Selective aortic arch perfusion with fresh whole blood or HBOC-201 reverses hemorrhage-induced traumatic cardiac arrest in a lethal model of noncompressible torso hemorrhage.

BACKGROUND: Hemorrhage-induced traumatic cardiac arrest (HiTCA) has a dismal survival rate. Previous studies demonstrated selective aortic arch perfusion (SAAP) with fresh whole blood (FWB) improved the rate of return of spontaneous circulation (ROSC) after HiTCA, compared with resuscitative endovascular balloon occlusion of the aorta and cardiopulmonary resuscitation (CPR). Hemoglobin-based oxygen carriers, such as hemoglobin-based oxygen carrier (HBOC)-201, may alleviate the logistical constraints of using FWB in a prehospital setting. It is unknown whether SAAP with HBOC-201 is equivalent in efficacy to FWB, whether conversion from SAAP to extracorporeal life support (ECLS) is feasible, and whether physiologic derangement post-SAAP therapy is reversible. METHODS: Twenty-six swine (79 ± 4 kg) were anesthetized and underwent HiTCA which was induced via liver injury and controlled hemorrhage. Following arrest, swine were randomly allocated to resuscitation using SAAP with FWB (n = 12) or HBOC-201 (n = 14). After SAAP was initiated, animals were monitored for a 20-minute prehospital period prior to a 40-minute damage control surgery and resuscitation phase, followed by 260 minutes of critical care. Primary outcomes included rate of ROSC, survival, conversion to ECLS, and correction of physiology. RESULTS: Baseline physiologic measurements were similar between groups. ROSC was achieved in 100% of the FWB animals and 86% of the HBOC-201 animals (p = 0.483). Survival (t = 320 minutes) was 92% (11/12) in the FWB group and 67% (8/12) in the HBOC-201 group (p = 0.120). Conversion to ECLS was successful in 100% of both groups. Lactate peaked at 80 minutes in both groups, and significantly improved by the end of the experiment in the HBOC-201 group (p = 0.001) but not in the FWB group (p = 0.104). There was no significant difference in peak or end lactate between groups. CONCLUSION: Selective aortic arch perfusion is effective in eliciting ROSC after HiTCA in a swine model, using either FWB or HBOC-201. Transition from SAAP to ECLS after definitive hemorrhage control is feasible, resulting in high overall survival and improvement in lactic acidosis over the study period.

Aortic Hemostasis and Resuscitation: Preliminary Experiments Using Selective Aortic Arch Perfusion With Oxygenated Blood and Intra-aortic Calcium Coadministration in a Model of Hemorrhage-induced Traumatic Cardiac Arrest.

OBJECTIVES: Selective aortic arch perfusion (SAAP) uses a thoracic aortic balloon occlusion catheter for heart and brain perfusion in cardiac arrest to achieve return of spontaneous circulation (ROSC). SAAP with oxygenated stored blood was studied in a model of hemorrhage-induced cardiac arrest. The study hypothesis was that intra-aortic calcium coadministration would be required to maintain normal aortic arch blood ionized calcium during SAAP and to achieve ROSC. METHODS: Twelve anesthetized, domestic swine underwent severe hemorrhage and liver injury resulting in cardiac arrest. Whole blood and packed red blood cells (RBCs) stored in citrate anticoagulant served as perfusates for SAAP. Experiments were performed with four combinations of SAAP with oxygenated stored blood and intra-aortic calcium gluconate infusion: 1) whole blood without calcium, 2) whole blood with calcium, 3) lactated Ringers-diluted packed RBCs with calcium, and 4) normal saline-diluted packed RBCs with calcium. Aortic arch blood ionized calcium was monitored. Occurrence of ventricular dysrhythmias, success rate for ROSC, and the need for simultaneous intra-aortic calcium infusion were assessed. RESULTS: Selective aortic arch perfusion using whole blood without intra-aortic calcium (n = 2) resulted in severe aortic blood ionized hypocalcemia, refractory ventricular fibrillation, and no ROSC. SAAP using whole blood with intra-aortic calcium (n = 4) resulted in ROSC in all four animals. Two of four developed ventricular fibrillation that was successfully defibrillated. SAAP using packed RBCs with intra-aortic calcium resulted in ROSC in all six animals, but the intra-aortic calcium dose needed to maintain normal aortic arch blood ionized calcium levels was one-third of that needed for SAAP with whole blood. Dilution of packed RBCs with lactated Ringers (n = 2) resulted in formation of small clots in the perfusion circuit which were not seen with packed RBCs diluted with normal saline (n = 4). CONCLUSIONS: Selective aortic arch perfusion with stored whole blood or packed RBCs requires simultaneous intra-aortic calcium infusion to overcome citrate anticoagulant calcium binding, avoid refractory ventricular fibrillation, and allow for ROSC.

Nitroglycerin attenuates vasoconstriction of HBOC-201 during hemorrhagic shock resuscitation.

BACKGROUND: Vasoconstriction, an inherent property of Hemoglobin Based Oxygen Carriers (HBOC) potentially due to nitric oxide (NO) scavenging, may increase cardiovascular complications in HBOC resuscitated trauma patients. The purpose of this study was to determine if co-administration of a weak NO donor, intravenous nitroglycerin (NTG), with HBOC-201 during resuscitation from hemorrhagic shock could safely attenuate HBOC-201 vasoconstriction. METHODS AND RESULTS: Hemorrhagic shock was induced in 44 swine randomized to receive fluid resuscitation with HBOC, HBOC+NTG10 mcg/kg/min, HBOC+NTG20 mcg/kg/min, HBOC+NTG40 mcg/kg/min, Hetastarch (HES), HES+NTG20 mcg/kg/min, NTG20 mcg/kg/min and Lactated Ringers (LR). HBOC resuscitation from hemorrhagic shock increased mean arterial pressure (MAP=94+/-33 mmHg), mean pulmonary artery pressure (MPAP=29+/-11 mmHg) and systemic vascular resistance (SVR=2684+/-871 dyns/cm(5)) in comparison to HES. Co-administration of NTG during HBOC resuscitation attenuated vasoconstriction with HBOC+40 mcg/kg/min demonstrating the most robust reduction in vasoconstriction (MAP=59+/-23 mmHg, MPAP=18+/-7 mmHg, and SVR=1827+/-511 dyns/cm(5)), although the effects were transient. Co-administration of NTG with HBOC did not alter base deficit, lactate, methemoglobin levels, nor cause profound hypotension during resuscitation. CONCLUSION: Nitroglycerin attenuates vasoconstrictive properties of HBOC when co-administered during resuscitation in this swine model of hemorrhagic shock. Translational survival studies are required to determine if this strategy of attenuation of the vasoconstriction of HBOC-201 reduces cardiovascular complications and improves outcome with HBOC fluid resuscitation for hemorrhagic shock.

The design and testing of a dual fiber textile matrix for accelerating surface hemostasis.

The standard treatment for severe traumatic injury is frequently compression and application of gauze dressing to the site of hemorrhage. However, while able to rapidly absorb pools of shed blood, gauze fails to provide strong surface (topical) hemostasis. The result can be excess hemorrhage-related morbidity and mortality. We hypothesized that cost-effective materials (based on widespread availability of bulk fibers for other commercial uses) could be designed based on fundamental hemostatic principles to partially emulate the wicking properties of gauze while concurrently stimulating superior hemostasis. A panel of readily available textile fibers was screened for the ability to activate platelets and the intrinsic coagulation cascade in vitro. Type E continuous filament glass and a specialty rayon fiber were identified from the material panel as accelerators of hemostatic reactions and were custom woven to produce a dual fiber textile bandage. The glass component strongly activated platelets while the specialty rayon agglutinated red blood cells. In comparison with gauze in vitro, the dual fiber textile significantly enhanced the rate of thrombin generation, clot generation as measured by thromboelastography, adhesive protein adsorption and cellular attachment and activation. These results indicate that hemostatic textiles can be designed that mimic gauze in form but surpass gauze in ability to accelerate hemostatic reactions.

Pulse contour cardiac output analysis in a piglet model of severe hemorrhagic shock.

OBJECTIVE: Pulse contour cardiac output (PCCO) analysis is a technique for continuous cardiac output (CO) monitoring through an arterial catheter after calibration by transpulmonary thermodilution (TPTD). Studies in adults show good correlation with pulmonary artery thermodilution (PATD) CO. Data are limited in children and patients with hemodynamic instability. The objective was to determine whether TPTD CO and PCCO analysis correlate with PATD CO in a piglet model of severe hemorrhagic shock. Mixed venous oxygen saturation (SVO2) was also compared with PATD CO. DESIGN: Prospective animal study. SETTING: University animal research laboratory. SUBJECTS: Domesticated piglets, 24-37 kg. INTERVENTIONS: Hemorrhagic shock was created by graded hemorrhage in anesthetized piglets. Hemorrhage was initiated to achieve mean arterial pressure plateaus of 60, 50, 40, 30, and 20 mm Hg. MEASUREMENTS AND MAIN RESULTS: CO was measured by PATD and simultaneously with two femoral artery PCCO catheters. At each mean arterial pressure plateau, one PCCO catheter was recalibrated by TPTD; the other catheter was not recalibrated during hemorrhage. TPTD CO, PCCO measurements from each catheter, and SVO2 were compared with PATD CO at each mean arterial pressure level. TPTD CO and recalibrated PCCO showed excellent correlation (r2 = .96 and .97) and small bias (+0.11 and +0.14 L/min), respectively, compared with PATD. Without recalibration, PCCO measurements were not accurate during rapid hemorrhage (r2 = .22). SVO2 decline did not correlate as well with PATD CO (r2 = .69). CONCLUSIONS: TPTD CO and recalibrated PCCO analysis correlate well with PATD CO in this severe hemorrhagic shock model. The mean difference is small (<0.15 L/min) and is not clinically significant. With rapid changes in blood pressure or intravascular volume, PCCO is not accurate unless recalibrated by TPTD CO. SVO2 did not correlate well with CO in this model.

HBOC-201 improves survival in a swine model of hemorrhagic shock and liver injury.

BACKGROUND: Blunt abdominal trauma that leads to hemorrhagic shock and cardiac arrest is almost always fatal in the prehospital setting. The current study investigated whether a hemoglobin-based oxygen carrier (HBOC-201) could maintain organ viability during an exsanguinating liver injury and allow for prolonged survival. This hypothesis was tested in a large animal model that simulated blunt abdominal trauma with major organ injury. METHODS: Swine underwent a liver crush, laceration and 50 ml/kg initial blood loss. The liver bled at 3 ml/kg per min during the resuscitation phase. No fluid (NF=6), hetastarch (HES=8), or HBOC-201 (HBOC=8) was given during the resuscitation phase. Swine alive 60 min after the initial injury underwent liver repair and 96 h observation. RESULTS: All HBOC swine survived 60 min versus none of the NF or HES swine (P<0.05). All HBOC swine survived 24 h and 7/8 survived 96 h with good functional recovery. CONCLUSIONS: HBOC resuscitation during liver bleeding in a swine model of hemorrhagic shock and liver injury allowed for 96 h survival. No fluid or HES in the same model was fatal.