Pre-Injury Statin Exposure is Associated With Improved Outcomes in Injured Patients That Receive Whole Blood.

Introduction: Whole blood (WB) is associated with improved mortality while lowering blood product utilization. Furthermore, statin medications are associated with favorable outcomes in traumatic brain injury and risk reduction of venous thromboembolism. However, the use of statin medications has not been evaluated in those receiving WB. The objective of this study is to determine the effects of pre-injury statin exposure on patients receiving WB.Methods: Patients that underwent WB first resuscitation and received pre-injury statins were compared to those that did not receive pre-injury statins. Demographics as well as complication rates, blood product transfusion volumes, and mortality were evaluated. Univariate and multivariable analyses were used to determine independent predictors of mortality.Results: In the study period, 785 patients received WB as part of their resuscitation. One hundred and thirty five patients (17.3%) took statin medications prior to injury. Patients that were exposed to a pre-injury statin had a lower mortality rate than those that were not exposed (21.5% vs 32.5%, P = .01). After adjusting for imbalances, age, ISS, Glasgow Coma Scale, admission systolic blood pressures, and pre-injury statin use were independent predictors of mortality following multiple logistic regression. When evaluating outcomes based on statin intensity, the use of high-intensity statins was associated with lower mortality (OR: .37, 95% CI: .13-.93), whereas moderate and low-intensity statins were not.Conclusion: In patients resuscitated with WB, pre-injury statins use was associated with improved outcomes. Specifically, patients that received high-intensity pre-injury statins appeared to be the population that benefited.

Cecal volvulus secondary to mesodiverticular band.

Meckel's diverticula are one of the most common gastrointestinal anomalies, yet mesodiverticular bands are rare. The treatment of these bands commonly requires surgery. A healthy patient in his 20s presented to the emergency department with a 1 day history of acute onset abdominal pain. Computed tomography imaging was consistent with volvulus of the large intestine. In the operating room, the patient was noted to have a band between the ileal mesentery and tip of a Meckel's diverticulum, consistent with a mesodivertiular band, through which cecum had volvulized. The patient underwent resection. The patient recovered without major complications. Mesodiverticular bands are rare, but may present as hemoperitoneum, small bowel obstruction, or volvulus. Pre-operative diagnosis of a mesodiverticular band is often difficult and they are most commonly diagnosed intraoperatively. Treatment should include surgery and may include simple lysis of the band, bowel resection, or more extensive resection if other pathology is present.

Eliminating the benzos: A benzodiazepine-sparing approach to preventing and treating alcohol withdrawal syndrome.

BACKGROUND: Alcohol withdrawal syndrome (AWS) represents significant cost to the hospitalized trauma population from a clinical and financial perspective. Historically, AWS has been managed with benzodiazepines. Despite their efficacy, benzodiazepines carry a heavy adverse effect profile. Recently, benzodiazepine-sparing protocols for the prophylaxis and treatment of AWS have been used in medical patient populations. Most existing benzodiazepine-sparing protocols use phenobarbital, while ours primarily uses gabapentin and clonidine, and no such protocol has been developed and examined for safety and efficacy specifically within a trauma population. METHODS: In December of 2019, we implemented our benzodiazepine-sparing protocol for trauma patients identified at risk for alcohol withdrawal on admission. Trauma patients at risk for AWS admitted to an academic Level 1 trauma center before (conventional) and after (benzodiazepine-sparing [BS]) protocol implementation were compared. Outcomes examined include morphine milligram equivalent dosing rates and lorazepam equivalent dosing rates as well as the Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-Ar) scores, hospital length of stay, intensive care unit length of stay, and ventilator days. RESULTS: A total of 387 conventional and 134 benzodiazepine sparing patients were compared. Injury Severity Score (13 vs. 16, p = 0.10) and admission alcohol levels (99 vs. 149, p = 0.06) were similar. Patients in the BS pathway had a lower maximum daily CIWA-Ar (2.7 vs. 1.5, p = 0.04). While mean morphine milligram equivalent per day was not different between groups (31.5 vs. 33.6, p = 0.49), mean lorazepam equivalents per day was significantly lower in the BS group (1.1 vs. 0.2, p < 0.01). Length of stay and vent days were not different between the groups. CONCLUSION: Implementation of a benzodiazepine-sparing pathway that uses primarily clonidine and gabapentin to prevent and treat alcohol withdrawal syndrome in trauma patients is safe, reduces the daily maximum CIWA-Ar, and significantly decreases the need for benzodiazepines. Future studies will focus on outcomes affected by avoiding AWS and benzodiazepines in the trauma population. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Spontaneous rupture of nontraumatic hepatic artery pseudoaneurysm.

Spontaneous rupture of hepatic artery pseudoaneurysms (HAP) is a rare cause of intra-abdominal hemorrhage. Herein, we present a case of a spontaneous rupture of a nontraumatic HAP. A 61-year-old female, not on any anticoagulant or antiplatelet medications, presented with abdominal pain and hemorrhagic shock. Cross-sectional imaging revealed a left HAP with evidence of active bleeding. Emergent diagnostic angiography was performed, and angioembolization of an actively bleeding pseudoaneurysm was performed. Given the risk of rupture and high mortality rate associated with rupture, aggressive treatment of HAP should be pursued.

Win or lose, nighttime transcystic laparoscopic common bile duct exploration is a win.

Objectives: Although controversial, recent data suggest nighttime versus daytime laparoscopic cholecystectomy (LC) have comparable outcomes. Laparoscopic common bile duct exploration (LCBDE) for choledocholithiasis decreases length of stay (LOS) as compared with LC with endoscopic retrograde cholangiopancreatography (ERCP) but increases case complexity/time. The influence of time of day on LCBDE outcomes has not been evaluated. Our aim was to examine outcomes and LOS for nighttime (PM) compared with daytime LC+LCBDE (DAY). Methods: Consecutive patients who underwent LCBDE were reviewed. Demographics, operative duration, success of LCBDE, time to postoperative ERCP (if required), LOS, and complications were compared. PM procedures were defined as beginning 19:00-07:00 hours. Results: Between 2018 and 2022, sixty patients underwent LCBDE (PM 42%). Groups had equivalent age/sex and preoperative liver function tests (LFTs). LCBDE success was 69% PM versus 71% DAY (p=0.78). Operative duration did not differ (2.8 IQR: 2.2-3.3 hours vs. 2.8 IQR: 2.3-3.2 hours, p=0.9). LOS was compared, and PM LOS was shorter (p=0.03). Time to ERCP after a failed LCBDE at night was compared with daytime (13.8 IQR: 10.6-29.5 hours vs. 19.9 IQR: 18.7-54.4 hours, p=0.07). LOS for failed PM LCBDE requiring ERCP was similar to successful DAY LCBDE (p=0.29). One complication (transient hyperbilirubinemia) was reported in the DAY group, none in PM. Conclusion: PM LCBDE cases are equivalent in safety and success rate to DAY cases but have reduced LOS. Widespread adoption of acute care surgery-driven management of choledocholithiasis via LCBDE during cholecystectomy may decrease LOS, especially in PM cases. Level of evidence: Level IV.

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.

Spontaneous rupture of omental pseudoaneurysm in a patient on systemic anticoagulation.

A ruptured omental pseudoaneurysm is a rare cause of intra-abdominal hemorrhage. Herein, we present a case of bleeding ruptured omental pseudoaneurysm in a patient on systemic anticoagulation and successful treatment with surgery. A 72-year-old female on warfarin for atrial fibrillation presented with worsening abdominal pain. Cross-sectional imaging was obtained and was consistent with a large omental pseudoaneurysm (measuring 2.2 cm) as well as blood products within the abdomen. The patient was taken to the operating room where a pseudoaneurysm with evidence of active bleeding was identified. A diagnostic laparoscopy converted to exploratory laparotomy with partial omentectomy was performed. An omental pseudoaneurysm is a rare but potentially life-threatening cause of intra-abdominal hemorrhage. Given the risk of re-bleed, these lesions should be addressed promptly. In a facility that has the expertise, a catheter based approach with embolization may be considered, however, the mainstay of therapy should remain surgical resection.

Succinate Activation of SUCNR1 Predisposes Severely Injured Patients to Neutrophil-mediated ARDS.

OBJECTIVES: Identify the metabolites that are increased in the plasma of severely injured patients that developed ARDS versus severely injured patients that did not, and assay if these increased metabolites prime pulmonary sequestration of neutrophils (PMNs) and induce pulmonary sequestration in an animal model of ARDS. We hypothesize that metabolic derangement due to advanced shock in critically injured patients leads to the PMNs, which serves as the first event in the ARDS. Summary of Background Data: Intracellular metabolites accumulate in the plasma of severely injured patients. METHODS: Untargeted metabolomics profiling of 67 critically injured patients was completed to establish a metabolic signature associated with ARDS development. Metabolites that significantly increased were assayed for PMN priming activity in vitro. The metabolites that primed PMNs were tested in a 2-event animal model of ARDS to identify a molecular link between circulating metabolites and clinical risk for ARDS. RESULTS: After controlling for confounders, 4 metabolites significantly increased: creatine, dehydroascorbate, fumarate, and succinate in trauma patients who developed ARDS ( P < 0.05). Succinate alone primed the PMN oxidase in vitro at physiologically relevant levels. Intravenous succinate-induced PMN sequestration in the lung, a first event, and followed by intravenous lipopolysaccharide, a second event, resulted in ARDS in vivo requiring PMNs. SUCNR1 inhibition abrogated PMN priming, PMN sequestration, and ARDS. Conclusion: Significant increases in plasma succinate post-injury may serve as the first event in ARDS. Targeted inhibition of the SUCNR1 may decrease ARDS development from other disease states to prevent ARDS globally.

Do not drink and lyse: alcohol intoxication increases fibrinolysis shutdown in injured patients.

INTRODUCTION: High alcohol consumption has been associated with decreased fibrinolysis and enhanced thrombosis risk in cardiovascular disease. In trauma, alcohol has been associated with poor clot formation; however, its effect on fibrinolysis has not been fully investigated. We assessed the association of blood alcohol levels and fibrinolysis in trauma activation patients. METHODS: We queried our prospective registry of trauma activations from 2014 to 2016. Associations between viscoelastic measurements [rapid thrombelastography (rTEG)] and blood alcohol level (BAL) were determined and adjusted for confounders by a multinomial logistic regression. Lysis phenotypes were defined by the % lysis in 30 min (LY30) as follows: hyperfibrinolysis ≥ 3%, physiologic 0.9-2.9%, and fibrinolysis shutdown < 0.9%. RESULTS: Overall, 191 (43.8%) had BAL measured. There were 65 (34%) patients that had no detectable BAL, 32 (16.8%) had BAL of 10-150 mg/dL, and 94 (49.2%) patients had BAL > 150 mg/dL. BAL had a moderate, but significant inverse correlation with LY30 (Rho = - 0.315, p < 0.001), while there were no significant correlations between BAL and other TEG values. The distribution of fibrinolysis phenotypes varied significantly by BAL levels (p < 0.009, with high BAL having more shutdown and less hyperfibrinolysis than the other two BAL level groups. Multinomial logistic regression showed that after adjustment for confounders, BAL levels > 150 mg/dL were independently associated with a threefold increase in the odds of shutdown compared to undetectable BAL (OR 3.37, 95% CI 1.04-8.05, p = 0.006). High BAL was also significantly associated with higher odds of shutdown compared to low BAL (OR 2.63, 95% CI 1.15-6.06). Compared to physiologic fibrinolysis, fibrinolysis shutdown was associated with increased mortality (OR 2.87, 95% CI 1.41-5.83) and VFD < 28 (OR 2.54, 95% CI 1.47-4.39). CONCLUSION: In the injured patient, high blood alcohol levels are associated with increased incidence of fibrinolysis shutdown. This finding has implications for postinjury hemostatic resuscitation as these patients may be harmed by anti-fibrinolytics. Further research is needed to assess whether the association with fibrinolysis is modified by the chronicity and type of alcohol consumed and whether anti-fibrinolytic therapy in intoxicated patients produces adverse effects.

28-day thawed plasma maintains α2 -antiplasmin levels and inhibits tPA-induced fibrinolysis.

INTRODUCTION: Evidence supports the use of plasma-first resuscitation in the treatment of trauma-induced coagulopathy (TIC). While thawed plasma (TP) has logistical benefits, the ability of plasma proteins to attenuate fibrinolysis and correct TIC remain unknown. We hypothesize that TP retains the ability to inhibit tissue plasminogen activator(tPA)-induced fibrinolysis at 28-day storage. METHODS: Healthy volunteers underwent blood draws followed by 50% dilution of whole blood (WB) with TP at 28-, 21-, 14-, 7-, 5-, and, 0-day storage, normal saline (NS), and WB control. Samples underwent citrated tPA-challenge (75 ng/ml) thromboelastography (TEG). Plasminogen activator inhibitor-1 (PAI-1) and α2 -antiplasmin (α2 -AP) concentrations in thawed or stored plasma were determined. RESULTS: In the presence of tPA, 28-day TP inhibited tPA-induced coagulopathy as effectively as WB. 28-day TP had a similar R-time, MA, and fibrinolysis (P > 0·05 for all) compared to WB, while angle was enhanced (P = 0·02) compared to WB. Significant correlations were present between storage time and clot strength (P = 0·04) and storage time and fibrinolysis (P = 0·0029). Active PAI-1 levels in thawed plasma were 1·10 ± 0·54 ng/mL while total PAI-1 levels were 4·79 ± 1·41 ng/mL. There was no difference of α2 -AP levels in FFP (40·45 ± 3·5 µg/mL) compared to plasma thawed for 14 (36·78 ± 5·39 µg/mL, P = 0·65) or 28 days (45·16 ± 5·61 µg/mL, P = 0·51). DISCUSSION: Thawed plasma retained the ability to inhibit tPA-induced fibrinolysis over 28-day storage at 1-4°C. α2 -AP levels were maintained in plasma thawed for 28 days and FFP. These in vitro results suggest consideration should be made to increasing the storage life of TP.

Effects of Blood Components and Whole Blood in a Model of Severe Trauma-Induced Coagulopathy.

BACKGROUND: Plasma resuscitation ameliorates hyperfibrinolysis (HF) and trauma-induced coagulopathy (TIC). However, the use of other blood components to reduce HF has not been evaluated. Therefore, our aim was to determine the effect of individual blood components and whole blood (WB) on an in vitro model of severe HF/TIC. METHODS: A "TIC" solution was made with 1:1 dilution of WB with saline and exacerbated with tissue plasminogen activator (tPA). Components were added in proportions equivalent to the thromboelastography (TEG) based goal-directed resuscitation used at our institution. Whole blood was added at proportions equal to what has been transfused in injured patients. Samples (n = 9) underwent citrated native and tPA-challenge (75 ng/mL) TEG with analysis of R-time, angle, MA, and LY30. Statistical analyses were completed employing the nonparametric Kruskal-Wallis and Dunn's multiple comparisons tests. RESULTS: TIC solution, when compared to control, had a decrease in clot strength (MA 41 mm versus 51.5 mm, P < 0.01). The addition of tPA resulted in a severe coagulopathy (MA 24.5 mm versus 41 mm and LY30 52.8% versus 2.4%, P < 0.03 for all). The addition of 4U of WB improved clot strength compared to TIC + tPA (P = 0.03). No individual blood component resulted in improved fibrinolysis (P > 0.7). Cryoprecipitate improved R-time (7.5 versus 11.9 min, P < 0.01), angle (56.8 versus 30.2°) and MA (49 mm versus 36.25 mm), while platelets improved MA (44 mm versus 36.25 mm) compared to TIC + tPA (P < 0.03 for all). CONCLUSIONS: No single blood component or volume of whole blood led to attenuation of tPA-mediated fibrinolysis in an in vitro model of TIC. Cryoprecipitate was the most effective at improving coagulation function.

Examining the Effect of Hypertonic Saline Administered for Reduction of Intracranial Hypertension on Coagulation.

BACKGROUND: Hypertonic saline (23.4%, HTS) bolus administration is common practice for refractory intracranial hypertension, but its effects on coagulation are unknown. We hypothesize that 23.4% HTS in whole blood results in progressive impairment of coagulation in vitro and in vivo in a murine model of traumatic brain injury (TBI). STUDY DESIGN: For the in vitro study, whole blood was collected from 10 healthy volunteers, and citrated native thrombelastography was performed with normal saline (0.9%, NS) and 23.4% HTS in serial dilutions (2.5%, 5%, and 10%). For the in vivo experiment, we assessed the effects of 23.4% HTS bolus vs NS on serial thrombelastography and tail-bleeding times in a TBI murine model (n = 10 rats with TBI and 10 controls). RESULTS: For the in vitro work, clinically relevant concentrations of HTS (2.5% dilution) shortened time to clot formation and increased clot strength (maximum amplitude) compared with control and NS. With higher HTS dosing (5% and 10% blood dilution), there was progressive prolongation of time to clot formation, decreased angle, and decreased maximum amplitude. In the in vivo study, there was no significant difference in thrombelastography measurements or tail-bleeding times after bolus administration of 23.4% HTS compared with NS at 2.5% blood volume. CONCLUSIONS: At clinically relevant dilutions of HTS, there is a paradoxical shortening of time to clot formation and increase in clot strength in vitro and no significant effects in a murine TBI model. However, with excess dilution, caution should be exercised when using serial HTS boluses in TBI patients at risk for trauma-induced coagulopathy.

Variability in international normalized ratio and activated partial thromboplastin time after injury are not explained by coagulation factor deficits.

BACKGROUND: Conventional coagulation assays (CCAs), prothrombin time (PT)/international normalized ratio (INR) and activated partial thromboplastin time (aPTT), detect clotting factor (CF) deficiencies in hematologic disorders. However, there is controversy about how these CCAs should be used to diagnose, treat, and monitor trauma-induced coagulopathy. Study objectives were to determine whether CCA abnormalities are reflective of deficiencies of coagulation factor activity in the setting of severe injury. METHODS: Patients without previous CF deficiency within a prospective database at an ACS-verified Level I trauma center had CF activity levels, PT/INR, aPTT, and fibrinogen levels measured upon emergency department arrival from 2014 to 2017. Linear regression assessed how CF activity explained the aPTT and PT/INR variation. Prolonged CCA values were set as INR greater than 1.3 and aPTT greater than 34 seconds. CF deficiency was defined as less than 30% activity, except for fibrinogen, defined as less than 150 mg/dL. RESULTS: Sixty patients with a mean age of 35.8 (SD, 13.6) years and median New Injury Severity Score of 32 (interquartile range, 12-43) were included; 53.3% sustained blunt injuries, 23.3% required massive transfusion, and mortality was 11.67%. Overall, 44.6% of the PT/INR variance and 49.5% of the aPTT variance remained unexplained by CF activity. Deficiencies of CFs were: common pathway, 25%; extrinsic pathway, 1.7%; and intrinsic pathway, 6.7%. The positive predictive value for CF deficiencies were: (1) PT/INR greater than 1.3:4.4% for extrinsic pathway, 56.5% for the common pathway; (2) aPTT greater than 34 seconds:16.7% for the intrinsic pathway, 73.7% for the common pathway. CONCLUSION: Almost half of the variances of PT/INR and aPTT were unexplained by CF activity. Prolonged PT/INR and aPTT were poor predictors of deficiencies in the intrinsic or extrinsic pathways; however, they were indicators of common pathway deficiencies. LEVEL OF EVIDENCE: Prognostic, 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.