Current use and utility of magnetic resonance cholangiopancreatography, endoscopic retrograde cholangiopancreatography, and pancreatic duct stents: A secondary analysis from the Western Trauma Association multicenter trials group on pancreatic injuries.

INTRODUCTION: The single most important predictor of pancreas-specific complications (PSCs) after pancreatic trauma is injury to the main pancreatic duct (MPD). Pancreatography has been recommended to evaluate the integrity of the MPD. In addition, pancreatic duct stents have been proposed to prevent or treat PSC. The primary purpose of this study was to determine the accuracy of magnetic resonance cholangiopancreatography (MRCP) in diagnosing MPD injury. We further sought to determine whether stents were effective in preventing PSC or facilitated the resolution of pancreatic leaks or fistulae. METHODS: A secondary analysis of a multicenter retrospective review of pancreatic injuries in patients 15 years and older from 2010 to 2018, focusing on patients who underwent MRCP or endoscopic retrograde cholangiopancreatography (ERCP), was performed. Final pancreatic injury grade was determined based on all available assessments, ultimately adjudicated by the site principal investigator. Data were analyzed using various statistical tests where appropriate. RESULTS: Thirty-three centers reported on 1,243 patients. A total of 216 underwent pancreatography-137 had MRCP and 115 ERCP, with 36 having both. The sensitivity of MRCP for MPD injury was 37%, the specificity was 94%, the positive predictive value was 77%, and the negative predictive value was 73%. When compared with ERCP, MRCP findings were discordant in 64% of cases. Pancreatic stents were placed in 77 patients; 48 (62%) were to treat PSC, with no clear benefit. Twenty-nine had prophylactic stents placed. There did not appear to be benefit in reduced PSC compared with the entire study group or among patients with high-grade pancreatic injuries. CONCLUSION: The accuracy of MRCP to evaluate the integrity of the MPD does not appear to be superior to computed tomography scan. Consequently, the results of MRCP should be interpreted with caution. The current data do not support prophylactic use of pancreatic stents; they should be studied in a prospective trial. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Aortic balloon occlusion in distal zone 3 reduces blood loss from obstetric hemorrhage in placenta accreta spectrum.

BACKGROUND: Peripartum hemorrhage is a significant cause of maternal death. We developed a standardized, multidisciplinary cesarean hysterectomy protocol for placenta accreta spectrum (PAS) using prophylactic resuscitative endovascular balloon occlusion of the aorta (REBOA). We initially placed the balloon in proximal zone 3, below the renal arteries. An internal review revealed more bleeding than expected, and we subsequently changed our protocol to occlude the origin of the inferior mesenteric artery (distal zone 3), to decrease blood flow through collateral circulation. We hypothesized that distal zone 3 occlusion would reduce blood loss and transfusion volume and may permit a longer duration of occlusion compared with proximal zone 3 occlusion without increasing ischemic complications. METHODS: We conducted a single-center retrospective cohort study of patients with suspected PAS who underwent REBOA-assisted cesarean hysterectomy from December 2018 to March 2022. Medical records of all patients with PAS were reviewed. Data were extracted from hospital admission through 3 months postpartum. RESULTS: Forty-four patients met the inclusion criteria. Nine never had the balloon inflated. Eighteen patients had placement in proximal zone 3, whereas twenty-six patients had placement in distal zone 3. Background and clinical characteristics were similar in both groups. Placental pathology was obtained in every case. After adjusting for relevant risk factors, multivariate analysis revealed that distal occlusion was associated with a 45.9% (95% confidence interval, 23.8-61.6%) decrease in estimated blood loss, 41.5% (13.7-60.4%) decrease in red blood cell transfusion volume, and 44.9% (13.5-64.9%) reduction in total transfusion volume. There were no vascular access or resuscitative endovascular balloon occlusion of the aorta-related complications in either group. CONCLUSION: This study highlights the safety of prophylactic REBOA in planned cesarean hysterectomy for PAS and provides a rationale for distal zone 3 positioning to reduce blood loss. Resuscitative endovascular balloon occlusion of the aorta should be considered at other institutions with placenta accreta programs, especially in patients with extensive collateral flow. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

A Systematic Review of Tranexamic Acid-Associated Venous Thromboembolic Events in Combat Casualties and Considerations for Prolonged Field Care.

INTRODUCTION: Tranexamic acid (TXA) is a standard component of Tactical Combat Casualty Care. Recent retrospective studies have shown that TXA use is associated with a higher rate of venous thromboembolic (VTE) events in combat-injured patients. We aim to determine if selective administration should be considered in the prolonged field care environment. MATERIALS AND METHODS: We performed a systematic review using the 2020 Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Clinical trials and observational studies of combat casualties published between January 1, 1960, and June 20, 2022, were included. We analyzed survival and VTE outcomes in TXA recipients and non-recipients. We discussed the findings of each paper in the context of current and future combat environments. RESULTS: Six articles met criteria for inclusion. Only one study was powered to report mortality data, and it demonstrated a 7-fold increase in survival in severely injured TXA recipients. All studies reported an increased risk of VTE in TXA recipients, which exceeded rates in civilian literature. However, five of the six studies used overlapping data from the same registry and were limited by a high rate of missingness in pertinent variables. No VTE-related deaths were identified. CONCLUSIONS: There may be an increased risk of VTE in combat casualties that receive TXA; however, this risk must be considered in the context of improved survival and an absence of VTE-associated deaths. To optimize combat casualty care during prolonged field care, it will be essential to ensure the timely administration of VTE chemoprophylaxis as soon as the risk of significant hemorrhage permits.

A comparison of management and outcomes following blunt versus penetrating pancreatic trauma: A secondary analysis from the Western Trauma Association Multicenter Trials Group on Pancreatic Injuries.

BACKGROUND: The impact of injury mechanism on outcomes of pancreatic trauma has not been well studied, and current guidelines do not differentiate recommendations for blunt and penetrating injuries. The purpose of this study was to analyze interventions and outcomes as they relate to mechanism. We hypothesized that penetrating pancreatic trauma results in greater morbidity than blunt trauma because of more frequent operative exploration without imaging and thus more aggressive surgical management. METHODS: Secondary analysis of a multicenter retrospective review of pancreatic injuries in patients 15 years and older from 2010 to 2018 was performed. Deaths within 24 hours of admission were excluded from analysis of the primary outcome, pancreas-related complications (PRCs). Data were analyzed by injury mechanism using various statistical tests where appropriate. RESULTS: Thirty-three centers reported on 1,240 patients (44% penetrating). Penetrating trauma patients were twice as likely to undergo resection (45% vs. 23%) and suffer PRCs (39% vs. 20%). However, differences varied widely based on injury grade and management. There were fewer resections and more nonoperative management in blunt grades I to III injury. Pancreas-related complications occurred in 40% of high-grade injuries with no difference between mechanisms and in 40% of patients after resection, regardless of mechanism or injury grade. High-grade pancreatic injury (odds ratio [OR], 2.39; 95% confidence interval [CI], 1.55-3.67), penetrating injury (OR, 1.99; 95% CI, 1.31-3.05), and management in a low-volume center (i.e., five or fewer cases/year) (OR, 1.65; 95% CI, 1.16-2.35) were independent predictors of PRCs. CONCLUSION: Management of grades I to III, but not grades IV/V, pancreatic injuries varies based on mechanism. Penetrating injury is an independent risk factor for PRCs, but main pancreatic duct injury and resection are associated with high rates of PRCs regardless of the injury mechanism. Resection appears to offer better outcomes for grade IV/V injuries, and grade I and II injuries should be managed nonoperatively. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Recognition and management of traumatic fetal injuries.

Trauma during pregnancy is the leading non-obstetric cause of morbidity and mortality, and accounts for five per 1000 fetal deaths. Direct fetal injury due to trauma during pregnancy is rare, and limited information is available about how to optimize fetal outcomes after injury. Early recognition and appropriate management of direct fetal trauma may improve outcomes for the fetus. There are currently no available guidelines to direct management of the injured fetus. We provide a detailed literature review of the management and outcomes of direct fetal injury following blunt and penetrating injury during pregnancy, and describe a suggested initial approach to the injured pregnant patient with a focus on evaluation for fetal injury. We identified 45 reported cases of blunt trauma resulting in direct fetal injury, with 21 surviving past the neonatal period, and 33 of penetrating trauma resulting in direct fetal injury, with 24 surviving past the neonatal period. Prenatal imaging identified fetal injury in 19 cases of blunt trauma and was used to identify bullet location relative to the fetus in 6 cases. These reports were used to develop management algorithms for the injured fetus.

Fetal and neonatal outcomes following maternal aortic balloon occlusion for hemorrhage in pregnancy: A review of the literature.

BACKGROUND: Hemorrhage is a leading cause of maternal death worldwide, with increased risk in women with abnormal placentation. Aortic balloon occlusion (ABO), including resuscitative endovascular balloon occlusion, has been used for obstetrical hemorrhage for 20 years, and is associated with decreased operative blood loss, fewer transfusions, and lower rates of hysterectomy. However, the effect of aortic occlusion on fetal/neonatal outcomes is not well known. METHODS: A literature review on ABO for obstetrical or traumatic hemorrhage was performed. Cases were included if fetal/neonatal outcomes were reported. Data were collected on timing of balloon inflation (predelivery or postdelivery), fetal/neonatal mortality, and Apgar scores. Secondary maternal outcomes included blood loss, need for hysterectomy, ABO-related complications, and mortality. RESULTS: Twenty-one reports of ABO in 825 cases of obstetrical hemorrhage were reviewed (nine case reports/series and twelve comparative studies). 13.5% (111/825) had aortic occlusion prior to delivery of the fetus. Comparative cohorts included 448 patients who underwent iliac artery balloon occlusion (n = 219) or no vascular balloon occlusion (n = 229). The most common neonatal outcome reported was Apgar scores, with no difference in fetal/neonatal outcomes between ABO and non-ABO patients in any study. One neonatal mortality occurred in the sole reported case of ABO use in a pregnant trauma patient at 24 weeks gestation. One maternal mortality occurred because of aortic dissection. Five comparative studies reported significantly decreased blood loss in ABO patients compared to non-ABO patients, and four studies reported significantly lower rates of hysterectomy in ABO patients. ABO-related complications were reported in 1.6% of patients (13/825). CONCLUSION: Obstetrical hemorrhage is a devastating complication, and ABO may potentially decrease blood loss and reduce the hysterectomy rate without compromising fetal and neonatal outcomes. Further research is needed to determine the safety of predelivery aortic occlusion as this occurred in 14% of the cases.

Blunt cerebrovascular injuries: Outcomes from the American Association for the Surgery of Trauma PROspective Observational Vascular Injury Treatment (PROOVIT) multicenter registry.

BACKGROUND: Administering antithrombotics (AT) to the multiply injured patient with blunt cerebrovascular injury (BCVI) requires a thoughtful assessment of the risk of stroke and death associated with nontreatment. Large, multicenter analysis of outcomes stratified by injury grade and vessel injured is needed to inform future recommendations. METHODS: Nine hundred and seventy-one BCVIs were identified from the PROspective Vascular Injury Treatment registry in this retrospective analysis. Using multivariate analysis, we identified predictors of BCVI-related stroke and death. We then stratified these risks by injury grade and vessel injured. We compared the risk of adverse outcomes in the nontreatment group with those treated with antiplatelet agents and/or anticoagulants. RESULTS: Stroke was identified in 7% of cases. Overall mortality was 12%. Both increased with increasing BCVI grade. Treatment with ATs was associated with lower mortality and was not significantly affected by the choice of agent. Withholding ATs was associated with an increased risk of stroke and/or death across all subgroups (Grade I/II: odds ratio [OR], 4.66; 95% confidence interval [CI], 2.48-8.75; Grade III: OR, 7.0; 95% CI, 2.01-24.5; Grade IV: OR, 4.43; 95% CI, 1.76-11.1) even after controlling for covariates. Predictors of death included more severe trauma, Grade IV injury, and the occurrence of stroke. Arterial occlusion, hypotension, and endovascular intervention were significant predictors of stroke. Patients that experienced a BCVI-related stroke were at a 4.2× increased risk of death. The data set lacked the granularity necessary to evaluate AT timing or dosing regimen, which limited further analysis of stroke prevention strategies. CONCLUSION: Stroke and death remain significant risks for all BCVI grades regardless of the vessel injured. Antithrombotics represent the only management strategy that is consistently associated with a lower incidence of stroke and death in all BCVI categories. In the multi-injured BCVI patient with a high risk of bleeding on anticoagulation, antiplatelet agents are an efficacious alternative. Given the 40% mortality rate in patients who survived their initial trauma and developed a BCVI-related stroke, nontreatment may no longer be a viable option. LEVEL OF EVIDENCE: Epidemiological III; Therapeutic IV.

Resuscitative endovascular balloon occlusion of the aorta in combat casualties: The past, present, and future.

BACKGROUND: Noncompressible torso hemorrhage is a leading cause of preventable death on the battlefield. Intra-aortic balloon occlusion was first used in combat in the 1950s, but military use was rare before Operation Iraqi Freedom and Operation Enduring Freedom. During these wars, the combination of an increasing number of deployed vascular surgeons and a significant rise in deaths from hemorrhage resulted in novel adaptations of resuscitative endovascular balloon occlusion of the aorta (REBOA) technology, increasing its potential application in combat. We describe the background of REBOA development in response to a need for minimally invasive intervention for hemorrhage control and provide a detailed review of all published cases (n = 47) of REBOA use for combat casualties. The current limitations of REBOA are described, including distal ischemia and reperfusion injury, as well as ongoing research efforts to adapt REBOA for prolonged use in the austere setting. LEVEL OF EVIDENCE: Level V.

Partial Resuscitative Endovascular Balloon Occlusion of the Aorta: A Systematic Review of the Preclinical and Clinical Literature.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) has become a standard adjunct for the management of life-threatening truncal hemorrhage, but the technique is limited by the sequalae of ischemia distal to occlusion. Partial REBOA addresses this limitation, and the recent Food and Drug Administration approval of a device designed to enable partial REBOA will broaden its application. We conducted a systematic review of the available animal and clinical literature on the methods, impacts, and outcomes associated with partial REBOA as a technique to enable targeted proximal perfusion and limit distal ischemic injury. We hypothesize that a systematic review of the published animal and human literature on partial REBOA will provide actionable insight for the use of partial REBOA in the context of future wider clinical implementation of this technique. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols guidelines, we conducted a search of the available literature which used partial inflation of a REBOA balloon catheter. Findings from 22 large animal studies and 14 clinical studies met inclusion criteria. RESULTS: Animal and clinical results support the benefits of partial REBOA including extending the resuscitative window extended safe occlusion time, improved survival, reduced proximal hypertension, and reduced resuscitation requirements. Clinical studies provide practical physiologic targets for partial REBOA including a period of total occlusion followed by gradual balloon deflation to achieve a target proximal pressure and/or target distal pressure. CONCLUSIONS: Partial REBOA has several benefits which have been observed in animal and clinical studies, most notably reduced ischemic insult to tissues distal to occlusion and improved outcomes compared with total occlusion. Practical clinical protocols are available for the implementation of partial REBOA in cases of life-threatening torso hemorrhage.

A novel partial resuscitative endovascular balloon aortic occlusion device that can be deployed in zone 1 for more than 2 hours with minimal provider titration.

BACKGROUND: Hemorrhage is a leading cause of mortality in trauma. Resuscitative endovascular balloon occlusion of the aorta (REBOA) can control hemorrhage, but distal ischemia, subsequent reperfusion injury, and the need for frequent balloon titration remain problems. Improved device design can allow for partial REBOA (pREBOA) that may provide hemorrhage control while also perfusing distally without need for significant provider titration. METHODS: Female Yorkshire swine (N = 10) were subjected to 40% hemorrhagic shock for 1 hour (mean arterial pressure [MAP], 28-32 mm Hg). Animals were then randomized to either complete aortic occlusion (ER-REBOA) or partial occlusion (novel pREBOA-PRO) without frequent provider titration or distal MAP targets. Detection of a trace distal waveform determined partial occlusion in the pREBOA-PRO arm. After 2 hours of zone 1 occlusion, the hemorrhaged whole blood was returned. After 50% autotransfusion, the balloon was deflated over a 10-minute period. Following transfusion, the animals were survived for 2 hours while receiving resuscitation based on objective targets: lactated Ringer's fluid boluses (goal central venous pressure, ≥ 6 mm Hg), a norepinephrine infusion (goal MAP, 55-60 mm Hg), and acid-base correction (goal pH, >7.2). Hemodynamic variables, arterial lactate, lactate dehydrogenase, aspartate aminotransferase, and creatinine levels were measured. RESULTS: All animals survived throughout the experiment, with similar increase in proximal MAPs in both groups. Animals that underwent partial occlusion had slightly higher distal MAPs. At the end of the experiment, the partial occlusion group had lower end levels of serum lactate (p = 0.006), lactate dehydrogenase (p = 0.0004) and aspartate aminotransferase (p = 0.004). Animals that underwent partial occlusion required less norepinephrine (p = 0.002), less bicarbonate administration (p = 0.006), and less fluid resuscitation (p = 0.042). CONCLUSION: Improved design for pREBOA can decrease the degree of distal ischemia and reperfusion injury compared with complete aortic occlusion, while providing a similar increase in proximal MAPs. This can allow pREBOA zone-1 deployment for longer periods without the need for significant balloon titration.

Serum citrullinated histone H3 concentrations differentiate patients with septic verses non-septic shock and correlate with disease severity.

PURPOSE: Microbial infection stimulates neutrophil/macrophage/monocyte extracellular trap formation, which leads to the release of citrullinated histone H3 (CitH3) catalyzed by peptidylarginine deiminase (PAD) 2 and 4. Understanding these molecular mechanisms in the pathogenesis of septic shock will be an important next step for developing novel diagnostic and treatment modalities. We sought to determine the expression of CitH3 in patients with septic shock, and to correlate CitH3 levels with PAD2/PAD4 and clinically relevant outcomes. METHODS: Levels of CitH3 were measured in serum samples of 160 critically ill patients with septic and non-septic shock, and healthy volunteers. Analyses of clinical and laboratory characteristics of patients were conducted. RESULTS: Levels of circulating CitH3 at enrollment were significantly increased in septic shock patients (n = 102) compared to patients hospitalized with non-infectious shock (NIC) (n = 32, p < 0.0001). The area under the curve (95% CI) for distinguishing septic shock from NIC using CitH3 was 0.76 (0.65-0.86). CitH3 was positively correlated with PAD2 and PAD4 concentrations and Sequential Organ Failure Assessment Scores [total score (r = 0.36, p < 0.0001)]. The serum levels of CitH3 at 24 h (p < 0.01) and 48 h (p < 0.05) were significantly higher in the septic patients that did not survive. CONCLUSION: CitH3 is increased in patients with septic shock. Its serum concentrations correlate with disease severity and prognosis, which may yield vital insights into the pathophysiology of sepsis.

Reperfusion repercussions: A review of the metabolic derangements following resuscitative endovascular balloon occlusion of the aorta.

BACKGROUND: Current resuscitative endovascular balloon occlusion of the aorta (REBOA) literature focuses on improving outcomes through careful patient selection, diligent catheter placement, and expeditious definitive hemorrhage control. However, the detection and treatment of post-REBOA ischemia-reperfusion injury (IRI) remains an area for potential improvement. Herein, we provide a review of the metabolic derangements that we have encountered while managing post-REBOA IRI in past swine experiments. We also provide data-driven clinical recommendations to facilitate resuscitation post-REBOA deflation that may be translatable to humans. METHODS: We retrospectively reviewed the laboratory data from 25 swine across three varying hemorrhagic shock models that were subjected to complete REBOA of either 45 minutes, 60 minutes, or 90 minutes. In each model the balloon was deflated gradually following definitive hemorrhage control. Animals were then subjected to whole blood transfusion and critical care with frequent electrolyte monitoring and treatment of derangements as necessary. RESULTS: Plasma lactate peaked and pH nadired long after balloon deflation in all swine in the 45-minute, 60-minute, and 90-minute occlusion models (onset of peak lactate, 32.9 ± 6.35 minutes, 38.8 ± 10.55 minutes, and 49.5 ± 6.5 minutes; pH nadir, 4.3 ± 0.72 minutes, 26.9 ± 12.32 minutes, and 42 ± 7.45 minutes after balloon deflation in the 45-, 60-, and 90-minute occlusion models, respectively). All models displayed persistent hypoglycemia for more than an hour following reperfusion (92.1 ± 105.5 minutes, 125 ± 114.9 minutes, and 96 ± 97.8 minutes after balloon deflation in the 45-, 60-, and 90-minute occlusion groups, respectively). Hypocalcemia and hyperkalemia occurred in all three groups, with some animals requiring treatment more than an hour after reperfusion. CONCLUSION: Metabolic derangements resulting from REBOA use are common and may worsen long after reperfusion despite resuscitation. Vigilance is required to detect and proactively manage REBOA-associated IRI. Maintaining a readily available "deflation kit" of pharmacological agents needed to treat common post-REBOA electrolyte abnormalities may facilitate management. LEVEL OF EVIDENCE: Level V.

Dose optimization of valproic acid in a lethal model of traumatic brain injury, hemorrhage, and multiple trauma in swine.

BACKGROUND: Trauma is a leading cause of death, and traumatic brain injury is one of the hallmark injuries of current military conflicts. Valproic acid (VPA) administration in high doses (300-400 mg/kg) improves survival in lethal trauma models, but effectiveness of lower doses on survival is unknown. This information is essential for properly designing the upcoming clinical trials. We, therefore, performed the current study to determine the lowest dose at which VPA administration improves survival in a model of lethal injuries. METHODS: Swine were subjected to traumatic brain injury (10-mm cortical impact), 40% blood volume hemorrhage, and multiple trauma (femur fracture, rectus crush, and Grade V liver laceration). After 1 hour of shock, animals were randomized (n = 6/group) to four groups: normal saline (NS) resuscitation; or NS with VPA doses of 150 mg/kg (VPA 150) or 100 mg/kg (VPA 100) administered over 3 hours or 100 mg/kg over 2 hours (VPA 100 over 2 hours). Three hours after shock, packed red blood cells were given, and animals were monitored for another 4 hours. Survival was assessed using Kaplan-Meier and log-rank test. RESULTS: Without resuscitation, all of the injured animals died within 5 hours. Similar survival rates were observed in the NS (17%) and VPA 100 (0%) resuscitation groups. Survival rates in the 100-mg/kg VPA groups were significantly (p < 0.05) better when it was given over 2 hours (67%) compared to 3 hours (0%). 83% of the animals in the VPA 150 group survived, which was significantly higher than the NS and VPA 100 over 3 hours groups (p < 0.05). CONCLUSION: A single dose of VPA (150 mg/kg) significantly improves survival in an otherwise lethal model of multiple injuries. This is a much lower dose than previously shown to have a survival benefit and matches the dose that is tolerated by healthy human subjects with minimal adverse effects. LEVEL OF EVIDENCE: Therapeutic, level V.

Valproic acid improves survival and decreases resuscitation requirements in a swine model of prolonged damage control resuscitation.

BACKGROUND: Although damage control resuscitation (DCR) is routinely performed for short durations, prolonged DCR may be required in military conflicts as a component of prolonged field care. Valproic acid (VPA) has been shown to have beneficial properties in lethal hemorrhage/trauma models. We sought to investigate whether the addition of a single dose of VPA to a 72-hour prolonged DCR protocol would improve clinical outcomes. METHODS: Fifteen Yorkshire swine (40-45 kg) were subjected to lethal (50% estimated total blood volume) hemorrhagic shock (HS) and randomized to three groups: (1) HS, (2) HS-DCR, (3) HS-DCR-VPA (150 mg/kg over 3 hours) (n = 5/cohort). In groups assigned to receive DCR, Tactical Combat Casualty Care guidelines were applied (1 hour into the shock period), targeting a systolic blood pressure of 80 mm Hg. At 72 hours, surviving animals were given transfusion of packed red blood cells, simulating evacuation to higher echelons of care. Survival rates, physiologic parameters, resuscitative fluid requirements, and laboratory profiles were used to compare the clinical outcomes. RESULTS: This model was 100% lethal in the untreated animals. DCR improved survival to 20%, although this was not statistically significant. The addition of VPA to DCR significantly improved survival to 80% (p < 0.01). The VPA-treated animals also had significantly (p < 0.05) higher systolic blood pressures, lower fluid resuscitation requirements, higher hemoglobin levels, and lower creatinine and potassium levels. CONCLUSION: VPA administration improves survival, decreases resuscitation requirements, and improves hemodynamic and laboratory parameters when added to prolonged DCR in a lethal hemorrhage model.