Use of archival tissue in epidemiologic studies: collection procedures and assessment of potential sources of bias

Research Forum Abstracts

351

Hematologic Findings of Venom-Induced Consumption Coagulopathy following Korean Viper (Gloydius Species) Bite

Yoon JC, Kim SE, Ock S, Jo S, Jeong TO, Lee JB, Jin YH/Chonbuk National University Hosptial, Jeonju-si, Korea, Republic of

Study Objectives: Recent studies have demonstrated that coagulopathy following snake envenomation is a venom-induced consumption coagulopathy (VICC), in which venom activates coagulation factors at specific points rather than an entire pathway. The objectives of this study were to determine what factors are consumed when severe coagulopathy after Korean viper (Gloydius species) bite develops and what factors should be used to monitor the venom activity. Methods: We retrospectively investigated the medical records of 244 patients who were admitted to our emergency department (ED) from 2011 to 2016 due to snake envenomation. There were 25 patients (10.2%) of severe coagulopathy defined as international normalized ratio (INR) > 3.0 with or without unmeasurable activated partial thromboplastin time (aPTT) and/or hypofibrinogenemia (< 100 mg/dl). Coagulation factor levels were checked at onset of severe coagulopathy. The onset time, treatment, and recovery time of severe coagulopathy were noted. Results: Most cases of severe coagulopathy (23/25, 88.0%) developed lately (> 12 hours after the bite). All patients (20/20) showed hypofibrinogenemia. Decreased levels of factors II, V, and VIII were observed in 2 (10.5%), 10 (52.6%), and 3 (15.8%) patients, respectively, of the total 19 patients. Among these, 2 patients showed severe coagulation factor deficiency (< 30%) rather than fibrinogen in factor V. Fibrin(ogen) degradation product (FDP) and d-dimer levels were increased in all patients who were tested. Only 2 patients (of 19) showed a mildly decreased anti-thrombin III level. Increase of fibrinogen levels was paralleled by decrease of FDP levels as treatment with antivenin and fibrinogenrich product were started. Conclusions: This study showed isolated hypofibrinogenemia and hyperfibrin(ogen)olysis are major hematologic findings of VICC following Korean viper bite. We suggest that the FDP level reflect the effect of venom and should be monitored during treatment for severe coagulopathy.

352

A Comparison of Flow Rates and Hematologic Safety Between Intraosseous Blood Transfusion Strategies in a Swine (Sus scrofa) Model of Hemorrhagic Shock: A Pilot Study

Krepela A, Auten J, Mclean J, Fortner G, Murnan S, Kemp J, Roszko P, Fishback J, Combat Trauma Research Group/Naval Medical Center Portsmouth, Norfolk, VA

Study Objectives: Intraosseous (IO) access is used by military first responders administering fluids, blood, and medications during remote damage controlled resuscitation (rDCR). In cases where access is difficult, IO lines provide a noncollapsible method that serves as a bridge to therapy while preparations are made for central venous access. Increasing degrees of transfusion pressure are required to overcome the difference between bone and systemic circulation and improve flow rates. Current military IO transfusion strategies include gravity, pressure bags, rapid transfusion devices, and manual push-pull through a three way stopcock. The clinical effects of different pressurized IO transfusion strategies in skeletally mature adults are not fully understood. The goal of this pilot was to compare four different IO blood transfusion strategies utilized with varying degrees of transfusion pressure in a porcine model with bone density similar to an adult military servicemember. Methods: Subjects (n¼9) were placed under general anesthesia and vascular access was achieved. Through a controlled hemorrhage model, 20-25% of the subjects estimated blood volume was removed using the flow of gravity. The IO device was placed in the proximal humerus and 10-15% of the subject’s blood was infused autologously via one of the four methods assigned at random. Subjects were monitored 1 hour post infusion, blood was analyzed for lactate, thromboelastogram (TEG) and arterial blood gas values. Surviving animals were euthanized while under general anesthesia and samples collected. Two

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samples from upper and lower left lung were collected to assess for gross evidence of fat embolism and inflammation. The humerus of the second animal in each treatment arm was removed and cross sectioned proximal to transfusion site for histologic evaluation of the effects of transfusion on bony architecture. Results: Infusion rates were as follows: gravity 3 and 6 ml/min, Belmont rapid infuser 31.4 and 31.5 ml/min with an average of 7 overpressure alarms, Single site gravity 78 ml/min, double site gravity 103 ml/min, push/pull 108 and 110 ml/min. One animal died 7 minutes into push/pull infusion. The second animal displayed physiologic evidence of right heart strain; however, recovered after completing infusion. One animal was lost for analysis secondary to IO malposition through the humerus. There were no increased rates of inflammation changes in the lungs between arms. No pulmonary arterial fat embolism were noted. Bony architecture at transfusion site was unaffected by transfusion strategy. Conclusions: The optimal IO transfusion strategy for our injured service members appears to be single site transfusion with a 10-20 ml flush of normal saline followed immediately by transfusion under 300 mmHg pressure bag in the proximal humerus or sternum. The push pull and double barrel methods confer a benefit in speed of transfusion, but should be further studied under the full protocol to determine the effect increased transfusion pressures have on clinical end points like damage to the underlying bony matrix, changes in right heart pressures, and increased rates of hemolysis or pulmonary fat embolism.

EMF

353

Elevation of the Head and Thorax During Cardiopulmonary Resuscitation Improves Cerebral Blood Flow in a Swine Model of Prolonged Cardiac Arrest

Dodd KW, Moore JC, Segal N, Lick MC, Salverda BJ, Hinke MB, Robinson AE, Debaty G, Lurie KG/Hennepin County Medical Center, Minneapolis, MN; University of Minnesota, Minneapolis, MN; Minneapolis Medical Research Foundation, Hennepin County Medical Center, Minneapolis, MN; University Grenoble Alps/CNRS/CHU de Grenoble Alpes/TIMCIMAG UMR 5525, Grenoble, France

Study Objectives: Despite decades of research on cardiopulmonary resuscitation (CPR), the rate of neurologically intact survival following out-of-hospital cardiac arrest remains dismal. Blood flow to the brain after 5 minutes of active compression decompression cardiopulmonary resuscitation (ACD-CPR) with an impedance threshold device (ITD) in the head-up position (HUP) has been shown to be higher than supine body position (SUP) in a swine model of cardiac arrest. Since most CPR efforts last at least 15 minutes, the aim of the study was to compare cerebral blood flow blood during prolonged HUP and SUP ACD-CPR + ITD. Methods: Following anesthetized surgical preparation of female pigs, ventricular fibrillation (VF) was induced. The animals underwent 8 minutes of untreated VF followed by 2 minutes of SUP ACD-CPR + ITD with a 30:2 compression:ventilation ratio. Animals then underwent randomization to treatment with 18 minutes of continuous CPR in either HUP, in which the head and thorax were elevated at 30 , or SUP with asynchronous ventilation at 10 breaths per minute and 10 mL/kg. The compression phase was performed at a rate of 80 per minute with a 50% duty cycle and depth of 22.5% of the

Annals of Emergency Medicine S139

Research Forum Abstracts anteroposterior chest diameter. In the decompression phase, the chest was pulled upwards with a force of approximately 20 pounds using a suction cup device. Neutron-activated microspheres were injected before VF and then at 5 and 15 minutes after CPR initiation. Arterial blood gasses (ABG) and reference blood samples were drawn to determine washout curves. At the end of the experiment, animals were sacrificed and tissue samples from multiple areas of the brain, heart, and other organs were sent for analysis. Continuous data recordings included the ECG, aortic pressure, right atrial pressure, intracranial pressure (ICP), pulse oximetry, and end-tidal CO2 (ETCO2). Respiratory effort, or “gasping,” by the animals during CPR was timestamped. Cerebral perfusion pressure (CerPP) was calculated. A priori calculations, based on prior studies and assuming an alpha of 0.05 and 80% power, suggested the need for 11 animals per group to detect an 80% difference. Studies that did not meet inclusion criteria due to severe technical difficulties, such as catheter dislodgement or inability to adequately compress the chest, were not included in the results. Data are expressed as mean  standard deviation. An unpaired Student’s t-test was used to calculate p-values. Results: Eighteen female pigs weighing 39.5  8.2 kg were randomized to ACDCPR + ITD in either HUP (n ¼ 8) or SUP (n ¼ 10). Mean cerebral blood flow after 15 minutes of CPR was 0.42  0.05 mL/min/g in the HUP group and 0.21  0.04 in SUP (p < 0.01). Pigs treated with HUP also had lower ICP and higher CerPP when compared to SUP (see Table). Time to first gasp was 282  51 seconds for HUP group versus 437  185 seconds for SUP (p < 0.05). There was no difference in ETCO2 or ABG values between SUP and HUP. Conclusions: After prolonged ACD-CPR + ITD with 30 elevation of the thorax and head, cerebral blood flow was two-fold higher when compared to standard, supine body position. These findings provide additional, strong support to proceed with a clinical evaluation of HUP ACD-CPR + ITD in humans in cardiac arrest.

(CPR). However, the extent of loading force applied during infant ECC remains unknown. The objective of this crossover study was to quantify actual forces applied by two-finger (TF) and two-thumb (TT) methods. Methods: The study has a cross-over design in which forty-two emergency medical professionals performed lone rescuer infant CPR using TF and TT technique at a rate of at least 100 compressions per minute. SkillReporterTM (PC) with Resusci® Baby QCPR manikin equipped with a MatScan-pressure measurement system was used to collect data. Perceived exertion scale (modified Borg scale) was applied to rate the exercise intensity of chest compression. Results: During TT session, the rescuers performed CPR with higher compression depth, more correct depth, better ECC quality, and a lower percentage recoil than they did during the TF. The mean compression forces (in kg), delivered in the first and second minute, were 3.53  1.27 and 3.22  1.11, respectively (p ¼ 0.012) for TF; 4.11  1.80 and 4.04  1.83 (p ¼ 0.568) for TT. A pairwise comparison in the first minute of ECC indicates that the compression force delivered by the TF was inferior to that delivered by TT (mean difference -0.58, 95% confidence interval [CI], -1.15w-0.01, p ¼ 0.045). The force delivered by the TF was also inferior to that delivered by TT (mean difference -0.82, 95% CI, -1.39w-0.26, p ¼ 0.005) in the second minute. There was no statistical difference of decompression force between TF and TT in the first and second minutes. TF has higher perceived exertion than TT method (5.27  4.69 vs. 4.02  2.31, mean difference 2.78, 95% CI, 0.36w2.12, p ¼ 0.007). The median perceived exertions for TF and TT were 5 and 4 respectively. Two minutes of infant ECC was considered a “somewhat hard to strong” exercise. Conclusions: The two-thumb method produces greater loading force, less fatigue, and better ECC quality than two-finger method during infant CPR.

355

A Trial of Terlipressin Compared to Small Volume Resuscitation in a Swine (Sus scrofa) Model of Uncontrolled Hemorrhage and Severe Hemorrhagic Shock

Wootten B, Yoder J, Walker C, Davis C, Sulava E, Zarow G, Loomis A/Naval Medical Center Portsmouth, Portsmouth, VA

354

Biomechanical Aspect of Two-Finger Versus Two-Thumb Chest Compression for Cardiopulmonary Resuscitation in Infant Manikin Model

Chi C-H, Tsou J-Y, Kao C-L, Tu Y-F, Su F-C/National Cheng Kung University Hospital, Tainan, Taiwan; Fooyin University, Kaohsiung, Taiwan

Study Objectives: Previous studies has evaluated the quality of different external chest compression (ECC) methods delivered in infant cardiopulmonary resuscitation

S140 Annals of Emergency Medicine

Study Objectives: Arginine vasopressin (AVP) is a naturally occurring stress hormone that constricts peripheral blood vessels; raising blood pressure and increasing blood flow to vital organs. AVP has been shown in animal models to be an effective treatment for hemorrhagic shock and the use of AVP has shown benefit in trauma resuscitation. AVP is limited, however, by a short half-life and storage constraints that are not suitable for austere environments such as those found in combat. Terlipressin (TP) is a vasopressin analogue with similar effects, although with a much longer half-life of 4 to 6 hours. With potentially similar benefits, a longer half-life, and ease of storage, TP may be more suitable for a combat environment than AVP. Our study compares resuscitation with TP to Tactical Combat Causality Care (TCCC) guideline recommended colloid fluids (Hextend) in a swine hemorrhagic model. Methods: The randomized, prospective study protocol was approved by the Institutional Animal Care and Use Committee. Subjects (n¼37) were mature Landrace/Yorkshire cross swine (Sus scrofa domestica) weighing between 35 and 45 kg. The morning of the procedure each animal was anesthetized, intubated and vascular access was achieved. A femoral artery arteriotomy was created using a biopsy punch and a captive-bolt gun was used to induce a mid-shaft femur fracture to create physiological effects of combat trauma. Through an uncontrolled bleed, subjects’ mean arterial pressure (MAP) was maintained at fifty percent of the subjects’ baseline measurement or 25mmHg (whichever was lower) for 30 minutes followed by the application of a TCCC standard hemostatic gauze dressing. Simultaneously resuscitation began with one of three treatment cohorts: Hextend and Terlpressin (HexTP, n¼12), Hextend (Hex, n¼13) or Terilpressin (TP, n¼12). The primary endpoint was survival to 4 hours. Secondary endpoints included acidosis, blood lactate levels, kidney injury and liver damage. Results: Preliminary results (n¼37) show survivability trended higher for the HexTP group followed by Hex and then TP (100%, 91%, 80% respectively). The blood lactates did not differ significantly between the groups. The MAPs were

Volume 70, no. 4s : October 2017