Short-term CaMKII inhibition with tatCN19o does not erase pre-formed memory in mice and is neuroprotective in pigs.

The Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a central regulator of learning and memory, which poses a problem for targeting it therapeutically. Indeed, our study supports prior conclusions that long-term interference with CaMKII signaling can erase pre-formed memories. By contrast, short-term pharmacological CaMKII inhibition with the neuroprotective peptide tatCN19o interfered with learning in mice only mildly and transiently (for less than 1 h) and did not at all reverse pre-formed memories. These results were obtained with ≥500-fold of the dose that protected hippocampal neurons from cell death after a highly clinically relevant pig model of transient global cerebral ischemia: ventricular fibrillation followed by advanced life support and electrical defibrillation to induce the return of spontaneous circulation. Of additional importance for therapy development, our preliminary cardiovascular safety studies in mice and pig did not indicate any concerns with acute tatCN19o injection. Taken together, although prolonged interference with CaMKII signaling can erase memory, acute short-term CaMKII inhibition with tatCN19o did not cause such retrograde amnesia that would pose a contraindication for therapy.

A prospective, pragmatic non-inferiority study of emergency intubation success with the single-use i-view versus standard reusable video laryngoscope.

INTRODUCTION: Video laryngoscope (VL) technology improves first-pass success. The novel i-view VL device is inexpensive and disposable. We sought to determine the first-pass intubation success with the i-view VL device versus the standard reusable VL systems in routine use at each site. METHODS: We performed a prospective, pragmatic study at two major emergency departments (EDs) when VL was used. We rotated i-view versus reusable VL as the preferred device of the month based on an a priori schedule. An investigator-initiated interim analysis was performed. Our primary outcome was a first-pass success with a non-inferiority margin of 10% based on the per-protocol analysis. RESULTS: There were 93 intubations using the reusable VL devices and 81 intubations using the i-view. Our study was stopped early due to futility in reaching our predetermined non-inferiority margin. Operator and patient characteristics were similar between the two groups. The first-pass success rate for the i-view group was 69.1% compared to 84.3% for the reusable VL group. A non-inferiority analysis indicated that the difference (-15.1%) and corresponding 90% confidence limits (-25.3% to -5.0%) did not fall within the predetermined 10% non-inferiority margin. CONCLUSIONS: The i-view device failed to meet our predetermined non-inferiority margin when compared to the reusable VL systems with the study stopping early due to futility. Significant crossover occurred at the discretion of the intubating operator during the i-view month.

The employment of resuscitative endovascular balloon occlusion of the aorta in deployed settings.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) has been often used in place of open aortic occlusion for management of hemorrhagic shock in trauma. There is a paucity of data evaluating REBOA usage in military settings. STUDY DESIGN AND METHODS: We queried the Department of Defense Trauma Registry (DODTR) for all cases with at least one intervention or assessment available within the first 72 h after injury between 2007 and 2023. We used relevant procedural codes to identify the use of REBOA within the DODTR, and we used descriptive statistics to characterize its use. RESULTS: We identified 17 cases of REBOA placed in combat settings from 2017 to 2019. The majority of these were placed in the operating room (76%) and in civilian patients (70%). A penetrating mechanism caused the injury in 94% of cases with predominantly the abdomen and extremities having serious injuries. All patients subsequently underwent an exploratory laparotomy after REBOA placement, with moderate numbers of patients having spleen, liver, and small bowel injuries. The majority (82%) of included patients survived to hospital discharge. DISCUSSION: We describe 17 cases of REBOA within the DODTR from 2007 to 2023, adding to the limited documentation of patients undergoing REBOA in military settings. We identified patterns of injury in line with previous studies of patients undergoing REBOA in military settings. In this small sample of military casualties, we observed a high survival rate.

Association of freeze-dried plasma with 24-h mortality among trauma patients at risk for hemorrhage.

BACKGROUND: Blood products form the cornerstone of contemporary hemorrhage control but are limited resources. Freeze-dried plasma (FDP), which contains coagulation factors, is a promising adjunct in hemostatic resuscitation. We explore the association between FDP alone or in combination with other blood products on 24-h mortality. STUDY DESIGN AND METHODS: This is a secondary data analysis from a cross-sectional prospective observational multicenter study of adult trauma patients in the Western Cape of South Africa. We compare mortality among trauma patients at risk of hemorrhage in three treatment groups: Blood Products only, FDP + Blood Products, and FDP only. We apply inverse probability of treatment weighting and fit a multivariable Cox proportional hazards model to assess the hazard of 24-h mortality. RESULTS: Four hundred and forty-eight patients were included, and 55 (12.2%) died within 24 h of hospital arrival. Compared to the Blood Products only group, we found no difference in 24-h mortality for the FDP + Blood Product group (p = .40) and a lower hazard of death for the FDP only group (hazard = 0.38; 95% CI, 0.15-1.00; p = .05). However, sensitivity analyses showed no difference in 24-h mortality across treatments in subgroups with moderate and severe shock, early blood product administration, and accounting for immortal time bias. CONCLUSION: We found insufficient evidence to conclude there is a difference in relative 24-h mortality among trauma patients at risk for hemorrhage who received FDP alone, blood products alone, or blood products with FDP. There may be an adjunctive role for FDP in hemorrhagic shock resuscitation in settings with significantly restricted access to blood products.

Concurrent determination of cyanide and thiocyanate in human and swine antemortem and postmortem blood by high-performance liquid chromatography-tandem mass spectrometry.

Cyanide (in the form of cyanide anion (CN-) or hydrogen cyanide (HCN), inclusively represented as CN) can be a rapidly acting and deadly poison, but it is also a common chemical component of a variety of natural and anthropogenic substances. The main mechanism of acute CN toxicity is based on blocking terminal electron transfer by inhibiting cytochrome c oxidase, resulting in cellular hypoxia, cytotoxic anoxia, and potential death. Due to the well-established link between blood CN concentrations and the manifestation of symptoms, the determination of blood concentration of CN, along with the major metabolite, thiocyanate (SCN-), is critical. Because currently there is no method of analysis available for the simultaneous detection of CN and SCN- from blood, a sensitive method for the simultaneous analysis of CN and SCN- from human ante- and postmortem blood via liquid chromatography-tandem MS analysis was developed. For this method, sample preparation for CN involved active microdiffusion with subsequent chemical modification using naphthalene-2,3-dicarboxaldehyde (NDA) and taurine (i.e., the capture solution). Preparation for SCN- was accomplished via protein precipitation and monobromobimane (MBB) modification. The method produced good sensitivity for CN with antemortem limit of detection (LODs) of 219 nM and 605 nM for CN and SCN-, respectively, and postmortem LODs of 352 nM and 509 nM. The dynamic ranges of the method were 5-500 µM and 10-500 µM in ante- and postmortem blood, respectively. In addition, the method produced good accuracy (100 ± 15%) and precision (≤ 15.2% relative standard deviation). The method was able to detect elevated levels of CN and SCN- in both antemortem (N = 5) and postmortem (N = 4) blood samples from CN-exposed swine compared to nonexposed swine.

Navy En-Route Care in Future Distributed Maritime Operations: A Review of Clinician Capabilities and Roles of Care.

OBJECTIVE: As the United States Navy transitions from Operation Iraqi Freedom/Operation Enduring Freedom to preparing for a near-peer competition, an increasing focus of wartime strategy relies upon a network of distributed naval assets for total sea control, known as Distributed Maritime Operations (DMO). Historically, embedded medical personnel have provided care at sea in times of war. Recent reviews of shipboard and evacuated mass casualty incidents have alluded to weaknesses in the existing Navy Medicine approach that will require advances in care provision to sustain high-quality care that would benefit from industry and civilian academic collaboration. To gain input from civilian prehospital expertise and insight, the current DMO and Navy En-Route Care (ERC) systems must be plainly described for non-Navy military and civilian leaders, clinicians, and researchers to understand. METHODS: N/A. RESULTS: In this review, we translate US Navy structure and vernacular into common civilian and non-Navy language, describe the maritime role-tiered ERC system, elucidate the medical assets on each naval warship, and discuss clinician levels and capabilities while deployed to help communicate the inherent challenges of US Navy maritime medical care during routine operations, casualty treatment, stabilization, and evacuation. CONCLUSIONS: We describe the roles of care, clinician levels, and medical assets within the Navy ERC system for researchers and military leaders who aim to mitigate the inherent challenges of future maritime trauma care in the age of Distributed Maritime Operations. This paper lays the framework of the Navy deployed medical system to enable research in maritime en-route care, and prompt inclusion of identified solutions into common use in the US Navy.

A Retrospective Analysis of Combat Injury Patterns and Prehospital Interventions Associated with the Development of Sepsis.

BACKGROUND: Combat injury related wound infections are common. Untreated, these wound infections may progress to sepsis and septic shock leading to increased morbidity and mortality rates. Understanding infectious complications, patterns, progression, and correlated prehospital interventions are vital to understand the development of sepsis. We aim to analyze demographics, injury patterns, and interventions associated with sepsis in battlefield settings. MATERIALS AND METHODS: This is a secondary analysis of previously published data from the Department of Defense Trauma Registry (DoDTR) from 2007 to 2020. We searched for casualties diagnosed with sepsis (excluding line-sepsis) throughout their initial hospitalization. Regression models were used to seek associations. RESULTS: Our initial request yielded 28,950 encounters, of which 25,654 (88.6%) were adults that met inclusion, including 243 patients (0.9%) diagnosed with sepsis. Patients included US military (34%), non-North Atlantic Treaty Organization (NATO) military (33%) and humanitarian (30%) groups. Patients diagnosed with sepsis had a significantly lower survival rate than non-septic patients (78.1% vs. 95.7%, p < 0.001). There was no significant difference in administration of prehospital antibiotics between septic and the general populations (10.6% vs. 12.3%, p = 0.395). Prehospital intraosseous access (OR 1.56, 95% CI 1.27-1.91, p = 0.207) and packed red cell administration (1.63, 1.24-2.15, 0.029) were the interventions most associated with sepsis. CONCLUSIONS: Sepsis occurred infrequently in the DoDTR when evacuation from battlefield is not delayed, but despite increased intervention frequency, developing sepsis demonstrates a significant drop in survival rates. Future research would benefit from the development of risk mitigation measures.

An Analysis of 13 Years of Prehospital Combat Casualty Care: Implications for Maintaining a Ready Medical Force.

Background: Most potentially preventable deaths occur in the prehospital setting before reaching a military treatment facility with surgical capabilities. Thus, optimizing the care we deliver in the prehospital combat setting represents a ripe target for reducing mortality. We sought to analyze prehospital data within the Department of Defense Trauma Registry (DODTR). Materials and methods: We requested all encounters with any prehospital activity (e.g., interventions, transportation, vital signs) documented within the DODTR from January 2007 to March 2020 along with all hospital-based data that was available. We excluded from our search casualties that had no prehospital activity documented. Results: There were 28,950 encounters that met inclusion criteria. Of these, 25,897 (89.5%) were adults and 3053 were children (10.5%). There was a steady decline in the number of casualties encountered with the most notable decline occurring in 2014. U.S. military casualties comprised the largest proportion (n = 10,182) of subjects followed by host nation civilians (n = 9637). The median age was 24 years (interquartile range/IQR 21-29). Most were battle injuries (78.6%) and part of Operation ENDURING FREEDOM (61.8%) and Operation IRAQI FREEDOM (24.4%). Most sustained injuries from explosives (52.1%) followed by firearms (28.1%), with serious injury to the extremities (24.9%) occurring most frequently. The median injury severity score was 9 (IQR 4-16) with most surviving to discharge (95.0%). A minority had a documented medic or combat lifesaver (27.9%) in their chain of care, nor did they pass through an aid station (3.0%). Air evacuation predominated (77.9%). Conclusions: Within our dataset, the deployed U.S. military medical system provided prehospital medical care to at least 28,950 combat casualties consisting mostly of U.S. military personnel and host nation civilian care. There was a rapid decline in combat casualty volumes since 2014, however, on a per-encounter basis there was no apparent drop in procedural volume.

Characterizing pediatric supermassive transfusion and the contributing injury patterns in the combat environment.

BACKGROUND: Trauma is the leading cause of pediatric mortality in the United States. Often, these patients require supermassive transfusion (SMT), which we define as receipt of >80 mL/kg blood products, double the proposed volume for standard pediatric massive transfusion (MT). Evaluating the blood volumes, injury patterns, clinical findings, and prehospital interventions predictive for SMT are critical to reducing pediatric mortality. We describe the pediatric casualties, injury patterns, and clinical findings that comprise SMT. METHODS: We retrospectively analyzed pediatric trauma data from the Department of Defense Trauma Registry from January 2007-2016. We stratified patients into two cohorts based on blood products received in the first 24 h after injury: 1) those who received 40-80 mL/kg (MT), or 2) those who received >80 mL/kg (SMT). We evaluated demographics, injury patterns, prehospital interventions, and clinical findings. RESULTS: Our original dataset included 3439 pediatric casualties. We identified 536 patients who met inclusion parameters (receipt of ≥40 mL/kg of blood products [whole blood, packed red blood cells, fresh frozen plasma, platelets, or cryoprecipitate]). The MT cohort included 271 patients (50.6%), and the SMT cohort comprised 265 patients (49.4%). Survival to discharge was significantly lower (78% for SMT, 86% for MT; p < 0.011) in the SMT cohort. Multivariable analysis of injury patterns revealed serious injuries (Abbreviated Injury Scale 3-6) to the extremities (OR 2.13, 95% CI 1.45-3.12) and abdomen (OR 1.65, 1.08-2.53) were associated with SMT. Wound dressings (41% versus 29%; p = 0.003), tourniquets (23% vs 12%; p = 0.001), and IO access (17% vs 10%; p = 0.013) were more common in the SMT group. Age-adjusted hypotension was significantly higher in the SMT group (41%, n = 100 vs 23%, n = 59; p < 0.001) with no statistical difference detected in tachycardia (87%, n = 223 vs 87%, n = 228; p = 0.932). CONCLUSIONS: Our research demonstrates that pediatric SMT patients are at increased risk of mortality. Our study highlights the seriousness of extremity injuries in pediatric trauma patients, identifying associations between severe injuries to the extremities and abdomen with the receipt of SMT. Prehospital interventions of wound dressing, tourniquets, and IO access were more frequent in the SMT cohort. Our research determined that hypotension was associated with SMT, but tachycardia was not a reliable predictor of SMT over MT.

Performance comparison of intraosseous devices and setups for infusion of whole blood in a cadaveric swine bone model.

OBJECTIVES: Intraosseous (IO) access can provide a critical bridge for blood product infusion when peripheral venous access is not obtainable. Successful pressurized IO infusion requires flow rates sufficient to preserve life, but with infusion pressures low enough to avoid clinical complications (e.g., hemolysis, bone damage, fat emboli). However, the optimal method for pressured IO delivery of blood was unknown. METHODS: Three trained physicians infused 500 mL of whole blood through a 15-gauge, 45 mm IO catheter into fresh, high bone density cadaveric swine proximal humeri. Participants applied eight different pressure infusion strategies: (1) gravity, (2) pressure bag, (3) pressure bag actively maintained at or above 300 mmHg, (4) hand pump, (5) hand pump with pressure bag, (6) push-pull with 10 mL syringe, (7) push-pull with 60 mL syringe, and a (8) Manual Rapid Infuser in a randomized within-subjects design (30 trials per method, 240 trials total). The primary outcomes of flow rates, mean and peak pressures, and user ratings were contrasted using ANOVA at p < 0.05. RESULTS: The Manual Rapid Infuser conferred the highest flow rates (199 ± 3 mL/min) and most favorable user ratings, but also the highest mean and peak pressures. Push-pull conferred the next highest flow rates (67 ± 5 mL/min for 60 mL, 56 ± 2 mL/min for 10 mL) and pressures, with intermediate-to-high user ratings. Hand pump flow rates were essentially identical with (45 ± 4 mL/min) or without (44 ± 3 mL/min) pressure bag, with high user ratings without a pressure bag. Pressure bag and gravity methods conferred low flow rates and user ratings. CONCLUSIONS: Some pressured IO infusion methods can achieve flow rates adequate to serve as a resuscitative bridge in the massively hemorrhaged trauma victim, but flow rates and pressures vary greatly across IO pressurized infusion methods. Manual Rapid Infuser and push-pull methods conferred high flow rates but also relatively high pressures, highlighting the importance of using in vivo models in future research to assess the possible clinical complications of using these promising methods. Combined, present findings highlight the importance of studying pressurized IO methods towards preserving the life of the critically injured trauma victim.

An analysis of outcomes for pediatric trauma warm fresh whole blood recipients in Iraq and Afghanistan.

BACKGROUND: Whole blood therapy-which contains the ideal balance of components, and particularly fresh whole blood-has been shown to be beneficial in adult trauma. It remains unclear whether there is potential benefit in the pediatric population. STUDY DESIGN AND METHODS: This is a secondary analysis of previously published data analyzing pediatric casualties undergoing massive transfusion in the Department of Defense Trauma Registry. Pediatric patients with traumatic injury who were transfused at least one blood product were included in the analysis. We compared children who received component therapy exclusively to those who received any amount of warm fresh whole blood. RESULTS: Of the 3439 pediatric casualties within our dataset, 1244 were transfused at least one blood product within the first 24 h. There were 848 patients without severe head injury. Within this cohort, 23 children received warm fresh whole blood overall, 20 of whom did not have severe head injury. In an adjusted analysis, the odds ratio (95% confidence interval [CI]) for survival for warm fresh whole blood recipients was 2.86 (0.40-20.45). After removing children with severe brain injury, there was an independent association with improved survival for warm fresh whole blood recipients with an odds ratio (95% CI) of 58.63 (2.70-1272.67). DISCUSSION: Our data suggest that warm fresh whole blood may be associated with improved survival in children without severe head injury. Larger prospective studies are needed to assess the efficacy and safety of whole blood in children with severe traumatic bleeding.

Impact of a Standardized EMS Handoff Tool on Inpatient Medical Record Documentation at a Level I Trauma Center.

BACKGROUND: The emergency department (ED) poses challenges to effective handoff from emergency medical services (EMS) personnel to ED staff. Despite the importance of a complete and accurate patient handoff report between EMS and trauma staff, communication is often interrupted, incomplete, or otherwise ineffective. The Mechanism of injury/Medical Complaint, Injuries or Inspections head to toe, vital Signs, and Treatments (MIST) report initiative was implemented to standardize the handoff process. The objective of this study was to evaluate whether documentation of prehospital care in the inpatient medical record improved after MIST implementation. METHODS: Research staff abstracted data from the EMS and inpatient medical records of trauma patients transported by EMS and treated at a Level I trauma center from January 2015 through June 2017. Data included patient demographics, mechanism and location of injury, vital signs, treatments, and period of data collection (pre-MIST and post-MIST). We summarized the MIST elements in EMS and inpatient medical records and assessed the presence or absence of data elements in the inpatient record from the EMS record and the agreement between the two sets of records over time to determine if implementation of MIST improved documentation. RESULTS: We analyzed data from 533 trauma patients transported by EMS and treated in a Level I trauma center (pre-MIST: n = 281; post-MIST: n = 252). For mechanism of injury, agreement between the two records was ≥96% before and after MIST implementation. Cardiac arrest and location of injury were under-reported in the inpatient record before MIST; post-MIST, there were no significant discrepancies, indicating an improvement in reporting. Reporting of prehospital hypotension improved from 76.5% pre-MIST to 83.3% post-MIST. After MIST implementation, agreement between the EMS and inpatient records increased for the reporting of fluid administration (45.6% to 62.7%) and decreased for reporting of pain medications (72.2% to 61.9%). CONCLUSIONS: The use of the standardized MIST tool for EMS to hospital patient handoff was associated with a mixed value on inpatient documentation of prehospital events. After MIST implementation, agreement was higher for mechanism and location of injury and lower for vital signs and treatments. Further research can advance the prehospital to treatment facility handoff process.

Intramuscular cobinamide as an antidote to methyl mercaptan poisoning.

BACKGROUND: Methyl mercaptan occurs naturally in the environment and is found in a variety of occupational settings, including the oil, paper, plastics, and pesticides industries. It is a toxic gas and deaths from methyl mercaptan exposure have occurred. The Department of Homeland Security considers it a high threat chemical agent that could be used by terrorists. Unfortunately, no specific treatment exists for methyl mercaptan poisoning. METHODS: We conducted a randomized trial in 12 swine comparing no treatment to intramuscular injection of the vitamin B12 analog cobinamide (2.0 mL, 12.5 mg/kg) following acute inhalation of methyl mercaptan gas. Physiological and laboratory parameters were similar in the control and cobinamide-treated groups at baseline and at the time of treatment. RESULTS: All six cobinamide-treated animals survived, whereas only one of six control animals lived (17% survival) (p = 0.0043). The cobinamide-treated animals returned to a normal breathing pattern by 3.8 ± 1.1 min after treatment (mean ± SD), while all but one animal in the control group had intermittent gasping, never regaining a normal breathing pattern. Blood pressure and arterial oxygen saturation returned to baseline values within 15 minutes of cobinamide-treatment. Plasma lactate concentration increased progressively until death (10.93 ± 6.02 mmol [mean ± SD]) in control animals, and decreased toward baseline (3.79 ± 2.93 mmol [mean ± SD]) by the end of the experiment in cobinamide-treated animals. CONCLUSION: We conclude that intramuscular administration of cobinamide improves survival and clinical outcomes in a large animal model of acute, high dose methyl mercaptan poisoning.

The diamond of death: Hypocalcemia in trauma and resuscitation.

INTRODUCTION: Early recognition and management of hemorrhage, damage control resuscitation, and blood product administration have optimized management of severe trauma. Recent data suggest hypocalcemia exacerbates the ensuing effects of coagulopathy in trauma. OBJECTIVE: This narrative review of available literature describes the physiology and role of calcium in trauma resuscitation. Authors did not perform a systematic review or meta-analysis. DISCUSSION: Calcium is a divalent cation found in various physiologic forms, specifically the bound, inactive state and the unbound, physiologically active state. While calcium plays several important physiologic roles in multiple organ systems, the negative hemodynamic effects of hypocalcemia are crucial to address in trauma patients. The negative ramifications of hypocalcemia are intrinsically linked to components of the lethal triad of acidosis, coagulopathy, and hypothermia. Hypocalcemia has direct and indirect effects on each portion of the lethal triad, supporting calcium's potential position as a fourth component in this proposed lethal diamond. Trauma patients often present hypocalcemic in the setting of severe hemorrhage secondary to trauma, which can be worsened by necessary transfusion and resuscitation. The critical consequences of hypocalcemia in the trauma patient have been repeatedly demonstrated with the associated morbidity and mortality. It remains poorly defined when to administer calcium, though current data suggest that earlier administration may be advantageous. CONCLUSIONS: Calcium is a key component of trauma resuscitation and the coagulation cascade. Recent data portray the intricate physiologic reverberations of hypocalcemia in the traumatically injured patient; however, future research is needed to further guide the management of these patients.

Pediatric Prehospital Intraosseous Access During Combat Operations in Iraq and Afghanistan.

BACKGROUND: Vascular access in critically ill pediatric patients can be challenging with delays potentially leading to worse outcomes. Intraosseous (IO) access has a low rate of complications and can be utilized to administer lifesaving medications. Combat medics are trained to treat adults but may also be required to treat children in the deployed setting. Vascular access in children can be challenging, especially in a hypovolemic state. There are limited data on prehospital lifesaving interventions in children in the combat setting. We sought to characterize the use of IO access in pediatric patients who sustained trauma in the combat setting. METHODS: We queried the Department of Defense Trauma Registry for all pediatric patients admitted to fixed-facilities and forward surgical teams in Iraq and Afghanistan from January 2007 to January 2016. Within that population, we searched for all subjects with a documented prehospital IO or intravenous (IV) access obtained. Subjects with both an IO and IV documented were placed into the IO category. We separated subjects by age groupings: younger than 1, 1 to 4, 5 to 9, 10 to 14, and 15 to 17 years. RESULTS: During the study period, there were 3439 subjects 17 years or younger. There were 177 in the IO cohort and 803 in the IV cohort. Most subjects in the IO cohort were in the 10- to 14-year-old age group (35.6%), male (79.1%), located in Afghanistan (95.5%), and injured by explosive (52.0%), with lower survival rates than the IV cohort (68.9% vs 90.7%, P < 0.001). Hemostatic dressing application, tourniquet application, intubation, cardiopulmonary resuscitation, sedative administration, ketamine administration, and paralytic administration were all higher in the IO cohort. CONCLUSIONS: Pediatric IO placement in the prehospital setting occurred infrequently. Pediatric subjects receiving an IO had higher injury severity scores and higher mortality rates compared with those who received an IV only. Intraosseous use appears to be used more often in critically ill pediatric subjects.

The Effect of Chest Compression Location and Occlusion of the Aorta in a Traumatic Arrest Model.

BACKGROUND: Recent evidence demonstrates that closed chest compressions directly over the left ventricle (LV) in a traumatic cardiac arrest (TCA) model improve hemodynamics and return of spontaneous circulation (ROSC) when compared with traditional compressions. Resuscitative endovascular balloon occlusion of the aorta (REBOA) also improves hemodynamics and controls hemorrhage in TCA. We hypothesized that chest compressions located over the LV would result in improved hemodynamics and ROSC in a swine model of TCA using REBOA. MATERIALS AND METHODS: Transthoracic echo was used to mark the location of the aortic root (traditional location) and the center of the LV on animals (n = 26), which were randomized to receive chest compressions in one of the two locations. After hemorrhage, ventricular fibrillation was induced to simulate TCA. After a period of 10 min of ventricular fibrillation, basic life support (BLS) with mechanical cardiopulmonary resuscitation was initiated and performed for 10 min followed by advanced life support for an additional 10 min. REBOA balloons were inflated at 6 min into BLS. Hemodynamic variables were averaged during the final 2 min of the BLS and advanced life support periods. Survival was compared between this REBOA cohort and a control group without REBOA (no-REBOA cohort) (n = 26). RESULTS: There was no significant difference in ROSC between the two REBOA groups (P = 0.24). Survival was higher with REBOA group versus no-REBOA group (P = 0.02). CONCLUSIONS: There was no difference in ROSC between LV and traditional compressions when REBOA was used in this swine model of TCA. REBOA conferred a survival benefit regardless of compression location.

Does administration of haloperidol or ketorolac decrease opioid administration for abdominal pain patients? A retrospective study.

BACKGROUND: Haloperidol and ketorolac have been recommended as therapies that may decrease opioid use for treatment of pain in emergency department patients. The objective of our study is to determine if administration of haloperidol or ketorolac is associated with lower use of i.v. opioids for patients with non-specific abdominal pain. METHODS: A retrospective cohort study of adults (Age 18-60) with non-specific abdominal pain presenting to an emergency department in a large healthcare system. Cases were identified using ICD-10 codes and variables were abstracted from electronic health records. The association between administration of haloperidol or ketorolac with 1) any i.v. opioid administration and 2) receiving >1 dose of i.v. opioids were measured using adjusted odds ratios (AOR) from nominal logistic regression. The model included potential confounders related to both opioid and ketorolac or haloperidol administration. RESULTS: Of 11,688 patients 4091 received one or more doses of an i.v. opioid, 240 received haloperidol and 1788 received ketorolac. The majority of patients were women (67%) and the median age was 32 years. Odds ratios were adjusted for variables associated with opioids, ketorolac or haloperidol use. Haloperidol was not associated with decreased i.v. opioid use (AOR for receiving iv opioids 2.0, 95% CI 1.5 to 2.6) or a lower odds of reciving >1 dose of (AOR 2.0, 95% CI 1.3 to 3.1). Ketorolac was associated with a modest decrease in i.v. opioid use (AOR 0.84 95% CI.0.76 to 0.94 for receiving iv opioids) and a modest decrease for receiving multiple dose of iv opioids (AOR 0.79 95% CI 0.63 to 0.99). CONCLUSIONS: Haloperidol was not associated with decreased i.v. opioid use. Ketorolac was associated with a modest decrease in i.v. opioid use. Providers should consider the use of haloperidol and ketorolac as potentially beneficial in some cases, but there is a need for high quality studies before they can be recommended as standard therapy.

Efficacy of Oral Administration of Sodium Thiosulfate and Glycine in a Large, Swine Model of Oral Cyanide Toxicity.

STUDY OBJECTIVE: Cyanide is a deadly poison, particularly with oral exposure, in which larger doses can occur before any symptoms develop. Multiple governmental agencies highlight oral cyanide as an agent that can be used in a terrorist attack because it can be easily weaponized and is readily available. Currently, there are no Food and Drug Administration-approved antidotes specifically for oral cyanide. An oral countermeasure that can neutralize and prevent absorption of cyanide from the gastrointestinal tract after oral exposure is needed. The objective of this study is to determine if the combination of glycine and sodium thiosulfate administered orally is effective in reducing mortality in a large, swine model of oral cyanide toxicity. METHODS: Nine swine (45 to 55 kg) were instrumented, sedated, and stabilized. Potassium cyanide (at 8 mg/kg) in saline solution was delivered as a onetime bolus through an orogastric tube. Three minutes after cyanide administration, animals that were randomized to the treatment group received sodium thiosulfate (508.2 mg/kg, 3.25-M solution) and glycine (30 mg/kg, 3.5-M solution) through an orogastric tube. Survival at 60 minutes was the primary outcome. We compared survival between groups by log-rank Mantel-Cox analysis and trended laboratory results and vital signs. RESULTS: At baseline and treatment, all animals were similar. Survival at 60 minutes was 100% in treated animals compared with 0% in the control group (P=.003). By the study end, defined as death or 60 minutes after cyanide administration, there was a significant difference in the lactate concentration between the treatment and control groups (control 9.43 mmol/L [SD 4.08]; treatment 1.66 mmol/L [SD 0.82]; difference between means 7.69 mmol/L [SD 2.07]; 95% confidence interval difference -14.05 to -1.32). Mean arterial pressure was significantly different between the treatment and control groups at study end (control 26 mm Hg [SD 6.7]; treatment 81 mm Hg [SD 14]; difference between means 55.2 mm Hg [SD 7.1]; 95% confidence interval difference 37.8 to 72.6). pH and oxygen saturation were also significantly different between the treatment and control groups at study end. CONCLUSION: The combination of oral sodium thiosulfate and glycine significantly improved survival and physiologic parameters in a large-animal model of oral cyanide toxicity.

A prospective, randomized trial of intravenous hydroxocobalamin versus noradrenaline or saline for treatment of lipopolysaccharide-induced hypotension in a swine model.

Early, non-clinical studies support the use of hydroxocobalamin to treat sepsis-induced hypotension, but there is no translational, large animal model. The objective of this study was to compare survival in a sepsis model where large swine had endotoxaemia induced with lipopolysaccharide (LPS) and were treated with intravenous hydroxocobalamin (HOC), noradrenaline (NA), or saline. Thirty swine (45-55 kg) were anaesthetized, intubated, and instrumented with continuous femoral and pulmonary artery pressure monitoring. Hypotension, predefined as 50% of baseline, was induced with LPS. Animals then received HOC, NA, or saline and monitored for 3 hours. The main outcome was survival to the conclusion of the study. Using a power of 80% and an alpha of 0.05, 10 animals were used per group. Secondary outcomes included: mean arterial pressure (MAP), systemic vascular resistance (SVR) and cardiac output (CO) along with several markers of sepsis. No differences were detected between groups at baseline or after hypotension. The survival distributions of the three groups were significantly different with more HOC animals surviving (10/10) compared with NA (8/10) or Saline (5/10) (log-rank P < 0.03). MAP was found to be higher in both the HOC and NA groups and HOC achieved the highest SVR. In this large animal, translational study of an endotoxaemic model of sepsis, hydroxocobalamin improved survival when compared with saline.

Expert Consensus Guidelines for Stocking of Antidotes in Hospitals That Provide Emergency Care.

We provide recommendations for stocking of antidotes used in emergency departments (EDs). An expert panel representing diverse perspectives (clinical pharmacology, medical toxicology, critical care medicine, hematology/oncology, hospital pharmacy, emergency medicine, emergency medical services, pediatric emergency medicine, pediatric critical care medicine, poison centers, hospital administration, and public health) was formed to create recommendations for antidote stocking. Using a standardized summary of the medical literature, the primary reviewer for each antidote proposed guidelines for antidote stocking to the full panel. The panel used a formal iterative process to reach their recommendation for both the quantity of antidote that should be stocked and the acceptable timeframe for its delivery. The panel recommended consideration of 45 antidotes; 44 were recommended for stocking, of which 23 should be immediately available. In most hospitals, this timeframe requires that the antidote be stocked in a location that allows immediate availability. Another 14 antidotes were recommended for availability within 1 hour of the decision to administer, allowing the antidote to be stocked in the hospital pharmacy if the hospital has a mechanism for prompt delivery of antidotes. The panel recommended that each hospital perform a formal antidote hazard vulnerability assessment to determine its specific need for antidote stocking. Antidote administration is an important part of emergency care. These expert recommendations provide a tool for hospitals that offer emergency care to provide appropriate care of poisoned patients.