Real-Time Measurements of Oral Mucosal Carbon Dioxide (POMCO2) Reveals an Inverse Correlation With Blood Pressure in a Porcine Model of Coagulopathic Junctional Hemorrhage.

INTRODUCTION: Shock states that occur during, for example, profound hemorrhage can cause global tissue hypoperfusion leading to organ failure. There is an unmet need for a reliable marker of tissue perfusion during hemorrhage that can be followed longitudinally. Herein, we investigated whether longitudinal POMCO2 tracks changes in hemodynamics in a swine model of coagulopathic uncontrolled junctional hemorrhage. MATERIALS AND METHODS: Female Yorkshire-crossbreed swine (n = 7, 68.1 ± 0.7 kg) were anesthetized and instrumented for continuous measurement of mean arterial pressure (MAP). Coagulopathy was induced by the exchange of 50 to 60% of blood volume with 6% Hetastarch over 30 minutes to target a hematocrit of <15%. A 4.5-mm arteriotomy was made in the right common femoral artery with 30 seconds of free bleeding. POMCO2 was continuously measured from baseline through hemodilution, hemorrhage, and a subsequent 3-h intensive care unit period. Rotational thromboelastometry and blood gases were measured. RESULTS: POMCO2 and MAP showed no significant changes during the hemodilution phase of the experiment, which produced coagulopathy evidenced by prolonged clot formation times. However, POMCO2 increased because of the uncontrolled hemorrhage by 11.3 ± 3.1 mmHg and was inversely correlated with the drop (17.9 ± 5.9 mmHg) in MAP (Y = -0.4122*X + 2.649, P = .02, r2 = 0.686). In contrast, lactate did not significantly correlate with the changes in MAP (P = .35) or POMCO2 (P = .37). CONCLUSIONS: Despite the logical appeal of measuring noninvasive tissue CO2 measurement as a surrogate for gastrointestinal perfusion, prior studies have only reported snapshots of this readout. The present investigation shows real-time longitudinal measurement of POMCO2 to confirm that MAP inversely correlates to POMCO2 in the face of coagulopathy. The simplicity of measuring POMCO2 in real time can provide an additional practical option for military or civilian medics to monitor trends in hypoperfusion during hemorrhagic shock.

Evaluation of novel hemostatic agents in a coagulopathic swine model of junctional hemorrhage.

BACKGROUND: Hemostatic dressings are used extensively in both military and civilian trauma to control lethal noncompressible hemorrhage. The ideal topical hemostatic agent would provide reliable hemostasis in patients with profound acidosis, coagulopathy, and shock. This study aimed to compare next-generation hemostatic agents against the current military standard in a translational swine model of vascular injury and coagulopathy. METHODS: Female Yorkshire swine were randomized to eight groups (total n = 63; control n = 14, per group n = 7) of hemostatic agents and included: QuikClot Combat Gauze (Teleflex, Morrisville, NC), which served as the control; BloodSTOP IX (LifeScience Plus, Mountain View, CA); Celox Rapid (Medtrade Product, Crewe, United Kingdom); ChitoSAM 100 (Sam Medical, Tualatin, OR); EVARREST Fibrin Sealant Patch (Ethicon, Raritan, NJ); TAC Wrapping Gauze (H&H Medical, Williamsburg, VA); ChitoGauze XR Pro (Tricol Biomedical, Portland, OR); and X-Stat 30 (RevMedX, Wilsonville, OR). Hemodilution via exchange transfusion of 6% hetastarch was performed to induce acidosis and coagulopathy. An arteriotomy was created, allowing 30 seconds of free bleeding followed by application of the hemostatic agent and compression via an external compression device. A total of three applications were allowed for continued/recurrent bleeding. All blood loss was collected, and hemostatic agents were weighed to calculate blood volume loss. Following a 180-minute observation period, angiography was completed to evaluate for technical complication and distal perfusion of the limb. Finally, the limb was ranged five times to assess for rebleeding and clot stability. RESULTS: All swine were confirmed coagulopathic with rotational thromboelastography and acidotic (pH 7.2 ± 0.02). BloodSTOP IX allowed a significant increase in blood loss and number of applications required to obtain hemostasis compared with all other groups. BloodSTOP IX demonstrated a decreased survival rate (29%, p = 0.02). All mortalities were directly attributed to exsanguination as a result of device failure. In surviving animals, there was no difference in extravasation. BloodSTOP IX had an increased rebleeding rate after ranging compared with QuikClot Combat Gauze ( p = 0.007). CONCLUSION: Most novel hemostatic agents demonstrated comparable efficacy compared with the currently military standard hemostatic dressing, CG.

Development, refinement, and characterization of a nonhuman primate critical care environment.

BACKGROUND: Systemic inflammatory response remains a poorly understood cause of morbidity and mortality after traumatic injury. Recent nonhuman primate (NHP) trauma models have been used to characterize the systemic response to trauma, but none have incorporated a critical care phase without the use of general anesthesia. We describe the development of a prolonged critical care environment with sedation and ventilation support, and also report corresponding NHP biologic and inflammatory markers. METHODS: Eight adult male rhesus macaques underwent ventilation with sedation for 48-96 hours in a critical care setting. Three of these NHPs underwent "sham" procedures as part of trauma control model development. Blood counts, chemistries, coagulation studies, and cytokines/chemokines were collected throughout the study, and histopathologic analysis was conducted at necropsy. RESULTS: Eight NHPs were intentionally survived and extubated. Three NHPs were euthanized at 72-96 hours without extubation. Transaminitis occurred over the duration of ventilation, but renal function, acid-base status, and hematologic profile remained stable. Chemokine and cytokine analysis were notable for baseline fold-change for Il-6 and Il-1ra (9.7 and 42.7, respectively) that subsequently downtrended throughout the experiment unless clinical respiratory compromise was observed. CONCLUSIONS: A NHP critical care environment with ventilation support is feasible but requires robust resources. The inflammatory profile of NHPs is not profoundly altered by sedation and mechanical ventilation. NHPs are susceptible to the pulmonary effects of short-term ventilation and demonstrate a similar bioprofile response to ventilator-induced pulmonary pathology. This work has implications for further development of a prolonged care NHP model.

Advanced partial occlusion controller allows for increased precision during targeted regional optimization in a porcine model of hemorrhagic shock.

BACKGROUND: Targeted regional optimization (TRO), a partial resuscitative endovascular balloon occlusion of the aorta strategy, may mitigate distal ischemia and extend the window of effectiveness for this adjunct. An automated device may allow greater control and precise regulation of flow past the balloon, while being less resource-intensive. The objective of this study was to assess the technical feasibility of the novel advanced partial occlusion controller (APOC) in achieving TRO at multiple distal pressures. METHODS: Female swine (n = 48, 68.1 ± 0.7 kg) were randomized to a target distal mean arterial pressure (MAP) of 25 mm Hg, 35 mm Hg, or 45 mm Hg by either manual (MAN) or APOC regulation (n = 8 per group). Uncontrolled hemorrhage was generated by liver laceration. Targeted regional optimization was performed for 85 minutes, followed by surgical control and a 6-hour critical care phase. Proximal and distal MAP and flow rates were measured continuously. RESULTS: At a target distal MAP of 25 mm Hg, there was no difference in the MAP attained (APOC: 26.2 ± 1.05 vs. MAN: 26.1 ± 1.78 mm Hg) but the APOC had significantly less deviance (10.9%) than manual titration (14.9%, p < 0.0001). Similarly, at a target distal MAP of 45 mm Hg, there was no difference in mean pressure (44.0 ± 0.900 mm Hg vs. 45.2 ± 1.31 mm Hg) but APOC had less deviance (9.34% vs. 11.9%, p < 0.0001). There was no difference between APOC and MAN in mean (34.6 mm Hg vs. 33.7 mm Hg) or deviance (9.95% vs. 10.4%) at a target distal MAP of 35 mm Hg, respectively. The APOC made on average 77 balloon volume adjustments per experiment compared with 29 by manual titrations. CONCLUSION: The novel APOC consistently achieved and sustained precisely regulated TRO across all groups and demonstrated reduced deviance at the 25 mm Hg and 45 mm Hg groups compared with manual titration.

A New Pressure-Regulated, Partial Resuscitative Endovascular Balloon Occlusion of the Aorta Device Achieves Targeted Distal Perfusion.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) reduces blood loss and improves hemodynamics. Complete occlusion results in distal ischemia, limiting its use for prolonged care. This study evaluated two next-generation partial REBOA (pREBOA) catheters and their ability to achieve targeted distal aortic flow. MATERIALS AND METHODS: Swine underwent hemorrhagic shock, complete aortic occlusion, controlled continuous balloon deflation, and targeted distal perfusion (TDP; 300-mL/min) phases. They were randomized into three groups (n = 6/group), one managed with the current ER-REBOA (ER), and two with the new pREBOA technologies: a bilobed (BL) device and a semicompliant pREBOA-PRO (PRP). Hemodynamics including flow rates and mean arterial pressures at the carotid artery and infrarenal aorta were recorded. RESULTS: Hemodynamics were comparable between groups during hemorrhage and complete occlusion phases. During the controlled continuous balloon deflation phase, the distal aortic flow rate strongly correlated with percent balloon volume in BL and PRP groups, suggesting a precise control of distal perfusion. The slope of flow-balloon-volume curves was greater in the ER group than BL and PRP groups, indicating the change in distal aortic flow rate was more sensitive to the balloon volume (less titratable) when using ER. During the TDP phase, variation in distal aortic flow and mean arterial pressure with respect to the target flow was lower in ER and PRP groups, than the BL group. CONCLUSIONS: Pressure-regulated occlusion using the next-generation pREBOA catheters is more controlled than the first-generation ER-REBOA catheter and allow for targeted and precise distal perfusion.