Survival and neurologic outcomes following aortic occlusion for trauma and hemorrhagic shock in a hybrid operating room

Background: Outcomes following aortic occlusion for trauma and hemorrhagic shock are poor, leading some to question the clinical utility of aortic occlusion in this setting. This study evaluates neurologically intact survival following resuscitative endovascular balloon occlusion of the aorta (REBOA) vs. resuscitative thoracotomy at a center with a dedicated trauma hybrid operating room with angiographic capabilities. Methods: This retrospective cohort analysis compared patients who underwent zone 1 aortic occlusion via resuscitative thoracotomy (n=13) vs. REBOA (n=13) for blunt or non-thoracic, penetrating trauma and refractory hemorrhagic shock (systolic blood pressure less than 90 mmHg despite volume resuscitation) at a level 1 trauma center with a dedicated, trauma hybrid operating room. The primary outcome was survival to hospital discharge. The secondary outcome was neurologic status at hospital discharge, assessed by Glasgow Coma Scale (GCS) scores. Results: Overall median age was 40 years, 27% had penetrating injuries, and 23% had pre-hospital closed-chest cardiopulmonary resuscitation. In both cohorts, median Injury Severity Scores and head Abbreviated Injury Scores were 26 and 2, respectively. The resuscitative thoracotomy cohort had lower systolic blood pressure on arrival (0 [0-75] vs. 76 [65-99], p=0.009). Hemorrhage control (systolic blood pressure 100 mmHg without ongoing vasopressor or transfusion requirements) was obtained in 77% of all REBOA cases and 8% of all resuscitative thoracotomy cases (p=0.001). Survival to hospital discharge was greater in the REBOA cohort (54% vs. 8%, p=0.030), as was discharge with GCS 15 (46% vs. 0%, p=0.015). Conclusions: Among patients undergoing aortic occlusion for blunt or non-thoracic, penetrating trauma and refractory hemorrhagic shock at a center with a dedicated, trauma hybrid operating room, nearly half of all patients managed with REBOA had neurologically intact survival. The high death rate in resuscitative thoracotomy and differences in patient cohorts limit direct comparison.


Introduction
Hemorrhage accounts for approximately 40% of all trauma-related deaths overall and more than 80% of all trauma deaths that occur in operating room (1)(2)(3). Early hemorrhage control can mitigate the most common cause of potentially preventable traumatic death (4).
The optimal approach to hemorrhage control remains controversial and is in uenced by mechanism and anatomic region of injury. For penetrating trauma, resuscitative thoracotomy has an approximately 15% overall survival; though for blunt and non-thoracic penetrating trauma, outcomes are worse, with in hospital mortality for blunt trauma and cardiopulmonary resuscitation (CPR) greater than 5 minutes approaching 100% (5,6). Alternatively, resuscitative endovascular balloon occlusion of the aorta (REBOA) may control sub-diaphragmatic arterial hemorrhage and restore blood ow to the heart and brain.
In a sentinel comparison between resuscitative thoracotomy and REBOA among 285 patients in the prospective, multi-center Aortic Occlusion in Resuscitation for Trauma and Acute Care Surgery (AORTA) registry, overall survival to discharge was 2.5% for resuscitative thoracotomy and 9.6% for REBOA; median discharge Glasgow Coma Scale (GCS) scores among survivors was 3 for resuscitative thoracotomy and 9 for REBOA (7). Resuscitative thoracotomy and REBOA cohorts had different baseline characteristics, hindering direct comparisons and suggesting that patient factors in uenced surgical decision-making for aortic occlusion procedures. Regardless, outcomes for aortic occlusion in hemorrhagic shock due to blunt or non-thoracic, penetrating trauma are poor, and some question its clinical utility (8).
The authors observed greater survival and discharge GCS in a small, mixed population of trauma and non-trauma patients undergoing REBOA at their center (9). Notably, the authors' level 1 trauma center features a dedicated, trauma hybrid operating room with uniplanar angiographic capabilities; these technologies could affect the technical performance, timing, and e cacy of REBOA balloon positioning and other angiographic hemorrhage control procedures (10)(11)(12). The study adds to the literature by assessing overall outcomes for REBOA and comparing outcomes between resuscitative thoracotomy versus REBOA for refractory hemorrhagic shock due to blunt or non-penetrating, thoracic injury at a level 1 trauma center featuring a dedicated, trauma hybrid operating room. This study tested the hypothesis that REBOA would be associated with greater incidence of neurologically intact survival.

Study population
This retrospective cohort analysis included 26 consecutive adult trauma patients with blunt or nonthoracic, penetrating injuries and refractory hemorrhagic shock managed at a level 1 trauma center with a dedicated trauma hybrid operating room. Derivation of the study population is illustrated in Supplemental Twenty-six adult (age 18 years or greater) patients with blunt or non-thoracic, penetrating trauma that underwent zone 1 aortic occlusion for refractory hemorrhagic shock, de ned as systolic blood pressure less than 90 mmHg with a transient or no response to volume resuscitation. Aortic occlusion was performed by resuscitative thoracotomy and aortic cross-clamping in 13 patients and by REBOA in 13 patients. Cases of penetrating, thoracic injuries with hemorrhagic shock are a contraindication for REBOA and were therefore excluded. In these patients, thoracotomy alone provides direct exposure for operative control of exsanguinating hemorrhage. Institutional Review Board approval was obtained.

Primary outcome and power analysis
The primary outcome was survival to hospital discharge. A power analysis was performed to estimate the number of subjects per cohort that would be necessary to detect a statistically signi cant difference in survival to hospital discharge. Because the availability of a dedicated trauma hybrid operating room could affect the technical performance, timing, and e cacy of REBOA balloon positioning and other angiographic hemorrhage control procedures, the power analysis was performed using data from the authors' institution. In a prior study of REBOA use in a mixed population of trauma and non-trauma patients from the author's institution, 30-day survival was 38%; survival among eight patients undergoing resuscitative thoracotomy during the same period was 0% (9). During internal quality control audits of the REBOA experience at the authors' institution, it was noted that survival to discharge had reached 54%. Using these proportions and setting α and β to conventional values of 0.05 and 0.80, respectively, the present study would be adequately powered to detect a statistically signi cant difference in survival to hospital discharge with 13 patients in each cohort (13).

Secondary outcome and data collection
The secondary outcome was discharge GCS among survivors. Discharge GCS and other variables that were not available within the authors' prospective institutional trauma registry were obtained by manual review of the electronic health records. Variables describing patient characteristics are shown in Table   1. Variables describing patient management are shown in Table 2. Timing of hemorrhage control was de ned as attaining systolic blood pressure 100 mmHg or greater without ongoing vasopressor or blood product transfusion requirements or subsequent episodes of hypotension with systolic blood pressure less than 90 mmHg, consistent with consensus recommendations regarding blood pressure targets in damage control resuscitation after trauma (14). Variables describing resuscitation included tranexamic acid administration within four hours and transfusion of red blood cells and plasma within 24 hours. Additional, tertiary outcomes included survival past the emergency department, survival past the operating room, lengths of stay in the hospital and ICU, days on mechanical ventilation, discharge disposition, and complications classi ed by the Clavien-Dindo system that was adapted for trauma by Naumann et al. (15) Trauma hybrid operating room, REBOA equipment, technique, and staff training Our institution built a dedicated trauma hybrid operating room in a repurposed and remodeled angiography suite on the second oor of the hospital directly above the emergency department. The hybrid operating room contains a ceiling-mounted C-arm and a uoroscopy-compatible table with tilt functions. The hybrid operating room is immediately adjacent to a uoroscopy control room.
According to institutional protocols, REBOA catheters were placed by trauma surgeons for patients with blunt or non-thoracic penetrating trauma, hemorrhagic shock (i.e., systolic blood pressure <90 mmHg), and a transient response or no response to volume resuscitation (9). The REBOA procedure was either initiated in the emergency department for some patients or in the operating room for others, depending on their clinical trajectory and hemodynamic response to resuscitation. Balloon in ation was initially performed in Zone 1 for all patients. Subsequent balloon de ation and relocation to Zone 3 was at the discretion of the attending trauma surgeon based on hemodynamic response, completion of operative hemorrhage control techniques, and injury patterns. Initially, REBOA was performed with a 12-Fr introducer and aortic occlusion balloon designed by Cook Medical (Bloomington, Indiana). Subsequently, REBOA was performed using a 7-Fr introducer and aortic occlusion balloon designed by Prytime Medical (Boerne, Texas). Notably, both aortic occlusion balloon catheters must be de ated to obtain distal aortic blood ow around the balloon, in contrast to newer catheters that allow a more controlled amount of distal aortic blood ow through channels within the balloon. The senior author trained trauma surgeons and senior residents (i.e., PGY4 and PGY5 residents) in REBOA concepts and techniques with a series of 90-minute audiovisual presentations followed by hands-on simulation training (9).

Statistical analysis
To determine whether REBOA would be associated with a higher rate of neurologically intact survival, the primary outcome (hospital discharge alive) and secondary outcome (GCS at hospital discharge) were directly compared between resuscitative thoracotomy and REBOA cohorts. To understand whether potential differences in outcomes were attributable to baseline patient characteristics and other hemorrhage control and resuscitation parameters, these factors were also directly compared between resuscitative thoracotomy and REBOA cohorts. Continuous variables were compared by the nonparametric Kruskal-Wallis test and reported as median values with interquartile ranges. Binary variables were compared by Fisher's Exact test and reported as raw numbers with percentages. Signi cance level was set at 5%.

Results
The resuscitative thoracotomy cohort had greater magnitude of shock Patient characteristics are listed in Table 1. Overall median age was 40 years, 23% were female, 27% had penetrating injuries, and 23% had pre-hospital, closed-chest cardiopulmonary resuscitation of unknown duration. Median Injury Severity Scores and head Abbreviated Injury Scale scores were 26 and 2, respectively. The REBOA cohort had somewhat greater age compared with the resuscitative thoracotomy cohort, though the difference was not statistically signi cant (58 vs. 37 years, p=0.064). The incidence of pre-hospital traumatic arrest was 38% in the resuscitative thoracotomy cohort and 8% in the REBOA cohort (p=0.160). Although median GCS on arrival in the emergency department was 3 in both groups, the distribution of GCS scores in the REBOA cohort was greater (p=0.015). The resuscitative thoracotomy cohort also had lower systolic blood pressure on arrival (0 [0-75] vs. 76 [65-99], p=0.009), and greater magnitude of acidosis, though the differences were not statistically signi cant (pH: 7.08 vs. 7.19, p=0.067; lactic acid: 8.2 vs. 4.0, p=0.056). Hemoglobin values and coagulation parameters were similar between cohorts.
The REBOA cohort had a greater incidence of hemorrhage control in the operating room Hemorrhage control procedures and resuscitation parameters are listed in Table 2. Aortic occlusion was performed in the emergency department for 85% of all resuscitative thoracotomy cases and 15% of all REBOA cases (p<0.001), and was performed in the operating room for the remaining cases. There was a somewhat higher incidence of consultation with Interventional Radiology and therapeutic angiography performed in the REBOA cohort, though the differences were not statistically signi cant (31% vs. 0%, p=0.096). The frequencies of other hemorrhage control and adjunctive operative procedures were similar between cohorts. The most commonly performed procedures in both cohorts were solid organ repair or ligation of a named vessel. Intraoperative consultation with Cardiothoracic or Vascular Surgery was obtained in one resuscitative thoracotomy case (8%) and none of the REBOA cases. Hemorrhage control was obtained in 77% of all REBOA cases and 8% of all resuscitative thoracotomy cases (p=0.001). The median time to hemorrhage control (SBP 100 with no ongoing vasopressor or transfusion requirements) in the REBOA cohort was 112 minutes after arrival and 60 minutes after operating room start time. Administration of tranexamic acid within four hours and blood products within 24 hours was similar between cohorts.
The REBOA cohort had greater incidence of neurologically intact survival Survival through phases of hospital admission is illustrated in Figure 2. Survival past the emergency department was similar between cohorts (resuscitative thoracotomy: 85%; REBOA: 100%). Survival past the operating room was somewhat greater in the REBOA cohort, though the difference was not statistically signi cant (92% vs. 54%, p=0.073). Survival past discharge was signi cantly greater in the REBOA cohort (54% vs. 8%, p=0.030), as was discharge with GCS 15 (46% vs. 0%, p=0.015). Median GCS at discharge was also greater in the REBOA cohort when considering all patients (9 [3][4][5][6][7][8][9][10][11][12][13][14][15] Table 3. In the REBOA cohort, three deaths occurred after the family decided to withdraw life support (type 5A complication) and three deaths occurred during active treatment (type 5B complication); in the resuscitative thoracotomy cohort, all twelve deaths occurred during active treatment (p=0.001). One REBOA patient developed a common femoral artery pseudoaneurysm, which did not require procedural intervention. Three REBOA patients developed acute kidney injury, which may have been related to a combination of suprarenal balloon occlusion of the aorta and prolonged hemorrhagic shock. No other complications were directly attributable to REBOA. The REBOA cohort had longer lengths of stay in the hospital and ICU and had more days on mechanical ventilation, as expected given greater survival.

Discussion
In this study of patients with blunt or non-thoracic, penetrating trauma and refractory hemorrhagic shock, patients undergoing resuscitative thoracotomy had greater magnitude of shock and poor outcomes, and patients undergoing REBOA had a high incidence of neurologically intact survival.
Due to the greater magnitude of shock in the resuscitative thoracotomy group, the authors do not conclude that REBOA is superior to resuscitative thoracotomy. Differences in patient demographics between cohorts suggests that there was procedural selection bias, which may be appropriate in many cases. A greater magnitude of shock may imply pulseless femoral artery, where percutaneous femoral access is technically di cult and femoral artery cut-down may not be as expeditious as left anterolateral thoracotomy and aortic cross-clamping. Rather, the analysis suggests that patient factors contributed to surgical decision-making regarding the performance of aortic occlusion procedures, and that outcomes following REBOA were surprisingly good. More than three quarters of the REBOA cohort obtained hemorrhage control and hemodynamic stability in the operating room, and nearly half were discharged alive with GCS 15. In addition, only half of all in-hospital mortalities in the REBOA cohort occurred during active treatment. This may have important implications for family members and caregivers who would prefer the opportunity to visit their loved one prior to withdrawal of life support and those who would consider organ donation.
Previous studies have reported similar results for resuscitative thoracotomy, but less favorable results for REBOA (6, 7). As experience with REBOA among institutions and individual providers increases, the authors expect that REBOA outcomes will improve over time; indeed, improved mortality rates have been demonstrated recently (16). Institutional resources may also affect REBOA outcomes. One of the reasons for performing the present study was that the authors believe that a dedicated, trauma hybrid operating room with biplanar angiographic capabilities may affect the technical performance, timing, and e cacy of REBOA balloon positioning and other angiographic hemorrhage control procedures. In particular, the availability of a ceiling-mounted C-arm and uoroscopy-compatible operating room table facilitates uoroscopic assessment of balloon in ation and positioning as well as the performance of adjunctive endovascular stenting and embolization, without substantially interrupting the performance of operative hemorrhage control procedures. Adjunctive angiographic hemorrhage control procedures may offer performance advantages for several injury patterns, such as hemodynamically unstable pelvic fractures and some solid organ injuries (17-21). In addition, certain patients with major, hepatic venous injuries may bene t from resuscitative endovascular balloon occlusion of the vena cava (REBOVC) and selective embolization of portal venous hemorrhage (18, 22-24). Dedicated trauma hybrid operating rooms have been adopted in other countries, but are rare in the United States (10-12). More commonly, trauma surgeons have access to hybrid operating rooms that are shared with interventional radiologists as well as cardiac and vascular surgeons, and these rooms may be occupied with a non-trauma case when they are needed for managing a trauma patient presenting in extremis.
Other observations from this study are consistent with previous work. Differences in baseline characteristics of patients undergoing resuscitative thoracotomy versus REBOA are similar to those reported in the AORTA registry (7). Although hybrid operating room use has been associated with shorter intervals between arrival and the start time of interventions for hemorrhage control, time to hemorrhage control has not been previously reported (10,11). However, in a review regarding hemorrhage control after severe truncal injury, Holcomb discusses unpublished observations from the Pragmatic Randomized Optimal Platelet and Plasma Ratio (PROPPR) study, in which time to hemostasis after arrival in the operating room was approximately 67 minutes (25). Notably, time to hemostasis was also variable among sites involved in the study and was independently associated with reduced 30-day mortality. Based on subsequent publications from the PROPPR group, anatomic hemostasis was determined by the surgeon's assessment that bleeding within the surgical eld was controlled and no further hemostatic interventions were anticipated (26). This de nition is different than the one used in the present study; however, it seems reasonable to conclude that time to hemorrhage control in our study was generally consistent with the experience of centers involved in the PROPPR study.
This study was limited by selection bias inherent to its retrospective design and lack of generalizability inherent to its single institution design. The authors attempted to minimize selection bias by including all consecutive cases meeting inclusion criteria. It is possible to perform prospective investigations of trauma patients presenting in hemorrhagic shock, as demonstrated by Brenner et al. (7); however, prospective enrollment was beyond the scope of this study. Although the single-institution design of this study limits generalizability, it also allows for a unique assessment of REBOA outcomes in the context of a dedicated, trauma hybrid operating room, which is novel in the United States; this assessment may have value for other centers that are considering the implementation of a trauma hybrid operating room. While the sample size was small, the power analysis suggested that this study was adequately powered to detect a statistically signi cant difference in the primary outcome. The authors again emphasize that differences in baseline patient characteristics between resuscitative thoracotomy and REBOA cohorts precludes the conclusion that REBOA is superior to resuscitative thoracotomy for zone 1 aortic occlusion in blunt or non-thoracic, penetrating trauma and refractory hemorrhagic shock. These ndings support the hypothesis that that patient factors contribute to surgical decision-making regarding the performance of resuscitative thoracotomy vs. REBOA, and that further investigation is necessary to establish consensus recommendations regarding aortic occlusion in this patient population. Similarly, we were unable to control for patients who presented in hemorrhagic shock who proceeded directly to operating room without resuscitative thoracotomy or REBOA. It is possible that the REBOA patients may have bene ted from expeditious, open surgical hemorrhage control regardless of REBOA placement.

Conclusions
Among patients undergoing zone 1 aortic occlusion for blunt or non-thoracic, penetrating trauma and refractory hemorrhagic shock at a center with a dedicated, trauma hybrid operating room, nearly half of all patients managed with REBOA had neurologically intact survival. Differences in baseline characteristics of patients undergoing resuscitative thoracotomy versus REBOA support the hypothesis that that patient factors contribute substantially to surgical decision-making regarding controversial hemorrhage control procedures for trauma patients presenting in extremis. Speci cally, resuscitative thoracotomy may be favored for patients with greater magnitude of shock, more urgency for hemorrhage control, and pulseless femoral arteries that are di cult to cannulate for REBOA insertion. Further research is needed to determine the potential advantages in early hemorrhage control offered by a dedicated, trauma hybrid operating room.

Declarations
-Ethical Approval and Consent to participate: Institutional Review Board approval was obtained (#202001256). As a retrospective review, no consent was required.
-Consent for publication The authors provide consent for publication. By submitting our article we agree to pay the APC in full if our article is accepted for publication -Availability of data and materials Raw data may be made available upon request.
-Competing interests: I declare that the authors have no competing interests as de ned by BMC, or other interests that might be perceived to in uence the results and/or discussion reported in this paper.      Figure 1 Forty-six percent of all patients undergoing REBOA for blunt or non-thoracic, penetrating trauma and hemorrhagic shock achieved survival to discharge with GCS 15.

Figure 2
This image is not available with this version.

Supplementary Files
This is a list of supplementary les associated with this preprint. Click to download. SupplementalFig1AOstudypopulation.tiff