Swine Model Of Hemorrhagic Shock Research Articles

229 A Comparison of Intraosseous Pressure Transfusion Strategies in a High Bone Density In Vivo Swine Model of Hemorrhagic Shock

229 A Comparison of Intraosseous Pressure Transfusion Strategies in a High Bone Density In Vivo Swine Model of Hemorrhagic Shock

MILD THERAPEUTIC HYPOTHERMIA REDUCES ISCHEMIA-REPERFUSION INJURY AFTER ZONE 1 REBOA IN A SWINE HEMORRHAGIC SHOCK MODEL.

Background: Resuscitative balloon occlusion of the aorta (REBOA) is an endovascular hemostasis method used for the management of traumatic abdominal and pelvic hemorrhages. However, REBOA-associated ischemia-reperfusion injury complication limits its blocking time. We hypothesized that mild therapeutic hypothermia would relieve ischemia-reperfusion injury caused by prolonged zone 1 REBOA. Methods: Ten pigs were anesthetized, intubated, and subsequently struck with the experimental sliding-chamber ballistic gun to inflict liver damage. Animals were randomized to hypothermia (60 min of zone 1 REBOA with external cooling for 180 min, n = 5) or control (60 min of zone 1 REBOA with no external cooling, n = 5). Physiological and laboratory parameters were monitored and assessed. Distal organs were obtained for histologic analysis. Results: At 180 min, compared with the control, the hypothermia animals exhibited significantly increased pH and significantly reduced lactate, hemoglobin, and hematocrit (all P < 0.05). The change of lactate from 0 to 180 min in hypothermia animals was less than that in the control ( P = 0.02). The total bleeding in the control group was significantly less than the hypothermia ( P < 0.01). In the hypothermia group, prothrombin time at 120 and 180 min was significantly longer than that at baseline (all P < 0.05). Compared with the control, animals in the hypothermia group showed slighter pathological injury of the distal organs and significantly lower overall injury score (all P < 0.05). Conclusions: Mild therapeutic hypothermia during prolonged zone 1 REBOA offered extraordinary distal organ preservation and decreased metabolic acidosis.

Adaptive Balloon Weaning Algorithm With Automated REBOA Facilitates Proximal Homeostasis During Reperfusion in a Swine Hemorrhagic Shock Model

Restoration of distal blood flow is critical to successfully salvage patients with resuscitative endovascular balloon occlusion of the aorta (REBOA). Yet, ideal methods for REBOA deflation to restore flow and simultaneously avoid proximal hypotension, remain undefined. Adaptive balloon titration algorithms to guide deflation may prevent large hemodynamic fluctuations during weaning. We hypothesize that automated REBOA weaning can both augment proximal hemodynamics and avoid hypotension during resuscitation in a swine model of hemorrhagic shock. Fifteen swine underwent 30% controlled hemorrhage followed by 30 minutes of zone 1 REBOA. Next, the REBOA was deflated with an automated syringe running an adaptive algorithm that prioritized proximal mean arterial blood pressure (pMAP) of >62.5 mm Hg during transfusion of shed blood. Upon post hoc analysis, animal pMAP responses (hypertensive [HTN] vs normotensive [NORM]) and the discovery of low volume distal flow during the intended complete REBOA allowed us to identify two distinct cohorts. The performance of the adaptive weaning algorithm was compared between the groups. The two cohorts (HTN, n = 5; NORM, n = 10) differed in pMAP (P = .001) and distal flow (P = .001) during REBOA. During the wean phase, cohorts were similar in pMAP, time with carotid flow within 90% of baseline, and time above the pMAP threshold of 62.5 mm Hg (P = .20, P = .59, and P = .95, respectively) despite the weaning algorithm permitting 14.5 mL/kg more distal aortic flow for the HTN cohort (P = .001). Automated REBOA weaning is feasible and maintains consistent hemodynamics across various physiological profiles. Automated endovascular devices that can interpret and adapt to a range of hemodynamic physiology will soon facilitate precision resuscitation for patients requiring endovascular aortic occlusion. These findings highlight the need for adaptive control to overcome variability in hemodynamics and differences in resuscitation intensity across clinical contexts.

Elamipretide mitigates ischemia-reperfusion injury in a swine model of hemorrhagic shock

ischemia-reperfusion injury (IRI) after hemorrhage is potentiated by aortic occlusion or resuscitative endovascular balloon occlusion of the aorta (REBOA). Given the central role of mitochondrial injury in shock, we hypothesized that Elamipretide, a peptide that protects mitochondria, would mitigate IRI after hemorrhagic shock and REBOA. Twelve pigs were subjected to hemorrhagic shock and 45 min of REBOA. After 25 min of REBOA, animals received either saline or Elamipretide. Animals were transfused with autologous blood during balloon deflation, and pigs were resuscitated with isotonic crystalloids and norepinephrine for 4.25 h. Elamipretide-treated animals required less crystalloids than the controls (62.5 [50–90] and 25 [5–30] mL/kg, respectively), but similar amounts of norepinephrine (24.7 [8.6–39.3] and 9.7 [2.1–12.5] mcg/kg, respectively). Treatment animals had a significant reduction in serum creatinine (control: 2.7 [2.6–2.8]; Elamipretide: 2.4 [2.4–2.5] mg/dL; p = 0.04), troponin (control: 3.20 [2.14–5.47] ng/mL, Elamipretide: 0.22 [0.1–1.91] ng/mL; p = 0.03), and interleukin-6 concentrations at the end of the study. There were no differences in final plasma lactate concentration. Elamipretide reduced fluid requirements and protected the kidney and heart after profound IRI. Further understanding the subcellular consequences of REBOA and mitochondrial rescue will open new therapeutic avenues for patients suffering from IRI after hemorrhage.

Quantifying the Cardiovascular Physiology of REBOA and Partial REBOA: How REBOA Facilitates Resuscitation but Also Strains the Left Ventricle

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is increasingly used as an endovascular approach to aortic occlusion. This can provide complete or partial aortic occlusion and is thereby known to augment afterload relative to the extent of occlusion. Despite the increasing use of this tool, little cardiovascular physiology has been quantified across clinically relevant REBOA transitions: placement of occlusive REBOA, then transition to partially occlusive REBOA, and lastly, REBOA removal. The goal of this study is to use pressure-volume loop analysis and direct left coronary artery blood flow measurements to capture these transitions in a swine model of hemorrhagic shock to elucidate the underlying physiologic mechanism of clinical REBOA use. Swine underwent complex surgical and vascular access instrumentation to capture real-time left ventricular pressure-volume loops and directly measure left coronary flow (Figure 1). Animals were hemorrhaged to 45 mmHg with subsequent placement of fully occlusive REBOA, followed by transition to partial REBOA while these data were captured. A full methodological protocol has been published: https://doi.org/10.21203/rs.3.pex-1646/v1. Five male swine underwent this protocol (mean weight, 53.6 ± 3.6 kg). Hemorrhagic shock was induced and maintained with reduction of stroke work (baseline: 3.1 L × mmHg vs shock: 1.2 L × mmHg; P < .01) and average end systolic pressure (109.8 vs 59.6 mmHg; P = .02). REBOA augmented the end systolic pressure volume relationship. Stroke work evolved with placement of occlusive REBOA (1.2 vs 4.3 mmHgL; P < .01). End systolic elastance was augmented from baseline by shock and REBOA placement (1.01 vs 0.39 vs 4.50 mL/mmHg; P < .01) and remained elevated with transition to partial REBOA (3.22 mL/mmHg) (Figure 2). Percent time in antegrade coronary blood flow decreased during shock (94% to 71.8%; P < .01) and was rescued with REBOA, but REBOA also increased peak coronary flow compared with shock (271 vs 93 mL/min; P < .01) and total coronary flow, even beyond baseline (peak: 2136 vs baseline: 424 mL/min; P < .01). No REBOA state augmented the end diastolic pressure volume relationship. REBOA maintains the end diastolic pressure volume relationship, but increases afterload, thereby augmenting the end systolic pressure volume relationship and left ventricle contractility with partial REBOA. REBOA alters coronary artery blood flow by reversing shock-induced retrograde coronary flow, and increasing peak coronary artery flow, therefore increasing total flow. The afterload modulation from REBOA underlies its resuscitative capability but may drive the mechanism of cardiovascular injury. Partial REBOA with resuscitation balances the afterload improvement against undue left ventricle strain.Fig 2End systolic elastance (Ees; the slope of the end systolic pressure volume relationship) evolution across study periods. *P = .003; **P = .048; ***P = .01; ****P = .015.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

The physiology of aortic flow and pressures during partial resuscitative endovascular balloon occlusion of the aorta in a swine model of hemorrhagic shock

Partial resuscitative endovascular balloon occlusion of the aorta (REBOA) has shown promise as a method to extend REBOA, but there lacks a standard definition of the technique. The purpose of this study was to investigate the relationships between distal and proximal mean arterial pressure (MAP) and distal aortic flow past a REBOA catheter. We hypothesize that a relationship between distal aortic flow and distal MAP in Zone 1 partial REBOA (pREBOA) is conserved and that there is no apparent relationship between aortic flow and proximal MAP. A retrospective data analysis of swine was performed. Cohort 1 underwent 20% controlled hemorrhage and then randomized to aortic flow of 400 mL/min or complete occlusion for 20 minutes (n = 11). Cohort 2 underwent 30% controlled hemorrhage followed by complete aortic occlusion for 30 minutes (n = 29). Then, they all underwent REBOA wean in a similar stepwise fashion. Blood pressure was collected from above (proximal) and below (distal) the REBOA balloon. Aortic flow was measured using a surgically implanted supraceliac aortic perivascular flow probe. The time period of balloon wean was taken as the time point of interest. A linear relationship between distal MAP and aortic flow was observed ( R2 value, 0.80), while no apparent relationship appeared between proximal MAP and aortic flow ( R2 value, 0.29). The repeated-measures correlation coefficient for distal MAP (0.94; 95% confidence interval, 0.94-0.94) was greater than proximal MAP (-0.73; 95% confidence interval, -0.74 to -0.72). The relationship between MAP and flow will be a component of next-generation pREBOA control inputs. This study provides evidence that pREBOA techniques should rely on distal rather than proximal MAP for control of distal aortic flow. These data could inform future inquiry into optimal flow rates and parameters based on distal MAP in both translational and clinical contexts.

Assessment of left ventricle myocardial deformation in a hemorrhagic shock swine model by two-dimensional speckle tracking echocardiography.

Trauma-induced secondary cardiac injury has been associated with significant adverse cardiovascular events. Speckle tracking echocardiography is a novel technology that allows an accurate and reproducible cardiac structure and function assessment. We evaluated the left ventricle (LV) myocardial deformation by speckle tracking echocardiography in a hemorrhagic shock (HS) swine model. Seven healthy male Landrace pigs were included in this study. Severe HS was reached through three sequentially blood withdraws of 20% of estimated blood volume, and it was maintained for 60 minutes. Volume resuscitation was performed using all precollected blood volume. A 1.8- to 4.2-MHz phased-array transducer was used to acquire the two-dimensional echocardiography images. Strain measurements were obtained semiautomatically by wall motion tracking software. Results are presented as medians and interquartile ranges and compared using Wilcoxon rank-sum test. A p value of <0.05 was considered statistically significant. The median weight was 32 (26.1-33) kg, and the median total blood volume withdrawn was 1,100 (1,080-1,190) mL. During the severe HS period, the median arterial systemic pressure was 39 (36-46) mm Hg, and the cardiac index was 1.7 (1.6-2.0) L/min/m 2 . There was statistically significant absolute decrease in the global longitudinal strain 2 hours postresuscitation comparing with the basal measurements (-9.6% [-10.7 to -8.0%] vs. -7.9% [-8.1 to -7.4%], p = 0.03). There were no statistically significant differences between the basal and 2 hours postresuscitation assessments in the invasive/noninvasive hemodynamic, other two-dimensional echocardiogram (LV ejection fraction, 49.2% [44-54.3%] vs. 53.2% [51.5-55%]; p = 0.09), and circumferential strain (-10.6% [-14.4 to -9.0%] vs. -8.5% [-8.6 to -5.2%], p = 0.06) parameters. In this experimental swine model of controlled HS, LV global longitudinal strain analysis accurately characterizes the timing and magnitude of subclinical cardiac dysfunction associated with trauma-induced secondary cardiac injury.

Dimethyl malonate slows succinate accumulation and preserves cardiac function in a swine model of hemorrhagic shock.

Succinate (SI) is a citric acid cycle metabolite that accumulates in tissues during hemorrhagic shock (HS) due to electron transport chain uncoupling. Dimethyl malonate (DMM) is a competitive inhibitor of SI dehydrogenase, which has been shown to reduce SI accumulation and protect against reperfusion injury. Whether DMM can be therapeutic after severe HS is unknown. We hypothesized that DMM would prevent SI buildup during resuscitation (RES) in a swine model of HS, leading to better physiological recovery after RES. The carotid arteries of Yorkshire pigs were cannulated with a 5-Fr catheter. After placement of a Swan-Ganz catheter and femoral arterial line, the carotid catheters were opened and the animals were exsanguinated to a mean arterial pressure (MAP) of 45 mm. After 30 minutes in the shock state, the animals were resuscitated to a MAP of 60 mm using lactated ringers. A MAP above 60 mm was maintained throughout RES. One group received 10 mg/kg of DMM (n = 6), while the control received sham injections (n = 6). The primary end-point was SI levels. Secondary end-points included cardiac function and lactate. Succinate levels increased from baseline to the 20-minute RES point in control, while the DMM cohort remained unchanged. The DMM group required less intravenous fluid to maintain a MAP above 60 (450.0 vs. 229.0 mL; p = 0.01). The DMM group had higher pulmonary capillary wedge pressure at the 20-minute and 40-minute RES points. The DMM group had better recovery of cardiac output and index during RES, while the control had no improvement. While lactate levels were similar, DMM may lead to increased ionized calcium levels. Dimethyl malonate slows SI accumulation during HS and helps preserve cardiac filling pressures and function during RES. In addition, DMM may protect against depletion of ionized calcium. Dimethyl malonate may have therapeutic potential during HS.

Swine hemorrhagic shock model and pathophysiological changes in a desert dry-heat environment.

BackgroundThis study aimed to establish a traumatic hemorrhagic shock (THS) model in swine and examine pathophysiological characteristics in a dry-heat environment.MethodsForty domestic Landrace piglets were randomly assigned to four study groups: normal temperature non-shock (NS), normal temperature THS (NTHS), desert dry-heat non-shock (DS), and desert dry-hot THS (DTHS) groups. The groups were exposed to either normal temperature (25°C) or dry heat (40.5°C) for 3 h. To induce THS, anesthetized piglets in the NTHS and DTHS groups were subjected to liver trauma and hypovolemic shock until death, and piglets in the NS and DS groups were euthanized at 11 h and 4 h, respectively. Body temperature, blood gas, cytokine production, and organ function were assessed before and after environmental exposure at 0 h and at every 30 min after shock to death. Hemodynamics was measured post exposure and post-shock at 0 h and at every 30 min after shock to death.ResultsSurvival, body temperature, oxygen delivery, oxygen consumption, and cardiac output were significantly different for traumatic hemorrhagic shock in the dry-heat groups compared to those in the normal temperature groups. Lactic acid and IL-6 had a marked increase at 0.5 h, followed by a progressive and rapid increase in the DTHS group.ConclusionsOur findings suggest that the combined action of a dry-heat environment and THS leads to higher oxygen metabolism, poorer hemodynamic stability, and earlier and more severe inflammatory response with higher mortality.

Abstract 143: The Modified Shock Index Separates Survivors from Non-Survivors in a Swine Model of Hemorrhagic Shock and Traumatic Brain Injury

The ratio between heart rate and arterial blood pressure during hemorrhagic shock has been shown useful to identify individuals at risk of death. We herein compared the index using the systolic arterial pressure (SI) and using the mean arterial pressure (MSI) along with other measurements including cardiac index and lactate in a swine model of hemorrhagic shock and traumatic brain injury developed to model injury in the battlefield. The parent study was designed to compare three different types of vasopressin agonists with control solution while practicing fluid-restricted resuscitation. The present analysis included 60 experiments focused on the initial 240 minutes with induction of hemorrhagic shock by liver laceration removing approximately 1,000 ml of blood in 30 minutes. Eight animals died during the acute phase and compare to 52 survivors, they had higher (median, IQR) MSI (4.6; 3.3 - 5.4 vs 2.5; 2.0 - 3.1; p &lt; 0.001), SI (2.7; 2.1 - 3.1 vs 1.8; 1.6 - 2.2; p &lt; 0.001), lower cardiac index (2.8; 2.3 - 3.4 vs 3.7; 3.2 - 4.2; p &lt; 0.001), but no differences in lactate levels. Three of the eight non-survivors (37.5%) and 42 of the 52 survivors (80.1%) received a vasopressin analog (p = 0.019). Compared to other measurements of hemodynamic stability, monitoring the ratio between the heart rate and mean arterial pressure is a feasible and practical approach to deploy in various out of hospital settings including the battlefield as well as in civilian trauma. This approach could also guide interventions including the use of vasopressor agents, which our studies demonstrate having a survival effect during acute bleeding caused by hemorrhagic shock.

Pulse Oximeter Plethysmograph Variation During Hemorrhage in Beta-Blocker–Treated Swine

BackgroundBeta-blockers blunt the stress response to hemorrhage. Our aim was to investigate the feasibility of noninvasive pulse oximeter plethysmographic waveform variation (PoPV) for predicting blood volume loss in an esmolol-treated swine hemorrhagic shock model. Materials and MethodsControlled hemorrhage was induced in eight male domestic pigs. In four pigs, a total of 15% and 30% blood volume was drawn step-by-step over 10 min in each step (controlled hemorrhage–only pigs). In the other four pigs, the heart rate (HR) was reduced and maintained by 30% from baseline by esmolol infusion before controlled hemorrhage (esmolol-treated pigs). Diagnostic abilities of HR, pulse pressure variation (PPV), PoPV, and mean arterial pressure for 15% and 30% blood volume loss were determined by the area under the receiver operating characteristic curve (AUC). ResultsPoPV was well correlated with PPV in controlled hemorrhage–only pigs (r = 0.717) and esmolol-treated pigs (r = 0.532). In controlled hemorrhage-only pigs, HR (AUC = 0.841 and 0.864), PPV (0.878 and 0.843), and PoPV (0.779 and 0.793) accurately predicted 15% and 30% of blood volume loss. In esmolol-treated pigs, the diagnostic ability of HR was decreased (AUC = 0.766 and 0.733). However, diagnostic abilities of PPV (0.848 and 0.804) and PoPV (0.808 and 0.842) were not deteriorated. ConclusionsThe diagnostic ability of HR for blood volume loss was blunted by esmolol. However, those of PPV and PoPV were not altered. PoPV may be considered to be a useful noninvasive tool to predict blood volume loss in injured patients taking beta-blockers.

Validation of a novel partial resuscitative endovascular balloon occlusion of the aorta device in a swine hemorrhagic shock model: Fine tuning flow to optimize bleeding control and reperfusion injury.

Partial restoration of aortic flow during resuscitative endovascular balloon occlusion of the aorta (REBOA) is advocated by some to mitigate distal ischemia. Our laboratory has validated the mechanics and optimal partial REBOA (pREBOA) flow rates using a prototype device. We hypothesize that pREBOA will increase survival when compared with full REBOA (fREBOA) in prolonged nonoperative management of hemorrhagic shock. Twenty swine underwent placement of aortic flow probes, zone 1 REBOA placement, and 20% blood volume hemorrhage. They were randomized to either solid organ or abdominal vascular injury. The pREBOA arm (10 swine) underwent full inflation for 10 minutes and then deflation to a flow rate of 0.5 L/min for 2 hours. The fREBOA arm (10 swine) underwent full inflation for 60 minutes, followed by deflation/resuscitation. The primary outcome is survival, and secondary outcomes are serologic/pathologic signs of ischemia-reperfusion injury and quantity of hemorrhage. Two of 10 swine survived in the fREBOA group (2/5 solid organ injury; 0/5 abdominal vascular injury), whereas 7 of 10 swine survived in the pREBOA group (3/5 solid organ injury, 4/5 abdominal vascular injury). Survival was increased (p = 0.03) and hemorrhage was higher in the pREBOA group (solid organ injury, 1.36 ± 0.25 kg vs. 0.70 ± 0.33 kg, p = 0.007; 0.86 ± 0.22 kg vs. 0.71 ± 0.28 kg, not significant). Serum evidence of ischemia was greater with fREBOA, but this was not significant (e.g., lactate, 16.91 ± 3.87 mg/dL vs. 12.96 ± 2.48 mg/dL at 120 minutes, not significant). Swine treated with pREBOA that survived demonstrated trends toward lower alanine aminotransferase, lower potassium, and higher calcium. The potassium was significantly lower in survivors at 60 minutes and 90 minutes time points (5.97 ± 0.60 vs. 7.53 ± 0.90, p = 0.011; 6.67 ± 0.66 vs. 8.15 ± 0.78, p = 0.029). Calcium was significantly higher at 30 minutes, 60 minutes, and 90 minutes (8.56 ± 0.66 vs. 7.50 ± 0.40, p = 0.034; 8.63 ± 0.62 vs. 7.15 ± 0.49, p = 0.019; 8.96 ± 0.64 vs. 7.00, p = 0.028). Prolonged pREBOA at a moderate distal flow rate provided adequate hemorrhage control, improved survival, and had evidence of decreased ischemic injury versus fREBOA. Prophylactic aggressive calcium supplementation may have utility before and during the reperfusion phase.

Heparin Attenuates Visceral Apoptosis in a Swine Model of Hemorrhagic Shock and Reperfusion Injury

The use of unfractionated heparin in hypovolemic shock, aortic clamping, and visceral reperfusion is still not established, despite evidence of inhibition of early cell damage. This study investigated the potential protective effect of unfractionated heparin on hepatic and renal apoptosis in a porcine ischemia and reperfusion model. Twenty-one male swine (Sus scrofa) were divided into 3 groups: sham (n=5), heparin (n=8), and nonheparin (n=8). The heparin and nonheparin groups underwent hypovolemic shock for 30min, supraceliac aortic clamping for 1h and reperfusion for 3h. Unfractionated heparin 200mg/kg was administered to the heparin group during aortic clamping. Hemodynamic and laboratory parameters were monitored, including aminotransferase and serum urea. Histological lesion scores were applied to hematoxylin and eosin-stained liver and kidney sections. Apoptosis quantification was performed by caspase-3 immunohistochemistry. The proposed model caused a severe cardiocirculatory disturbance in the heparin and nonheparin groups, observed by the carotid-femoral pressure gradient and lactic acidosis. There was no significant difference in hemodynamic and laboratory parameters between these two groups. The mean values of liver and renal histological lesion scores did not present any significant differences. Caspase-3 immunoexpression was lower in the heparin than the nonheparin group for both liver and kidney. Attenuation of liver and kidney cell apoptosis in pigs undergoing systemic heparinization suggests a potential use for heparin in modulating cell death under critical hemodynamic conditions.

Monitoring Organs Susceptible to Ischemia/Reperfusion Injury after Prolonged Resuscitative Endovascular Balloon Occlusion of the Aorta in a Hemorrhagic Shock Swine Model

Monitoring Organs Susceptible to Ischemia/Reperfusion Injury after Prolonged Resuscitative Endovascular Balloon Occlusion of the Aorta in a Hemorrhagic Shock Swine Model

Safety of Pressurized Intraosseous Blood Infusion Strategies in a Swine Model of Hemorrhagic Shock

BackgroundCurrent guidelines support intraosseous access for trauma resuscitation when intravenous access is not readily available. However, safety of intraosseous blood transfusions with varying degrees of infusion pressure has not been previously characterized. Materials and methodsAdult female Yorkshire swine (Sus scrofa; n = 36; mean (M): 80 kg, 95% CI: 78-82 kg) were cannulated and then bled approximately 30% total blood volume. Swine were randomly assigned to proximal humerus intraosseous blood infusion with either Rapid Infuser, or Pressure Bag, or Push-Pull methods (n = 12 each). Flow rates, infusion pressures, vitals, biochemical variables, and pulmonary and renal tissue pathology were contrasted between groups. ResultsFlow rates were greater for the Push-Pull strategy than Pressure Bag (96.5 mL/min versus 72.6 mL/min, P = 0.02) or Rapid Infuser (96.5 mL/min versus 60 mL/min, P = 0.002) strategies. The pressures generated during the Push-Pull transfusion (3058 mmHg) were greater than the other strategies (≤360 mmHg). After the observation period, plasma-free hemoglobin levels were higher in the Push-Pull strategy than in the Rapid Infuser (40 mg/dL versus 12 mg/dL, P = 0.02) or Pressure Bag (40 mg/dL versus 12 mg/dL, P = 0.01). Groups did not significantly differ in vitals, biochemical variables, or tissue pathology. ConclusionsPush-Pull conferred the highest flow rates, but with higher infusion pressures and evidence of intravascular hemolysis. Rapid Infuser and Pressure Bag infusions had no increase from baseline in plasma-free hemoglobin. Pressure Bag infusion was noted to confer an advantage in flow rates over Rapid Infuser. Intraosseous blood transfusion with pressure bags can safely bridge toward central access in the early phases of trauma resuscitation.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) in a swine model of hemorrhagic shock and blunt thoracic injury.

While resuscitative endovascular balloon occlusion of the aorta (REBOA) is contraindicated in patients with aortic injuries, this technique may benefit poly-trauma patients with less extreme thoracic injuries. The purpose of this study was to characterize the effects of thoracic injury on hemodynamics during REBOA and the changes in pulmonary contusion over time in a swine model. Twelve swine were anesthetized, instrumented, and randomized to receive either a thoracic injury with 5 impacts to the chest or no injury. All animals underwent controlled hemorrhage of 25% blood volume followed by 45min of Zone 1 REBOA. Animals were then resuscitated with shed blood, observed during a critical care period, and euthanized after 6h of total experimental time. There were no differences between the groups at baseline. The only difference after 6 h was a lower hemoglobin in the thoracic trauma group (8.4 ± 0.8 versus 9.4 ± 0.6g/dL, P = 0.04). The average proximal mean arterial pressures were significantly lower in the thoracic trauma group during aortic occlusion [103 (98-108) versus 117 (115-124) mmHg, P = 0.04]. There were no differences between the pulmonary contusion before REBOA and at the end of the experiment in size (402 ± 263 versus 356 ± 291mL, P = 0.782) or density (- 406 ± 127 versus - 299 ± 175 HFU, P = 0.256). Thoracic trauma blunted the proximal arterial pressure augmentation during REBOA but had minimal impacts on resuscitative outcomes. This initial study indicates that REBOA does not seem to exacerbate pulmonary contusion in swine, but blunt thoracic injuries may attenuate the expected rises in proximal blood pressure during REBOA.

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

IntroductionTrauma 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 methodsTwenty-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. ResultsDuring 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 ± 23.9 and 191.9 ± 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. ConclusionNeither 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 induced myocardial injury is mitigated by endovascular variable aortic control.

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. 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. 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. 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.

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

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. 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. 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. 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.

7 Performance of Single Versus Double Site Intraosseous Blood Transfusion Strategies in a Swine [Sus Scrofa] Model of Hemorrhagic Shock

1. Discuss and clarify the utility of intraosseous blood transfusions for treating hypovolemic battlefield injuries in military out-of-hospital settings 2. Compare the advantages and complications of humeral versus sternal intraosseous access for resuscitation of hemorrhagic shock. 3. Identify flow rates, degree of intravascular hemolysis, and occurrence of coagulopathy in single versus double site intraosseous blood transfusion. The American College of Surgeons Advance Trauma Life Support (ATLS) endorses the use of intraosseous devices for the adult trauma patient in extremis. Intraosseous access is frequently used by military physicians administering fluids, blood, and medications for victims of severe battlefield trauma. The optimal intraosseous blood transfusion strategy appears to involve pressure bag transfusion through either the sternum or proximal humerus. Double anatomic site IO catheter placement has the potential to augment resuscitation in cases where vascular access is challenging. We sought to compare flow rates and complications among 4 single and double anatomic site transfusion strategies in a swine model of hemorrhagic shock. 48 Yorkshire swine were placed under general anesthesia during the study protocol. Data from 12 animals completed to date is presented below. Following intra-arterial catheter placement, 30-40% of the animal’s estimated blood volume was removed using the flow of gravity. Subsequently, 15-20% of the animals estimated blood volume was autologously infused via pressure bag through 1 of 4 randomly assigned treatment arms: 1) Proximal Humerus (n=12), 2) Sternum (n=12), 3) Proximal Humerus + Sternum (n=12), 4) Double Proximal Humerus (n=12). Flow rates, intravascular hemolysis, and coagulopathy were recorded. Presence of pulmonary arterial fat embolism was evaluated for by a pathologist blinded to treatment arm. The average weight of swine was 77.8 kg. Average bone density on DEXA scan of the proximal humerus and sternum was 1.001 cm/gm2 and 0.242 cm/gm2, respectively. Average transfusion pressures were 360 mmHg. Infusion rates were as follows: Single Humerus 58.8 ml/min; Sternum 54 ml/min; Sternum + Single Humerus 126 ml/min and Double Humerus 120.3 ml/min. Plasma free hemoglobin levels (baseline, post transfusion) were: Single Humerus 9, 13.2 μg/ml; Sternum 10.5, 18.4 μg/ml; Double Humerus 11.4, 17.8 μg/ml and Sternum + Single Humerus 8.8, 13.9 μg/ml. No significant differences in post transfusion coagulopathy were observed. Blinded pathologist review of pulmonary tissue for edema, inflammation and presence of pulmonary fat emboli between treatment arms is underway. In an animal model of hemorrhagic shock, double site IO transfusion under a pressure bag appears to confer a significant advantage in flow rates. Proximal humerus and sternal IO transfusions achieved similar flow rates in a model that closely resembles the bone density of an adult male. No significant differences between strategies were noted in regard to intravascular hemolysis or coagulopathy. In cases of severe trauma with challenging vascular access, double site access in either bilateral proximal humerus or sternum and proximal humerus may confer a clinical advantage in speed of transfusion without significant complications.