Renal effects of three endoaortic occlusion strategies in a swine model of hemorrhagic shock.

INTRODUCTION: Trauma patients are predisposed to kidney injury. We hypothesized that in shock, zone 3 REBOA would increase renal blood flow (RBF) compared to control and that a period of zone 3 occlusion following zone 1 occlusion would improve renal function compared to zone 1 occlusion alone. MATERIALS AND METHODS: Twenty-four anesthetized swine underwent hemorrhagic shock, 45 min of zone 1 REBOA (Z1, supraceliac), zone 3 REBOA (Z3, infrarenal), or no intervention (control) followed by resuscitation with shed blood and 5 h of critical care. In a fourth group (Z1Z3), animals underwent 55 min of zone 3 REBOA following zone 1 occlusion. Physiologic parameters were recorded, blood and urine were collected at specified intervals. RESULTS: During critical care, there were no differences in RBF between the Z1 and Z3 groups. The average RBF during critical care in Z1Z3 was significantly lower than in Z3 alone (98.2 ±â€¯23.9 and 191.9 ±â€¯23.7 mL/min; p = 0.046) and not different than Z1. There was no difference in urinary neutrophil gelatinase-associated lipocalin-to-urinary creatinine ratio between Z1 and Z1Z3. Animals in the Z1Z3 group had a significant increase in the ratio at the end of the experiment compared to baseline [median (IQR)] [9.2 (8.2-13.2) versus 264.5 (73.6-1174.6)]. Following Z1 balloon deflation, RBF required 45 min to return to baseline. CONCLUSION: Neither zone 3 REBOA alone nor zone 3 REBOA following zone 1 REBOA improved renal blood flow or function. Following zone 1 occlusion, RBF is restored to baseline levels after approximately 45 min.

Resuscitative Endovascular Balloon Occlusion of the Aorta: Review of the Literature and Applications to Veterinary Emergency and Critical Care.

While hemorrhagic shock might be the result of various conditions, hemorrhage control and resuscitation are the corner stone of patient management. Hemorrhage control can prove challenging in both the acute care and surgical settings, especially in the abdomen, where no direct pressure can be applied onto the source of bleeding. Resuscitative endovascular balloon occlusion of the aorta (REBOA) has emerged as a promising replacement to resuscitative thoracotomy (RT) for the management of non-compressible torso hemorrhage in human trauma patients. By inflating a balloon at specific levels (or zones) of the aorta to interrupt blood flow, hemorrhage below the level of the balloon can be controlled. While REBOA allows for hemorrhage control and augmentation of blood pressure cranial to the balloon, it also exposes caudal tissue beds to ischemia and the whole body to reperfusion injury. We aim to introduce the advantages of REBOA while reviewing known limitations. This review outlines a step-by-step approach to REBOA implementation, and discusses common challenges observed both in human patients and during translational large animal studies. Currently accepted and debated indications for REBOA in humans are discussed. Finally, we review possible applications for veterinary patients and how REBOA has the potential to be translated into clinical veterinary practice.

Resuscitative endovascular balloon occlusion of the aorta induced myocardial injury is mitigated by endovascular variable aortic control.

BACKGROUND: The cardiac effects of resuscitative endovascular balloon occlusion of the aorta (REBOA) are largely unknown. We hypothesized that increased afterload from REBOA would lead to cardiac injury, and that partial flow using endovascular variable aortic control (EVAC) would mitigate this injury. METHODS: Eighteen anesthetized swine underwent controlled 25% blood volume hemorrhage. Animals were randomized to either Zone 1 REBOA, Zone 1 EVAC, or no intervention (control) for 45 minutes. Animals were then resuscitated with shed blood, observed during critical care, and euthanized after a 6-hour total experimental time. Left ventricular function was measured with a pressure-volume catheter, and blood samples were drawn at routine intervals. RESULTS: The average cardiac output during the intervention period was higher in the REBOA group (9.3 [8.6-15.4] L/min) compared with the EVAC group (7.2 [5.8-8.0] L/min, p = 0.01) and the control group (6.8 [5.8-7.7] L/min, p < 0.01). At the end of the intervention, the preload recruitable stroke work was significantly higher in both the REBOA and EVAC groups compared with the control group (111.2 [102.5-148.6] and 116.7 [116.6-141.4] vs. 67.1 [62.7-87.9], p = 0.02 and p < 0.01, respectively). The higher preload recruitable stroke work was maintained throughout the experiment in the EVAC group, but not in the REBOA group. Serum troponin concentrations after 6 hours were higher in the REBOA group compared with both the EVAC and control groups (6.26 ± 5.35 ng/mL vs 0.92 ± 0.61 ng/mL and 0.65 ± 0.38 ng/mL, p = 0.05 and p = 0.03, respectively). Cardiac intramural hemorrhage was higher in the REBOA group compared with the control group (1.67 ± 0.46 vs. 0.17 ± 0.18, p = 0.03), but not between the EVAC and control groups. CONCLUSION: In a swine model of hemorrhagic shock, complete aortic occlusion resulted in cardiac injury, although there was no direct decrease in cardiac function. EVAC mitigated the cardiac injury and improved cardiac performance during resuscitation and critical care.

Endovascular Perfusion Augmentation for Critical Care: Partial Aortic Occlusion for Treatment of Severe Ischemia-Reperfusion Shock.

BACKGROUND: The resuscitation of patients in shock is materially intensive and many patients are refractory to maximal therapy. We hypothesized that partial inflation of an intra-aortic balloon, termed Endovascular Perfusion Augmentation for Critical Care (EPACC), would minimize material requirements while improving physiologic metrics. METHODS: Swine underwent a 25% controlled bleed and 45 min of complete aortic occlusion to create a severe ischemia-reperfusion shock state. Animals received either standardized critical care (SCC) composed of IV fluids and norepinephrine delivered through an algorithmically controlled platform or EPACC in addition to SCC. Physiologic parameters were collected, and blood was sampled for analysis. Primary outcomes were total IV fluids and average MAP during the critical care phase. Differences (P < 0.05) were measured with t test (continuous data) and Wilcoxon rank-sum test (ordinal data). RESULTS: There were no differences in baseline characteristics. There were no differences in the maximum lactate; however, animals in the EPACC group had a higher average MAP (EPACC 65 mmHg, 95% confidence interval [CI], 65-66; SCC 60 mmHg, 95% CI, 57-63; P < 0.01) and remained within goal MAP for a greater period of time (EPACC 95.3%, 95% CI, 93.2-97.4; SCC 51.0%, 95% CI, 29.5-72.6; P < 0.01). EPACC animals required less IV fluids when compared with the SCC group (EPACC 21 mL/kg, 95% CI, 0-42; SCC 96 mL/kg, 95% CI, 76-117; P < 0.01). There were no differences in final lactate. Animals in the EPACC group had a higher final creatinine (EPACC 2.3 mg/dL, 95% CI, 2.1-2.5; SCC 1.7 mg/dL, 95% CI, 1.4-2.0; P < 0.01), but there were no differences in renal cellular damage on histology (P = 0.16). CONCLUSION: Using a swine model of severe shock, the addition of EPACC to SCC significantly reduced fluid resuscitation requirements and improved blood pressure. This is the first description of a new therapy for patients in refractory shock or in resource-limited settings.

Pharmacokinetics of Tranexamic Acid via Intravenous, Intraosseous, and Intramuscular Routes in a Porcine (Sus scrofa) Hemorrhagic Shock Model.

BACKGROUND: Intravenous (IV) tranexamic acid (TXA) is an adjunct for resuscitation in hemorrhagic shock; however, IV access in these patients may be difficult or impossible. Intraosseous (IO) or intramuscular (IM) administration could be quickly performed with minimal training. We investigated the pharmacokinetics of TXA via IV, IO, and IM routes in a swine model of controlled hemorrhagic shock. METHODS: Fifteen swine were anesthetized and bled of 35% of their blood volume before randomization to a single 1g/10mL dose of IV, IO, or IM TXA. Serial serum samples were obtained after TXA administration. These were analyzed with high-pressure liquid chromatography-mass spectrometry to determine drug concentration at each time point and define the pharmacokinetics of each route. RESULTS: There were no significant differences in baseline hemodynamics or blood loss between the groups. Peak concentration (Cmax) was significantly higher in IV and IO routes compared with IM (p = .005); however, the half-life of TXA was similar across all routes (p = .275). CONCLUSION: TXA administration via IO and IM routes during hemorrhagic shock achieves serum concentrations necessary for inhibition of fibrinolysis and may be practical alternatives when IV access is not available.

Endovascular variable aortic control (EVAC) versus resuscitative endovascular balloon occlusion of the aorta (REBOA) in a swine model of hemorrhage and ischemia reperfusion injury.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is effective at limiting hemorrhage from noncompressible sources and restoring but causes progressive distal ischemia, supraphysiologic pressures, and increased cardiac afterload. Endovascular variable aortic control (EVAC) addresses these limitations, while still controlling hemorrhage. Previous work demonstrated improved outcomes following a 90-minute intervention period in an uncontrolled hemorrhage model. The present study compares automated EVAC to REBOA over an occlusion period reflective of contemporary REBOA usage. METHODS: Following instrumentation, 12 Yorkshire-cross swine underwent controlled 25% hemorrhage, a 45-minute intervention period of EVAC or REBOA, and subsequent resuscitation with whole blood and critical care for the remainder of a 6-hour experiment. Hemodynamics were acquired continuously, and laboratory parameters were assessed at routine intervals. Tissue was collected for histopathologic analysis. RESULTS: No differences were seen in baseline parameters. During intervention, EVAC resulted in more physiologic proximal pressure augmentation compared with REBOA (101 vs. 129 mm Hg; 95% confidence interval [CI], 105-151 mm Hg; p = 0.04). During critical care, EVAC animals required less than half the amount of crystalloid (3,450 mL; 95% CI, 1,215-5,684 mL] vs. 7,400 mL [95% CI, 6,148-8,642 mL]; p < 0.01) and vasopressors (21.5 ng/kg [95% CI, 7.5-35.5 ng/kg] vs. 50.5 ng/kg [95% CI, 40.5-60.5 ng/kg]; p = 0.05) when compared with REBOA animals. Endovascular variable aortic control resulted in lower peak and final lactate levels. Endovascular variable aortic control animals had less aortic hyperemia from reperfusion with aortic flow rates closer to baseline (36 mL/kg per minute [95% CI, 30-44 mL/kg per minute] vs. 51 mL/kg per minute [95% CI, 41-61 mL/kg per minute]; p = 0.01). CONCLUSIONS: For short durations of therapy, EVAC produces superior hemodynamics and less ischemic insult than REBOA in this porcine-controlled hemorrhage model, with improved outcomes during critical care. This study suggests EVAC is a viable strategy for in-hospital management of patients with hemorrhagic shock from noncompressible sources. Survival studies are needed to determine if these early differences persist over time.

Location is everything: The hemodynamic effects of REBOA in Zone 1 versus Zone 3 of the aorta.

OBJECTIVES: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an emerging technology to augment proximal blood pressure during the resuscitation of patients with noncompressible torso hemorrhage. Currently, placement choice, supraceliac (Zone 1) versus infrarenal (Zone 3) aorta, depends on injury patterns, but remains a highly debated topic. We sought to compare the proximal hemodynamic support provided by Zone 1 versus Zone 3 REBOA placement and the degree of hemodynamic instability upon reperfusion following intervention. METHODS: Eighteen anesthetized swine underwent controlled hemorrhage of 25% total blood volume, followed by 45 minutes of Zone 1 REBOA, Zone 3 REBOA, or no intervention (control). They were then resuscitated with shed blood, aortic balloons were deflated, and 5 hours of critical care ensued prior to euthanasia. Physiologic parameters were recorded continuously, and blood was drawn for analysis at specified intervals. Significance was defined as p < 0.05. RESULTS: There were no significant differences between groups at baseline or during the initial 30 minutes of hemorrhage. During the intervention period, average proximal MAP was significantly greater in Zone 1 animals when compared with Zone 3 animals (127.9 ± 1.3 vs. 53.4 ± 1.1 mm Hg) and greater in Zone 3 animals when compared with control animals (42.9 ± 0.9 mm Hg). Lactate concentrations were significantly higher in Zone 1 animals (9.6 ± 0.4 mmol/L) when compared with Zone 3 animals (5.1 ± 0.3 mmol/L) and control animals (4.2 ± 0.8 mmol/L). CONCLUSIONS: In our swine model of hemorrhagic shock, Zone 3 REBOA provided minimal proximal hemodynamic support when compared with Zone 1 REBOA, albeit with less ischemic burden and instability upon reperfusion. In cases of impending hemodynamic collapse, Zone 1 REBOA placement may be more efficacious regardless of injury pattern, whereas Zone 3 should be reserved only for relatively stable patients with ongoing distal hemorrhage.

Lower extremity cooling reduces ischemia-reperfusion injury following Zone 3 REBOA in a porcine hemorrhage model.

BACKGROUND: New strategies to mitigate ischemia during REBOA and to prolong its maximal duration are needed. We hypothesized that simple external cooling of the hind limbs would decrease ischemia-reperfusion injury following prolonged Zone 3 REBOA. METHODS: Twelve swine were anesthetized, instrumented, splenectomized, and then underwent 15% total blood volume hemorrhage. Animals were randomized to hypothermia or control followed by 4 hours of Zone 3 REBOA, resuscitation with shed blood, and 3 hours of critical care. Physiologic parameters were continuously recorded, and laboratory specimens were obtained at regular intervals. Baseline and end-of-study muscle biopsies were obtained for histologic analysis. RESULTS: There were no significant differences between groups at baseline or after hemorrhage. Maximum creatine kinase was significantly lower in the hypothermia group compared with the normothermia group (median [interquartile range] = 3,445 U/mL [3,380-4,402 U/mL] vs. 22,544 U/mL [17,030-24,981 U/mL]; p < 0.01). Maximum serum myoglobin was also significantly lower in the hypothermia group (1,792 ng/mL [1,250-3,668 ng/mL] vs. 21,186 ng/mL [14,181-24,779 ng/mL]; p < 0.01). Fascial compartment pressures were significantly lower during critical care in the hypothermia group (p = 0.03). No histologic differences were observed in hind limb skeletal muscle. CONCLUSIONS: External cooling during prolonged Zone 3 REBOA decreased ischemic muscle injury and resulted in lower compartment pressures following reperfusion. Hypothermia may be a viable option to extend the tolerable duration of Zone 3 occlusion, beyond what is currently achievable. Future survival studies are required to assess functional outcomes.

EAST Multicenter Trial on targeted temperature management for hanging-induced cardiac arrest.

BACKGROUND: We sought to determine the outcome of suicidal hanging and the impact of targeted temperature management (TTM) on hanging-induced cardiac arrest (CA) through an Eastern Association for the Surgery of Trauma (EAST) multicenter retrospective study. METHODS: We analyzed hanging patient data and TTM variables from January 1992 to December 2015. Cerebral performance category score of 1 or 2 was considered good neurologic outcome, while cerebral performance category score of 3 or 4 was considered poor outcome. Classification and Regression Trees recursive partitioning was used to develop multivariate predictive models for survival and neurologic outcome. RESULTS: A total of 692 hanging patients from 17 centers were analyzed for this study. Their overall survival rate was 77%, and the CA survival rate was 28.6%. The CA patients had significantly higher severity of illness and worse outcome than the non-CA patients. Of the 175 CA patients who survived to hospital admission, 81 patients (46.3%) received post-CA TTM. The unadjusted survival of TTM CA patients (24.7% vs 39.4%, p < 0.05) and good neurologic outcome (19.8% vs 37.2%, p < 0.05) were worse than non-TTM CA patients. However, when subgroup analyses were performed between those with an admission Glasgow Coma Scale score of 3 to 8, the differences between TTM and non-TTM CA survival (23.8% vs 30.0%, p = 0.37) and good neurologic outcome (18.8% vs 28.7%, p = 0.14) were not significant. Targeted temperature management implementation and post-CA management varied between the participating centers. Classification and Regression Trees models identified variables predictive of favorable and poor outcome for hanging and TTM patients with excellent accuracy. CONCLUSION: Cardiac arrest hanging patients had worse outcome than non-CA patients. Targeted temperature management CA patients had worse unadjusted survival and neurologic outcome than non-TTM patients. These findings may be explained by their higher severity of illness, variable TTM implementation, and differences in post-CA management. Future prospective studies are necessary to ascertain the effect of TTM on hanging outcome and to validate our Classification and Regression Trees models. LEVEL OF EVIDENCE: Therapeutic study, level IV; prognostic study, level III.