A novel, reverse-phase-shifting, thermoreversible foaming hydrogel containing antibiotics for the treatment of thermal burns in a swine model - A pilot study.

BACKGROUND: This study compared a novel topical hydrogel burn dressing (CI-PRJ012) to standard of care (silver sulfadiazine) and to untreated control in a swine thermal burn model, to assess for wound healing properties both in the presence and absence of concomitant bacterial inoculation. METHODS: Eight equal burn wounds were created on six Yorkshire swine. Half the wounds were randomized to post-burn bacterial inoculation. Wounds were subsequently randomized to three treatments groups: no intervention, CI-PRJ012, or silver sulfadiazine cream. At study end, a blinded pathologist evaluated wounds for necrosis and bacterial colonization. RESULTS: When comparing CI-PRJ012 and silver sulfadiazine cream to no treatment, both agents significantly reduced the amount of necrosis and bacteria at 7 days after wound creation (p < 0.01, independently for both). Further, CI-PRJ012 was found to be significantly better than silver sulfadiazine (p < 0.02) in reducing bacterial colonization. For wound necrosis, no significant difference was found between silver sulfadiazine cream and CI-PRJ012 (p = 0.33). CONCLUSIONS: CI-PRJ012 decreases necrosis and bacterial colonization compared to no treatment in a swine model. CI-PRJ012 appeared to perform comparably to silver sulfadiazine. CI-PRJ012, which is easily removed with the application of room-temperature water, may provide clinical advantages over silver sulfadiazine.

Development of a Novel Epidural Hemorrhage Model in Swine.

INTRODUCTION: Traumatic brain injury is a major public health concern. Among patients with severe traumatic brain injury, epidural hemorrhage is known to swiftly lead to brain herniation and death unless there is emergent neurosurgical intervention. However, immediate neurosurgeon availability is frequently a problem outside of level I trauma centers. In this context, the authors desired to test a novel device for the emergent management of life-threatening epidural hemorrhage. A review of existing animal models determined that all were inadequate for this purpose, as they were found to be either inappropriate or obsolete. Here, we describe the development of a new epidural hemorrhage model in swine (Sus scrofa, 18-26 kg) ideal for translational device testing. MATERIALS AND METHODS: Vascular access was achieved using an ultrasound-guided percutaneous Seldinger catheter-over-wire technique with 5 Fr catheters placed in the bilateral carotid arteries, for continuous blood pressure and to allow for withdrawal of blood for creation of epidural hemorrhage. To simulate an actively bleeding and life-threatening epidural hemorrhage, unadulterated autologous blood was infused from the vascular access point into the epidural space. To be useful for this application and clinical scenario, brain death needed to occur after the planned intervention time but before the end of the protocol period (if no intervention took place). An iterative approach to model development determined that this could be achieved with an initial infusion rate of 1.0 mL/min, slowed to 0.5 mL/min after the first 10 minutes, paired with an intervention time at 15 minutes. All experiments were performed at Oregon Health & Science University, an Association for Assessment and Accreditation of Laboratory Animal Care accredited facility. Oregon Health & Science University's Institutional Animal Care and Use Committee, as well as the United States Army Animal Care and Use Review Office, reviewed and approved this protocol before the initiation of experiments (respectively, protocol numbers IP00002901 and 18116010.e001). RESULTS: The final developed model allows for the infusion of a known volume of autologous, unadulterated blood directly into the epidural space, without the use of a balloon or other restricting membranes, and is rapidly fatal in the absence of intervention. CONCLUSIONS: This animal model is the first to mirror the expected clinical course of epidural hemorrhage in a physiologically relevant manner, while allowing translational testing of emergency devices. This model successfully allowed the initial testing of a novel interventional device for the emergent management of epidural hemorrhage that was designed for use in the absence of traditional neurosurgical capabilities.

Thermoreversible Reverse-Phase-Shift Foam for Treatment of Noncompressible Torso Hemorrhage, a Safety Trial in a Porcine Model.

INTRODUCTION: Noncompressible torso hemorrhage is the leading cause of exsanguination on the battlefield. A self-expanding, intraperitoneal deployed, thermoreversible foam has been developed that can be easily administered by a medic in austere settings to temporarily tamponade noncompressible torso hemorrhage. The purpose of this study was to assess the long-term safety and physical characteristics of using Fast Onset Abdominal Management (FOAM; Critical Innovations LLC) in swine. MATERIALS AND METHODS: Yorkshire swine (40-60 kg) were sedated, intubated, and placed on ventilatory support. An external jugular catheter was placed for sampling of blood. Continuous heart rate, temperature, saturation of peripheral oxygen, end-tidal carbon dioxide, and peak airway pressures were monitored for a 4-hour period after intervention (i.e., FOAM agent injection or a sham introducer without agent delivery). The FOAM agent was injected to obtain an intra-abdominal pressure of 60 mmHg for at least 10 minutes. After 4 hours, the animals were removed from ventilatory support and returned to their housing for a period of 7-14 days. Group size analysis was not performed, as this was a descriptive safety study. Blood samples were obtained at baseline and at 1-hour post-intervention and then on days 1, 3, 7, and 14. Euthanasia, necropsy, and harvesting of samples for histologic analysis (from kidneys, terminal ilium, liver, pancreas, stomach, spleen, and lungs) were performed upon expiration. Histologic scoring for evidence of ischemia, necrosis, and abdominal compartment sequela was blinded and reported by semi-quantitative scale (range 0-4; 0 = no change, 1 = minimal, 2 = mild, 3 = moderate, and 4 = marked). Oregon Health & Science University's Institutional Animal Care and Use Committee, as well as the U.S. Army Animal Care and Use Review Office, approved this protocol before the initiation of experiments (respectively, protocol numbers IP00003591 and MT180006.e002). RESULTS: Five animals met a priori inclusion criteria, and all of these survived to their scheduled endpoints. Two animals received sham injections of the FOAM agent (one euthanized on day 7 and one on day 14), and three animals received FOAM agent injections (one euthanized on day 7 and two on day 14). A transitory increase in creatinine and lactate was detected during the first day in the FOAM injected swine but resolved by day 3. No FOAM agent was observed in the peritoneal cavity upon necropsy at day 7 or 14. Histologic data revealed no clinically relevant differences in any organ system between intervention and control animals upon sacrifice at day 7 or 14. CONCLUSIONS: This study describes the characteristics, survival, and histological analysis of using FOAM in a porcine model. In our study, FOAM reached the desired intra-abdominal pressure endpoint while not significantly altering basic hematologic parameters, except for transient elevations of creatinine and lactate on day 1. Furthermore, there was no clinical or histological relevant evidence of ischemia, necrosis, or intra-abdominal compartment syndrome. These results provide strong support for the safety of the FOAM device and will support the design of further regulatory studies in swine and humans.

Efficacy of past, present, and future fluid strategies in an improved large animal model of non-compressible intra-abdominal hemorrhage.

BACKGROUND: Noncompressible hemorrhage is a leading cause of potentially survivable combat death, with the vast majority of such deaths occurring in the out-of-hospital environment. While large animal models of this process are important for device and therapeutic development, clinical practice has changed over time and past models must follow suit. Developed in conjunction with regulatory feedback, this study presents a modernized, out-of-hospital, noncompressible hemorrhage model, in conjunction with a randomized study of past, present, and future fluid options following a hypotensive resuscitation protocol consistent with current clinical practice. METHODS: We performed a randomized controlled experiment comparing three fluid resuscitation options in Yorkshire swine. Baseline data from animals of same size from previous experiments were analyzed (n = 70), and mean systolic blood pressure was determined, with a permissive hypotension resuscitation target defined as a 25% decrease from normal (67 mm Hg). After animal preparation, a grade IV to V liver laceration was induced. Animals bled freely for a 10-minute "time-to-responder" period, after which resuscitation occurred with randomized fluid in boluses to the goal target: 6% hetastarch in lactated electrolyte injection (HEX), normal saline (NS), or fresh whole blood (FWB). Animals were monitored for a total simulated "delay to definitive care" period of 2 hours postinjury. RESULTS: At the end of the 2-hour study period, 8.3% (1 of 12 swine) of the HEX group, 50% (6 of 12 swine) of the NS group, and 75% (9 of 12 swine) of the FWB had survived (p = 0.006), with Holm-Sidak pairwise comparisons showing a significant difference between HEX and FWB and (p = 0.005). Fresh whole blood had significantly higher systemic vascular resistance and hemoglobin levels compared with other groups (p = 0.003 and p = 0.001, respectively). CONCLUSION: Survival data support the movement away from HEX toward NS and, preferably, FWB in clinical practice and translational animal modeling. The presented model allows for future research including basic science, as well as translational studies of novel diagnostics, therapeutics, and devices.

Efficacy of a novel chest tube system in a swine model of hemothorax.

BACKGROUND: Tube thoracostomy is the definitive treatment for most significant chest trauma, including injuries resulting in pneumothorax, hemothorax, and hemopneumothorax. However, traditional chest tubes fail to sufficiently remove blood up to 20% of the time (i.e., retained hemothorax), which can lead to empyema and fibrothorax, as well as significant morbidity and mortality. Here we describe the use of a novel chest tube system in a swine model of hemothorax. METHODS: This was an intra-animal-paired, randomized-controlled study of hemothorax evacuation using the PleuraPath™ Thoracostomy System (PPTS) compared to a traditional chest tube in large Yorkshire-Landrace swine (75-85 kg). One liter of autologous whole blood was infused into each pleural cavity simultaneously with subsequent drainage from each device individually monitored for a total of 120 minutes, before the end of the experiment and necroscopy. RESULTS: Six animals completed the full protocol. On average, the PPTS removed 17% more blood (P=0.049) and left 19.1% less residual hemothorax (P=0.023) as compared to the standard of care during the first two hours of use. No complications or iatrogenic injury were identified in any animal for either device. CONCLUSIONS: The novel PPTS device was superior to the traditional chest tube drainage system in this acute, large-animal model of retained hemothorax. While this study supports clinical translation, further research will be required to assess efficacy and optimize device use in humans.

Thermoreversible Reverse-Phase-Shift Foam for Treatment of Noncompressible Torso Hemorrhage.

BACKGROUND: Noncompressible torso hemorrhage (NCTH) is a leading cause of traumatic exsanguination, requiring emergent damage control surgery performed by a highly trained surgeon in a sterile operating environment. A self-expanding, intraabdominally deployed, thermoreversible foam is one proposed method to potentially task shift temporizing hemostasis to earlier providers and additional settings. The purpose of this study was to assess the feasibility of using Fast Onset Abdominal Management (FOAM) in a lethal swine model of NCTH. METHODS: This was a proof-of-concept study comparing FOAM intervention in large Yorkshire swine to historical control animals in the established Ross-Burns model of NCTH. After animal preparation, a Grade IV liver laceration was surgically induced, followed by a free bleed period of 10 min. FOAM was then deployed to a goal intraabdominal pressure of 60 mm Hg for 5 min, followed by a total 60-min observation period following injury. RESULTS: At the end of the experiment, the FOAM agent was found to be distributed throughout the peritoneal cavity in all animals, without signs of iatrogenic injury. The FOAM group demonstrated a significantly higher mean arterial pressure compared with historical controls and a trend toward improved survival: 82% (9/11) compared with 50% for controls (7/14; P = 0.082). CONCLUSIONS: This is the first study to describe the use of a thermoresponsive foam to manage NCTH and successfully demonstrated proof-of-concept feasibility of FOAM deployment. These results provide strong support for future, higher-powered studies to confirm improved survival with this novel intervention.

The readiness of emergency and trauma care in low- and middle-income countries: a cross-sectional descriptive study of 42 public hospitals in Albania.

BACKGROUND: Traumatic injuries have become a substantial but neglected epidemic in low- and middle-income countries (LMICs), but emergency rooms (ERs) in these countries are often staffed with healthcare providers who have minimal emergency training and experience. The aim of this paper was to describe the specialized training, available interventions, and the patient management strategies in the ERs in Albanian public hospitals. METHODS: A cross-sectional descriptive study of 42 ERs in the Republic of Albania between September 5, 2014, and December 29, 2014 was performed. Assessment subcategories included the following: (1) specialized training and/or certifications possessed by healthcare providers, (2) interventions performed in the ER, and (3) patient management strategies. RESULTS: Across the 42 ERs surveyed, less than half (37.1-42.5 %) of physicians and one third of nurses (7.1-26.0 %) working in the ERs received specialized trauma training. About half (47.9-57.1 %) of the ER physicians and one fifth of the nurses (18.3-22.9 %) possessed basic life support certification. This survey demonstrated some significant differences in the emergency medical care provided between primary, secondary, and tertiary hospitals across Albania (the significance level was set at 0.05). Specifically, these differences involved spinal immobilization (p = 0.01), FAST scan (p = 0.04), splinting (p = 0.01), closed reduction of displaced fractures (p = 0.02), and nurses performing cardiopulmonary resuscitation (CPR) (p = 0.01). Between 50.0 and 71.4 % of the facilities cited a combined lack of training and supplies as the reason for not offering interventions such as rapid sequence induction, needle thoracotomy, chest tube insertion, and thrombolysis. Mass casualty triage was utilized among 39.1 % primary hospitals, 41.7 % of secondary, and 28.6 % of tertiary. CONCLUSIONS: The emergency services in Albania are currently staffed with inadequately trained personnel, who lack the equipment and protocols to meet the needs of the population.

Development and usage of wiki-based software for point-of-care emergency medical information.

OBJECTIVE: To describe the creation and evaluate the usage of the first medical wiki linked to dedicated mobile applications. METHODS: With the support of multiple current and past contributors, we developed an emergency medicine wiki linked to offline mobile applications (WikEM) in 2009. First deployment was at the Harbor-UCLA Medical Center emergency medicine residency program, with the wiki later opened to public use. To evaluate the project, we performed a post hoc analysis of system use and surveyed 8 years of current and past residents. Outcomes included website and application analytics, as well as survey analysis by composite response categories. RESULTS: Over the 6-year period of this project, the wiki grew to over 7250 pages and 45 500 edits. The website receives more than 85 000 user sessions per month, with over 150 million page views to date. There have been over 200 000 installs of the mobile applications, progressing to produce over 5000 mobile sessions daily. Of potential survey respondents, 87.7% (107) completed the Internet-based survey. Among those who contributed to the wiki, 74.6% reported that it benefited their understanding of core emergency medicine content. Of program graduates, the vast majority reported use of the wiki as a resource after residency (93.8%) along with improvement in clinical efficiency (89.7%). Residents reported higher use and a more favorable opinion of wiki usefulness compared to graduates (P < .001). CONCLUSIONS: A wiki paired with mobile applications is beneficial for resident education and useful in post-residency clinical practice.

Accuracy of the Broselow Tape in South Sudan, "The Hungriest Place on Earth".

OBJECTIVES: The Broselow tape is a length-based tool used for the rapid estimation of pediatric weight and was developed to reduce dosage-related errors during emergencies. This study seeks to assess the accuracy of the Broselow tape and age-based formulas in predicting weights of South Sudanese children of varying nutritional status. METHODS: This was a retrospective, cross-sectional study using data from existing acute malnutrition screening programs for children less than 5 years of age in South Sudan. Using anthropometric measurements, actual weights were compared with estimated weights from the Broselow tape and three age-based formulas. Mid-upper arm circumference was used to determine if each child was malnourished. Broselow accuracy was assessed by the percentage of measured weights falling into the same color zone as the predicted weight. For each method, accuracy was assessed by mean percentage error and percentage of predicted weights falling within 10% of actual weight. All data were analyzed by nutritional status subgroup. RESULTS: Only 10.7% of malnourished and 26.6% of nonmalnourished children had their actual weight fall within the Broselow color zone corresponding to their length. The Broselow method overestimated weight by a mean of 26.6% in malnourished children and 16.6% in nonmalnourished children (p < 0.001). Age-based formulas also overestimated weight, with mean errors ranging from 16.2% over actual weight (Advanced Pediatric Life Support in nonmalnourished children) to 70.9% over actual (Best Guess in severely malnourished children). CONCLUSIONS: The Broselow tape and age-based formulas selected for comparison were all markedly inaccurate in both the nonmalnourished and the malnourished populations studied, worsening with increasing malnourishment. Additional studies should explore appropriate methods of weight and dosage estimation for populations of low- and low-to-middle-income countries and regions with a high prevalence of malnutrition.

Pediatric emergency medical care in Yerevan, Armenia: a knowledge and attitudes survey of out-of-hospital emergency physicians.

BACKGROUND: Out-of-hospital emergency care is at an early stage of development in Armenia, with the current emergency medical services (EMS) system having emergency physicians (EPs) work on ambulances along with nurses. While efforts are underway by the Ministry of Health and other organizations to reform the EMS system, little data exists on the status of pediatric emergency care (PEC) in the country. We designed this study to evaluate the knowledge and attitudes of out-of-hospital emergency physicians in pediatric rapid assessment and resuscitation, and identify areas for PEC improvement. METHODS: We distributed an anonymous, self-administered Knowledge and Attitudes survey to a convenience sample of out-of-hospital EPs in the capital, Yerevan, from August to September 2012. RESULTS: With a response rate of 80%, the majority (89.7%) of respondents failed a 10-question knowledge test (with a pre-defined passing score of ≥7) with a mean score of 4.17 ± 1.99 SD. Answers regarding the relationship between pediatric cardiac arrest and respiratory issues, compression-to-ventilation ratio in neonates, definition of hypotension, and recognition of shock were most frequently incorrect. None of the participants had attended pediatric-specific continuing medical education (CME) activities within the preceding 5 years. χ2 analysis demonstrated no statistically significant association between physician age, length of EMS experience, type of ambulance (general vs. resuscitation/critical care), or CME attendance and pass/fail status. The majority of participants agreed that PEC education in Armenia needs improvement (98%), that there is a need for pediatric-specific CME (98%), and that national out-of-hospital PEC guidelines would increase PEC safety, efficiency, and effectiveness (96%). CONCLUSIONS: Out-of-hospital emergency physicians in Yerevan, Armenia are deficient in pediatric-specific emergency assessment and resuscitation knowledge and training, but express a clear desire for improvement. There is a need to support additional PEC training and CME within the EMS system in Armenia.

A survey of national physicians working in an active conflict zone: the challenges of emergency medical care in Iraq.

INTRODUCTION: There has been limited research on the perspectives and needs of national caregivers when confronted with large-scale societal violence. In Iraq, although the security situation has improved from its nadir in 2006-2007, intermittent bombings, and other hostilities continue. National workers remain the primary health resource for the affected populace. PROBLEM: To assess the status and challenges of national physicians working in the Emergency Departments of an active conflict area. METHODS: This study was a survey of civilian Iraqi doctors working in Emergency Departments (EDs) across Iraq, via a convenience sample of physicians taking the International Medical Corps (IMC) Doctor Course in Emergency Medicine, given in Baghdad from December 2008 through August 2009. RESULTS: The 148 physician respondents came from 11 provinces and over 50 hospitals in Iraq. They described cardiovascular disease, road traffic injuries, and blast and bullet injuries as the main causes of death and reasons for ED utilization. Eighty percent reported having been assaulted by a patient or their family member at least once within the last year; 38% reported they were threatened with a gun. Doctors reported seeing a median of 7.5 patients per hour, with only 19% indicating that their EDs had adequate physician staffing. Only 19% of respondents were aware of an established triage system for their hospital, and only a minority had taken courses covering ACLS- (16%) or ATLS-related (24%) material. Respondents reported a wide diversity of prior training, with only 3% having some type of specialized emergency medicine degree. CONCLUSIONS: The results of this study describe some of the challenges faced by national health workers providing emergency care to a violence-stricken populace. Study findings demonstrate high levels of violent behavior directed toward doctors in Iraqi Emergency Departments, as well as staffing shortages and a lack of formal training in emergency medical care.

Using tele-education to train civilian physicians in an area of active conflict: certifying Iraqi physicians in Pediatric Advanced Life Support from the United States.

Years of violence have resulted in a lack of trained health care providers in Iraq. To address this need, International Medical Corps has implemented a national emergency care program for the country. As part of this program, we implemented via tele-education the country's first civilian course in Pediatric Advanced Life Support.

Injury burden during an insurgency: the untold trauma of infrastructure breakdown in Baghdad, Iraq.

BACKGROUND: Injuries as a result of the ongoing violence in Iraq have been a topic of both lay and academic interest. However, to date, attempts to quantify injuries in the country have focused primarily on direct mortality, which represents only a small portion of overall injury burden and ignores those injuries indirectly resulting from the conflict-induced breakdown of Iraqi infrastructure. METHODS: We performed a cross-sectional household survey from October to November, 2009, within the Baghdad Governorate of central Iraq. Using two-stage cluster-sampling with a proportional-to-size methodology, we randomized a total of 60 clusters to Baghdad's five governmental districts. Within each cluster, we interviewed heads of households regarding all injuries during the last 3 months. RESULTS: We surveyed 1,172 households, gathering information regarding 7,396 individuals. Only 8.4% of injuries were intentional, and fatalities represented only a small fraction (1.7%) of overall injury burden. The well-publicized intentional explosions in Baghdad, although accounting for close to half (44%) of all intentional injuries, made up only 4% of the total. Other injuries at least partially attributable to the conflict-induced breakdown of Iraqi infrastructure proved a much larger burden, for example, those from electric shock, unintentional explosions, unintentional gunshot wounds, and falls. CONCLUSIONS: Past and current fighting in Baghdad continues to adversely affect the Iraqi populace, where the indirect effects of infrastructure breakdown are likely the primary source of injury. When measuring the burden of large-scale violence, health researchers should account for the full injury burden, including both injury morbidity and indirect injuries.

The development of civilian emergency medical care during an insurgency: current status and future outlook in Iraq.

We review the development of civilian out-of-hospital and hospital-based emergency medical care in Iraq, focusing on the non-Kurdish regions. Emergency medicine in the country has made encouraging steps during the last several years, including the establishment of national emergency medicine policy, the training of out-of-hospital caregivers, the education of physicians currently working in Iraqi emergency departments, and the development of emergency medicine residency programs, among others. The utilization of a national Emergency Medicine Working Group has been a key resource in the development of emergency medicine in the country, a strategy we recommend to others aiding low- and middle-income nations.