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Efficacy of intermittent versus standard resuscitative endovascular balloon occlusion of the aorta in a lethal solid organ injury model

Kuckelman, John DO; Derickson, Michael MD; Barron, Morgan MD; Phillips, Cody J. DO; Moe, Donald MD; Levine, Tiffany MD; Kononchik, Joseph P. PhD; Marko, Shannon T. DVM; Eckert, Matthew MD; Martin, Matthew J. MD

Journal of Trauma and Acute Care Surgery: July 2019 - Volume 87 - Issue 1 - p 9–17
doi: 10.1097/TA.0000000000002307
Editor's Choice

BACKGROUND High-grade solid organ injury is a major cause of mortality in trauma. Use of resuscitative endovascular balloon occlusion of the aorta (REBOA) can be effective but is limited by ischemia-reperfusion injury. Intermittent balloon inflation/deflation has been proposed as an alternative, but the safety and efficacy prior to operative hemorrhage control is unknown.

METHODS Twenty male swine underwent standardized high-grade liver injury, then randomization to controls (N = 5), 60-min continuous REBOA (cR, n = 5), and either a time-based (10-minute inflation/3-minute deflation, iRT = 5) or pressure-based (mean arterial pressure<40 during deflation, iRP = 5) intermittent schedule. Experiments were concluded after 120 minutes or death.

RESULTS Improved overall survival was seen in the iRT group when compared to cR (p < 0.01). Bleeding rate in iRT (5.9 mL/min) was significantly lower versus cR and iRP (p = 0.02). Both iR groups had higher final hematocrit (26% vs. 21%) compared to cR (p = 0.03). Although overall survival was lower in the iRP group, animals surviving to 120 minutes with iRP had decreased end organ injury (Alanine aminotransferase [ALT] 33 vs. 40 in the iRT group, p = 0.03) and lower lactate levels (13 vs. 17) compared with the iRT group (p = 0.03). No differences were seen between groups in terms of coagulopathy based on rotational thromboelastometry.

CONCLUSION Intermittent REBOA is a potential viable adjunct to improve survival in lethal solid organ injury while minimizing the ischemia-reperfusion seen with full REBOA. The time-based intermittent schedule had the best survival and prolonged duration of tolerable zone 1 placement. Although the pressure-based schedule was less reliable in terms of survival, when effective, it was associated with decreased acidosis and end-organ injury.

From the Department of Surgery (J.K., M.D., M.B., C.P., D.M., J.K., M.E., M.J.M.), Department of Clinical Investigations (T.L., S.M.), Madigan Army Medical Center, Tacoma, Washington; and Trauma and Emergency Surgery Service (M.J.M.), Legacy Emanuel Medical Center, Portland, Oregon.

This article was given at the 32nd Annual Meeting of the Eastern Association for the Surgery of Trauma, on January 15, 2019 in Austin, Texas.

Address for reprints: Matthew J. Martin, MD, Department of Surgery, ATTN: MCHJ-SGY-G, Madigan Army Medical Center, 9040-A Fitzsimmons Avenue, Tacoma, WA 98431; email:

Online date: April 25, 2019

Noncompressible truncal or torso hemorrhage (NCTH) remains the most common potentially preventable cause of mortality and morbidity in both military and civilian trauma settings.1,2 Currently, up to one third of soldiers succumbing to hemorrhagic shock during transport to a hospital without intervention. Nearly half of the patients who make it to the hospital will go on to die in the trauma bay. Similar data are reflected in the literature with respect to civilian patients with NCTH.3–5 The ability of military and civilian trauma systems to provide point of injury care is improving with increased placement of providers and skilled personnel readily available either at the scene of the trauma or within very short distances.6,7 Until recently, there were no available and effective prehospital or early in-hospital interventions to control bleeding from NCTH and act as a bridge to definitive hemorrhage control. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is one of the most promising new adjuncts for early hemorrhage control for NCTH.8–11 Analysis of military battlefield deaths have identified that nearly 20% died of major intracavitary hemorrhage, such as a fatal solid organ injury, and could have potentially been amenable to REBOA.2,5 Despite our improving ability to intervene early, transport to more definitive care remains around 30 minutes in the best of circumstances in the deployed or rural trauma environment. This is problematic even in the event that a timely REBOA catheter is placed as prolonged supra celiac (zone 1) occlusion can lead to the now well recognized and described, rapidly fatal ischemia reperfusion injury.6,10,12,13 There is also accumulating evidence, albeit less robust, that high proximal aortic pressures above the level of balloon occlusion may lead to adverse effects including pulmonary edema, cerebral edema, and heart failure.6–8

Our laboratory has previously evaluated the use of zone 1 REBOA with simple intermittent inflation and deflations schedules (iREBOA) to curb the effects of ischemia reperfusion in a fatal abdominal vascular injury model.14 We found that these intermittent schedules were feasible and effective at controlling isolated concurrent venous and arterial vascular trauma while lessening the severity of reperfusion injury and thus the hemodynamic effects. Clinically, the management of solid organ injury differs greatly from isolated vascular injuries. Liver and spleen are the most commonly injured organs in blunt abdominal trauma with the majority being amendable to nonoperative management. However, when severe enough, bleeding from these injuries are rapidly fatal.5,15,16 For example, grade V splenic injuries are fatal in 22% of patients and grade V or VI hepatic injures are rapidly fatal in up to 92% of patients, and are typically due to combined parenchymal, venous, and arterial bleeding.15 Thus, it is unclear if data from models of major vascular injury can be extrapolated to hemorrhage from high-grade solid organ injury.

Standard REBOA has previously been shown to be effective for both solid organ injuries as well as major abdominal vein injuries.6,17,18 This led our group to believe that we may be able to successfully transfer our iREBOA techniques to extend to the use of REBOA in a rapidly fatal solid organ injury. More specifically we hypothesized that intermittent REBOA schedules would perform superiorly when compared with continuous REBOA for prolonged use in terms of hemorrhage control, ischemia reperfusion injury and end organ damage. Our primary objective were to examine these indices between intermittent and continuous REBOA techniques. Secondary objectives included comparison intermittent REBOA in a severe solid organ injury (hepatic) model, to identify the optimal iREBOA schedule for solid organ injury hemorrhage using the time and pressure based techniques previously developed in our model of iREBOA for major vascular injury.14

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Institutional Animal Care and Use Committee application was completed and approval was granted prior to experiment commencement. All animals were maintained in accordance with the Guide for the Care and Use of Laboratory Animals published by the Institute of Laboratory Animal Research. Initial set up of Adult Yorkshire swine was similar to previously described methods from publications from our laboratory.14,19 All animals were male and weighed between 40 kg and 50 kg. Prior to the beginning of experiment all animals underwent general endotracheal anesthesia. A midline neck dissection was completed for direct access of a 5-Fr carotid arterial line and a jugular 10-Fr sheath with Swan-Ganz pulmonary artery catheter placement. A 7-Fr contralateral jugular vein catheter was placed for central venous access independent from the pulmonary artery access line to be utilized for controlled hemorrhage and combat resuscitation described below. An upper midline celiotomy was completed and an intra-abdominal bladder Foley catheter was also placed prior to the injury creation. High-grade solid organ injury was completed through this incision and is shown below. The midline incision was reapproximated after injury completed. Animals were randomized to one of four groups to include a control group (no intervention after solid organ injury), intervention with standard continuous REBOA (cR), or intermittent REBOA based on either a time-based algorithm or a pressure-based schedule (iRT or iRP, respectively).

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Controlled Hemorrhage and Combat Resuscitation

Hemorrhage and resuscitation was standardized and similar to our previously described methods.14 A weight based 20% total blood volume controlled hemorrhage was performed using the 7-Fr sheath without any concomitant resuscitation. Blood volume was removed as fast as tolerated by the animal based on mean arterial pressure (MAP) to induce hemorrhagic shock physiology. Hemorrhaged blood was transferred and maintained in citrate bags for autologous use for post injury resuscitation.

A combat resuscitation analogous to what is currently used by deployed medics was developed using guideline proved by tactical combat casualty care.20 Resuscitation was only utilized after controlled hemorrhage and solid organ injury had been completed. Sequence of the resuscitation was standard for all animals beginning with a 250-mL bolus of starch-based colloid when MAP less than 40 mm Hg. If there was no improvement in MAP, colloid was followed by autologous whole blood and was limited to the volume removed during controlled hemorrhage. Resuscitation was held for MAP greater than 40 mm Hg and restarted for MAP less than 40 mm Hg independent of REBOA intervention.

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REBOA Placement and Solid Organ Injury Creation

All animals had a ER-REBOA (Prytime Medical, Boerne, TX) preplaced through a 7-Fr sheath in the left iliac artery prior solid organ injury utilizing standard techniques which we have previously described.14 Placement was in zone 1 in all animals and confirmed by extra-anatomic measurement before placement and by palpation at the completion of the experiment.

Once set up and controlled hemorrhage was completed a standardized high-grade liver injury was completed. Injury commenced with identification of the retro-hepatic vena cava. The liver was then grasped medial to the vena cava (left lobe) and retracted caudally into the midline celiotomy for adequate exposure. Using a large Mayo scissors the hepatic parenchyma was cut first approximately 5 cm posteriorly toward the vena cava then medially just distal to the confluence of segment 4 and the left lateral hepatic veins (Fig. 1). This functionally simulated a traumatic avulsion of the left lobe of the liver. The avulsed section of liver was placed in situ and the midline celiotomy was rapidly closed.

Figure 1

Figure 1

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Experiment Intervention Groups

Animals were computer randomized one of the four previously described intervention groups. No REBOA intervention was used in control animals, then animals were monitored after injury and the experiment was concluded when MAP less than 20 mm Hg. When REBOA was utilized, successful occlusion of the aorta was confirmed by loss of distal pulses in the right lower extremity with increase of the MAP by carotid arterial readings by 75% to 100% of baseline and balloon inflation with injectable saline was standard between cR and iR groups. To avoid unrecoverable decrease in MAP deflation occurred over 30 seconds and was completed when all 10 mL of saline was removed from the balloon. In cR animals, inflation was continuous for 60 minutes to simulate the average transport time needed to get to the next level of care in a deployed environment.5 Combat resuscitation was utilized as needed for the cR group, and the experiment was concluded if MAP less than 20 mm Hg or 120-minute survival is achieved.

Similar to the previous study using a vascular injury, the iREBOA groups were randomized to either a time-based schedule (iRT) or a pressure-based schedule (iRP). The first inflation of the balloon was 15 minutes in both group and was used for initial hemorrhage control. Following the first 15-minute inflation, the balloon was fully deflated for 3 minutes regardless in the iRT group and for as long the MAP maintained greater than 35 mm Hg in the iRP group. Reinflation occurred after 3 minutes in the iRT group or when the MAP less than 35 mm Hg in the iRP was maintained for 10 minutes in both groups. The MAP thresholds were based on observations of stability in our large animal laboratory during the development phase and from previously developed large animal shock models. This sequence was continued for up to 120-minute survival or until the MAP less than 20 mm Hg.

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Data Collection and Analysis

Animals were continuously monitored and data was recorded throughout the experiment utilizing the invasive lines and catheters discussed above. Laboratory evaluation was gathered at baseline, after controlled hemorrhage and then every 30 minutes throughout the experiment and included arterial blood gas, hematocrit, basic metabolic panel, lactate, and rotational thromboelastometry (ROTEM, Tem International, Munich, Germany). The experiment was terminated at 120 minutes (Fig. 2). Immediately at the conclusion of the experiment, tissues samples from kidney and small bowel were harvested for histological evaluation using hematoxylin and eosin staining.

Figure 2

Figure 2

Data were electronically stored and analyzed using a secure network. Descriptive statistics, analysis of variance with Tukey post-hoc was performed using IBM® SPSS® Statistics 22 (IBM Corp., Armonk, NY). Comparisons were made between the four experimental groups for all data points. Statistical significance was set at a p value less than 0.05.

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Twenty swine were evaluated and randomized to the one of four experimental groups to include five animals in each the control, cR, iRT, and iRT groups. Sample size estimates were calculated a priori based on results from our prior series of REBOA experiments. All animals had similar baseline characteristics (Table 1) as well as baseline hemodynamics and laboratory values (Table 2). Average weight was 44.2 kg (±7.7 kg). Average time to death after injury was 72 minutes, with no intervention (control) being universally fatal in all animals at an average of 15.3 minutes. All animals showed signs of hemorrhagic shock after controlled hemorrhage with average heart rate of 107 bpm, MAP of 47 mm Hg, and systemic vascular resistance (SVR) of 1,300 d·s−1·cm5. Average decrease in hematocrit from controlled hemorrhage was 24% to 22% before liver injury. After injury and with REBOA intervention all animals showed signs of reperfusion injury after deflation of the REBOA balloon with average increase lactate every 30 minutes being 4.4 mg/dL across all groups.





Table 1 displays animal characteristics and response to injury and intervention in terms of blood loss, time to death and total inflation time of REBOA balloon. Importantly, there were no differences between or within groups for average weight of the animals or total blood resuscitation needed. The weight of the avulsed liver had a trend toward significant difference with Tukey post hoc analysis revealing that this trend was related to the iRP specimens being slightly larger than the cR animals at 160 g versus 130 g, respectively (p = 0.59). Clot weight was significantly higher in the control animals at 2.0 kg compared to both the cR at 1.3 kg (p = 0.02) and iRT at 1.05 kg (p = 0.001). This was reflected as well in the cumulative total blood loss, with better overall hemorrhage control in the iRT animals at 700 mL compared to 1,480 mL in controls (p = 0.01). With the significant difference in survival times between groups, total blood loss was indexed to survival time for direct comparisons. Evaluation of bleeding rate demonstrated that the iRT group had significantly slower blood loss at 5.9 mL/min comparted to 44 mL/min in iRP (p = 0.02) and 96 mL/min the controls (p < 0.01).

Overall survival is shown in the Kaplan-Meier curves in Figure 2. The iRT group showed significantly improved survival, with all animals surviving to 120 minutes (p < 0.01). Average survival in the iRP group was significantly lower versus the iRT group, but was skewed by the early death of two animals (12 and 13 minutes after liver injury). The remaining three iRP animals also survived to 120 minutes. Balloon inflation time was significantly shorter in the iRP group (Table 1) as those who survived had early hemorrhage control with stable MAPs and thus minimal need for additional cycles of inflation/deflation.

Table 2 shows hemodynamic and laboratory values between the groups. Results from Student's t testing are denoted for significant differences within the table. Animals in the iRP group had more physiologic MAPs at 30 minutes, 60 minutes, and 90 minutes when compared with the iRT group (see Table 2) as well as lower final lactic acidosis at 120 minutes with 17.1 mg/dL in the iRT group compared to 11.8 mg/dL (p = 0.03). Lactate was also significantly lower in the cR animals at 60 minutes (12.8 mg/dL) when compared with iRT at 120 minutes (p = 0.02). Liver function was statistically worse at 120 minutes in the iRT group with ALT of 40 U/dL when compared with 33 in the iRP group (p = 0.03). Final hematocrit was significantly lower after 60 minutes at 21.5% in the cR animals when compared with both intermittent groups at 26.5 in iRP and 25.6 in the iRT groups at 120 minutes (p = 0.03) There were no difference seen in ROTEM values between any of the group. Table 2.

Kidney and small bowel histological evaluation showed evidence of ischemic injury with early tissue loss in all intermittent arms as well as the cR group. These changes were not seen in the control animals. Representative samples from all three groups can be seen in Figure 3 for the small bowel and Figure 4 for kidney. For small bowel, there was more blunting of microvilli per magnification of both 5× and 20× with continuous REBOA when compared with the intermittent groups. The cR group also saw complete loss of villi (Fig. 3B) where this was not seen in intermittent REBOA animals using either the time-based or pressure-based protocol. Kidney tissue samples displayed more areas of hemorrhagic necrosis with increased perinephric inflammatory cell infiltration (Fig. 4B) in the cR animals as compared with samples harvested from those in the iRT/iRP groups (Fig. 4C).

Figure 3

Figure 3

Figure 4

Figure 4

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This study is the first to our knowledge to investigate and compare simplified and readily applicable bedside protocols for performing intermittent REBOA for NCTH due to severe solid organ injury. The clinical syndrome of NCTH has only recently been defined and characterized and includes physiologic disturbance in the setting of a source of major torso hemorrhage.21 Additional work has characterized the epidemiology and high mortality and morbidity with NCTH in both civilian and military cohorts.22–24 Although the use of this “catch-all” terminology is helpful epidemiologically, it is important to appreciate each specific cause of NCTH as a separate entity when studying interventions and treatment adjuncts, such as REBOA. The majority of translational studies examining REBOA for NCTH have utilized major abdominal vascular injury models, which may behave significantly differently than models utilizing other common causes of NCTH, such as severe solid-organ injury or major pelvic fractures. We performed this study using a major solid organ injury model as a follow-on to our previously reported analysis of intermittent REBOA in a vascular NCTH model.14 As suspected, based on our prior anecdotal experience, we found significant differences in the behavior and response to interventions between these two models. These areas of similarity and significant differences should be considered in any clinical applications of these data and in the testing and validation of REBOA or other interventions for NCTH.

Within the past few years, the trauma community has continued to investigate and better characterize optimal use of the REBOA catheter as a useful adjunct for NCTH.14,17,25–27 This has included efforts to improve the device and the associated algorithms and techniques for placement to minimize time to deployment and optimize it for use earlier in the immediate post-injury phase. Appropriate imaging free placement was one of the first examples of improving the time needed from placement to safe and effective inflation of the balloon. These techniques range from extracorporeal measurements, to population-based blind placement target distances and even smart phone based infrared technologies.28–30 The advent of a 7-Fr wire-free catheter (ER REBOA Catheter, Prytime Inc.) has enabled providers to be more comfortable placing these devices and decreased the overall morbidity of surgical intervention.31–33 Studies out of Japan have found survival was improved with early prehospital placement which they report doing in nearly 2% of cases.34,35 Further, rapid placement of a femoral arterial line (typically 5 Fr) is reasonable for all hemodynamically unstable patients and can be easily exchanged over a wire with a 7-Fr sheath for REBOA deployment should the clinical scenario call for it, effectively decreasing precious intervention time.34 These advances in both the technology as well as provider experience have made REBOA a more common and viable option to control hemorrhage in patients with NCTH.

The association of reperfusion injury, particularly with zone 1 placement has become a well-described phenomenon with prolonged inflation times beyond 45 minutes to 60 minutes being largely fatal.14,36–38 Zone 1 placement can also create significant supra-celiac pressure that may contribute to morbidity after REBOA use and definitive intervention.39 Intracranial pressures alone have been thought to create or worsen devastating intracranial hemorrhage.31,40 Thus, mitigation to avoid the consequences of zone 1 REBOA use has now become an important area of focus in the literature surrounding REBOA. One of the first studies to evaluate possible strategies was by Russo et al.41 in 2016 who were able to develop a model where complete occlusion was compared with a REBOA balloon that was deflated to a 50% blood pressure gradient across the occlusion in a controlled hemorrhage swine model. They were able to demonstrate improved physiology in terms of proximal MAP, duodenal necrosis, and final lactate levels over their 45-minute study time. They demonstrated similar findings when a 30% liver injury (similar to the one in our study) was created.6 One of the most significant limitations discussed is these studies is that the REBOA balloon utilized is a noncompliant balloon, and partial deflation of the currently available balloon is not clinically applicable.6,41 A study evaluating controlled restoration of distal flow to minimize the effects of rebound hypotension and potential clot destabilization showed that benefits to incremental deflation of the balloon.12 Based on their findings, they further recommended continued investigation of augmenting the way the REBOA balloon is utilized to improve outcomes.

More recently, a highly sophisticated system entitled endovascular variable aortic control, developed by Williams et al.42 utilizes concomitant bicannulation of the carotid and femoral arteries allowing carotid pressure dependent extracorporeal oxygenated blood flow distal to the REBOA occlusion during zone 1 occlusion to aide in distal perfusion. Their studies have found that use of endovascular variable aortic control may result in the need for less resuscitation, lower lactate levels, and higher levels of angiotensin II.43,44 Although these results are provocative from an academic standpoint, the need for large bore access of an additional two arteries and the requirement of a novel extracorporeal perfusion device, one can foresee profound difficulties in transitioning this system to a clinical setting much less a deployed or prehospital setting.

Clinically, partial balloon inflations have begun to be more formally evaluated as well. Although anecdotal use is common in many trauma centers in both the United States and Japan, the majority of published clinical data comes from the multicenter DIRECT-IABO investigators of Japan.32,34,35 This group has reported that partial occlusion is utilized in up to 70% of cases and is associated with a more consistent ability to achieve hemodynamic stability (78% of patients compared to 51%, p = 0.007) as well as ability for longer occlusion times at 58 minutes in the partial occlusion group compared with 33 minutes (p = 0.04).32 However, partial occlusion is not well defined in these studies, making it difficult to identify specific advantages to develop more standardized methods for prescription and wider implementation. Further, the ability to achieve reproducible and reliable partial occlusion with the noncompliant balloons that are currently available is unproven, and tight control of partial flow is not possible with existing devices. Achieving true “partial REBOA” with the ability to accurately and reliably dial-in the amount of desired flow will require redesign of both the balloon-occlusion system and the inflation/deflation system. There are currently several experimental prototype devices aiming to achieve this goal, but until these are available and validated, we must optimize strategies to minimize ischemia-reperfusion and increase the tolerable duration of zone 1 aortic occlusion.

Our laboratory has recently published the results of using our intermittent system in a 120-minute survival study for a rapidly fatal major abdominal combined arteriovenous vascular injury.14 In that study, we were able to show the feasibility of using simple deflation and inflation schedules to effectively control NCTH while preventing fatal reperfusion injury. Using identical intermittent REBOA schedules, 120-minute survival was seen in all animals which was significantly superior to the continuous REBOA at 63 minutes of survival (average, 3 minutes after deflation, p < 0.001). This improvement in survival was also accompanied by improved hemodynamic profiles as 60 minutes in intermittent groups as well as lower lactate levels. There was significantly larger blood loss in the intermittent groups (>1 L compared with 250 mL in continuous REBOA animals, p < 0.001) which was reflected in a heavier intra-abdominal clot weight and need for larger-volume blood resuscitation. Comparison in that study between the time-based intermittent group and the pressure-based group found that the total ischemia time was significantly longer in the time-based group (90 minutes vs. 48 minutes, p < 0.001) which resulted in worsened lactic acidosis in the time-based group.

The data presented here support some of the findings from our previous study. We were able to redemonstrate that our simple intermittent schedules are easily reproducible, feasible, and successful for controlling NCTH utilizing proximal MAPs for intervention monitoring and guidance. For this rapidly fatal liver injury, a time-based schedule was clearly beneficial in terms of survival to 120 minutes when compared with iRP and cR groups. For animals who were able to survive iRP, presumably early clot formation led to minimal need for proximal occlusion which in turn resulted in a more normal physiology with minimal ongoing hemorrhage over the subsequent 120 minutes. Furthermore, although not significant, there was a trend toward larger specimen weight in our iRP group (Table 1) when compared with the cR and iRT groups which may have contributed to the two early deaths seen in the iRP group. Interestingly, we found increased rate of hemorrhage as well as total hemorrhage in our cR group when compared with our iREBOA groups. We believe this may be attributed to the fact that there is some continuous venous and portal bleeding from hepatic injury even after REBOA inflation over the course of the experiment. Mean arterial pressure continues to rise in the cR group, causing significant heart strain and ultimately increases in CVP. A phenomenon not seen with intermittent strategies that may contribute to an increase in venous blood loss in the cR groups. Finally, we were able to appreciate marked differences in distal organ necrosis and ischemic changes with less damage seen in the intermittent arms when compared to continuous REBOA animals. This is remarkable given that the overall balloon inflation time was approximately 90 minutes in most intermittent animals while it was only 60 minutes in the continuous animals. If it were possible to harvest tissue at the same time point in both groups, it would have been likely even more evident. Clinically, it is recognized that the effects of end organ ischemia are progressive over time and that the relatively short survival period may even underestimate any true differences.

The findings presented here are limited by the preclinical nature of the study in an animal model and as such may not be directly applicable for human implementation. The injury and hemorrhage were standardized and do not accurately represent the largely variable nature of NCTH that occurs from traumatic injury. Further liver injury that was developed is extreme, rapidly fatal, is rare, and represents a small subset of patients; however, such model was meant to evaluate a “worst case scenario” in terms of solid organ injury for NCTH. Animals were never awakened from anesthesia, and thus, we were unable to evaluate or comment on more long-term outcomes or survival. Although early changes were seen with small bowel and kidney histology in terms of ischemic necrosis, it is difficult to comment on eventual clinical manifestations because we did not see any other physiologic differences at the 30 minutes and 60 minutes time points between the groups. Finally, given that a prolonged need for REBOA is most likely to be needed in a combat-associated, prolonged field care scenario, the resuscitation and timelines used were made to mimic such circumstances and are less applicable to centralized civilian trauma centers with early access to operating rooms or interventional angiography.

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Resuscitative endovascular balloon occlusion of the aorta has recently emerged as one of the only currently available modalities to intervene in cases of NCTH outside of the operating room or angiography-suite environment. Overwhelming ischemia-reperfusion injury continues to limit prolonged REBOA use prior to definitive interventions, particularly for zone I deployment. Previously studied partial inflation schedules of REBOA for fatal solid organ injuries have not adequately provided a simple standard approach that would be applicable in a limited resource setting. Prolonged tolerance of zone 1 REBOA for NCTH due to severe solid organ injury appears feasible with both time-based and pressure-based schedules. A simple, reproducible time-based schedule had improved overall survival while a pressure-based schedule had lower survival but resulted in less physiologic injury for animals surviving to 120 minutes. Ideally, this will be further evaluated in a prospective nature in patients with NCTH in a clinical setting.

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All authors conducted and contributed to the literature search. All authors contributed to study design. J.K., M.B., D.M., C.P., T.L. and J.K. collected the data. J.K., M.D., C.P., M.E., and M.M. interpreted the data. J.K., M.B., D.M., SM., and M.M. wrote the article. All authors critically revised the final article.

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This work was supported by a Department of Defense Medical Research and Development Program (DMRDP), DHP 6.7 research grant.

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The authors declare no conflicts of interest.

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Editorial Critique

Kuckleman and colleagues present here their well-designed examination of the impact of different approaches to REBOA implementation in a porcine hemorrhage model. The use of this adjunct continues to grow in modern trauma care and is now expanding to use in other clinical arenas plagued by the challenge of hemorrhage from non-compressible sources – including post-partum hemorrhage. In the context of this expanded use, attention has rightly turned to the mitigation of the dangers of prolonged ischemic time and re-perfusion injury. The authors here examine two approaches that are increasingly being utilized – partial balloon occlusion (p-REBOA) and intermittent REBOA.

The investigators demonstrate that both of these modalities have the potential to improve outcomes among patients for whom REBOA is employed. It is important to note, however, that each has potential challenges. Intermittent approaches, with full balloon deflation, represents the less controlled of the two modalities with regards to distal flow re-establishment. As a consequence, the theoretic risk for the dislodgement of distal clot and acute decompensation may be greater compared to p-REBOA.

By comparison, p-REBOA represents a more controlled re-introduction of distal flow and can be titrated to achieve the desired hemodynamic states above and below the level of occlusion. In this fashion, an ideal response would facilitate normotension above the balloon – to optimally perfuse both the brain and the heart – while facilitating a hypotensive resuscitative state for the tissues below the balloon – mitigating the risk for clot disruption until definitive hemorrhage control can be achieve. P-REBOA is, however, a more task intensive intervention at present – and may prove exceptionally challenging in the task saturated conditions common to emergent hemorrhage control.

Additional investigation of the optimal utilization of REBOA is required – but the authors here provide the first stones of a foundation upon which those practices can be built. I salute their very important work and look forward to their continued investigations in this arena. Their work – combined with further technological innovation that may provide assistance in achieving greater fine control of balloon titration, promise to improve outcomes among those patients for which REBOA is employed.

Joseph DuBose, MD


Intermittent REBOA; partial REBOA; prolonged field care; ischemia reperfusion injury; noncompressible truncal hemorrhage control; solid organ injury

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