Warfarin, not direct oral anticoagulants nor antiplatelet therapy, is associated with increased bleeding risk in emergency general surgery patients: implications in this new era of novel anticoagulants: An EAST Multicenter study.

INTRODUCTION: To assess perioperative bleeding complications & in-hospital mortality in patients requiring emergency general surgery (EGS) presenting with a history of antiplatelet (AP) vs. direct oral anticoagulant (DOAC) vs warfarin use. METHODS: Prospective observational study across 21 centers between 2019-2022. Inclusion criteria were age ≥ 18 years, & DOAC, warfarin or AP use within 24 hours of an EGSP. Outcomes included perioperative bleeding and in-hospital mortality. The study was conducted using ANOVA, Chi-square, and multivariable regression models. RESULTS: Of the 413 patients, 221 (53.5%) reported AP use, 152 (36.8%) DOAC use, & 40 (9.7%) warfarin use. Most common indications for surgery were obstruction (23% (AP), 45% (DOAC), 28% (warfarin)), intestinal ischemia (13%, 17%, 23%), & diverticulitis/peptic ulcers (7%, 7%, 15%). Compared to DOAC use, warfarin use was associated with significantly higher perioperative bleeding complication (OR 4.4 [2.0, 9.9]). There was no significant difference in perioperative bleeding complication between DOAC & AP use (OR 0.7 [0.4, 1.1]). Compared to DOAC use, there was no significant difference in mortality between warfarin use (0.7 [0.2, 2.5]) or AP use (OR 0.5 [0.2, 1.2]). After adjusting for confounders, warfarin use (OR 6.3 [2.8, 13.9]), medical history and operative indication were associated with an increase in perioperative bleeding complications. However, warfarin was not independently associated with risk of mortality (OR 1.3 [0.39, 4.7]), whereas intraoperative vasopressor use (OR 4.7 [1.7, 12.8)), medical history & postoperative bleeding (OR 5.5 [2.4, 12.8]) were. CONCLUSIONS: Despite ongoing concerns about the increase in DOAC use & lack of readily available reversal agents, this study suggests that warfarin, rather than DOACs, is associated with higher perioperative bleeding complications. However, that risk does not result in an increase in mortality, suggesting that perioperative decisions should be dictated by patient disease & comorbidities rather than type of antiplatelet or anticoagulant use.

Failure rates of nonoperative management of low-grade splenic injuries with active extravasation: an Eastern Association for the Surgery of Trauma multicenter study.

Objectives: There is little evidence guiding the management of grade I-II traumatic splenic injuries with contrast blush (CB). We aimed to analyze the failure rate of nonoperative management (NOM) of grade I-II splenic injuries with CB in hemodynamically stable patients. Methods: A multicenter, retrospective cohort study examining all grade I-II splenic injuries with CB was performed at 21 institutions from January 1, 2014, to October 31, 2019. Patients >18 years old with grade I or II splenic injury due to blunt trauma with CB on CT were included. The primary outcome was the failure of NOM requiring angioembolization/operation. We determined the failure rate of NOM for grade I versus grade II splenic injuries. We then performed bivariate comparisons of patients who failed NOM with those who did not. Results: A total of 145 patients were included. Median Injury Severity Score was 17. The combined rate of failure for grade I-II injuries was 20.0%. There was no statistical difference in failure of NOM between grade I and II injuries with CB (18.2% vs 21.1%, p>0.05). Patients who failed NOM had an increased median hospital length of stay (p=0.024) and increased need for blood transfusion (p=0.004) and massive transfusion (p=0.030). Five patients (3.4%) died and 96 (66.2%) were discharged home, with no differences between those who failed and those who did not fail NOM (both p>0.05). Conclusion: NOM of grade I-II splenic injuries with CB fails in 20% of patients. Level of evidence: IV.

Tranexamic acid is not associated with a higher rate of thrombotic-related reintervention after major vascular injury repair.

BACKGROUND: Tranexamic acid (TXA) is associated with lower mortality and transfusion requirements in trauma patients, but its role in thrombotic complications associated with vascular repairs remains unclear. We investigated whether TXA increases the risk of thrombosis-related technical failure (TRTF) in major vascular injuries (MVI). METHODS: The PROspective Observational Vascular Injury Treatment (PROOVIT) registry was queried from 2013 to 2022 for MVI repaired with an open or endovascular intervention. The relationship between TXA administration and TRTF was examined. RESULTS: The TXA group (n = 297) had higher rates of hypotension at admission (33.6% vs. 11.5%, p < 0.001), need for continuous vasopressors (41.4% vs. 18.4%, p < 0.001), and packed red blood cell transfusion (3.2 vs. 2.0 units, p < 0.001) during the first 24 hours compared with the non-TXA group (n = 1941), although demographics, injury pattern, and interventions were similar. Cryoprecipitate (9.1% vs. 2%, p < 0.001), and anticoagulant administration during the intervention (32.7% vs. 43.8%, p < 0.001) were higher in the TXA group; there was no difference in the rate of factor VII use between groups (1% vs. 0.7%, p = 0.485). Thrombosis-related technical failure was not different between the groups (6.3% vs. 3.8 p = 0.141) while the rate of immediate need for reoperation (10.1% vs. 5.7%, p = 0.006) and overall reoperation (11.4% vs. 7%, p = 0.009) was significantly higher in the TXA group on univariate analysis. There was no significant association between TXA and a higher rate of immediate need for reintervention (odds ratio [OR], 1.19; 95% confidence interval [CI], 0.75-1.88; p = 0.465), overall reoperation rate (OR, 1.33; 95% CI, 0.82-2.17; p = 0.249) and thrombotic events in a repaired vessel (OR, 1.07; 95% CI, 0.60-1.92; p = 0.806) after adjusting for type of injury, vasopressor infusions, blood product and anticoagulant administration, and hemodynamics. CONCLUSION: Tranexamic acid is not associated with a higher risk of thrombosis-related technical failure in traumatic injuries requiring major vascular repairs. Further prospective studies to examine dose-dependent or time-dependent associations between TXA and thrombotic events in MVIs are needed. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Anticoagulation in emergency general surgery: Who bleeds more? The EAST multicenter trials ACES study.

BACKGROUND: While direct oral anticoagulant (DOAC) use is increasing in the Emergency General Surgery (EGS) patient population, our understanding of their bleeding risk in the acute setting remains limited. Therefore, the objective of this study was to determine the prevalence of perioperative bleeding complications in patients using DOACs versus warfarin and AP therapy requiring urgent/emergent EGS procedures (EGSPs). METHODS: This was a prospective observational trial, conducted between 2019 and 2022, across 21 centers. Inclusion criteria were 18 years or older, DOAC, warfarin/AP use within 24 hours of requiring an urgent/emergent EGSP. Demographics, preoperative, intraoperative, and postoperative data were collected. ANOVA, χ 2 , and multivariable regression models were used to conduct the analysis. RESULTS: Of the 413 patients enrolled in the study, 261 (63%) reported warfarin/AP use and 152 (37%) reported DOAC use. Appendicitis and cholecystitis were the most frequent indication for operative intervention in the warfarin/AP group (43.4% vs. 25%, p = 0.001). Small bowel obstruction/abdominal wall hernias were the main indication for operative intervention in the DOAC group (44.7% vs. 23.8%, p = 0.001). Intraoperative, postoperative, and perioperative bleeding complications and in-hospital mortality were similar between the two groups. After adjusting for confounders, a history of chemotherapy (odds ratio [OR], 4.3; p = 0.015) and indication for operative intervention including occlusive mesenteric ischemia (OR, 4.27; p = 0.016), nonocclusive mesenteric ischemia (OR, 3.13; p = 0.001), and diverticulitis (OR, 3.72; p = 0.019) were associated with increased perioperative bleeding complications. The need for an intraoperative transfusion (OR, 4.87; p < 0.001), and intraoperative vasopressors (OR, 4.35; p = 0.003) were associated with increased in-hospital mortality. CONCLUSION: Perioperative bleeding complications and mortality are impacted by the indication for EGSPs and patient's severity of illness rather than a history of DOAC or warfarin/AP use. Therefore, perioperative management should be guided by patient physiology and indication for surgery rather than the concern for recent antiplatelet or anticoagulant use. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; Level III.

Validation of the American Association for the Surgery of Trauma Emergency General Surgery Grading System for Colorectal Resection: An EAST Multicenter Study.

BACKGROUND: The American Association for the Surgery of Trauma (AAST) has developed a grading system for emergency general surgery (EGS) conditions. We sought to validate the AAST EGS grades for patients undergoing urgent/emergent colorectal resection. METHODS: Patients enrolled in the "Eastern Association for the Surgery of Trauma Multicenter Colorectal Resection in EGS-to anastomose or not to anastomose" study undergoing urgent/emergent surgery for obstruction, ischemia, or diverticulitis were included. Baseline demographics, comorbidity severity as defined by Charlson comorbidity index (CCI), procedure type, and AAST grade were prospectively collected. Outcomes included length of stay (LOS) in-hospital mortality, and surgical complications (superficial/deep/organ-space surgical site infection, anastomotic leak, stoma complication, fascial dehiscence, and need for further intervention). Multivariable logistic regression models were used to describe outcomes and risk factors for surgical complication or mortality. RESULTS: There were 367 patients, with a mean (± SD) age of 62 ± 15 years. 39% were women. The median interquartile range (IQR) CCI was 4 (2-6). Overall, the pathologies encompassed the following AAST EGS grades: I (17, 5%), II (54, 15%), III (115, 31%), IV (95, 26%), and V (86, 23%). Management included laparoscopic (24, 7%), open (319, 87%), and laparoscopy converted to laparotomy (24, 6%). Higher AAST grade was associated with laparotomy (P = .01). The median LOS was 13 days (8-22). At least 1 surgical complication occurred in 33% of patients and the mortality rate was 14%. Development of at least 1 surgical complication, need for unplanned intervention, mortality, and increased LOS were associated with increasing AAST severity grade. On multivariable analysis, factors predictive of in-hospital mortality included AAST organ grade, CCI, and preoperative vasopressor use (odds ratio (OR) 1.9, 1.6, 3.1, respectively). The American Association for the Surgery of Trauma emergency general surgery grade was also associated with the development of at least 1 surgical complication (OR 2.5), while CCI, preoperative vasopressor use, respiratory failure, and pneumoperitoneum were not. CONCLUSION: The American Association for the Surgery of Trauma emergency general surgery grading systems display construct validity for mortality and surgical complications after urgent/emergent colorectal resection. These results support incorporation of AAST EGS grades for quality benchmarking and surgical outcomes research.

Colorectal resection in emergency general surgery: An EAST multicenter trial.

OBJECTIVE: Evidence comparing stoma creation (STM) versus anastomosis after urgent or emergent colorectal resection is limited. This study examined outcomes after colorectal resection in emergency general surgery patients. METHODS: This was an Eastern Association for the Surgery of Trauma-sponsored prospective observational multicenter study of patients undergoing urgent/emergent colorectal resection. Twenty-one centers enrolled patients for 11 months. Preoperative, intraoperative, and postoperative variables were recorded. χ, Mann-Whitney U test, and multivariable logistic regression models were used to describe outcomes and risk factors for surgical complication/mortality. RESULTS: A total of 439 patients were enrolled (ANST, 184; STM, 255). The median (interquartile range) age was 62 (53-71) years, and the median Charlson Comorbidity Index (CCI) was 4 (1-6). The most common indication for surgery was diverticulitis (28%). Stoma group was older (64 vs. 58 years, p < 0.001), had a higher CCI, and were more likely to be immunosuppressed. Preoperatively, STM patients were more likely to be intubated (57 vs. 15, p < 0.001), on vasopressors (61 vs. 13, p < 0.001), have pneumoperitoneum (131 vs. 41, p < 0.001) or fecal contamination (114 vs. 33, p < 0.001), and had a higher incidence of elevated lactate (149 vs. 67, p < 0.001). Overall mortality was 13%, which was higher in STM patients (18% vs. 8%, p = 0.02). Surgical complications were more common in STM patients (35% vs. 25%, p = 0.02). On multivariable analysis, management with an open abdomen, intraoperative blood transfusion, and larger hospital size were associated with development of a surgical complication, while CCI, preoperative vasopressor use, steroid use, open abdomen, and intraoperative blood transfusion were independently associated with mortality. CONCLUSION: This study highlights a tendency to perform fecal diversion in patients who are acutely ill at presentation. There is a higher morbidity and mortality rate in STM patients. Independent predictors of mortality include CCI, preoperative vasopressor use, steroid use, open abdomen, and intraoperative blood transfusion. Following adjustment by clinical factors, method of colon management was not associated with surgical complications or mortality. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Laboratory measures of coagulation among trauma patients on NOAs: results of the AAST-MIT.

BACKGROUND: Warfarin is associated with poor outcomes after trauma, an effect correlated with elevations in the international normalized ratio (INR). In contrast, the novel oral anticoagulants (NOAs) have no validated laboratory measure to quantify coagulopathy. We sought to determine if use of NOAs was associated with elevated activated partial thromboplastin time (aPTT) or INR levels among trauma patients or increased clotting times on thromboelastography (TEG). METHODS: This was a post-hoc analysis of a prospective observational study across 16 trauma centers. Patients on dabigatran, rivaroxaban, or apixaban were included. Laboratory data were collected at admission and after reversal. Admission labs were compared between medication groups. Traditional measures of coagulopathy were compared with TEG results using Spearman's rank coefficient for correlation. Labs before and after reversal were also analyzed between medication groups. RESULTS: 182 patients were enrolled between June 2013 and July 2015: 50 on dabigatran, 123 on rivaroxaban, and 34 apixaban. INR values were mildly elevated among patients on dabigatran (median 1.3, IQR 1.1-1.4) and rivaroxaban (median 1.3, IQR 1.1-1.6) compared with apixaban (median 1.1, IQR 1.0-1.2). Patients on dabigatran had slightly higher than normal aPTT values (median 35, IQR 29.8-46.3), whereas those on rivaroxaban and apixaban did not. Fifty patients had TEG results. The median values for R, alpha, MA and lysis were normal for all groups. Prothrombin time (PT) and aPTT had a high correlation in all groups (dabigatran p=0.0005, rivaroxaban p<0.0001, and apixaban p<0.0001). aPTT correlated with the R value on TEG in patients on dabigatran (p=0.0094) and rivaroxaban (p=0.0028) but not apixaban (p=0.2532). Reversal occurred in 14%, 25%, and 18% of dabigatran, rivaroxaban, and apixaban patients, respectively. Both traditional measures of coagulopathy and TEG remained within normal limits after reversal. DISCUSSION: Neither traditional measures of coagulation nor TEG were able to detect coagulopathy in patients on NOAs. LEVEL OF EVIDENCE: Level IV.

Differential protein expression in exosomal samples taken from trauma patients.

Traumatic brain injuries (TBI) are among the most misdiagnosed and underreported types of head trauma. The potential long-term impact of undiagnosed or incorrectly identified concussions and other head injuries are potentially devastating, as evidenced by the increasing societal burden exhibited by soldiers returning from combat and athletes in contact sports. Concussions and TBI are notoriously difficult to correctly diagnose and prognosis for these injuries is poorly understood. In order to increase the likelihood of successful diagnosis, treatment, and prediction of outcomes, a definitive differential diagnosis will need to be established. The establishment of a "trauma-specific profile" or a panel of known trauma markers will significantly aid in this goal. Small membrane vesicles called exosomes have been shown to contain proteins and injury-specific biomarkers. In the future it is possible that they could become an important tool, utilized for their diagnostic and therapeutic potential.

Pelvic fracture pattern predicts the need for hemorrhage control intervention-Results of an AAST multi-institutional study.

BACKGROUND: Early identification of patients with pelvic fractures at risk of severe bleeding requiring intervention is critical. We performed a multi-institutional study to test our hypothesis that pelvic fracture patterns predict the need for a pelvic hemorrhage control intervention. METHODS: This prospective, observational, multicenter study enrolled patients with pelvic fracture due to blunt trauma. Inclusion criteria included shock on admission (systolic blood pressure <90 mm Hg or heart rate >120 beats/min and base deficit >5, and the ability to review pelvic imaging). Demographic data, open pelvic fracture, blood transfusion, pelvic hemorrhage control intervention (angioembolization, external fixator, pelvic packing, and/or REBOA [resuscitative balloon occlusion of the aorta]), and mortality were recorded. Pelvic fracture pattern was classified according to Young-Burgess in a blinded fashion. Predictors of pelvic hemorrhage control intervention and mortality were analyzed by univariate and multivariate regression analyses. RESULTS: A total of 163 patients presenting in shock were enrolled from 11 Level I trauma centers. The most common pelvic fracture pattern was lateral compression I, followed by lateral compression I, and vertical shear. Of the 12 patients with an anterior-posterior compression III fracture, 10 (83%) required a pelvic hemorrhage control intervention. Factors associated with the need for pelvic fracture hemorrhage control intervention on univariate analysis included vertical shear pelvic fracture pattern, increasing age, and transfusion of blood products. Anterior-posterior compression III fracture patterns and open pelvic fracture predicted the need for pelvic hemorrhage control intervention on multivariate analysis. Overall in-hospital mortality for patients admitted in shock with pelvic fracture was 30% and did not differ based on pelvic fracture pattern on multivariate analysis. CONCLUSION: Blunt trauma patients admitted in shock with anterior-posterior compression III fracture patterns or patients with open pelvic fracture are at greatest risk of bleeding requiring pelvic hemorrhage control intervention. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III.

Novel oral anticoagulants and trauma: The results of a prospective American Association for the Surgery of Trauma Multi-Institutional Trial.

BACKGROUND: The number of anticoagulated trauma patients is increasing. Trauma patients on warfarin have been found to have poor outcomes, particularly after intracranial hemorrhage (ICH). However, the effect of novel oral anticoagulants (NOAs) on trauma outcomes is unknown. We hypothesized that patients on NOAs would have higher rates of ICH, ICH progression, and death compared with patients on traditional anticoagulant and antiplatelet agents. METHODS: This was a prospective observational trial across 16 trauma centers. Inclusion criteria was any trauma patient admitted on aspirin, clopidogrel, warfarin, dabigatran, rivaroxaban, or apixaban. Demographic data, admission vital signs, mechanism of injury, injury severity scores, laboratory values, and interventions were collected. Outcomes included ICH, progression of ICH, and death. RESULTS: A total of 1,847 patients were enrolled between July 2013 and June 2015. Mean age was 74.9 years (SD ± 13.8), 46% were female, 77% were non-Hispanic white. At least one comorbidity was reported in 94% of patients. Blunt trauma accounted for 99% of patients, and the median Injury Severity Score was 9 (interquartile range, 4-14). 50% of patients were on antiplatelet agents, 33% on warfarin, 10% on NOAs, and 7% on combination therapy or subcutaneous agents.Patients taking NOAs were not at higher risk for ICH on univariate (24% vs. 31%) or multivariate analysis (incidence rate ratio, 0.78; confidence interval 0.61-1.01, p = 0.05). Compared with all other agents, patients on aspirin (90%, 81 mg; 10%, 325 mg) had the highest rate (35%) and risk (incidence rate ratio, 1.27; confidence interval, 1.13-1.43; p < 0.001) of ICH. Progression of ICH occurred in 17% of patients and was not different between medication groups. Study mortality was 7% and was not significantly different between groups on univariate or multivariate analysis. CONCLUSION: Patients on NOAs were not at higher risk for ICH, ICH progression, or death. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III.

Loop ileostomy versus total colectomy as surgical treatment for Clostridium difficile-associated disease: An Eastern Association for the Surgery of Trauma multicenter trial.

OBJECTIVES: The mortality of patients with Clostridium difficile-associated disease (CDAD) requiring surgery continues to be very high. Loop ileostomy (LI) was introduced as an alternative procedure to total colectomy (TC) for CDAD by a single-center study. To date, no reproducible results have been published. The objective of this study was to compare these two procedures in a multicentric approach to help the surgeon decide what procedure is best suited for the patient in need. METHODS: This was a retrospective multicenter study conducted under the sponsorship of the Eastern Association for the Surgery of Trauma. Demographics, medical history, clinical presentation, APACHE score, and outcomes were collected. We used the Research Electronic Data Capture tool to store the data. Mann-Whitney (continuous data) and Fisher exact (categorical data) were used to compare TC with LI. Logistic regression was performed to determine predictors of mortality. A propensity score analysis was done to control for potential confounders and determine adjusted mortality rates by procedure type. RESULTS: We collected data from 10 centers of patients who presented with CDAD requiring surgery between July 1, 2010 and July 30, 2014. Two patients died during the surgical procedure, leaving 98 individuals in the study. The overall mortality was 32%, and 75% had postoperative complications. Median age was 64.5 years; 59% were male. Concerning preoperative patient conditions, 54% were on pressors, 47% had renal failure, and 36% had respiratory failure. When comparing TC and LI, there was no statistical difference regarding these conditions. Univariate preprocedure predictors of mortality were age, lactate, timing of operation, vasopressor use, and acute renal failure. There was no statistical difference between the APACHE score of patients undergoing either procedure (TC, 22 vs LI, 16). Adjusted mortality (controlled for preprocedure confounders) was significantly lower in the LI group (17.2% vs 39.7%; p = 0.002). CONCLUSIONS: This is the first multicenter study comparing TC with LI for the treatment of CDAD. In this study, LI carried less mortality than TC. In patients without contraindications, LI should be considered for the surgical treatment of CDAD. LEVEL OF EVIDENCE: Therapeutic study, level III.

Predictors of failure in the Advanced Trauma Life Support course.

BACKGROUND: Over 1 million healthcare providers have participated in the Advanced Trauma Life Support course. No studies have evaluated factors that predict course performance. This study aims to identify these predictors. METHODS: All participants taking the course at 2 centers over a 4-year period were identified. Demographics, background, and performance data were extracted. Participants who failed were compared with those who did not. Stepwise logistic regression analysis was used to identify independent risk factors for failure. RESULTS: Seven hundred forty-four healthcare providers participated in the course; 89.5% passed and 10.5% failed. Failure rates were lowest (.0%) among Trauma/Surgical Critical Care (SCC) providers and highest among pediatric providers (28.6%). Stepwise logistic regression identified age greater than 55, English as a second language, pretest score less than 75, and non-Trauma/SCC and non-Emergency Medicine background as predictors of failure. CONCLUSIONS: A failure rate of 10.5% was demonstrated among the course participants. Age greater than 55, English as second language, pretest score less than 75, and non-Trauma/SCC and non-Emergency Medicine backgrounds were associated with failure. These subgroups may benefit from performance improvement measures.