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Cerebrovascular autoregulation (CA) is a protective mechanism that enables the cerebral vasculature to automodulate tone in response to changes in cerebral perfusion pressure to ensure constant levels of cerebral blood flow (CBF) and oxygen delivery. CA can be impaired after neurological injury and contributes to secondary brain injury. In this study, we report novel impedance indices using trans-ocular brain impedance (TOBI) during controlled systemic hemorrhage and hypotension to assess CA in comparison with pressure reactivity index (PRx). Yorkshire swine were instrumented to record intracranial pressure (ICP), mean arterial pressure (MAP), and CBF. TOBI was recorded using electrocardiographic electrodes placed on the closed eyelids. Impedance changes (dz) were recorded in response to introducing an alternating current (0.4 mA) through the electrodes. MAP, ICP, and CBF were also measured. Animals were subjected to a controlled hemorrhage to remove 30–40% of each animal’s total blood volume over 25–35 min. Hemorrhage was titrated to reach an MAP of approximately 35 mm Hg and end-tidal carbon dioxide above 28 mm Hg. PRx was calculated as a moving Pearson correlation between MAP and ICP. TOBI indices were calculated as the amplitude of the respiratory-induced changes in dz. DZx was calculated as a moving Pearson correlation between dz and MAP. TOBI indices (dz and DZx) were compared with hemodynamic indicators and PRx. dz was shown to be highly correlated with MAP, ICP, cerebral perfusion pressure, and CBF (r = − 0.823, − 0.723, − 0.813, and − 0.726), respectively (p

Gastroesophageal resuscitative occlusion of the aorta (GROA) has been shown effective in creating zone II aortic occlusion capable of temporarily improving survival in animal models of lethal noncompressible torso hemorrhage. In this study, tandem application of GROA transitioning to resuscitative endovascular balloon occlusion of the aorta (REBOA) is explored to demonstrate feasibility as a potential point-of-injury bridge to more advanced care, using a swine model of lethal abdominal hemorrhage.Swine (n = 19) were anesthetized, instrumented, and subjected to a combination of controlled and uncontrolled hemorrhage from a grade-V liver laceration. Animals were designated as intervention (n = 9; GROA to REBOA) or control (n = 10), for 60 minutes. Following intervention, devices were deactivated, and animals received blood and crystalloid resuscitation. Animals were monitored for 4 hours.Injury resulted in onset of class IV shock in all animals with a mean arterial pressure (SD) of 24.5 (4.11) mm Hg at the start of intervention. Nine of 10 controls died during the intervention period with a median (interquartile) survival time of 8.5 (9.25) minutes. All animals receiving the intervention survived both the 60-minute intervention period demonstrating a significant survival improvement ( p = 0.0007). Transition from GROA to REBOA was successful in all animals with a transition time ranging from 30 to 90 seconds. Mean arterial pressure significantly improved in animals receiving GROA to REBOA for the duration of intervention, regardless of the method of aortic occlusion, with a range of 70.9 (16.04) mm Hg to 101.1 (15.3) mm Hg. Additional hemodynamics, metrics of shock, and oxygenation remained stable during intervention.Less invasive technologies such as GROA may present an opportunity to control noncompressible torso hemorrhage more rapidly, with a subsequent transition to more advanced care such as REBOA.

Cerebrovascular autoregulation (CA) is often impaired following traumatic brain injury. Established technologies and metrics used to assess CA are invasive and conducive for measurement, but not for continuous monitoring. We developed a trans-ocular brain impedance (TOBI) method that may provide non-invasive and continuous indices to assess CA. In this study, we monitored impedance metrics such as respiratory-induced impedance amplitude changes (dz) as well as a novel impedance index (DZx), which is a moving Pearson correlation between mean arterial pressure (MAP) and dz. Yorkshire swine were instrumented to continuously record ICP, MAP, and cerebral blood flow (CBF). TOBI was recorded by placement of standard ECG electrodes on closed eyelids and connected to a data acquisition system. MAP, ICP and CBF were manipulated utilizing an intravenous vasopressor challenge. TOBI indices (dz and DZx) were compared to the hemodynamic indicators as well as pressure reactivity index (PRx). During the vasopressor challenge, dz was highly correlated with ICP, CPP, and CBF (r =

INTRODUCTION: Oxidation-reduction (redox) reactions, and the redox potential (RP) that must be maintained for proper cell function, lie at the heart of physiologic processes in critical illness. Imbalance in RP reflects systemic oxidative stress, and whole blood RP measures have been shown to correlate with oxygen debt level over time in swine traumatic shock. We hypothesize that RP measures will reflect changing concentrations of metabolites involved in oxidative stress. To test this hypothesis, we compared blood and urine RP with concentrations of multiple metabolites in a swine traumatic shock model to identify meaningful RP-metabolite relationships. METHODS: Seven swine were subjected to traumatic shock. Mixed venous (MV) RP, urine RP, and concurrent MV and urine metabolite concentrations were assessed at baseline, max O2 Debt (80mL/kg), end resuscitation, and 2 hrs post resuscitation. RP was measured at collection via open circuit potential using nanoporous gold electrodes with Ag/AgCl reference and a ParstatMC potentiostat. Metabolite concentrations were measured by quantitative 1H-NMR spectroscopy. MV and urine RP were compared with time-matched metabolites across all swine. LASSO regression with leave-one-out cross validation was used to determine meaningful RP/metabolite relationships. Metabolites had to maintain magnitude and direction of coefficients across 6 or more swine to be considered as having a meaningful relationship. KEGG IDs of these metabolites were uploaded into Metscape for pathway identification and evaluation for physiologic function. RESULTS: Meaningful metabolite relationships (and mean coefficients) with MV RP include: Choline (−6.27), ATP (−4.39), Glycine (5.93), ADP (1.84), Glucose (15.96), Formate (−13.09), Pyruvate (6.18), and Taurine (−7.18). Relationships with urine RP were: cis-Aconitate (4.55)Taurine (7.40), Glycine (−4.88) Creatine (8.16), Betaine (5.11), Urea (6.30), 3-Hydroxyisobutyrate (−6.44), N-Phenylacetylglycine, PAG (−15.48), Hippurate (10.66), and Formate (−5.36). Pathway analysis revealed these metabolites scavenge extracellular peroxide (pyruvate), inhibit ROS and activate cellular antioxidant defense (taurine), act as indicators of antioxidant mobilization against oxidative stress (glycine + PAG), and reflect renal hydroxyl radical trapping (hippurate), among other activity. CONCLUSIONS: Real-time RP measures demonstrate significant relationships with metabolites attributable to metabolic pathways involved in systemic responses to oxidative stress, as well as those active in these processes. These data support RP measures as a feasible, biologically relevant marker of oxidative stress. As a direct measure of redox state, RP may be a useful biomarker and clinical tool in guiding diagnosis and therapy in states of increased oxidative stress, and may offer value as a marker for organ injury in these states as well.

Large animal studies are an important step in the translation pathway, but single laboratory experiments do not replicate the variability in patient populations. Our objective was to demonstrate the feasibility of performing a multicenter, preclinical, randomized, double-blinded, placebo-controlled cardiac arrest trial. We evaluated the effect of epinephrine on coronary perfusion pressure (CPP) as previous single laboratory studies have reported mixed results.Forty-five swine from 5 different laboratories (Ann Arbor, MI; Baltimore, MD; Los Angeles, CA; Pittsburgh, PA; Toronto, ON) using a standard treatment protocol. Ventricular fibrillation was induced and left untreated for 6 min before starting continuous cardiopulmonary resuscitation (CPR). After 2 min of CPR, 9 animals from each lab were randomized to 1 of 3 interventions given over 12 minutes: (1) Continuous IV epinephrine infusion (0.00375 mg/kg/min) with placebo IV normal saline (NS) boluses every 4 min, (2) Continuous placebo IV NS infusion with IV epinephrine boluses (0.015 mg/kg) every 4 min or (3) Placebo IV NS for both infusion and boluses. The primary outcome was mean CPP during the 12 mins of drug therapy.There were no significant differences in mean CPP between the three groups: 14.4 ± 6.8 mmHg (epinephrine Infusion), 16.9 ± 5.9 mmHg (epinephrine bolus), and 14.4 ± 5.5 mmHg (placebo) (p = NS). Sensitivity analysis demonstrated inter-laboratory variability in the magnitude of the treatment effect (p = 0.004).This study demonstrated the feasibility of performing a multicenter, preclinical, randomized, double-blinded cardiac arrest trials. Standard dose epinephrine by bolus or continuous infusion did not increase coronary perfusion pressure during CPR when compared to placebo.

BACKGROUND Non-compressible torso hemorrhage management remains a challenge especially in the prehospital setting. We evaluated a device designed to occlude the aorta from the stomach (Gastroesophageal Resuscitative Occlusion of the Aorta (GROA)) for its ability to stop hemorrhage and improve survival in a swine model of lethal liver laceration and compared its performance to Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) and controls. METHODS Swine (n = 24) were surgically instrumented and a 30% controlled arterial hemorrhage over 20-minutes was followed by liver laceration. Animals received either GROA, REBOA, or control (no treatment) for 60-minutes. Following intervention, devices were deactivated, and animals received whole blood and crystalloid resuscitation. Animals were monitored for an additional four hours. RESULTS The liver laceration resulted in the onset of class IV shock. Mean arterial blood pressure ((MAP) (standard deviation)) decreased from 84.5 mmHg (11.69 mmHg) to 27.1 mmHg (5.65 mmHg) at the start of the intervention. Seven of eight control animals died from injury prior to the end of the intervention period with a median survival (interquartile) time of 10.5 minutes (12 minutes). All GROA and REBOA animals survived the duration of the intervention period (60-minutes) with median survival times of 86 minutes (232 minutes) and 79 minutes (199 minutes) after resuscitation, respectively. GROA and REBOA animals experienced a significant improvement in survival compared to controls (p = 0.01). REBOA resulted in higher MAP at the end of intervention 114.6 mmHg (22.9 mmHg) compared to GROA 88.2 mmHg (18.72 mmHg), (p = 0.024) as well as increased lactate compared to GROA 13.2 meq/L (1.56 meq/L) vs. 10.5 meq/L (1.89 meq/L), (p = 0.028). Histological examination of the gastric mucosa in surviving animals revealed mild ischemic injury from both GROA and REBOA. CONCLUSIONS GROA and REBOA devices were both effective at temporarily stanching lethal NCTH of the abdomen and prolonging survival. LEVEL OF EVIDENCE Basic Science; Does not require a level of evidence.

Background Non-compressible torso hemorrhage (NCTH) of the abdomen is a challenge to rapidly control and treat in the prehospital and emergency department settings. In this pilot study, we developed a novel intra-peritoneal hemostasis device (IPHD) prototype and evaluated its ability for slowing NCTH and prolonging survival in a porcine model of lethal abdominal multi-organ hemorrhage. Methods Yorkshire male swine (n=8) were instrumented under general anesthesia for monitoring of hemodynamics and blood sampling. Animals were subjected to a 30% controlled arterial hemorrhage followed by lacerating combinations of the liver, spleen, and kidney. The abdomen was closed and after 2 minutes of NCTH, the IPHD was inserted into the peritoneal cavity via an introducer (n=5). The balloon was inflated and maintained for 60 minutes. At 60-minutes post deployment the balloon was deflated and removed, and blood resuscitation was initiated followed by gauze packing for hemostasis. The remaining animals (n=3) were used as controls and subjected to the same injury without intervention. Results All animals managed with IPHD intervention (5/5) survived the duration of the intervention period (60 minutes) while all control animals (3/3) died at a time range of 15-43 minutes following organ injury (p=0.0042). Animals receiving IPHD remained hemodynamically stable with a mean arterial pressure range of 44.86 to 55.10mmHg, experienced increased cardiac output and decreased shock index after treatment. Controls experienced hemodynamic decline in all parameters until endpoints were met. Upon IPHD deflation and removal, all treated animals began to hemorrhage again and expired within 2-132 minutes despite packing. Conclusions Our data shows that the IPHD concept is capable of prolonging survival by temporarily stanching lethal NCTH of the abdomen. This device may be an effective temporary countermeasure to NCTH of the abdomen that could be deployed in the pre-hospital environment or as a bridge to more advanced therapy. Level of evidence Basic Science; Does not require a level of evidence. Study type Therapeutic device.

Cerebrovascular autoregulation (CA) is a protective mechanism that enables the cerebral vasculature to automodulate tone in response to changes in cerebral perfusion pressure to ensure constant levels of cerebral blood flow (CBF) and oxygen delivery. CA can be impaired after neurological injury and contributes to secondary brain injury. In this study, we report novel impedance indices using trans-ocular brain impedance (TOBI) during controlled systemic hemorrhage and hypotension to assess CA in comparison with pressure reactivity index (PRx).Yorkshire swine were instrumented to record intracranial pressure (ICP), mean arterial pressure (MAP), and CBF. TOBI was recorded using electrocardiographic electrodes placed on the closed eyelids. Impedance changes (dz) were recorded in response to introducing an alternating current (0.4 mA) through the electrodes. MAP, ICP, and CBF were also measured. Animals were subjected to a controlled hemorrhage to remove 30-40% of each animal's total blood volume over 25-35 min. Hemorrhage was titrated to reach an MAP of approximately 35 mm Hg and end-tidal carbon dioxide above 28 mm Hg. PRx was calculated as a moving Pearson correlation between MAP and ICP. TOBI indices were calculated as the amplitude of the respiratory-induced changes in dz. DZx was calculated as a moving Pearson correlation between dz and MAP. TOBI indices (dz and DZx) were compared with hemodynamic indicators and PRx.dz was shown to be highly correlated with MAP, ICP, cerebral perfusion pressure, and CBF (r = - 0.823, - 0.723, - 0.813, and - 0.726), respectively (p 0.0001). During hemorrhage, cerebral perfusion pressure and CBF had a mean percent decrease (standard deviation) from baseline of - 54.2% (12.5%) and - 28.3% (14.7%), respectively, whereas dz increased by 277% (268%). Receiver operator characteristics and precision-recall curves demonstrated high predictive performance of DZx when compared with PRx with an area under the curve above 0.82 and 0.89 for receiver operator characteristic and precision-recall curves, respectively, with high sensitivity and positive predictive power.TOBI indices appear to track changes in PRx and hemodynamics that affect CA during hemorrhage-induced hypotension. TOBI may offer a suitable, less invasive surrogate to PRx for monitoring and assessing CA.

To date, existing animal models of the acute respiratory distress syndrome (ARDS) have failed to translate preclinical discoveries into effective pharmacotherapy or diagnostic biomarkers. To address this translational gap, we developed a high-fidelity swine model of ARDS utilizing clinically-relevant lung injury exposures. Fourteen male swine were anesthetized, mechanically ventilated, and surgically instrumented for hemodynamic monitoring, blood, and tissue sampling. Animals were allocated to one of three groups: 1) Indirect lung injury only: animals were inoculated by direct injection of E. coli into the kidney parenchyma, provoking systemic inflammation and distributive shock physiology; 2) Direct lung injury only: animals received volutrauma, hyperoxia, and bronchoscope-delivered gastric particles; 3) Combined indirect and direct lung injury: animals were administered both above-described indirect and direct lung injury exposures. Animals were monitored for up to 12 hours, with serial collection of physiologic data, blood samples, and radiographic imaging. Lung tissue was acquired post-mortem for pathological examination. In contrast to indirect lung injury only and direct lung injury only groups, animals in the combined indirect and direct lung injury group exhibited all of the physiological, radiographic, and histopathologic hallmarks of human ARDS: impaired gas exchange (mean PaO2/FiO2 ratio 124.8 ± 63.8), diffuse bilateral opacities on chest radiographs, and extensive pathologic evidence of diffuse alveolar damage. Our novel porcine model of ARDS, built on clinically-relevant lung injury exposures, faithfully recapitulates the physiologic, radiographic, and histopathologic features of human ARDS, and fills a crucial gap in the translational study of human lung injury.

Introduction: Respiratory infections can occur through the transmission of virus-containing aerosols from infected individuals. It remains unclear whether cardiac arrest (CA) resuscitation generates aerosols that have the potential to transmit diseases including COVID-19. Hypothesis: In a swine CA model, chest compression and defibrillation generate aerosols (≤10 μm) that could contain respiratory viruses. Methods: To simulate witnessed CA with bystander-initiated CPR, 3 female non-intubated swine underwent 4 minutes of untreated ventricular fibrillation CA followed by ten 2-minute cycles of mechanical chest compression and defibrillation without ventilation. The diameter (0.3 - 10 μm) and quantity of aerosols generated during 45-second intervals of no-flow, chest compression, and after each defibrillation were collected via a nose cone by the TSI Optical Particle Sizer. Aerosol generated from the coughs of 4 healthy human subjects were also compared to the swine data. Results: There was no significant difference between the total aerosols generated during chest compression compared to no-flow. In contrast, defibrillation followed by chest compression generated significantly more aerosols than chest compression or no-flow alone (72.4 ± 41.6 x10 4 vs 12.3 ± 8.3 x10 4 vs 10.5 ± 11.2 x10 4 ; p < 0.0001), particularly at the larger-sized aerosols. Two consecutive human coughs generated 54.7 ± 33.9 x10 4 aerosols with a size distribution much smaller than post-defibrillation CPR (Table). Conclusion: Chest compression generated comparable aerosols to no-flow in a swine CA model. In contrast, defibrillation followed by chest compression generated significantly more aerosols than chest compression or no-flow alone, with a distribution shift toward larger aerosols. Additional research is needed to elucidate the mechanisms by which aerosol generation during chest compression is modified by defibrillation and to assess rescuer risk during CA resuscitation.

Background Resuscitative endovascular balloon occlusion of the aorta (REBOA) has been shown to be effective for management of noncompressible torso hemorrhage. However, this technique requires arterial cannulation, which can be time-consuming and not amendable to placement in austere environments. We present a novel, less invasive aortic occlusion device and technique designated gastroesophageal resuscitative occlusion of the aorta (GROA). In this study, we aimed to characterize the physiological tolerance and hemodynamic effects of a prototype GROA device in a model of severe hemorrhagic shock and resuscitation and compare with REBOA. Methods Swine (N = 47) were surgically instrumented for data collection. A 35% controlled arterial hemorrhage was followed by randomizing animals to 30-minute, 60-minute, or 90-minute interventions of GROA, REBOA, or control. Following intervention, devices were deactivated, and animals received whole blood and crystalloid resuscitation. Animals were monitored for an additional 4 hours. Results All animals except one GROA 90-minute application survived the duration of their intervention periods. Survival through resuscitation phase in GROA, REBOA, and control groups was similar in the 30-minute and 60-minute groups. The 90-minute occlusion groups exhibited deleterious effects upon device deactivation and reperfusion with two GROA animals surviving and no REBOA animals surviving. Mean (SD) arterial pressure in GROA and REBOA animals increased across all groups to 98 (31.50) mm Hg and 122 (24.79) mm Hg, respectively, following intervention. Lactate was elevated across all GROA and REBOA groups relative to controls during intervention but cleared by 4 hours in the 30-minute and 60-minute groups. Postmortem histological examination of the gastric mucosa revealed mild to moderate inflammation across all GROA groups. Conclusion In this study, the hemodynamic effects and physiological tolerance of GROA was similar to REBOA. The GROA device was capable of achieving high zone II full aortic occlusion and may be able to serve as an effective method of aortic impingement.

Aim It remains unclear whether cardiac arrest (CA) resuscitation generates aerosols that can transmit respiratory pathogens. We hypothesize that chest compression and defibrillation generate aerosols that could contain the SARS-CoV-2 virus in a swine CA model. Methods To simulate witnessed CA with bystander-initiated cardiopulmonary resuscitation, 3 female non-intubated swine underwent 4 min of ventricular fibrillation without chest compression or defibrillation (no-flow) followed by ten 2-min cycles of mechanical chest compression and defibrillation without ventilation. The diameter (0.3–10 μm) and quantity of aerosols generated during 45-s intervals of no-flow and chest compression before and after defibrillation were analyzed by a particle analyzer. Aerosols generated from the coughs of 4 healthy human subjects were also compared to aerosols generated by swine. Results There was no significant difference between the total aerosols generated during chest compression before defibrillation compared to no-flow. In contrast, chest compression after defibrillation generated significantly more aerosols than chest compression before defibrillation or no-flow (72.4 ± 41.6 × 104 vs 12.3 ± 8.3 × 104 vs 10.5 ± 11.2 × 104; p

Background Most elderly trauma patients suffer blunt head injury and many utilize antithrombotic (AT) medications. The utility of delayed CT-head (D-CTH) in neurologically intact elderly patients using AT who have an intracranial hemorrhage (ICH) on presentation is unknown. We hypothesized that D-CTH would not alter clinical management and aimed to evaluate the role of D-CTH in this population. Methods A retrospective cohort study was performed. Patients ≥65 years sustaining blunt head injuries from January 2010 to July 2017 were identified using our level 1 trauma center database. AT-patients presenting with ICH who underwent D-CTH were included. Patients with worsened ICH were compared to those with stable to improved ICH on D-CTH. AT-patients were compared to a cohort of non-AT patients. Fisher’s Exact and Mann-Whitney U tests were utilized and a power analysis conducted. Results 137 A T and 34 non-AT patients were identified. There was no difference in hemorrhage progression or appearance of new ICH. No patient had a change in management from D-CTH in either cohort. AT-patients were slightly older (p 50 AT-patients with worsened ICH were compared to 87 with stable ICH. There was no difference in cohort demographics. Hemorrhage progression did not vary with type of AT used but did increase if multiple types of synchronous ICH were present (p Conclusions Our data supports abstaining from routine D-CTH of elderly ICH patients with an intact neurologic examination who are utilizing aspirin, clopidogrel or warfarin. Conclusions cannot be drawn regarding new oral anticoagulants (NOACs) given low enrollment. Further multicenter study is required to provide adequate power and detect small levels of management change.

Cerebrovascular autoregulation (CA) is often impaired following traumatic brain injury. Established technologies and metrics used to assess CA are invasive and conducive for measurement, but not for continuous monitoring. We developed a trans-ocular brain impedance (TOBI) method that may provide non-invasive and continuous indices to assess CA. In this study, we monitored impedance metrics such as respiratory-induced impedance amplitude changes (dz) as well as a novel impedance index (DZx), which is a moving Pearson correlation between mean arterial pressure (MAP) and dz. Yorkshire swine were instrumented to continuously record ICP, MAP, and cerebral blood flow (CBF). TOBI was recorded by placement of standard ECG electrodes on closed eyelids and connected to a data acquisition system. MAP, ICP and CBF were manipulated utilizing an intravenous vasopressor challenge. TOBI indices (dz and DZx) were compared to the hemodynamic indicators as well as pressure reactivity index (PRx). During the vasopressor challenge, dz was highly correlated with ICP, CPP, and CBF (r = - 0.49, p 0.0001). ICP, CPP, and CBF had a mean percent increase (standard deviation) from baseline of 29(23.2)%, 70(25)%, and 37(72.6)% respectively while dz decreased by 31(15.6)%. Receiver operator curve test showed high predictive performance of DZx when compared to PRx with area under the curve above 0.86, with high sensitivity and specificity. Impedance indices appear to track changes in PRx and hemodynamics that affect cerebral autoregulation. TOBI may be a suitable less invasive surrogate to PRx and capable of tracking cerebral autoregulation.

Aim: High-dose valproic acid (VPA) improves the survival and neurologic outcomes after asphyxial cardiac arrest (CA) in rats. We characterized the pharmacokinetics, pharmacodynamics, and safety of high-dose VPA in a swine CA model to advance clinical translation. Methods: After 8 ​min of untreated ventricular fibrillation CA, 20 male Yorkshire swine were resuscitated until return of spontaneous circulation (ROSC). They were block randomized to receive placebo, 75 ​mg/kg, 150 ​mg/kg, or 300 ​mg/kg VPA as 90-min intravenous infusion (n ​= ​5/group) beginning at ROSC. Animals were monitored for 2 additional hours then euthanized. Experimental operators were blinded to treatments. Results: The mean(SD) total CA duration was 14.8(1.2) minutes. 300 ​mg/kg VPA animals required more adrenaline to maintain mean arterial pressure ≥80 ​mmHg and had worse lactic acidosis. There was a strong linear correlation between plasma free VPA Cmax and brain total VPA (r2 ​= ​0.9494; p ​

There is no standard protocol for the management of non-operative liver or spleen injuries (LSI). In 2011, our institution changed the non-operative management (NOM) protocol of LSI from prolonged bed rest (PBR) to early mobilization (EM). We aim to show that EM safely decreases length of stay (LOS), ICU LOS, and cost. We conducted a retrospective review in which non-operative LSI patients observed PBR from January 2008 through July 2011 and were mobilized early from August 2011 through December 2014. Endpoints assessed were length of bed rest, hospital LOS, ICU LOS, failure of NOM, cost, angiography/embolization, and mortality. There were a total of 184 patients with LSI who met study criteria and were not excluded. 77 patients utilized PBR between 2008 and 2011 and 107 followed EM protocol between 2011 and 2014. There was no significant difference in the male to female ratio, age, ISS, anticoagulant use, or MOI. Both groups had similar injury profiles. PBR included 34 liver injuries, 45 splenic injuries and two patients with both. EM included 63 liver injuries, 55 splenic injuries and 11 patients with both (for liver injury p = 0.053, for splenic injury p = 0.37, and for combined p = 0.08). LOS and cost were significantly decreased in the EM cohort. LOS was shortened by 1.07 days (p = 0.005) and cost of hospitalization was reduced by $7077 (p = 0.046). There was no difference in NOM failure, angiography/embolization, or mortality. EM in non-operative LSI is safe and cost-effective. It results in decreased LOS and cost without increasing failure of NOM, angiography, embolization, or mortality.

Cerebrovascular autoregulation (CAR) is the ability of vessels to modulate their tone in response to changes in pressure. As an auto-protective mechanism, CAR is critical in preventing secondary brain injury post-trauma. Monitoring of changes in cerebral blood volume might be valuable in evaluating CAR and response to various therapies. In this study, we utilized an ocular-brain bioimpedance interface to assess real time changes in cerebral blood volume in response to a number of physiological challenges. We hypothesize that changes in brain bioimpedance (dz) would track changes in cerebral blood volume. Anesthetized animals were instrumented for monitoring of intracranial pressure (ICP), mean arterial blood pressure, cerebral perfusion pressure (CPP) and cerebral blood flow (CBF). Bioimpedance was monitored continuously through electrocardiographic electrodes placed over the eyelids. Interventions such as hyperventilation, vasopressor administration, creation of an epidural hematoma, and systemic hemorrhage were used to manipulate levels of ICP, CPP, and CBF. The dz correlated with changes in ICP, CPP, and CBF (r = -0.72 to -0.88, p 0.0001). The receiver operating characteristic for dz at different thresholds of CPP and CBF showed high impedance performance with area under the curve between 0.80-1.00 (p 0.003) and sensitivity and specificity varying between 83%-100% and 70%-100%, respectively. Our preliminary tests show that brain bioimpedance as measured through the ocular-brain interface tracks changes in CPP and CBF with high precision and may prove to be valuable in the future in assessing changes in cerebral blood volume and CAR.

Background Missing life-threatening injuries is a persistent concern in any trauma program. Autopsy is a tool routinely utilized to determine an otherwise occult cause of death in many fields of medicine. It has been adopted as a required component of the trauma peer review (PR) process by both the American College of Surgeons and the Pennsylvania Trauma Foundation. We hypothesized that autopsy would not identify preventable deaths for augmentation of the PR process. Materials and methods A retrospective chart review using our institutional trauma registry of all trauma deaths between January 2012 and December 2015 was performed. Per the protocol of our level 1 center, all trauma deaths are referred to the medical examiner (ME) and reviewed as part of the trauma PR process. All autopsy results are evaluated with relation to injury severity score (ISS), trauma injury severity score (TRISS), nature of death, and injuries added by autopsy. ME reports are reviewed by the trauma medical director and referred back to the trauma PR committee if warranted. Trauma injury severity score methodology determines the probability of survival (Ps) given injuries identified. A patient with Ps of ≥0.5 is expected to survive their injuries. Cohorts were created based on when in the hospitalization death occurred: 48 h, or late death. A comparison was conducted between the ISS and Ps calculated during trauma workup and on autopsy using chi-square and Fischer's exact tests. Results A total of 173 patient deaths were referred to the ME with 123 responses received. Average length of stay was 2.61 d. Twenty-six patients had autopsy declined by the ME, 25 received an external examination only, and 72 received a full autopsy. Autopsy identified one case that was reconsidered in PR (P = 0.603) and added diagnoses, but not injuries, to one patient in the early death group (P = 1) and two in the late death group (P = 0.4921). No preventable cause of death was uncovered, and educational use was minimal. Autopsy did identify injuries in seven cases that were initially not consistent with expected mortality, but postmortem Ps was consistent with expected mortality (P = 0.254). Mean ISS was 34.48, and mean Ps was 0.275 among all patients. The most commonly identified injuries added by autopsy were rib injuries, lung injuries, and intracranial hemorrhage. Conclusions Autopsy does not identify causes of preventable in an otherwise highly functioning trauma program and may be a poor use of institutional resources. In fact, it adds few diagnoses when death occurs after a full trauma assessment has had time to take place. Autopsy may be of use to identify protocol failure in maturing trauma programs, to give answers to grieving families and in select situations where death was unanticipated even after a full evaluation took place.

Introduction: High-dose valproic acid (VPA) has been shown to improve the survival and neurologic outcomes in preclinical brain injury models including asphyxial cardiac arrest (CA) in rats. However, its pharmacokinetics, pharmacodynamics, and safety profiles in large animal CA models are unknown. Hypothesis: High-dose VPA can be safely administered after return of spontaneous circulation (ROSC) and cross the blood-brain barrier dose-dependently in a swine CA model. Methods: After 8 minutes of untreated ventricular fibrillation CA, male Yorkshire swine [43.3 (3.0) kg] were resuscitated for up to 16 minutes until ROSC. They were randomized to receive placebo, 75 mg/kg, 150 mg/kg, or 300 mg/kg VPA as 90-minute intravenous infusion (n=5 per group) beginning 20 minutes after sustained ROSC. Animals were monitored for 2 additional hours after infusion ended and then euthanized. Experimental operators were blinded to the treatments. Results: The mean total cardiac arrest duration was 15.0 (1.6) minutes, with no significant differences between groups. At end of infusion, the serum free VPA concentration increased dose dependently, from 139.2 (10.1) mcg/mL [75 mg/kg VPA] to 287.2 (24.6) mcg/mL [150 mg/kg VPA] to 565.6 (36.5) mcg/mL [300 mg/kg VPA] (p2 =0.98). All animals survived until euthanasia, although the 300 mg/kg group required more epinephrine to maintain mean arterial pressure greater than or equal to 80 mmHg and had higher lactic acidosis. Conclusion: Brain VPA concentrations correlate strongly with serum free VPA when high-dose intravenous VPA is given after ROSC in a swine CA model. These results provide the foundation for dose-optimization studies of high-dose VPA as a neuroprotective therapy following resuscitation from CA.

Background Cervical spinal cord injuries often necessitate ventilator support (VS). Prolonged endotracheal tube use has conveyed substantial morbidity in prospective study. Tracheostomy is recommended if VS is anticipated to be 7 days or longer, which defines prolonged ventilation (PV). Identifying these patients on arrival and before tracheostomy need is readily evident could prevent morbidity while lowering hospital costs. We aimed to create a tracheostomy score (trach score) to identify patients requiring PV and who could benefit from immediate tracheostomy. Methods A review of patients with cervical spine fractures and cervical spinal cord injuries from 2005 to 2017 from the Pennsylvania Trauma Outcome Study database was performed. Patients were excluded for missing data, no use of VS or death in less than 7 days. Patients were selected for a training set or validation set by state identification number. We used automated forward stepwise selection to select a logistic model. Significant continuous variables were dichotomized to create a simplified screening score (trach score) and this was applied to the validation set. Results Needing ventilation for 7 or more days was positively associated with higher Injury Severity Scores having a complete or anterior injury, and having a motor cord injury from C1 to C4. Application of the logistic model to the validation data produced a receiver operating characteristic curve with area under the curve of 0.7712, with 95% confidence limit (CL) of 0.6943 to 0.8481. The validation receiver operating characteristic curve was statistically better than chance using a contrast test with χ with p value less than 0.01. In the validation set, a trach score of 0 correlated to 33% needing PV, a score of 1 with 67% needing PV, 2 with 85%, and 3 with 98%. Conclusion Use of the trach score identified the majority of patients requiring prolonged VS in our study. An early tracheostomy protocol using predictive modeling could aid in reduction of intensive care unit length of stay and improving ventilator weaning in these patients. External verification of this predictive tool and of an early tracheostomy protocol is needed. Level of evidence This work is a retrospective prognostic cohort study and meets evidence Level III criteria.

Background The systemic responses to infection and its progression to sepsis remains poorly understood. Progress in the field has been stifled by the shortcomings of experimental models which include poor replication of the human condition. To address these challenges, we developed and piloted a novel large animal model of severe infection that is capable of generating multi-system clinically relevant data. Methods Male swine (n = 5) were anesthetized, mechanically ventilated, and surgically instrumented for continuous hemodynamic monitoring and serial blood sampling. Animals were inoculated with uropathogenic E. coli by direct injection into the renal parenchyma and were maintained until a priori endpoints were met. The natural history of the infection was studied. Animals were not resuscitated. Multi-system data were collected hourly to 6 hours; all animals were euthanized at predetermined physiologic endpoints. Results Core body temperature progressively increased from mean (SD) 37.9(0.8)°C at baseline to 43.0(1.2)°C at experiment termination (p = 0.006). Mean arterial pressure did not begin to decline until 6h post inoculation, dropping from 86(9) mmHg at baseline to 28(5) mmHg (p = 0.005) at termination. Blood glucose progressively declined but lactate levels did not elevate until the last hours of the experiment. There were also temporal changes in whole blood concentrations of a number of metabolites including increases in the catecholamine precursors, tyrosine (p = 0.005) and phenylalanine (p = 0.005). Lung, liver, and kidney function parameters worsened as infection progressed and at study termination there was histopathological evidence of injury in these end-organs. Conclusion We demonstrate a versatile, multi-system, longitudinal, swine model of infection that could be used to further our understanding of the mechanisms that underlie infection-induced multi-organ dysfunction and failure, optimize resuscitation protocols and test therapeutic interventions. Such a model could improve translation of findings from the bench to the bedside, circumventing a significant obstacle in sepsis research.

AIM: We examined the use of a Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) catheter during cardiopulmonary resuscitation (CPR) after cardiac arrest (CA) to assess its effect on haemodynamics such as coronary perfusion pressure (CPP), common carotid artery blood flow (CCA-flow) and end-tidal CO(2) (PetCO(2)) which are associated with increased return of spontaneous circulation (ROSC). METHODS: Six male swine were instrumented to measure CPP, CCA-Flow, and PetCO2. A 7Fr REBOA was advanced into zone-1 of the aorta through the femoral artery. Ventricular fibrillation was induced and untreated for 8 min. CPR (manual then mechanical) was initiated for 24 min. Continuous infusion of adrenaline (epinephrine) was started at minute-4 of CPR. The REBOA balloon was inflated at minute-16 for 3 min and then deflated/inflated every 3 min for 3 cycles. Animals were defibrillated up to 6 times after the final cycle. Animals achieving ROSC were monitored for 25 min. RESULTS: Data showed significant differences between balloon deflation and inflation periods for CPP, CCA-Flow, and PetCO(2) (p < 0.0001) with an average difference (SD) of 13.7 (2.28) mmHg, 15.5 (14.12) mL min(−1) and −4 (2.76) mmHg respectively. Three animals achieved ROSC and had significantly higher mean CPP (54 vs. 18 mmHg), CCA-Flow (262 vs. 135 mL min(−1)) and PetCO(2) (16 vs. 8 mmHg) (p < 0.0001) throughout inflation periods than No-ROSC animals. Aortic histology did not reveal any significant changes produced by balloon inflation. CONCLUSION: REBOA significantly increased CPP and CCA-Flow in this model of prolonged CA. These increases may contribute to the ability to achieve ROSC.

Introduction: Despite advancements in CPR, survival to hospital discharge remains low for in- and out-of-hospital cardiac arrest (CA). Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) is an evolving tool for temporary control of non-compressible truncal hemorrhage. In this investigation, we examined whether REBOA use during non-traumatic CA would produce favorable hemodynamic changes associated with return of spontaneous circulation (ROSC). Hypothesis: We hypothesized that REBOA use during CPR would result in higher coronary perfusion pressure (CPP) and common carotid artery blood flow (C-Flow) in a prolonged model of CA. Methods: Six male swine were anesthetized and instrumented to measure and monitor CPP, and C-Flow. A REBOA catheter (Prytime Medical Devices) was advanced into zone 1 of the aorta through the femoral artery. Ventricular fibrillation was electrically induced and untreated for 8 minutes. CPR was started manually at minute-8, then changed to mechanical CPR at minute-12 for the duration of the experiment. Continuous infusion of epinephrine (0.0024mg/kg/min) was simultaneously started with mechanical CPR. The REBOA balloon was inflated beginning at minute-16 for 3 minutes then deflated for 3 minutes for a total of 6 cycles. At the end of the final cycle (REBOA inflation), CPR was stopped (after 33 minutes of total arrest time) and animals were defibrillated using 200 J biphasic shocks, repeated up to 6 times. Animals achieving ROSC were monitored for an additional 25 minutes. Results: Analysis using repeated measure ANOVA showed significant differences between balloon deflation and inflation periods for CPP (p Conclusion: REBOA significantly increased CPP and C-Flow in this swine model of prolonged CA. These increases may have contributed to the ability to achieve ROSC after greater than 30 min of CA.

Background: Extracorporeal CPR (ECPR) is used to provide circulatory stability for organ perfusion and oxygen delivery (DO 2 ) after refractory cardiac arrest (CA). Hemodynamic measurements during ECPR may not necessarily indicate adequate perfusion at the microcirculatory level where DO 2 , oxygen consumption (VO 2 ), and oxygen exchange (O 2 ER) are most critical. In this study, we used sidestream dark-field imaging to measure total vessel density (TVD) to evaluate sublingual microcirculatory flow in a swine model of refractory CA and ECPR. Hypothesis: We hypothesize that TVD can provide real-time assessment of tissue perfusion during post-cardiac arrest ECPR that correlates with traditional measures of tissue oxygenation. Methods: Swine (8) were anesthetized and instrumented for hemodynamic monitoring. Ventricular fibrillation (VF) was induced and CPR initiated after 8min. CPR was administered using a combination of manual and mechanical chest compressions. During CPR the femoral vessels were instrumented for delivery of veno-arterial ECPR. ECPR was initiated 45min after arrest to simulate refractory CA. Sublingual TVD was measured at baseline and after 15min, 1, 2, and 3 hours of ECPR. Results: A one-way ANOVA showed significant difference between baseline TVD: 12.2(2.3)mm -1 and at 3 hours into ECPR: 6.4(3.0)mm -1 (p=0.005). TVD was highly correlated with circuit flow but not with Mean Arterial Pressure (MAP) (r=0.903, p=0.036; r=0.063, p=0.920). In addition, TVD was highly correlated with DO 2 , and lactate, (r= 0.897, p=0.039; r=-0.883, p=0.047) and moderately with VO 2 , O 2 ER, and ScvO 2 (r= 0.776, -0.370, 0.558) respectively. Conclusion: TVD appears to provide a reliable real-time assessment of tissue perfusion during post-cardiac arrest ECPR. The relationships between TVD and MAP, and TVD and flow also suggest that optimization of flow may be more important than optimizing pressure to achieve adequate tissue perfusion during ECPR.

Introduction: Prolonged cardiac arrest (CA) eligible for ECPR has pathologic features that are more pronounced than CA durations in which ROSC is typically achieved. One such feature is consumptive coagulopathy resulting in microvascular thrombosis and no-reflow. In this study we examined the impact of no-flow time on CA coagulopathy during prolong CPR in swine Hypothesis: No-flow time amplifies the coagulopathy of prolonged cardiac arrest. Methods: Animals were anesthetized and instrumented for hemodynamic monitoring. After 4 or 8 min of untreated ventricular fibrillation (groups CA-4 and CA-8, n=5/group), goal-directed CPR was initiated and continued for a total arrest time of 45 minutes. Viscoelastic properties of clot formation and fibrinolysis were measured by TEG in whole blood at baseline and at the end of resuscitation protocol. Rate of fibrin activation (Angle alpha), Maximum amplitude (MA), Time to MA (TMA), and reduction of clot after 30 min (CL30) were measured to describe coagulation status. Results: TEG showed reduction in clot strength after the CPR protocol. For groups CA-4 and CA-8, Alpha declined from 71(4) to 55(7) and from 68(5) to 51(9) deg, MA reduced from 75(2) to 58(7) and from 73(3) to 53(11) mm and TMA prolonged from 21(2) to 27(4) and from 20(4) to 25(2) min. CL30 increased from 95(2) to 97(2) and from 96(2) to 100(1) % (all p Conclusion: In this clinically relevant model of prolonged CA with consumptive coagulopathy, the reduction of clot formation and clot strength after 45 minutes of CA and CPR was not significantly different with 4 and 8 min no-flow time. However, clot lysis was more reduced after 8-min no-flow. Further studies are needed to determine the impact of no-flow time on CA coagulopathy at the microvascular level.

Introduction: The interval from cardiac arrest (CA) to initiation of chest compressions (no-flow time) plays an important role in outcome of CA. The purpose of this study was to evaluate impact of no-flow time on the effectiveness of a goal-direct CPR strategy during prolonged cardiac arrest. Hypothesis: The effectiveness of goal-directed CPR declines with increased no-flow time. Methods: Porcine model of CA was utilized with a period of untreated ventricular fibrillation of 4 or 8 min (groups CA-4, CA-8, n=5/group) followed by a goal-directed CPR protocol for up to 40 minutes. Manual and mechanical chest compressions with impedance threshold device were used sequentially to achieve PetCO2 goal >20 mmHg. Epinephrine infusion and boluses were adjusted with the goal of achieving an arterial diastolic blood pressure >35 mmHg. Hemodynamic parameters were collected throughout the protocol, averaged in 5-minute intervals and compared between groups by an unpaired t-test. Results: A higher average DBP was achieved in the CA-4 vs. CA-8 group during CPR (19 ± 11 mmHg vs. 12 ± 9 mmHg: p Conclusion: In this swine model of prolonged VF cardiac arrest, increased no-flow time limits the effectiveness of a goal-directed CPR strategy. Moreover, the response to standard dose of epinephrine was higher after shorter no-flow time.

Coagulation monitoring is essential for perioperative care and thrombosis treatment. However, existing assays for coagulation monitoring have limitations such as a large footprint and complex setup. In this work, we developed a miniaturized device for point-of-care blood coagulation testing by measuring dynamic clot retraction force development during blood clotting. In this device, a blood drop was localized between a protrusion and a flexible force-sensing beam to measure clot retraction force. The beam was featured with micropillar arrays to assist the deposition of carbon nanotube films, which served as a strain sensor to achieve label-free electrical readout of clot retraction force in real time. We characterized mechanical and electrical properties of the force-sensing beam and optimized its design. We further demonstrated that this blood coagulation monitoring device could obtain results that were consistent with those using an imaging method and that the device was capable of differentiating blood samples with different coagulation profiles. Owing to its low fabrication cost, small size, and low consumption of blood samples, the blood coagulation testing device using carbon nanotube strain sensors holds great potential as a point-of-care tool for future coagulation monitoring.

Background A novel arterial everter device was engineered to simplify microvascular coupling of arteries by reliably securing the stiff, muscular wall of arteries over coupler pins. We compare microvascular coupling with the everter device to manual suturing for arterial anastomoses in a live large animal model. Materials and Methods In this preliminary study, bilateral external femoral arteries of five male swine were exposed and sharply divided. Arteries were anastomosed using either interrupted sutures (n = 5) or the everter device and Synovis Coupler (n = 5). The efficiency in engaging coupler pins, the time taken to perform the anastomosis, and vessel patency immediately post-op and at 1-week postanastomosis were evaluated. Vessel wall injury and luminal stenosis were compared between groups using histomorphometric analyses. Results On an average, 80% of coupler pins engaged the vessel walls after a single pass of the everter. The average time to perform the anastomosis was significantly less when using the everter/coupler compared with manual suturing (6:35 minutes versus 25:09 minutes, p Conclusions Successful arterial anastomoses using the everter device with the Synovis Coupler was easier and significantly more efficient when compared with a standard hand-sewn technique. Both techniques had acceptable patency rates and similar effects on the vessel wall and intima.

INTRODUCTION: Oxidation-reduction reactions involve electron exchanges that require optimal balance for proper cell function. This balance is measured via redox potential and reflects oxidative stress. Despite the critical role of oxidative stress in critical illness and injury, little is known regarding redox potential. We hypothesize redox potential measurements will correlate with accumulation of O(2) debt produced by hemorrhage over time. METHODS: Ten swine were studied using a polytrauma hemorrhagic shock model. Whole blood and plasma redox potential measures were obtained at defined stages of O(2) debt (20, 40, 60, 80mL/kg), and through resuscitation. Redox potential was determined by measuring open circuit potential using novel gold nanoporous electrodes with Ag/AgCl reference. RESULTS: Whole blood redox potential showed negative change as O(2) debt accumulated, exhibiting positive response during resuscitation, and correlated with O(2) debt across all animals (p

A continuous microfluidic viscometer is used to measure blood coagulation. The viscometer operates by flowing oil and blood into a cross section where droplets are generated. At a set pressure, the length of the droplets is inversely proportional to the viscosity of the blood sample being delivered. Because blood viscosity increases during coagulation as the blood changes from a liquid to a solid gel, the device allows to monitor coagulation by simply measuring the drop length. Experiments with swine blood were carried out in its native state and with the addition of coagulation activators and inhibitors. The microfluidic viscometer detected an earlier initiation of the coagulation process with the activator and a later initiation with the inhibitor compared to their corresponding controls. The results from the viscometer were also compared with the clinical method of thromboelastography (TEG), which was performed concurrently for the same samples. The time to initiation of coagulation in the microfluidic viscometer was correlated with the reaction time in TEG. Additionally, the total time for the measurement of clot strengthening in TEG correlated with the time for the maximum viscosity observed in the microfluidic viscometer. The microfluidic viscometer measured changes in viscosity due to coagulation faster than TEG detected the clot formation. The present viscometer is a simple technology that can be used to further study the entire coagulation process.

Increasing active longevity has created an increasing surge of elderly trauma patients. The majority of these patients suffer blunt trauma and many are taking antithrombotic agents. The literature is mixed regarding the utility of routine repeat head CT in patients taking antithrombotic medications with a GCS of 15 and initial negative head CT. We hypothesized that scheduled delayed CT head 12 h after admission (D-CTH) in elderly blunt trauma victims would not identify clinically significant new hemorrhages or change management. A retrospective chart review using our institutional trauma registry of patients ≥65 years sustaining blunt head injuries from 2010 to 2012 was performed. By hospital protocol, all such patients on antithrombotic therapy receive a routine D-CTH. All of these patients were included. Demographics, injuries, medications, laboratory values, LOS, mental status, and management were analyzed. Of the 234 patients meeting inclusion criteria, 8 initially were identified as having D-ICH. Upon further review, five patients had the same findings on both initial and delayed CT scans and one patient was determined to actually have had a hemorrhage stroke. Ultimately, only two patients (0.85%, 95% CI 0.1–3.1%) had new ICH discovered on D-CTH. None of the patients on warfarin demonstrated any new injury on D-CTH (95% CI ≤ 4.6%). Only one patient taking aspirin as a sole agent had a delayed injury on D-CTH (1.1%, 95% CI 0–4.2%). The remaining patient was taking a combination of aspirin and clopidogrel representing 2.2% of 45 patients on combination therapy (95% CI 0.1–11.8%). Only two patients taking a direct thrombin inhibitor (dabigatran) met inclusion criteria and neither endured a bleed (95% CI ≤ 77.6%). Further analysis revealed no cases with clinical changes or surgical intervention for new ICH on delayed imaging. No inference could be made to predict which patients would suffer D-ICH. D-CTH in elderly trauma patients taking antithrombotic agents shows no statistically significant or clinical benefit for diagnosing delayed intracranial hemorrhage after minor head injury. In those with delayed imaging showing new ICH, management was not significantly altered. Not enough data were available to predict which patients would develop D-ICH, even if asymptomatic.

Whole blood coagulation testing provides valuable diagnostic information on diseases such as bleeding disorders, heart attack, deep venous thrombosis, etc. On page 3926, J. Fu and co-workers develop a miniaturized hemoretractometer to measure clot contraction upon blood coagulation with good reproducibility and robustness. This device design shows great application potential in point-of-care testing. Photo credit: David Peyer from University of Michigan.

Blood coagulation is a critical hemostatic process that must be properly regulated to maintain a delicate balance between bleeding and clotting. Disorders of blood coagulation can expose patients to the risk of either bleeding disorders or thrombotic diseases. Coagulation diagnostics using whole blood is very promising for assessing the complexity of the coagulation system and for global measurements of hemostasis. Despite the clinic values that existing whole blood coagulation tests have demonstrated, these systems have significant limitations that diminish their potential for point-of-care applications. In this work, we leverage recent advancements in device miniaturization using functional soft materials to develop a miniaturized clot retraction force assay device termed mHemoRetractoMeter (mHRM). The mHRM is capable of precise measurements of dynamic clot retraction forces in real time using minute amounts of whole blood. To further demonstrate the clinical utility of the mHRM, we conduct systematic studies using the mHRM to examine the effects of assay temperature, treatments of clotting agents, and pro- and anti-coagulant drugs on clot retraction force developments of whole blood samples. The mHRM's low fabrication cost, small size, and consumption of only minute amounts of blood samples make the technology promising as a point-of-care tool for future coagulation monitoring.

BACKGROUND: Hemorrhage is the leading cause of death for both civilian and battlefield injuries. Hemorrhage from pelvic vascular wounds is of concern since it is difficult to control before surgical intervention. This has resulted in renewed interest in developing presurgical endovascular approaches to hemorrhage control. However, it is likely that other short-term techniques may be needed as a bridge to such approaches. We tested a prototype device called the pelvic hemostasis belt (PHB) for its ability to reduce or halt blood flow in a lethal model of pelvic arterial injury. METHODS: Seventeen male swine, 42 (5.2)kg were anesthetized, instrumented, and then randomized into three groups (control, military antishock trousers [MAST], and PHB). Animals underwent laparotomy with placement of a 4-0 stainless steel monofilament suture through the right iliac artery. The laparotomy was closed, and the iliac suture was exteriorized. Hemorrhage was produced by pulling the suture through the iliac artery. In both PHB and MAST groups, the devices were applied over the pelvis and lower abdomen for 60 minutes, followed by release and monitoring for 30 minutes or until the animal expired. Hetastarch (500 mL) was infused immediately after commencement of hemorrhage. RESULTS: All PHB group animals and only two from the MAST group survived for 60 minutes. Mean (SD) survival time for the control group was 13 (12.3) minutes. Log-rank (Mantel-Cox) survival analysis demonstrated a significant difference in survival time when comparing all groups (p < 0.0001) as well as when comparing PHB and MAST groups (p = 0.018). Significant differences were noted between groups in mean arterial pressure, lactate, and central venous hemoglobin oxygen saturation levels. CONCLUSION: The PHB was successful in improving survival for 60 minutes after a lethal vascular injury. Such a device may be helpful to bridge endovascular methods of hemorrhage control.