Publications by authors named "Rachel Russo"

47 Publications

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

J Trauma Acute Care Surg 2021 Jun;90(6):987-995

From the University of California Davis Medical Center, Department of Surgery, Division of Trauma, Acute Care Surgery, and Surgical Critical Care (R.R., J.G.), Sacramento; David Grant Medical Center, Department of Surgery (R.R.), Travis AFB, Fairfield, California; University of Michigan, Department of Surgery, Division of Vascular Surgery (A.D.), Ann Arbor, Michigan; Northwestern University, Feinberg School of Medicine, Department of Surgery (H.A.), Chicago, Illinois; University of Maryland R Adams Cowley Shock Trauma Center (J.D., T.S.), Baltimore, Maryland; University of Tennessee Health Sciences Center, Department of Surgery (T.F.), Memphis, Tennessee; University of Wisconsin Madison Medical Center, Department of Surgery (S.S.), Madison, Wisconsin; Uniformed Services University of the Health Sciences, Department of Surgery, Division of Trauma and Acute Care Surgery (J.H., R.R.), Bethesda, Maryland; and Uniformed Services University of the Health Sciences, Department of Surgery, Division of Vascular Surgery (T.R.), Bethesda, Maryland.

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.
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http://dx.doi.org/10.1097/TA.0000000000003127DOI Listing
June 2021

Assessment of the Cytoprotective Effects of High-Dose Valproic Acid Compared to a Clinically Used Lower Dose.

J Surg Res 2021 May 11;266:125-141. Epub 2021 May 11.

Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan; Department of Surgery, Feinberg School of Medicine/Northwestern University, Chicago, Illinois. Electronic address:

Objective: Valproic acid (VPA) treatment improves survival in animal models of injuries on doses higher than those allowed by Food and Drug Administration (FDA). We investigated the proteomic alterations induced by a single high-dose (140mg/kg) of VPA (VPA140) compared to the FDA-approved dose of 30mg/kg (VPA30) in healthy humans. We also describe the proteomic and transcriptomic changes induced by VPA140 in an injured patient. We hypothesized that VPA140 would induce cytoprotective changes in the study participants.

Methods: Serum samples were obtained from healthy subjects randomized to two groups; VPA140 and VPA30 at 3 timepoints: 0h(baseline), 2h, and 24h following infusion(n = 3/group). Samples were also obtained from an injured patient that received VPA140 at 0h, 6h and 24h following infusion. Proteomic analyses were performed using liquid chromatography-mass spectrometry (LC-MS/MS), and transcriptomic analysis was performed using RNA-sequencing. Differentially expressed (DE) proteins and genes were identified for functional annotation and pathway analysis using iPathwayGuide and gene set enrichment analysis (GSEA), respectively.

Results: For healthy individuals, a dose comparison was performed between VPA140 and VPA30 groups at 2 and 24 h. Functional annotation showed that top biological processes in VPA140 versus VPA30 analysis at 2 h included regulation of fatty acid (P = 0.002) and ATP biosynthesis (P = 0.007), response to hypoxia (P = 0.017), cell polarity regulation (P = 0.031), and sequestration of calcium ions (P = 0.031). Top processes at 24 h in VPA140 versus VPA30 analysis included amino acid metabolism (P = 0.023), collagen catabolism (P = 0.023), and regulation of protein breakdown (P = 0.023). In the injured patient, annotation of the DE proteins in the serum showed that top biological processes at 2 h included neutrophil chemotaxis (P = 0.002), regulation of cellular response to heat (P = 0.008), regulation of oxidative stress (P = 0.008) and regulation of apoptotic signaling pathway (P = 0.008). Top biological processes in the injured patient at 24 h included autophagy (P = 0.01), glycolysis (P = 0.01), regulation of apoptosis (P = 0.01) and neuron apoptotic processes (P = 0.02).

Conclusions: VPA140 induces cytoprotective changes in human proteome not observed in VPA30. These changes may be responsible for its protective effects in response to injuries.
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http://dx.doi.org/10.1016/j.jss.2021.03.025DOI Listing
May 2021

REBOA in Combat Casualties: The Past, Present, and Future.

J Trauma Acute Care Surg 2021 Mar 12. Epub 2021 Mar 12.

From the Department of Surgery (S.C.S., C.M.T., S.A.Z., R.M.R.), University of California-Davis, Sacramento, California; Department of General Surgery (S.A.Z., R.M.R.), David Grant USAF Medical Center, Travis, California; Department of Vascular Surgery (J.J.D.), R Adams Cowley Shock Trauma Center, University of Maryland Medical System, Baltimore, Maryland; Department of Vascular Surgery (J.J.D.), United States Air Force, Baltimore, Maryland.

Abstract: Non-compressible 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 prior to 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.
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http://dx.doi.org/10.1097/TA.0000000000003166DOI Listing
March 2021

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

J Surg Res 2021 Jun 6;262:101-114. Epub 2021 Feb 6.

Prytime Medical Devices, Inc, Boerne, Texas. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jss.2020.12.054DOI Listing
June 2021

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.

J Trauma Acute Care Surg 2021 03;90(3):426-433

From the Department of Surgery (M.T.K., G.K.W., A.M.W., B.E.B., R.L.O., C.A.V., K.C., H.B.A.), University of Michigan, Ann Arbor, Michigan; Department of Surgery (R.M.R.), UC Davis Medical Center, Sacramento; US Air Force Medical Corps, 60th Medical Group (R.M.R.), Travis AFB, Fairfield, California; and Department of Surgery (H.B.A.), Northwestern University, Chicago, Illinois.

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.
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http://dx.doi.org/10.1097/TA.0000000000003042DOI Listing
March 2021

Elements of an Excellent Psychiatry Clerkship Experience: A Survey Study of Graduating Medical Students.

Acad Psychiatry 2021 Apr 7;45(2):174-179. Epub 2021 Jan 7.

Eastern Virginia Medical School, Norfolk, VA, USA.

Objective: One possible factor associated with choosing psychiatry as a career is students rating their psychiatry clerkship as excellent. Although this suggests that an excellent clerkship may improve recruitment into psychiatry, to our knowledge there has never been a multi-site survey study of graduating medical students that identify what factors lead to an excellent clerkship rating. The purpose of this study was to determine factors that medical student find important for an excellent psychiatry clerkship experience.

Methods: A total of 1457 graduating medical students at eight institutions were sent a 22-item Likert-type survey about what clinical and administrative factors they considered when rating their psychiatry clerkship via email in the fall of their last year. 357 (24.5%) responded and Z-test, t-tests, and multiple regression analyses were carried out.

Results: The factors which students rated higher than the mean included planned application to psychiatry residency, clear expectations, a transparent grading process, feeling part of a team, timely feedback by faculty, and a competent clerkship coordinator and director. Lectures, active learning, and self-study were rated as less pertinent, and the overall clerkship rating did differ between students going into psychiatry versus other specialties.

Conclusions: Although the low response undermines the validity of findings, by improving the administration of the clerkship with clear expectations, grading, feedback, and by encouraging clinical teams to fully integrate students clerkship ratings might improve which could potentially improve recruitment. Future research could further quantify and qualify these parameters and compare psychiatric clerkships to other clerkships.
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http://dx.doi.org/10.1007/s40596-020-01373-zDOI Listing
April 2021

Shocked Though the Heart and YouTube Is to Blame-The Rising Incidence of Accidental Trans-cardiac Electrocution From Do-It-Yourself Fractal Wood Art, and a Call to Action.

J Burn Care Res 2021 Mar;42(2):236-240

Department of Surgery, University of Michigan, Ann Arbor.

In the past year, we have become aware of a new mechanism of severe electrical injury ascribed to fractal wood art. This type of art has become increasingly popular and deadly due to exponential popularity in the use of Youtube type video teaching. This manuscript is one of the initial descriptions of the injury mode, presentation, treatment, and outcomes from four such cases treated at our institution. Additionally, we elicit a call for action in preventing further similar unnecessary injuries and deaths.
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http://dx.doi.org/10.1093/jbcr/iraa172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940498PMC
March 2021

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

Infection 2021 Feb 30;49(1):83-93. Epub 2020 Sep 30.

Department of Surgery, University of Michigan Health System, University of Michigan Medical School, 1500 E Medical Center Dr. SPC 5331, Ann Arbor, MI, 48109-5331, USA.

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.
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http://dx.doi.org/10.1007/s15010-020-01528-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527151PMC
February 2021

Millennials in Psychiatry: Exploring Career Choice Factors in Generation Y Psychiatry Interns.

Acad Psychiatry 2020 Dec 13;44(6):727-733. Epub 2020 Jul 13.

Emory University School of Medicine, Atlanta, GA, USA.

Objective: There is a national shortage of psychiatrists. To grow the workforce, educators must understand the factors that influence the choice of psychiatry as a specialty for medical students in the Generation Y cohort.

Methods: Psychiatry residents born between 1981 and 2000 were recruited from six psychiatry training programs across the USA and were interviewed in the fall of their first year. The interviews were coded and analyzed qualitatively for themes. Career Construction Theory (CCT) was applied to relate the themes within the four domains of Career Adaptability (a focus of CCT): concern, control, curiosity, and confidence.

Results: The majority of themes mapped onto the four domains. A fifth domain, "contribution," was created to capture additional themes. Themes associated with choosing psychiatry as a career included Practice Concerns and Economic/Lifestyle Concerns (concern), Changes in Stigma and Changes in Legitimacy (control), Exploring Humanity and Exposures to Psychiatry (curiosity), Abilities Called Upon by the Field, Recognized Qualities in the Participant, and Recognized Qualities in the Faculty/Residents (confidence), and Hoping to Make a Difference and Engaging in Research/Technology (contribution).

Conclusions: With the knowledge generated from this study, educators now have a guide for the kinds of learning experiences that may attract Generation Y students to the field, and can identify those with the background, values, or personality traits most likely to find a career in psychiatry to be attractive.
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http://dx.doi.org/10.1007/s40596-020-01272-3DOI Listing
December 2020

A new, pressure-regulated balloon catheter for partial resuscitative endovascular balloon occlusion of the aorta.

J Trauma Acute Care Surg 2020 08;89(2S Suppl 2):S45-S49

From the Department of Surgery (R.M.R., A.J.D., A.M.I., H.B.A.), University of Michigan, Ann Arbor, Michigan; United States Air Force Medical Corps (R.M.R., A.J.D., A.M.I.); and Prytime Medical Devices (C.J.F., P.L.C., D.G.B.), Boerne, Texas.

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http://dx.doi.org/10.1097/TA.0000000000002770DOI Listing
August 2020

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

J Trauma Acute Care Surg 2020 08;89(2S Suppl 2):S39-S44

From the Wake Forest School of Medicine (M.A.); Department of Surgery (L.P.N. T.K.W.), Wake Forest School of Medicine, Winston-Salem, North Carolina; Department of Surgery (R.M.R.), University of Michigan, Ann Arbor, Michigan; Division of Emergency Medicine, Department of Surgery (G.H., A.J.), University of Utah School of Medicine, Salt Lake City, Utah; Clinical Investigation Facility (J.K.G.), David Grant USAF Medical Center, Travis Air Force Base, Fairfield, California; R Adams Cowley Shock Trauma Center (J.J.D.), University of Maryland, Baltimore, Maryland; Bart's Health NHS Trust (R.L.), London's Air Ambulance (R.L.), The Helipad, Royal London Hospital, Whitechapel, London; NHS Lothian (R.L.) and Department of Anaesthesia, Critical Care and Pain Medicine (R.L.), Royal Infirmary of Edinburgh, Edinburgh, United Kingdom.

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.
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http://dx.doi.org/10.1097/TA.0000000000002761DOI Listing
August 2020

Life on the battlefield: Valproic acid for combat applications.

J Trauma Acute Care Surg 2020 08;89(2S Suppl 2):S69-S76

From the Department of Surgery (R.R., M.K., U.F.B., G.W., B.B., H.B.A.), University of Michigan Health System, Ann Arbor, Michigan; United States Air Force, Medical Corps (R.R.), David Grant Medical Center, Travis AFB, California; and Department of Pharmacology (M.P.), University of Michigan, Ann Arbor, Michigan.

The leading causes of death in military conflicts continue to be hemorrhagic shock (HS) and traumatic brain injury (TBI). Most of the mortality is a result of patients not surviving long enough to obtain surgical care. As a result, there is a significant unmet need for a therapy that stimulates a "prosurvival phenotype" that counteracts the cellular pathophysiology of HS and TBI to prolong survival. Valproic acid (VPA), a well-established antiepileptic therapy for more than 50 years, has shown potential as one such prosurvival therapy. This review details how VPA's role as a nonselective histone deacetylase inhibitor induces cellular changes that promote survival and decrease cellular pathways that lead to cell death. The review comprehensively covers more than two decades worth of studies ranging from preclinical (mice, swine) to recent human clinical trials of the use of VPA in HS and TBI. Furthermore, it details the different mechanisms in which VPA alters gene expression, induces cytoprotective changes, attenuates platelet dysfunction, provides neuroprotection, and enhances survival in HS and TBI. Valproic acid shows real promise as a therapy that can induce the prosurvival phenotype in those injured during military conflict.
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http://dx.doi.org/10.1097/TA.0000000000002721DOI Listing
August 2020

Optimizing the Impact of Academic Psychiatry Conferences.

Acad Psychiatry 2020 Apr 5;44(2):250-251. Epub 2020 Feb 5.

University of Texas Southwestern, Dallas, TX, USA.

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http://dx.doi.org/10.1007/s40596-020-01190-4DOI Listing
April 2020

Downstream Effects of Grade Policy Changes.

Acad Psychiatry 2019 12 4;43(6):654-655. Epub 2019 Sep 4.

University of Texas - Southwestern Medical Center, Dallas, TX, USA.

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http://dx.doi.org/10.1007/s40596-019-01110-1DOI Listing
December 2019

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

J Trauma Acute Care Surg 2019 11;87(5):1133-1139

From the Department of Surgery (B.E.B., A.M.W., I.S.D., N.J.G., K.C., A.Z.S., R.L.O., U.F.B., B.L., R.M.R., Y.L., H.B.A.), and Department of Clinical Pharmacy (M.P.P.), University of Michigan, Ann Arbor, Michigan.

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.
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http://dx.doi.org/10.1097/TA.0000000000002460DOI Listing
November 2019

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

J Trauma Acute Care Surg 2019 08;87(2):393-401

From the Department of Surgery (A.M.W., U.F.B., B.E.B., N.J.G., K.C., J.Z., I.S.D., R.G.K., C.A.V., R.M.R., Y.L., H.B.A.), University of Michigan Health System, Ann Arbor, Michigan; and Trauma Center, Department of Orthopedics and Traumatology (J.Z.), Peking University People's Hospital, Beijing, China.

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.
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http://dx.doi.org/10.1097/TA.0000000000002281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660397PMC
August 2019

What's New in Shock, May 2019?

Shock 2019 05;51(5):535-537

Department of General Surgery, University of Michigan, Ann Arbor, Michigan.

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http://dx.doi.org/10.1097/SHK.0000000000001322DOI Listing
May 2019

What Competencies are Needed to Run a Course or Clerkship?

Acad Psychiatry 2019 Jun 28;43(3):354-355. Epub 2019 Feb 28.

The University of Texas Medical Branch, Galveston, TX, USA.

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http://dx.doi.org/10.1007/s40596-019-01044-8DOI Listing
June 2019

Bloodstream infection in hematopoietic stem cell transplantation outpatients: risk factors for hospitalization and death.

Rev Inst Med Trop Sao Paulo 2018 Dec 20;61:e3. Epub 2018 Dec 20.

Universidade de São Paulo, Faculdade de Medicina, Departamento de Moléstias Infecciosas e Parasitárias, São Paulo, São Paulo, Brazil.

We described 235 bloodstream infection (BSI) episodes in 146 hematopoietic stem cell transplantation (HSCT) outpatients and evaluated risk factors for hospitalization and death. Records of outpatients presenting with positive blood cultures over a 5-year period (January 2005 to December 2008) were reviewed. Variables with p< 0.1 in bivariate analysis were used in a regression logistic model. A total of 266 agents were identified, being 175 (66.7%) gram-negative, 80 (30.3%) gram-positive bacteria and 9 (3.4%) fungi. The most common underlying disease was acute leukemia 40 (27.4%), followed by lymphoma non-Hodgkin 26 (18%) and 87 patients (59.6%) were submitted to allogeneic hematopoietic stem cell transplant (HSCT). BSI episodes were more frequent during the first 100 days after transplantation (183 or 77.8%), and ninety-one (38.7%) episodes of BSI occurred up to the first 30 days. Hospitalization occurred in 26% of the episodes and death in 10% of cases. Only autologous HSCT was protector for hospitalization. Although, central venous catheter (CVC) withdrawal and the Multinational Association of Supportive Care in Cancer (MASCC) score up to 21 points were protector factors for death in the bivariate analysis, only MASCC remained as protector.
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http://dx.doi.org/10.1590/S1678-9946201961003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300790PMC
December 2018

Mass casualty events: what to do as the dust settles?

Trauma Surg Acute Care Open 2018 9;3(1):e000210. Epub 2018 Oct 9.

Johns Hopkins University, Baltimore, Maryland, USA.

Care during mass casualty events (MCE) has improved during the last 15 years. Military and civilian collaboration has led to partnerships which augment the response to MCE. Much has been written about strategies to deliver care during an MCE, but there is little about how to transition back to normal operations after an event. A panel discussion entitled at the 76th Annual American Association for the Surgery of Trauma meeting on September 13, 2017 brought together a cadre of military and civilian surgeons with experience in MCEs. The events described were the First Battle of Mogadishu (1993), the Second Battle of Fallujah (2004), the Bagram Detention Center Rocket Attack (2014), the Boston Marathon Bombing (2013), the Asiana Flight 214 Plane Crash (2013), the Baltimore Riots (2015), and the Orlando Pulse Night Club Shooting (2016). This article focuses on the lessons learned from military and civilian surgeons in the days after MCEs.
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http://dx.doi.org/10.1136/tsaco-2018-000210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203142PMC
October 2018

Endocrine Effects of Simulated Complete and Partial Aortic Occlusion in a Swine Model of Hemorrhagic Shock.

Mil Med 2019 05;184(5-6):e298-e302

Clinical Investigation Facility, David Grant USAF Medical Center, 101 Bodin Circle, Travis Air Force Base, CA.

Introduction: Low distal aortic flow via partial aortic occlusion (AO) may mitigate ischemia induced by resuscitative endovascular balloon occlusion of the aorta (REBOA). We compared endocrine effects of a novel simulated partial AO strategy, endovascular variable aortic control (EVAC), with simulated REBOA in a swine model.

Materials And Methods: Aortic flow in 20 swine was routed from the supraceliac aorta through an automated extracorporeal circuit. Following liver injury-induced hemorrhagic shock, animals were randomized to control (unregulated distal flow), simulated REBOA (no flow, complete AO), or simulated EVAC (distal flow of 100-300 mL/min after 20 minutes of complete AO). After 90 minutes, damage control surgery, resuscitation, and full flow restoration ensued. Critical care was continued for 4.5 hours or until death.

Results: Serum angiotensin II concentration was higher in the simulated EVAC (4,769 ± 624 pg/mL) than the simulated REBOA group (2649 ± 429) (p = 0.01) at 180 minutes. There was no detectable difference in serum renin [simulated REBOA: 231.3 (227.9-261.4) pg/mL; simulated EVAC: 294.1 (231.2-390.7) pg/mL; p = 0.27], aldosterone [simulated EVAC: 629 (454-1098), simulated REBOA: 777 (575-1079) pg/mL, p = 0.53], or cortisol (simulated EVAC: 141 ± 12, simulated REBOA: 127 ± 9 ng/mL, p = 0.34) concentrations between groups.

Conclusions: Simulated EVAC was associated with higher serum angiotensin II, which may have contributed to previously reported cardiovascular benefits. Future studies should evaluate the renal effects of EVAC and the concomitant therapeutic use of angiotensin II.
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http://dx.doi.org/10.1093/milmed/usy287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525611PMC
May 2019

Making Feedback Meaningful: Using Student and Supervisor Feedback.

Acad Psychiatry 2018 06 8;42(3):430-431. Epub 2018 Feb 8.

VA North Texas Health Care System, Dallas, TX, USA.

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http://dx.doi.org/10.1007/s40596-018-0889-3DOI Listing
June 2018

The pitfalls of resuscitative endovascular balloon occlusion of the aorta: Risk factors and mitigation strategies.

J Trauma Acute Care Surg 2018 01;84(1):192-202

From the University of California Davis (A.J.D., R.M.R., J.J.D.), Sacramento, California; Kirov Military Medical Academy (V.A.R.), Saint-Petersburg, Russian Federation; R Adams Cowley Shock Trauma Medical Center (M.L.B.), Baltimore, Maryland; University of Texas Health Science Center (L.J.M.), Houston, Texas; Foothills Medical Centre (C.B.), University of Calgary, Calgary, Alberta, Canada; Harborview Medical Center (E.B.), University of Washington, Seattle, Washington; Denver Health (E.E.M.), Denver, Colorado; Uniformed Services (T.E.R.), University of the Health Sciences, Bethesda, Maryland.

Despite technological advancements, REBOA is associated with significant risks due to complications of vascular access and ischemia-reperfusion. The inherent morbidity and mortality of REBOA is often compounded by coexisting injury and hemorrhagic shock. Additionally, the potential for REBOA-related injuries is exaggerated due to the growing number of interventions being performed by providers who have limited experience in endovascular techniques, inadequate resources, minimal training in the technique, and who are performing this maneuver in emergency situations. In an effort to ultimately improve outcomes with REBOA, we sought to compile a list of complications that may be encountered during REBOA usage. To address the current knowledge gap, we assembled a list of anecdotal complications from high-volume REBOA users internationally. More importantly, through a consensus model, we identify contributory factors that may lead to complications and deliberate on how to recognize, mitigate, and manage such events. An understanding of the pitfalls of REBOA and strategies to mitigate their occurrence is of vital importance to optimize patient outcomes.
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http://dx.doi.org/10.1097/TA.0000000000001711DOI Listing
January 2018

Making Minutes Matter.

Authors:
Rachel M Russo

Mil Med 2017 11;182(11):1749-1751

Department of Surgery, University of California Davis Medical Center, 2315 Stockton Boulevard, Sacramento, CA 95817.

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http://dx.doi.org/10.7205/MILMED-D-17-00096DOI Listing
November 2017

A novel model of highly lethal uncontrolled torso hemorrhage in swine.

J Surg Res 2017 10 12;218:306-315. Epub 2017 Jul 12.

Division of Trauma, Acute Care Surgery, and Surgical Critical Care, UC Davis Medical Center, Sacramento, California; Department of General Surgery, David Grant USAF Medical Center, California.

Introduction: A reproducible, lethal noncompressible torso hemorrhage model is important to civilian and military trauma research. Current large animal models balancing clinical applicability with standardization and internal validity. As such, large animal models of trauma vary widely in the surgical literature, limiting comparisons. Our aim was to create and validate a porcine model of uncontrolled hemorrhage that maximizes reproducibility and standardization.

Methods: Seven Yorkshire-cross swine were anesthetized, instrumented, and splenectomized. A simple liver tourniquet was applied before injury to prevent unregulated hemorrhage while creating a traumatic amputation of 30% of the liver. Release of the tourniquet and rapid abdominal closure following injury provided a standardized reference point for the onset and duration of uncontrolled hemorrhage. At the moment of death, the liver tourniquet was quickly reapplied to provide accurate quantification of intra-abdominal blood loss. Weight and volume of the resected and residual liver segments were measured. Hemodynamic parameters were recorded continuously throughout each experiment.

Results: This liver injury was rapidly and universally lethal (11.2 ± 4.9 min). The volume of hemorrhage (35.8% ± 6% of total blood volume) and severity of uncontrolled hemorrhage (100% of animals deteriorated to a sustained mean arterial pressure <35 mmHg for 5 min) were consistent across all animals. Use of the tourniquet effectively halted preprocedure and postprocedure blood loss allowing for accurate quantification of amount of hemorrhage over a defined period. In addition, the tourniquet facilitated the creation of a consistent liver resection weight (0.0043 ± 0.0003 liver resection weight: body weight) and as a percentage of total liver resection weight (27% ± 2.2%).

Conclusions: This novel tourniquet-assisted noncompressible torso hemorrhage model creates a standardized, reproducible, highly lethal, and clinically applicable injury in swine. Use of the tourniquet allowed for consistent liver injury and precise control over hemorrhage. Recorded blood loss was similar across all animals. Improving reproducibility and standardization has the potential to offer improvements in large animal translational models of hemorrhage.

Level Of Evidence: Level I.
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http://dx.doi.org/10.1016/j.jss.2017.06.045DOI Listing
October 2017

Incremental balloon deflation following complete resuscitative endovascular balloon occlusion of the aorta results in steep inflection of flow and rapid reperfusion in a large animal model of hemorrhagic shock.

J Trauma Acute Care Surg 2017 07;83(1):139-143

From the Department of Surgery (A.J.D., R.M.R., S.-A.E.F., L.P.N.), UC Davis Medical Center, Sacramento, California; Department of General Surgery (A.J.D., R.M.R., L.P.N.), David Grant Medical Center, Travis Air Force Base, California; Division of Traumatology, Surgical Critical Care and Emergency Surgery (J.W.C.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; The Norman M. Rich Department of Surgery (J.W.C., T.E.R., L.P.N.), the Uniformed Services University of the Health Sciences, Bethesda, Maryland; Department of Emergency Medicine (A.M.J.), UC Davis Medical Center, Sacramento, California; and Heart, Lung and Vascular Center (T.K.W.), David Grant Medical Center, Travis Air Force Base, California.

Introduction: To avoid potential cardiovascular collapse after resuscitative endovascular balloon occlusion of the aorta (REBOA), current guidelines recommend methodically deflating the balloon for 5 minutes to gradually reperfuse distal tissue beds. However, anecdotal evidence suggests that this approach may still result in unpredictable aortic flow rates and hemodynamic instability. We sought to characterize aortic flow dynamics following REBOA as the balloon is deflated in accordance with current practice guidelines.

Methods: Eight Yorkshire-cross swine were splenectomized, instrumented, and subjected to rapid 25% total blood volume hemorrhage. After 30 minutes of shock, animals received 60 minutes of Zone 1 REBOA with a low-profile REBOA catheter. During subsequent resuscitation with shed blood, the aortic occlusion balloon was gradually deflated in stepwise fashion at the rate of 0.5 mL every 30 seconds until completely deflated. Aortic flow rate and proximal mean arterial pressure (MAP) were measured continuously over the period of balloon deflation.

Results: Graded balloon deflation resulted in variable initial return of aortic flow (median, 78 seconds; interquartile range [IQR], 68-105 seconds). A rapid increase in aortic flow during a single-balloon deflation step was observed in all animals (median, 819 mL/min; IQR, 664-1241 mL/min) and corresponded with an immediate decrease in proximal MAP (median, 30 mm Hg; IQR, 14.5-37 mm Hg). Total balloon volume and time to return of flow demonstrated no correlation (r = 0.016).

Conclusion: This study is the first to characterize aortic flow during balloon deflation following REBOA. A steep inflection point occurs during balloon deflation that results in an abrupt increase in aortic flow and a concomitant decrease in MAP. Furthermore, the onset of distal aortic flow was inconsistent across study animals and did not correlate with initial balloon volume or relative deflation volume. Future studies to define the factors that affect aortic flow during balloon deflation are needed to facilitate controlled reperfusion following REBOA.
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http://dx.doi.org/10.1097/TA.0000000000001502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5484091PMC
July 2017

The effect of resuscitative endovascular balloon occlusion of the aorta, partial aortic occlusion and aggressive blood transfusion on traumatic brain injury in a swine multiple injuries model.

J Trauma Acute Care Surg 2017 07;83(1):61-70

From the Department of Emergency Medicine, UC Davis Medical Center, Sacramento, California (M.A.J.); Clinical Investigation Facility, David Grant Medical Center, Travis Air Force Base, California (M.A.J., T.K.W., S.-A.E.F., A.J.D., R.M.R., J.K.G., L.P.N.), Heart, Lung and Vascular Center, David Grant Medical Center, Travis Air Force Base, California (T.K.W.); Department of Surgery, UC Davis Medical Center, Sacramento, California (S.-A.E.F., A.J.D., R.M.R., J.M.G.); Department of Surgery, Wright State University Boonshoft School of Medicine, Miami Valley Hospital, Dayton, Ohio (S.-A.E.F.); Department of Radiology, David Grant Medical Center, Travis Air Force Base, California (W.T.O.S.); and Division of Pediatric Surgery, Department of Surgery, Emory University School of Medicine, Atlanta, Georgia (L.P.N.).

Background: Despite clinical reports of poor outcomes, the degree to which resuscitative endovascular balloon occlusion of the aorta (REBOA) exacerbates traumatic brain injury (TBI) is not known. We hypothesized that combined effects of increased proximal mean arterial pressure (pMAP), carotid blood flow (Qcarotid), and intracranial pressure (ICP) from REBOA would lead to TBI progression compared with partial aortic occlusion (PAO) or no intervention.

Methods: Twenty-one swine underwent a standardized TBI via computer Controlled cortical impact followed by 25% total blood volume rapid hemorrhage. After 30 minutes of hypotension, animals were randomized to 60 minutes of continued hypotension (Control), REBOA, or PAO. REBOA and PAO animals were then weaned from occlusion. All animals were resuscitated with shed blood via a rapid blood infuser. Physiologic parameters were recorded continuously and brain computed tomography obtained at specified intervals.

Results: There were no differences in baseline physiology or during the initial 30 minutes of hypotension. During the 60-minute intervention period, REBOA resulted in higher maximal pMAP (REBOA, 105.3 ± 8.8; PAO, 92.7 ± 9.2; Control, 48.9 ± 7.7; p = 0.02) and higher Qcarotid (REBOA, 673.1 ± 57.9; PAO, 464.2 ± 53.0; Control, 170.3 ± 29.4; p < 0.01). Increases in ICP were greatest during blood resuscitation, with Control animals demonstrating the largest peak ICP (Control, 12.8 ± 1.2; REBOA, 5.1 ± 0.6; PAO, 9.4 ± 1.1; p < 0.01). There were no differences in the percentage of animals with hemorrhage progression on CT (Control, 14.3%; 95% confidence interval [CI], 3.6-57.9; REBOA, 28.6%; 95% CI, 3.7-71.0; and PAO, 28.6%; 95% CI, 3.7-71.0).

Conclusion: In an animal model of TBI and shock, REBOA increased Qcarotid and pMAP, but did not exacerbate TBI progression. PAO resulted in physiology closer to baseline with smaller increases in ICP and pMAP. Rapid blood resuscitation, not REBOA, resulted in the largest increase in ICP after intervention, which occurred in Control animals. Continued studies of the cerebral hemodynamics of aortic occlusion and blood transfusion are required to determine optimal resuscitation strategies for multi-injured patients.
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http://dx.doi.org/10.1097/TA.0000000000001518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5505178PMC
July 2017

Two lives, one REBOA: Hemorrhage control for urgent cesarean hysterectomy in a Jehovah's Witness with placenta percreta.

J Trauma Acute Care Surg 2017 09;83(3):551-553

From the Department of Surgery (R.M.R., M.D.H.), University of California Davis Medical Center, Sacramento, California; and Department of Obstetrics and Gynecology (E.G., V.K.), University of California Davis Medical Center, Sacramento, California.

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http://dx.doi.org/10.1097/TA.0000000000001602DOI Listing
September 2017

Small changes, big effects: The hemodynamics of partial and complete aortic occlusion to inform next generation resuscitation techniques and technologies.

J Trauma Acute Care Surg 2017 06;82(6):1106-1111

From the Department of Emergency Medicine (M.A.J.), University of California Davis Medical Center, Sacramento, California; Department of Surgery (A.J.D., R.M.R., S.-A.E.F., L.P.N.), University of California Davis Medical Center, Sacramento, California; Clinical Investigation Facility, David Grant USAF Medical Center (O.G.), Travis Air Force Base, California; The Norman M. Rich Department of Surgery (T.E.R.), the Uniformed Services University of the Health Sciences, Bethesda, Marland; Department of General Surgery (L.P.N.), David Grant USAF Medical Center, Travis Air Force Base, California; Department of General Surgery (L.P.N.), Uniformed Services University of the Health Sciences, Bethesda, Maryland; and Heart, Lung and Vascular Center (T.K.W.), David Grant USAF Medical Center, Travis Air Force Base, California.

Background: The transition from complete aortic occlusion during resuscitative endovascular balloon occlusion of the aorta can be associated with hemodynamic instability. Technique refinements and new technologies have been proposed to minimize this effect. In order to inform new techniques and technology, we examined the relationship between blood pressure and aortic flow during the restoration of systemic circulation following aortic occlusion at progressive levels of hemorrhage.

Methods: An automated supraceliac aortic clamp, capable of continuously variable degrees of occlusion, was applied in seven swine. The swine underwent stepwise removal of 40% of their total blood volume in four equal aliquots. After each aliquot, progressive luminal narrowing to the point of complete aortic occlusion was achieved over 5 minutes, sustained for 5 minutes, and then released over 5 minutes. Proximal and distal blood pressure and distal aortic flow were continuously recorded throughout the study.

Results: Upon release of the clamp, hyperemic aortic flow was observed following 10% and 20% hemorrhage (1,599 ± 785 mL/min, p < 0.01; and 1,070 ± 396 mL/min, p < 0.01, respectively). Proximal blood pressure exhibited a nonlinear relationship to aortic flow during clamp removal; however, distal blood pressure increased linearly with distal flow upon clamp opening across all hemorrhage volumes.

Conclusions: Hyperemic blood flow following return of circulation may contribute to cardiovascular collapse. Reintroduction of systemic blood flow after aortic occlusion should be guided by distal blood pressure rather than proximal pressure. Awareness of hemodynamic physiology during aortic occlusion is of paramount importance to the clinical implementation of next-generation resuscitative endovascular balloon occlusion of the aorta techniques and technologies.
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http://dx.doi.org/10.1097/TA.0000000000001446DOI Listing
June 2017