persistence of hypercoagulable state after resection of intra-abdominal malignancies

BACKGROUND The hypercoagulable state associated with cancer imparts considerable risk for venous thromboembolism. Surgical resection of malignancies should theoretically reverse tumor-induced hypercoagulability. However, coagulation changes in cancer patients postresection have not been described thoroughly. Conventional coagulation tests are unable to detect hypercoagulable states. In contrast, rotational thromboelastography (ROTEM) can detect hypo- or hypercoagulable conditions. We hypothesized that the cancer-induced hypercoagulable state would improve after surgical resection. METHODS After informed consent, blood samples of patients undergoing surgical resection for curative intent were analyzed with serial ROTEM. RESULTS Thirty-five patients (mean ± SD age 66 ± 17 years; 67% male) had cancers involving the pancreas (n = 12 [34%]), esophagus (n = 10 [29%]), stomach (n = 7 [20%]), bile ducts (n = 3 [9%]), and duodenum (n = 3 [9%]). Preoperative ROTEM identified 14 (40%) who were hypercoagulable. After surgical resection, patients became progressively hypercoagulable with more rapid clot formation time (low clot formation time, high alpha) and higher maximum clot firmness. By week one, 86% (n = 30) had abnormal ROTEM values, including 17 of 21 (81%) who had normal coagulation profiles preoperatively. Most (n = 30 [86%]) remained hypercoagulable at 3 to 4 weeks. CONCLUSIONS Rotational thromboelastography identifies baseline hypercoagulability in more than one third of patients with intra-abdominal malignancies. This is among the first studies to demonstrate progressive hypercoagulability that persists for at least 1 month after resection. These data support postdischarge thromboprophylaxis regimens in high-risk cancer patients.

Repeat head computed tomography after minimal brain injury identifies the need for craniotomy in the absence of neurologic change.

BACKGROUND In this era of cost containment, the value of routine repeat head computed tomography (CT) in patients with mild TBI (mTBI) and no interval neurologic change has been challenged. The purpose of this study was to test the hypothesis that routine repeat head CT provides critical information after mTBI even with no neurologic change. METHODS From January 1996 to May 2010, records from all patients admitted to our Level I trauma center with an arrival Glasgow Coma Scale (GCS) score of 13 to 15 and at least one head CT were retrospectively reviewed. RESULTS In 360 patients with mTBI and positive initial head CT finding, the most common abnormalities were subarachnoid hemorrhage (64%), intraparenchymal hemorrhage (57%), and subdural hemorrhage (40%). Scans were repeated in 8 ± 6 hours; 11% were recalled, 59% remained stable, but 30% showed injury progression. Those patients with worsening repeat head CT finding had higher Injury Severity Score (ISS), were more likely to be intubated and require craniotomy, had longer stay, and had higher mortality (all p < 0.001). On multiple logistic regression, altered GCS score (odds ratio, 3.1–4.0), ISS (odds ratio, 1.1), and presence of mass effect (odds ratio, 2.0) were independently associated with worsening repeat head CT finding. In patients receiving a neurosurgical operative intervention, 32% to 59% had no clinical decline before the worsening repeat CT finding. CONCLUSION After mTBI, worsening of repeat head CT finding is seen in a third of patients and is associated with worse outcomes. A substantial fraction of patients who require operative intervention will have no clinical changes in the first 8 hours, supporting the value of repeat head CT within this time frame. LEVEL OF EVIDENCE Care management study, level III.

Insertion of central venous catheters induces a hypercoagulable state

BACKGROUND Central venous catheters (CVCs) increase the risk of venous thromboembolism. We have previously demonstrated that pulmonary artery catheters are associated with a hypercoagulable state in an animal model and in patients. The purpose of this study is to determine whether the insertion of a CVC is associated with a similar response. METHODS Animal: 7F femoral artery catheters were placed in healthy anesthetized swine (N = 16). Serial arterial blood samples were drawn immediately before and after an 8.5F jugular vein CVC and then for 3 hours after CVC removal. Samples were analyzed using kaolin-activated thromboelastography (TEG) at precisely 2 minutes. Human: An institutional review board–approved prospective observational trial was conducted, with informed consent, in patients with critical illness (N = 8) at a Level I trauma center. Blood was drawn from indwelling arterial catheters immediately before and 60 minutes after CVC insertion. Samples were stored in sodium citrate for 15 minutes before TEG. Routine and special coagulation tests were performed on stored samples in the hospital pathology laboratory. RESULTS Insertion of a CVC decreased TEG clotting time (R) by 55% in swine and by 29% in humans (p < 0.001 and 0.019, respectively). Initial clot formation time (K) was reduced by 41% in swine and by 36% in humans (p = 0.003 and 0.019). Fibrin cross-linking (&agr;) was accelerated by 28% in swine and by 17% in humans (p = 0.007 and 0.896), but overall clot strength (maximum amplitude) was not affected. There was no change in routine or special coagulation factors, including von Willebrand factor, antithrombin III, prothrombin time, international normalized ratio, or activated partial thromboplastin time. In animals, the hypercoagulable TEG response was persistent for 3 hours after CVC removal and was prevented by pretreatment with enoxaparin (n = 4) but not heparin (n = 2). CONCLUSION In healthy swine and patients with critical illness, a systemic hypercoagulable state occurred after CVC insertion, and this may partially account for an increased risk of venous thromboembolism. However, because the sample size was small and not powered to detect changes in coagulation proteins, no inferences can be made about the mechanism for the hypercoagulable response.