Low-Dose Heparin Infusion as Venous Thromboembolism Chemoprophylaxis in Patients With Blunt Cerebrovascular Injury.

INTRODUCTION: Blunt cerebrovascular injury (BCVI) can result in devastating stroke. Because of operative inaccessibility, the most common treatment for BCVI is aspirin or a low-dose systemic heparin infusion. While it is assumed that low dose heparin infusion imparts venous thromboembolism (VTE) prophylaxis, this has not been evaluated in the BCVI population. The purpose of this study was to evaluate VTE rates in patients receiving low-dose heparin infusion as treatment for BCVI. METHODS: Patients diagnosed with BCVI between 2014 and 2018 were reviewed for initiation of low-dose systemic heparin treatment. VTE was defined as a deep vein thrombosis or pulmonary embolism. BCVI patients without systemic heparin treatment were compared to BCVI patients with heparin treatment for overall VTE rates. Comparisons were also made to injured patients without a BCVI in our Trauma Activation Protocol (TAP) database. RESULTS: During the 5-year study period, 265 patients were identified with a BCVI. The majority (61%) were men with a median injury severity score (ISS) 22 (interquartile range [IQR]:14-33). Of these patients, 146 (55.1%) received a heparin infusion to treat BCVI. VTE was identified in eight of these patients (5.5%). Compared to TAP patients (n = 1020) who received standard dosing of VTE chemoprophylaxis, there was no difference in VTE rates compared to BCVI patients who were started on a low dose heparin infusion (3% versus 5.5%, P = 0.16). Area under the receiver operating characteristics (AUROC) was used to evaluate the predictive power of time to initiation of heparin infusion (AUC = 0.64 95% CI 0.42-0.85, P = 0.2) and time to reaching PTT goal (AUC = 0.52 95% CI 0.27-0.77, P = 0.83) as a predictor VTE events. CONCLUSIONS: Low dose heparin infusion is frequently used as an initial treatment of BCVI. In injured patients with BCVI, a low dose heparin infusion is associated with a low rate of VTE, comparable to injured patients without BCVI that received standard VTE chemoprophylaxis.

Natural history and nonoperative management of penetrating cerebrovascular injury.

INTRODUCTION: There is a modern precedent for nonoperative management of select penetrating cerebrovascular injuries (PCVIs); however, there is minimal data to guide management. PATIENTS AND METHODS: This study assessed treatments, radiographic injury progression, and outcomes for all patients with PCVIs managed at an urban Level I trauma center from 2016 to 2021 that underwent initial nonoperative management (NOM). RESULTS: Fourteen patients were included. There were 11,635 trauma admissions, 378 patients with blunt cerebrovascular injury, and 18 patients with operatively-managed PCVI during this timeframe. All patients received antithrombotic therapy, but this was delayed in some due to concomitant injuries. Three patients had stroke (21%): two before antithrombotic initiation, and one with unclear timing relative to treatment. Three patients underwent endovascular interventions. On follow-up imaging, 14% had injury resolution, 36% were stable, 21% worsened, and 29% had no follow-up vascular imaging. One patient died (7%), one had a bleeding complication (7%), and no patient required delayed operative intervention. DISCUSSION: Early initiation of antithrombotic therapy, early surveillance imaging, and selective use of endovascular interventions are important for nonoperative management of PCVI.

Computational model of tranexamic acid on urokinase mediated fibrinolysis.

Understanding the coagulation process is critical to developing treatments for trauma and coagulopathies. Clinical studies on tranexamic acid (TXA) have resulted in mixed reports on its efficacy in improving outcomes in trauma patients. The largest study, CRASH-2, reported that TXA improved outcomes in patients who received treatment prior to 3 hours after the injury, but worsened outcomes in patients who received treatment after 3 hours. No consensus has been reached about the mechanism behind the duality of these results. In this paper we use a computational model for coagulation and fibrinolysis to propose that deficiencies or depletions of key anti-fibrinolytic proteins, specifically antiplasmin, a1-antitrypsin and a2-macroglobulin, can lead to worsened outcomes through urokinase-mediated hyperfibrinolysis.

"Bedside Anatomy": A Tool to Contextualize Learning and Introduce Surgical Careers.

BACKGROUND: Many medical students cite an unwelcoming culture in surgery and perceive surgeons as arrogant or unfriendly. These perceptions have been reported as factors discouraging medical students from applying to surgical residency programs. This highlights an opportunity early in medical education to address these negative stereotypes and create opportunities for positive interactions with surgeons. We hypothesize that positive experiences with surgical residents and introduction to representative surgical cases early in the medical school curriculum can provide a real-world context for learning anatomy and encourage students to consider a surgical career. METHODS: We developed and implemented a series of structured, one-hour, cadaver-based sessions cofacilitated by anatomists and surgical residents for medical students during their anatomy didactics. Sessions included common surgical cases and focused on critical thinking and problem-solving skills, while offering opportunities to review cadaver anatomy. Students completed a postcourse survey. RESULTS: Nine sessions were implemented with involvement of eight surgical residents and 185 students; 83 students completed a postcourse survey (response rate of 45%). A majority of students rated the sessions "very helpful" in terms of highlighting the importance of anatomy in medical education (n = 52, 63%) and providing clinical context (n = 59, 71%). 54% (n = 45) indicated interest in a surgical career and 64% (n = 53) agreed that session participation had increased their interest in surgery. CONCLUSIONS: Overall, students agreed that sessions provided clinical context for their learning and increased interest in a surgical career. Surgical faculty and residents should engage in preclinical medical education to bridge the basic science and clinical years and introduce positive surgical role models early during medical training.

Not all in your head (and neck): Stroke after blunt cerebrovascular injury is associated with systemic hypercoagulability.

BACKGROUND: Stroke secondary to blunt cerebrovascular injury (BCVI) most often occurs before initiation of antithrombotic therapy. Earlier treatment, especially in multiply injured patients with relative contraindications to antithrombotic agents, could be facilitated with improved risk stratification; furthermore, the relationship between BCVI-attributed stroke and hypercoagulability remains unknown. We hypothesized that patients who suffer BCVI-related stroke are hypercoagulable compared with those with BCVI who do not stroke. METHODS: Rapid thromboelastography (TEG) was evaluated for patients with BCVI-attributed stroke at an urban Level I trauma center from 2011 to 2018. Contemporary controls who had BCVI but did not stroke were selected for comparison using propensity-score matching with 20% caliper that accounted for age, sex, injury severity, and BCVI location and grade. RESULTS: During the study period, 15,347 patients were admitted following blunt trauma. Blunt cerebrovascular injury was identified in 435 (3%) patients, of whom 28 experienced associated stroke and had a TEG within 24 hours of arrival. Forty-nine patients who had BCVI but did not suffer stroke served as matched controls. Stroke patients formed clots faster as evident in their larger angle (77.5 degrees vs. 74.6 degrees, p = 0.03) and had greater clot strength as indicated by their higher maximum amplitude (MA) (66.9 mm vs. 61.9 mm, p < 0.01). Activated clotting time was shorter among stroke patients but not significantly (113 seconds vs. 121 seconds, p > 0.05). Increased angle and elevated MA were significant predictors of stroke with odds ratios of 2.97 for angle greater than 77.3 degrees and 4.30 for MA greater than 63.0 mm. CONCLUSION: Patients who suffer BCVI-related stroke are hypercoagulable compared with those with BCVI who remain asymptomatic. Increased angle or MA should be considered when assessing the risk of thrombosis and determining the optimal time to initiate antithrombotic therapy in patients with BCVI. LEVEL OF EVIDENCE: Prognostic, Level III.

Obesity is associated with postinjury hypercoagulability.

BACKGROUND: Obesity is linked to hypercoagulability with an increased risk of venous thromboembolic events (VTE) in the uninjured population. Therefore, we hypothesize that obesity (body mass index [BMI] ≥30 kg/m [BMI30]) is associated with a hypercoagulable state postinjury characterized by increased clot strength and resistance to fibrinolysis. METHODS: Our prospective Trauma Activation Protocol database includes all trauma activations patients for whom a rapid thrombelastography is obtained within 60 minutes postinjury prior to any transfusions. The data set was then stratified by BMI and subjects with BMI30 were compared with those with BMI less than 30 kg/m). The following thrombelastography measurements were obtained: activated clotting time, clot formation rate (angle), maximum clot strength (MA), and % clot lysis 30 minutes after MA (LY30, %). Fibrinolysis shutdown (SD) was defined as LY30 < 0.6% and hyperfibrinolysis (HF) as LY30 greater than 7.6%. Continuous variables are expressed as median (interquartile range). RESULTS: Overall, 687 patients were included of whom 161 (23%) had BMI30. The BMI30 group was older, had a lower proportion of males and of blunt trauma, and was less severely injured. After adjustment for confounders, BMI30 was independently associated with lower odds of MA less than 55 mm (odds ratio [OR], 0.28; 95% confidence interval [CI], 0.13-0.60) and of HF (OR, 0.31; 95% CI, 0.10-0.97) and higher odds of SD (OR, 1.82; 95% CI, 1.09-3.05). No independent association was observed with angle less than 65° (OR 0.57 95% CI 0.30-1.05). While VTEs were more frequent among BMI30 patients (5.0 vs. 3.3%), this did not reach significance after confounding adjustment (p = 0.11). CONCLUSION: Obesity was protective against diminished clot strength and hyperfibrinolysis, and obesity was associated with an increased risk of fibrinolytic SD in severely injured patients. These findings suggest a relative hypercoagulability. Although no difference in VTEs was noted in this study, these findings may explain the higher rate of VTEs reported in other studies. LEVEL OF EVIDENCE: Prognostic and Epidemiological, level III.

Discrepancies between conventional and viscoelastic assays in identifying trauma-induced coagulopathy.

BACKGROUND: Trauma-induced coagulopathy can present as abnormalities in a conventional or viscoelastic coagulation assay or both. We hypothesized that patients with discordant coagulopathies reflect different clinical phenotypes. METHODS: Blood samples were collected prospectively from critically injured patients upon arrival at two urban Level I trauma centers. International normalized ratio (INR), partial thromboplastin time (PTT), thromboelastography (TEG), and coagulation factors were assayed. RESULTS: 278 patients (median ISS 17, mortality 26%) were coagulopathic: 20% with isolated abnormal INR and/or PTT (CONVENTIONAL), 49% with isolated abnormal TEG (VISCOELASTIC), and 31% with abnormal INR/PTT and TEG (BOTH). Compared with VISCOELASTIC, CONVENTIONAL and BOTH had higher ISS, lower GCS, larger base deficit, and decreased factor activities (all p < 0.017). They received more blood products and had more ICU/ventilation days (all p < 0.017). Mortality was higher in CONVENTIONAL (40%) and BOTH (49%) than VISCOELASTIC (6%, p < 0.017). CONCLUSIONS: Although TEG-guided resuscitation improves survival after injury, INR and PTT identify coagulopathic patients with highest mortality regardless of TEG and likely represent distinct mechanisms independent of biochemical clot strength.

Trauma Resuscitation Consideration: Sex Matters.

BACKGROUND: Sex dimorphisms in coagulation have been recognized, but whole blood assessment of these dimorphisms and their relationship to outcomes in trauma have not been investigated. This study characterizes the viscoelastic hemostatic profile of severely injured patients by sex, and examines how sex-specific coagulation differences affect clinical outcomes, specifically, massive transfusion (MT) and death. We hypothesized that severely injured females are more hypercoagulable and therefore, have lower rates of MT and mortality. STUDY DESIGN: Hemostatic profiles and clinical outcomes from all trauma activation patients from 2 level I trauma centers were examined, with sex as an experimental variable. As part of a prospective study, whole blood was collected and thrombelastography (TEG) was performed. Coagulation profiles were compared between sexes, and association with MT and mortality were examined. Poisson regression with robust standard errors was performed. RESULTS: Overall, 464 patients (23% female) were included. By TEG, females had a more hypercoagulable profile, with a higher angle (clot propagation) and maximum amplitude (MA, clot strength). Females were less likely to present with hyperfibrinolysis or prolonged activating clotting time than males. In the setting of depressed clot strength (abnormal MA), female sex conferred a survival benefit, and hyperfibrinolysis was associated with higher case-fatality rate in males. CONCLUSIONS: Severely injured females have a more hypercoagulable profile than males. This hypercoagulable status conferred a protective effect against mortality in the setting of diminished clot strength. The mechanism behind these dimorphisms needs to be elucidated and may have treatment implications for sex-specific trauma resuscitation.

Dynamic coagulability after injury: Is delaying venous thromboembolism chemoprophylaxis worth the wait?

BACKGROUND: Severely injured patients often progress from early hypocoagulable to normal and eventually hypercoagulable states, developing increased risk for venous thromboembolism (VTE). Prophylactic anticoagulation can decrease this risk, but its initiation is frequently delayed for extended periods due to concerns for bleeding. To facilitate timely introduction of VTE chemoprophylaxis, we characterized the transition from hypo- to hypercoagulability and hypothesized that trauma-induced coagulopathy resolves within 24 hours after injury. METHODS: Serial blood samples were collected prospectively from critically injured patients for 120 hours after arrival at an urban Level I trauma center. Extrinsic thromboelastometry maximum clot firmness was used to classify patients as hypocoagulable (HYPO, <49 mm), normocoagulable (NORM, 49-71 mm), or hypercoagulable (HYPER, >71 mm) at each time point. Changes in coagulability over hospital course, VTE occurrence, and timing of prophylaxis initiation were analyzed. RESULTS: 898 patients (median Injury Severity Score, 13; mortality, 12%; VTE, 8%) were enrolled. Upon arrival, 3% were HYPO (90% NORM, 7% HYPER), which increased to 9% at 6 hours before down-trending. Ninety-seven percent were NORM by 24 hours, and 53% were HYPER at 120 hours. Median maximum clot firmness began in the NORM range, up-trended gradually, and entered the HYPER range at 120 hours. Patients with traumatic brain injury (TBI) followed a similar course and were not more HYPO at any time point than those without TBI. Failure to initiate prophylaxis by 72 hours was predicted by TBI and associated with VTE development (27% vs 16%, p < 0.05). CONCLUSIONS: Regardless of injury pattern, trauma-induced coagulopathy largely resolves within 24 hours, after which hypercoagulability becomes increasingly more prevalent. Deferring initiation of chemoprophylaxis, which is often biased toward patients with intracranial injuries, is associated with VTE development. LEVEL OF EVIDENCE: Prognostic study, level III; Therapeutic, level IV.

Citrated kaolin thrombelastography (TEG) thresholds for goal-directed therapy in injured patients receiving massive transfusion.

INTRODUCTION: Goal-directed hemostatic resuscitation based on thrombelastography (TEG) has a survival benefit compared with conventional coagulation assays such as international normalized ratio, activated partial thromboplastin time, fibrinogen level, and platelet count. While TEG-based transfusion thresholds for patients at risk for massive transfusion (MT) have been defined using rapid TEG, cutoffs have not been defined for TEG using other activators such as kaolin. The purpose of this study was to develop thresholds for blood product transfusion using citrated kaolin TEG (CK-TEG) in patients at risk for MT. METHODS: CK-TEG was assessed in trauma activation patients at two Level 1 trauma centers admitted between 2010 and 2017. Receiver operating characteristic (ROC) curve analyses were performed to test the predictive performance of CK-TEG measurements in patients requiring MT, defined as >10 units of red blood cells or death within the first 6 hours. The Youden Index defined optimal thresholds for CK-TEG-based resuscitation. RESULTS: Of the 825 trauma activations, 671 (81.3%) were men, 419 (50.8%) suffered a blunt injury, and 62 (7.5%) received a MT. Patients who had a MT were more severely injured, had signs of more pronounced shock, and more abnormal coagulation assays. CK-TEG R-time was longer (4.9 vs. 4.4 min, p = 0.0084), angle was lower (66.2 vs. 70.3 degrees, p < 0.0001), maximum amplitude was lower in MT (57 vs. 65.5 mm, p < 0.0001), and LY30 was greater (1.8% vs. 1.2%, p = 0.0012) in patients with MT compared with non-MT. To predict MT, R-time yielded an area under the ROC curve (AUROC) = 0.6002 and a cut point of >4.45 min. Angle had an AUROC = 0.6931 and a cut point of <67 degrees. CMA had an AUROC = 0.7425, and a cut point of <60 mm. LY30 had an AUROC = 0.623 with a cut point of >4.55%. CONCLUSION: We have identified CK-TEG thresholds that can guide MT in trauma. We propose plasma transfusion for R-time >4.45 min, fibrinogen products for an angle <67 degrees, platelet transfusion for MA <60 mm, and antifibrinolytics for LY30 >4.55%. LEVEL OF EVIDENCE: Therapeutic study, level V.

Time to stroke: A Western Trauma Association multicenter study of blunt cerebrovascular injuries.

BACKGROUND: Screening for blunt cerebrovascular injuries (BCVIs) in asymptomatic high-risk patients has become routine. To date, the length of this asymptomatic period has not been defined. Determining the time to stroke could impact therapy including earlier initiation of antithrombotics in multiply injured patients. The purpose of this study was to determine the time to stroke in patients with a BCVI-related stroke. We hypothesized that the majority of patients suffer stroke between 24 hours and 72 hours after injury. METHODS: Patients with a BCVI-related stroke from January 2007 to January 2017 from 37 trauma centers were reviewed. RESULTS: During the 10-year study, 492 patients had a BCVI-related stroke; the majority were men (61%), with a median age of 39 years and ISS of 29. Stroke was present at admission in 182 patients (37%) and occurred during an Interventional Radiology procedure in six patients. In the remaining 304 patients, stroke was identified a median of 48 hours after admission: 53 hours in the 144 patients identified by neurologic symptoms and 42 hours in the 160 patients without a neurologic examination and an incidental stroke identified on imaging. Of those patients with neurologic symptoms, 88 (61%) had a stroke within 72 hours, whereas 56 had a stroke after 72 hours; there was a sequential decline in stroke occurrence over the first week. Of the 304 patients who had a stroke after admission, 64 patients (22%) were being treated with antithrombotics when the stroke occurred. CONCLUSIONS: The majority of patients suffer BCVI-related stroke in the first 72 hours after injury. Time to stroke can help inform clinicians about initiation of treatment in the multiply injured patient. LEVEL OF EVIDENCE: Prognostic/Epidemiologic, level III.

Utilizing Group-based Trajectory Modeling to Understand Patterns of Hemorrhage and Resuscitation.

OBJECTIVE: The purpose of this study was to describe variations in blood-based resuscitation in an injured cohort. We hypothesize that distinct transfusion trajectories are present. BACKGROUND: Retrospective studies of hemorrhage utilize the concept of massive transfusion, where a set volume of blood is required. Patterns of hemorrhage vary and massive transfusion does little to describe these differences. METHODS: Patients were prospectively included from June 2012 to 2013. Time of transfusion for each packed red blood cell (PRBC) transfused was recorded, in minutes, for all patients. Additional measures included demographic and injury data, admission laboratory values, and vital signs and outcomes including mortality, tempo of transfusion, and operative requirements. Group-based trajectory modeling was utilized to describe transfusion trajectories throughout the cohort. RESULTS: Three hundred sixteen patients met the inclusion criteria. Among them, 72% were men and median age was 35 years (interquartile range [IQR] 24-50), median injury severity score was 13 (IQR 9-22), median 24-hour transfusion volume was 4 units of PRBCs (IQR 2-8), and mortality was 14%. Six transfusion trajectories were identified. Among the patients, 35% received negligible transfusions (group 1). Groups 2 and 3 received greater than 15 units PRBCs-the former as early resuscitation, whereas the latter intermittently throughout the day. Groups 4 and 5 had similar small resuscitations with distinct demographic differences. Group 6 suffered blunt injuries and required rapid resuscitation. CONCLUSIONS: Traditional definitions of massive transfusion are broad and imprecise. In cohorts of severely injured patients, there are distinct, identifiable transfusion trajectories. Identification of subgroups is important in understanding clinical course and to anticipate resuscitative and therapeutic needs.

The new metric to define large-volume hemorrhage: results of a prospective study of the critical administration threshold.

BACKGROUND: Definitions of massive transfusion (MT), 10 or more units of packed red blood cells (PRBCs) in 24 hours, focus on static volumes over fixed times. This arbitrary volume definition promotes survivor bias and fails to identify the "massively" transfused patient. In previous work, the critical administration threshold (CAT) was created to incorporate both rate and volume of transfusion. CAT proved a superior predictor of mortality compared with traditional MT. The purpose of this study was to prospectively validate CAT in a larger trauma population. METHODS: Patients receiving at least 1 U of PRBCs within the first day of admission were identified prospectively. Administration time of each unit of PRBCs was recorded in minutes. CAT status, defined as receipt of at least 3 U of blood in a 60-minute period, was identified for the first 24 hours. CAT+ patients were quantified by the number of times CAT+ was reached, that is, once (CAT1), twice (CAT2), three times (CAT3), or 4 or more times (CAT4). A multivariable Cox proportional hazard model with a time-varying covariate was used to quantify a patient's risk of death with increasing CAT status. RESULTS: A total of 316 met inclusion criteria, 161 of whom were CAT+. Seventy-six percent were male, mean age was 38 years, and median Injury Severity Score (ISS) was 15. CAT+ was associated with a twofold increased risk of death (hazard ratio, 1.809; 95% confidence interval, 1.020-3.209). Ninety-one patients were CAT+ and received less than 10 U of blood, thereby MT- (CAT+/MT-). CAT+/MT- had significant injury patterns, with a median ISS of 14, 43% penetrating injury, and 10% mortality. CONCLUSION: CAT allows early identification of injured patients at greatest risk of death. Encompassing both rate and volume of transfusion, CAT is a tool more sensitive than common MT definitions. Studies examining large-volume blood transfusions should use CAT to identify patients, to accurately identify cohorts of interest. LEVEL OF EVIDENCE: Diagnostic tests, level II.

Using critical administration thresholds to predict abbreviated laparotomy.

BACKGROUND: Early identification of trauma patients requiring abbreviated laparotomy (AL) is key to prevent prolonged operative times with associated hypothermia and acidosis. The critical administration threshold (CAT) is a novel method to define large-volume transfusion, accounting for rate and volume simultaneously. CAT may also serve as a simple trigger to distinguish patients benefiting from AL. The purpose of this study was to determine if CAT was predictive of the need for AL. METHODS: Trauma patients receiving at least 1 U of blood during Day 1 of admission were eligible. Patients were classified by the number of times they met CAT (≥ 3 U of blood in 1 hour) for 24 hours. Basic demographics, time to CAT+ status and completion of operative therapy, need for AL, and mortality were quantified. A multivariate Cox proportional hazard ratio with a time-varying covariate was used to compare CAT and AL. RESULTS: One hundred sixty-nine patients were included (70% new Injury Severity Score [ISS] > 10, 83% male). Significantly more AL patients (79%) were CAT+ compared with the patients with closed fascia (36%, p < 0.0001), and 94% of the patients reached CAT+ status before the end of their operative therapy (mean time to CAT+ status, 163 minutes; mean end operative time, 356 minutes). A Cox proportional hazard ratio demonstrated a nearly threefold increased risk for AL when a patient was CAT+ (odds ratio, 2.723; 95% confidence interval, 1.256-5.906). Failure to opt for an open abdomen with increasing CAT+ status was associated with a trend toward higher mortality. CONCLUSION: Severely injured patients requiring large-volume transfusions typically reach the first CAT threshold quickly, on average, in less than 3 hours. Further, CAT+ patients have a higher odds of AL and a trend toward greater mortality if time is taken to close the fascia. As such, CAT+ status serves as a logical early trigger to identify patients benefiting from AL. LEVEL OF EVIDENCE: Therapeutic outcome study, level III.

Diagnostic laparoscopy after anterior abdominal stab wounds: worth another look?

BACKGROUND: The National Institute of Medicine's report Hospital-Based Emergency Care: At the Breaking Point highlighted the critical issue of emergency department overcrowding. At our institution, patients with anterior abdominal stab wounds (AASW) have been managed with a protocol that uses diagnostic laparoscopy (DL) after positive result on local wound exploration. Patients with negative DL result are eligible for discharge directly from the recovery room. The purpose of this study was to evaluate the use of DL for AASWs in light of the recommendations that suggested serial abdominal examination (SAE) is preferred to determine the need for laparotomy. METHODS: Patients admitted to a Level 1 trauma center from January 2010 through August 2012 with AASWs were included (contemporary period to Western Trauma Association study). Information regarding baseline characteristics, diagnostic workup, injury management, and outcomes were retrospectively reviewed and compared with the SAE AASW algorithm. RESULTS: A total of 158 patients with AASWs were evaluated using our institutional algorithm. Thirty-eight patients (24%) went directly to the operating room for peritonitis, shock, or evisceration; 120 underwent local wound exploration; 99 had positive result (82%). Twenty-eight patients had immediate laparotomy owing to worsening clinical examination findings. Seventy had DL, and 19 of these patients were discharged home from the recovery room, with a mean length of stay of 6.4 hours. When comparing patients managed using the DL algorithm to those managed using the SAE-based algorithm, the nontherapeutic laparotomy rate was lower, although not statistically significant. However, the DL algorithm produced a significantly higher percentage of patients discharged directly home following local wound exploration. CONCLUSION: With some trauma centers suffering from emergency department overcrowding and constrained resources, DL may offer an alternative to SAE to efficiently use available resources. Both SAE and DL are safe and offer similar therapeutic laparotomy rates. The method used to evaluate patients after AASW should be tailored to institutional needs and resources. LEVEL OF EVIDENCE: Therapeutic/care management, level IV.

Dissociable effects of CB1 receptor blockade on anxiety-like and consummatory behaviors in the novelty-induced hypophagia test in mice.

RATIONALE: Central CB1 cannabinoid receptors regulate anxiety-like and appetitive consummatory behaviors. Pharmacological antagonism/inverse-agonism of CB1 receptors increases anxiety and decreases appetitive behaviors; however, neither well-defined dose nor context dependence of these effects has been simultaneously assessed in one behavioral assay. OBJECTIVES: We sought to determine the context and dose dependence of the effects of CB1 receptor blockade on anxiety-like and consummatory behaviors in a model that allowed for simultaneous detection of anxiety-like and consummatory-related behaviors. METHODS: We determined the effects of the CB1 receptor antagonist/inverse-agonist, rimonabant, in the novelty-induced hypophagia (NIH) assay in juvenile male ICR mice. RESULTS: Rimonabant dose-dependently decreased consumption of a palatable reward solution completely independent of contextual novelty. Grooming and scratching behavior was also increased by rimonabant in a context-independent manner. In contrast, rimonabant increased feeding latency, a measure of anxiety-like behaviors, only in a novel, mildly anxiogenic context. The effects of rimonabant were specific since no effects of rimonabant on despair-like behavior were observed in the tail suspension assay. Blockade of CB2 receptors had no effect on novelty-induced increases in feeding latency or palatable food consumption. CONCLUSIONS: Our findings indicate that CB1 receptor blockade decreases the hedonic value of palatable food irrespective of environmental novelty, whereas the anxiogenic-like effects are highly context-dependent. Blockade of CB2 receptors does not regulate either anxiety-like or consummatory behaviors in the NIH assay. These findings suggest that rimonabant modulates distinct and dissociable neural processes regulating anxiety and consummatory behavior to sculpt complex and context-dependent behavioral repertories.

Reversible gating of endocannabinoid plasticity in the amygdala by chronic stress: a potential role for monoacylglycerol lipase inhibition in the prevention of stress-induced behavioral adaptation.

Chronic stress is the primary environmental risk factor for the development and exacerbation of affective disorders, thus understanding the neuroadaptations that occur in response to stress is a critical step in the development of novel therapeutics for depressive and anxiety disorders. Brain endocannabinoid (eCB) signaling is known to modulate emotional behavior and stress responses, and levels of the eCB 2-arachidonoylglycerol (2-AG) are elevated in response to chronic homotypic stress exposure. However, the role of 2-AG in the synaptic and behavioral adaptations to chronic stress is poorly understood. Here, we show that stress-induced development of anxiety-like behavior is paralleled by a transient appearance of low-frequency stimulation-induced, 2-AG-mediated long-term depression at GABAergic synapses in the basolateral amygdala, a key region involved in motivation, affective regulation, and emotional learning. This enhancement of 2-AG signaling is mediated, in part, via downregulation of the primary 2-AG-degrading enzyme monoacylglycerol lipase (MAGL). Acute in vivo inhibition of MAGL had little effect on anxiety-related behaviors. However, chronic stress-induced anxiety-like behavior and emergence of long-term depression of GABAergic transmission was prevented by chronic MAGL inhibition, likely via an occlusive mechanism. These data indicate that chronic stress reversibly gates eCB synaptic plasticity at inhibitory synapses in the amygdala, and in vivo augmentation of 2-AG levels prevents both behavioral and synaptic adaptations to chronic stress.