Administration Of Epinephrine Research Articles

Management of Anaphylaxis During Peanut Oral Immunotherapy.

Peanut oral immunotherapy (POIT) has emerged as an active management option for peanut allergy, with an FDA-approved product now available for therapy. Allergic reactions, including anaphylaxis, can occur during therapy and their management is key in optimizing this treatment and patient outcomes. In this manuscript, we will review the rates of allergic reactions and anaphylaxis in seminal peanut oral immunotherapy research studies. We will examine factors that can alter the risk of anaphylaxis and describe various strategies, including adjunct therapies, that have the potential to mitigate anaphylaxis risk based on published evidence. Rates of anaphylaxis and epinephrine administration vary in different research studies, but there is consensus that most POIT-related allergic reactions are mild or moderate and not severe. Certain external factors (for example, tiredness, exercise, viral illness) as well as uncontrolled allergic co-morbidities (asthma, allergic rhinitis) have been shown to increase the risk of anaphylaxis during OIT. The search of biomarkers who may predict who is at risk for severe allergic reactions is ongoing. Adjunct therapies have shown promise, but further studies are required to optimize their use alongside POIT. Our understanding of anaphylaxis during POIT has increased in recent years, resulting in better management strategies. However, future plans will need to involve all stakeholders, including physicians, patients and families, researchers, public health authorities, and the food, hospitality, and catering industries.

Sex disparities in prehospital advanced cardiac life support in out-of-hospital cardiac arrests in Japan

ObjectiveSex disparities in out-of-hospital cardiac arrest (OHCA) care processes have been reported. This study aimed to investigate the association between sex and prehospital advanced cardiac life support (ACLS) interventions provided by emergency medical services in Japan. MethodsWe analyzed data from January 1, 2013, to December 31, 2020, from the All-Japan Utstein Registry of patients with OHCA aged ≥18 years who were resuscitated by bystanders. The primary outcomes were prehospital ACLS interventions, including advanced airway management (AAM) and epinephrine administration. Sex-based disparities in receiving prehospital ACLS interventions were assessed via multivariable logistic regression analyses. ResultsAmong 314,460 eligible patients, females with OHCA received fewer prehospital ACLS interventions than males: 83,571/187,834 (44.5%) males vs. 55,086/126,626 (43.5%) females (adjusted odds ratio [AOR] = 0.94, 95% confidence interval [CI] = 0.93–0.96) for AAM and 60,097/187,834 (32.0%) males vs. 35,501/126,626 (28.0%) females (AOR = 0.84, 95% CI = 0.83–0.85) for epinephrine administration. Similar results were also obtained in the subgroup analysis (groups included patients aged 18–74 years and ≥75 years and those with cardiac origin, ventricular fibrillation (VF), non-VF, non-family member witnessed, and family member witnessed). ConclusionCompared with males, females were less likely to receive prehospital ACLS. Emergency medical service staff must be made aware of this disparity, and off-the-job training on intravenous cannulation or AAM replacement must be conducted. Investigation of the impact of sex disparity on OHCA care processes can facilitate planning of future public health policies to improve survival outcomes.

Efficacy of Single Wound Infiltration With Bupivacaine and Adrenaline During Cesarean Delivery for Reduction of Postoperative Pain

Most women report moderate to severe pain after cesarean delivery. The extent of the ability of surgical wound infiltration with local anesthetic agents during cesarean delivery for the reduction of postoperative pain is uncertain. To examine the efficacy of single wound infiltration with bupivacaine and adrenaline during cesarean delivery for the reduction of postoperative pain. This randomized clinical trial was conducted between January 25, 2018, and May 30, 2020, at a university teaching hospital in Afula, Israel. A total of 288 women with singleton pregnancy who were scheduled for a planned cesarean delivery at term were randomized to receive single wound infiltration with bupivacaine and adrenaline during cesarean delivery (intervention group) or no single wound infiltration (control group) at a 1:1 ratio. In the intervention group, the subcutaneous layer was infiltrated on both sides of the wound by a mixture of bupivacaine and adrenaline before wound closure. Other perioperative techniques were similar between the groups. The primary outcome was mean pain intensity over the course of 24 hours after the operation, as measured by a visual analog scale (VAS) score ranging from 0 to 10 (with higher scores indicating greater pain intensity). To detect a mean (SD) reduction of 1 (3) points in the VAS score in the intervention group, 286 women were needed in total. Secondary outcomes included VAS score greater than 4 (indicating moderate pain) at 2 hours after the operation, use of rescue opioids, maternal satisfaction with the pain management procedure (using a scale of 1-5, with higher scores indicating greater satisfaction), duration of the operation, scar complications (hematoma, infection, and separation), and length of stay. Among 288 women (mean [SD] age, 32.5 [5.1] years; all of Arab or Jewish ethnicity), 143 were randomized to the intervention group, and 145 were randomized to the control group. Demographic and obstetric variables were similar between groups. The primary outcome (VAS pain score) was significantly lower in the intervention group (mean [SD], 2.21 [0.56]) compared with the control group (mean [SD], 2.41 [0.73]; P = .02). In the intervention group, 11 women (7.7%) had a VAS score greater than 4 at 2 hours compared with 22 women (15.2%) in the control group (odds ratio, 0.47; 95% CI, 0.22-1.00; P = .05). In addition, compared with the control group, the intervention group had significantly lower postpartum use of rescue opioid analgesics (19 women [13.3%] vs 37 women [25.5%]; P = .009) and greater satisfaction with pain management (mean [SD] score, 4.65 [0.68] vs 4.44 [0.76]; P = .007). In the intervention vs control groups, duration of the operation, scar complications (hematoma, infection, or separation), and length of stay were comparable. In this study, wound infiltration with a single administration of bupivacaine and adrenaline during cesarean delivery reduced postoperative pain and opioid use and may have improved maternal satisfaction with pain management. These findings suggest the technique is efficacious, safe, and easy to perform. ClinicalTrials.gov Identifier: NCT03395912.

The Neuroprotective Effects of Administration of Methylprednisolone in Cardiopulmonary Resuscitation in Experimental Cardiac Arrest Model.

Although advances in diagnosis and treatment of cardiac arrest (CA) could improve neurological outcomes after cardiopulmonary resuscitation (CPR), survival rate and neurological outcome after CA and CPR remain poor. This study aimed to investigate the effect of epinephrine (EP) alone and EP in combination with methylprednisolone (MP) (EP + MP) on some the apoptotic and anti-apoptotic genes and proteins levels expression of the cerebral cortex as well as neuronal death in a CA rat model. Forty-five male Sprague Dawley rats were randomly divided into three groups including the hypoxic CA + EP, hypoxic CA + EP + MP, and sham groups using a simple randomization procedure. In both hypoxic CA groups, CA was induced by asphyxia and immediately after confirmation of CA, the treatment strategies including chest compression or cardiac massage simultaneously with ventilation, and administration of EP alone (20mg/kg, every 3min) and EP (20mg/kg, every 3min) + 30 (mg/kg) of MP were done. The sham group only received anesthetic drugs without CA. Some neurological outcomes were investigated using histopathological, immunohistochemical, molecular, and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) assays at 5 and 48h post-CPR. The data obtained showed the highest up-regulation of apoptotic genes and proteins expression, the lowest expression of anti-apoptotic gene and protein expression, the most DNA fragmentation and histopathological changes belonged to the EP group on 48h post-CPR. While mild and intermediate histopathological changes, DNA fragmentation and apoptotic activity was detected in theEP alone and EP + MP groups at 5h and 48h post-CPR, respectively. As a novel finding, the present study showed that EP + MP protects neurons from death provoked/induced by hypoxia and reperfusion injury in an experimental model of CA through up and down-regulation of pro- (caspases 3 and 8) and anti-apoptotic (BCL2) molecules, respectively.

Abstract 149: Epinephrine Administration First Versus Advanced Airway Management First For Adult Patients With Out-of-hospital Cardiac Arrest

Introduction: Epinephrine administration and advanced airway management (AAM: ie, endotracheal intubation and supraglottic airway placement) have been commonly used for patients with out-of-hospital cardiac arrest (OHCA). However, the optimal sequence of these interventions remains unclear. We, therefore, compared epinephrine administration 1 st strategy with AAM 1 st strategy. Methods: We conducted a secondary analysis of a prospective, nationwide, population-based OHCA registry in Japan. We included emergency medical services (EMS)-treated adult (≥18 years) OHCA from 2014 through 2019, stratified into shockable or nonshockable rhythms. We excluded those who did not receive epinephrine or AAM. The primary outcome was 1-month survival and the secondary outcome was 1-month survival with favorable functional status, defined as a Cerebral Performance Category scale 1 or 2. To account for treatment selection bias between patients who received epinephrine before AAM and patients who received AAM before epinephrine, we calculated propensity score and used inverse probability treatment weighting analyses. Results: We included 8,854 patients with shockable and 79,687 patients with nonshockable rhythm. 1,825 patients (20.6%) of shockable rhythms and 11,769 patients (14.8%) of nonshockable rhythm received epinephrine before AAM. Among patients with shockable rhythm, epinephrine administration before AAM was associated with lower odds of 1-month survival (Odds ratio [OR] 0.83, 95% confidence interval [CI] 0.76 to 0.90) but not associated with favorable functional outcome (OR 0.94, 95% CI 0.82 to 1.70). Among patients with nonshockable rhythm, epinephrine administration before AAM was not associated with 1-month survival (OR 0.96, 95% CI 0.91 to 1.01) but was associated with higher odds of favorable functional status (OR 1.15, 95% CI 1.002 to 1.33). Conclusions: In this observational study, we found that epinephrine administration before AAM was associated with lower odds of 1-month survival among shockable rhythm but was associated with higher odds of 1-month survival with favorable functional status among nonshockable rhythm, suggesting that the optimal sequence of epinephrine administration and AAM may vary between initial rhythms.

Abstract 286: Hypothermic Out-of-hospital Cardiac Arrest: Favorable Outcomes, But With Limited Defibrillation Or Adrenaline Administration Effectiveness In The Prehospital Setting

Introduction: Hypothermic out-of-hospital cardiac arrest (OHCA) is assumed to be associated with favorable neurological outcomes compared with OHCA from other etiologies. However, supporting evidence is limited. In addition, inconsistencies for number of defibrillation and adrenaline administration attempts in prehospital management guidelines can be identified. Hypothesis: We evaluated whether hypothermic OHCA is associated with favorable outcomes compared with OHCA from other etiologies. Further, the effectiveness of defibrillation or adrenaline administration was evaluated. Methods: Using data from a nationwide, population-based retrospective study conducted in Japan from 2013 to 2016, we compared two OHCA patient groups: patients with hypothermic etiology and those with non-hypothermic etiology. The primary outcome measure was one-month favorable neurological outcomes, defined as Cerebral Performance Category score ≤ 2. Multivariable logistic regression was used to calculate odds ratios (ORs) and their confidence intervals (CIs) to evaluate the impact of hypothermic OHCA. We further looked for an association between prehospital management and neurological outcomes among patients with hypothermic etiology. Results: We divided the cohort of 477,606 OHCA patients into the hypothermic group (n=842) and the non-hypothermic group (n=476,763). The hypothermic group had significantly higher odds of favorable neurological outcomes (64/842 (7.6%) vs. 13,052/476,763 (1.4 %), adjusted OR 3.12, 95%, CI 1.96-4.96) compared with the non-hypothermic group. In the hypothermic group, prehospital defibrillation (OR 1.52, 95%, CI 0.86-2.68) and adrenaline administration (OR 1.32, 95%, CI 0.67-2.62) did not contribute to favorable neurological outcomes overall. However, when the data was stratified by age and number of shocks, three or less defibrillation attempts in patients under 65 years old (OR 3.37, 95%, CI 1.31-8.67) was associated with favorable neurological outcomes. Conclusion: We found that hypothermic OHCA was associated with a higher chance of a favorable neurological outcome. Even prehospital defibrillation seems to have limited efficacy for hypothermic OHCA.

Abstract 06: Feasibility Of Accelerated Code Team Activation With Code Button Triggered Smartphone Notifications

Introduction: In-hospital cardiac arrest mortality has improved only modestly in the past decade. Prior studies support the role of earlier defibrillation and epinephrine administration to improve outcomes. Timely code team activation facilitates expedient interventions and may provide an opportunity for quality improvement. We sought to accelerate the time to code team activation and increase the early distribution of patient-specific data to improve targeted treatments. Methods: We mapped code blue buttons present behind each patient bed to patient data through the Electronic Health Record. Use of the code blue button sent patient-specific data including admitting diagnosis, recent procedural history, presence of difficult airway, and most recent potassium, bicarbonate, troponin, and hemoglobin levels through a secure text messaging system to the code blue teams’ smartphones. Simultaneously, the code blue button contacted the hospital operator who activated the code blue team through traditional methods including overhead page and pager alerts. We piloted the system on four medicine inpatient units from November 2019 through May 2022. In our analysis, we evaluated the time from code blue button press to smartphone message receipt vs overhead page, time to epinephrine administration, and survival to hospital discharge. Results: There were 35 cardiac arrest events on the participating hospital units. The code blue button was the primary mode of code team activation for 12/35 (34.3%) of the events. The code team received smartphone notifications a median of 78 seconds (IQR = 47-127 seconds) before traditional notifications. The initial rhythm was non-shockable for 34/35 (97.1%) of the patients. The median time to documented epinephrine administration for codes activated with or without the code button was 2:57 and 4:00 (IQR = 0:34-6:07 vs. 2:07-4:30; p = 0.89). Survival to hospital discharge was 3/12 (25.0%) for codes activated with the code button and 4/23 (17.4%) when activated by other methods (p = 0.61). Conclusion: Implementation of a smartphone-based code button activated notification system reduced the time to code team activation by over one minute. Further evaluation in larger cohorts is necessary to assess the effect on patient outcomes.

Abstract 9689: Impact of Epinephrine Administration Route on the Outcomes of Cardiac Resuscitation of Acute Myocardial Infarction Patients With Cardiac Arrest in the Cardiac Catheterization Laboratory (iCPR Study)

Objectives: To compare the efficacy peripheral intravenous (IV), central IV, and intracoronary (IC) administration of epinephrine in acute myocardial infarction (AMI) patients with cardiac arrest in the cath lab. Methods: Prospective, two-center cohort pilot study of AMI patients with cardiac arrest in the cath lab. Patients who received mechanical circulatory support, primary fibrinolysis, anti-arrhythmic/vasopressors prior to cardiac arrest, or those with prior CAD or a cardiac arrest that lasted < 60 seconds were excluded. Outcomes included return of spontaneous circulation (ROSC), stent thrombosis, and survival-to-discharge with a favorable neurological outcome. Results: 158 patients were enrolled (Table 1). After adjusting for age and initial cardiac rhythm, the peripheral IV route had 5.5-fold lower odds (OR: 0.18, 95% CI: 0.07-0.49, p = 0.0007) of achieving ROSC compared with the central IV route, while the IC route had a similar odds compared to the central IV route ( p = 0.9516). Among those who achieved ROSC, the IC route had a higher odds for stent thrombosis compared to the central IV route (OR: 5.7, 95% CI: 1.9-17.2, p = 0.0022), but not the peripheral IV route ( p = 0.1277). The adjusted odds of achieving survival-to-discharge with a favorable neurological outcome were higher in the IC route compared to the peripheral IV route (OR: 7.8, 95% CI: 2.2 – 27.0, p = 0.0013), and similar in the IC and central IV routes ( p = 0.0585) (Table 2). Conclusions: Epinephrine administration via central IV has a higher odds achieving ROSC than via peripheral IV and a lower odds of stent thrombosis than via the IC route in patients with AMI who suffer from cardiac arrest during PCI.

Abstract 325: Evaluation Of The 2015 Cardiopulmonary Resuscitation Guidelines For Patients With Nonshockable Out-of-hospital Cardiac Arrest; Results From The All-japan Utstein Registry 2022

Background: In nonshockable cardiac arrest (CA) patients, the 2020 cardiopulmonary resuscitation (CPR) guidelines have stressed that high-quality CPR improves survival from CA, as with the 2015 CPR guidelines. However, it is unknown whether the 2015 guidelines contributed to the favorable neurological outcomes in adult CA patients. The present study aimed to clarify the effects of the 2015 guidelines on adult CA patients using the data of the All-Japan Utstein Registry, a prospective, nationwide, population-based registry of out-of-hospital CA (OHCA). Methods: From the data of this registry, between 2011 and 2020, we included adult witnessed OHCA patients due to cardiac etiology who had non-shockable rhythm as an initial rhythm. We excluded patients who received prehospital care in 2011, 2015, 2016, and 2020 because it was difficult to distinguish prehospital care based on either 2010 CPR guidelines, 2015, or 2020. We also excluded patients who received bystander CPR by citizens because we cannot assess the quality of bystander CPR. Study patients were divided into two groups based on the different CPR guidelines; the era of the 2010 guidelines (2010G) and the era of the 2015 guidelines (2015G). The endpoint was the favorable neurological outcome at 30 days after OHCA. Potential confounding factors based on biological plausibility and previous studies were included in the multivariable logistic regression analysis. These variables included the age, sex (male, female), advanced airway or not, the administration of adrenaline or not, the administration of saline or not, and time interval from call EMS to the scene. Results: Of the 1,259,960 patients registered in the All-Japan Utstein Registry, the data of 54,219 patients were included in this analysis. The 2015G was significantly higher in the 30-day favorable neurological outcome than the 2010G (2010G vs. 2015G = 1.5% vs. 1.8%: p=0.008). In the multivariate analysis, the adjusted odds ratio for 30-day favorable neurological outcome in OHCA patients in the 2015G compared to in the 2010G was 1.37 (95%CI 1.19-1.58, p<0.001). Conclusion: In the OHCA patients with non-shockable rhythm, the 2015 CPR guidelines were superior to the 2010 guidelines in terms of neurological benefits.

Abstract 250: Heart Rate And QRS Duration Predict Immediate Outcome In Pulseless Electrical Activity (PEA) During In-hospital Cardiac Arrest (IHCA)

Introduction: PEA is commonly observed in in-hospital cardiac arrest. ROSC is currently the only indication of treatment response. Studies suggest that QRS duration (QRSd) and heart rate (HR) develop differently in patients who obtain ROSC or not. The aim of this study was to assess prospectively how QRSd and HR affect the immediate outcome of patients with PEA. Method: We investigated 327 episodes of IHCA in 298 patients, collected at two US and one Norwegian hospital. We assessed the ECG in 559 segments of PEA, measuring QRSd and HR in pauses of compressions, and noted the clinical state that followed PEA. We investigated the development of HR, QRSd, and transitions to ROSC or noROSC in a joint linear mixed/ time-to-event model, using software R version 4.0.3 with the package ‘JMbayes2’. Results: A HR increase by 50bpm increased the intensity (“hazard”) of gaining ROSC by 42% (p<0.01), and a 50ms decrease in QRSd increased the intensity of gaining ROSC by 29% (p<0.01). A decreasing HR had no significant impact; however, if QRSd increased by 50ms this increased the probability of transitioning to other lethal states (ventricular tachycardia or fibrillation, asystole, or death) by 24% (p<0.01). Still, several patients experienced increasing QRSd before obtaining ROSC. The figure shows an example of how QRSd (lower left) and HR (upper left) developed in one PEA segment overlaid the linear model (blue line). The estimated probability of obtaining ROSC (green line with 95% CI) or transitioning to other arrest states (red line) over the next 4 minutes are displayed to the right. This patient obtained ROSC at approx. 7min. Conclusion: HR and QRSd conveys information of the immediate outcome (ROSC/noROSC) in PEA. This may guide the team in their efforts, and possibly allow for individual tailoring of treatment, e.g., by delaying a (potentially harmful) epinephrine administration. Due to low specificity, the model cannot support termination of resuscitation.

Abstract 13: Myocardial Metabolic And Electrolyte Derangements Linked To PEA Rearrest

Background: Cardiac rearrest after return of spontaneous circulation (ROSC) is a significant barrier to successful resuscitation, making it a high priority for emergency care research. Regardless of initial arrest rhythm, rearrest is commonly due to pulseless electrical activity (PEA). However, mechanisms underlying PEA rearrest are poorly understood. Previously, myocardial contractile function during ischemia-reperfusion has been tied to alterations in extracellular sodium (Na+) and calcium (Ca2+) concentrations. Objective: To determine physiological predictors and explore potential mechanisms underlying susceptibility to PEA rearrest. Methods: Acute myocardial infarction (AMI) induced by left anterior descending artery (LAD) occlusion was followed by 8 min of VF, then pigs were resuscitated (defibrillation, CPR, epinephrine) to ROSC and the LAD was reperfused. Pigs were instrumented to measure metabolic variables from arterial and coronary sinus venous blood gases, electrolytes, and hemodynamics. Subjects that had PEA rearrest (n=7) were compared to those that did not rearrest (n=4). Results: Hemodynamic and primary arrest characteristics were similar between PEA and no rearrest groups, including ischemia duration, time to ROSC, CPR events, and epinephrine administration. At ROSC, hemodynamic and metabolic variables including pH, myocardial lactate consumption, myocardial arterial/venous oxygen difference were also similar between groups. Importantly, post-ROSC myocardial lactate consumption was significantly increased in the PEA group (3.9 vs. 0.5 mmol, p<0.03) as was coronary sinus Na+ (147 vs. 135 mEq/L, p<.03); however, coronary sinus Ca2+ was significantly reduced (1.9 vs. 2.3 mEq/L, p<.01 ). Taken together, these data suggest that metabolic substrate depletion may promote local electrolyte shifts contributing to mechanical dysfunction underlying PEA. Conclusion: PEA rearrest was associated with increased myocardial lactate consumption and derangements in cardiac Na+ and Ca2+ in a translational model with well controlled arrest characteristics. Improved understanding of mechanisms underlying post-ROSC electrolyte shifts may identify novel mechanisms and therapeutic approaches to prevent and treat PEA.

Abstract 05: Hospital Variation In Epinephrine Administration Prior To Defibrillation For Cardiac Arrest Due To Shockable Rhythm

Background: Contrary to guidelines, we recently found that epinephrine administration before first defibrillation for in-hospital cardiac arrest (IHCA) due to a shockable rhythm is not uncommon. However, the extent to which the above practice varies across hospitals and its association with hospital-level survival is unknown. Methods: Using 2000-19 data from the Get With The Guidelines ® -Resuscitation (GWTG-R) registry, we identified 57,816 adult patients (521 sites) with an index IHCA due to an initial shockable rhythm who received at least 1 defibrillation prior to achieving return of spontaneous circulation. We constructed multivariable hierarchical regression models to examine site-level variation in epinephrine before first defibrillation and its association with hospital survival. Results: Overall, the median rate of epinephrine before defibrillation was 18.8% and varied markedly across hospitals (range: 0%-70.6%, median odds ratio [OR] 1.50; 95% C.I. 1.43 - 1.57). Compared to hospitals in the lowest quartile (Q1) for epinephrine before defibrillation, hospitals in the highest quartile (Q4) were more likely to be major teaching hospitals and have more hospital beds. After adjusting for baseline variables, the median risk-standardized survival was 42.5% (IQR: 39.2%-46.0%). Compared to Q1 hospitals (epinephrine first rate of 0-12.4%), there was a stepwise decline in risk-standardized survival at hospitals with higher rates of epinephrine before first defibrillation: Q2: RR 0.95 [0.90-0.99]; Q3: RR 0.91 [0.87-0.96]; Q4: RR 0.81 [0.77-0.86]; P value for trend <0.001. Conclusions: For patients with shockable IHCA, there is marked hospital variation in epinephrine administration prior to first defibrillation, and this practice is associated with lower rates of survival to discharge. Hospital efforts to prioritize immediate defibrillation for patients with shockable IHCA are urgently needed.

Abstract 155: Intra-arrest Epinephrine Administration is Associated with Increased Myocardial Injury and Inflammation in a Novel Murine Model of Cardiac Arrest

Introduction: Epinephrine (EPI) is routinely administered in cardiac arrest resuscitation. Using a novel murine model of cardiac arrest, this study aims to assess the effects of epinephrine on myocardial inflammation and injury. Hypothesis: Intra-arrest epinephrine use is associated with increased myocardial injury, inflammation and fibrosis. Methods: A total of 56 mice were included in the study. Both cardiac arrest (CA) and sham (SHAM) groups received intravenous potassium chloride either as a bolus (CA) or slow infusion (SHAM), inducing ECG-confirmed asystole (CA only) for 4-minutes prior to delivery of intravenous epinephrine (250ul, 30ug/ml) or saline (250ul) and manual chest compressions (300BPM) for 4-minutes (Fig A). Mice were recovered for assessments at 24- or 72-hour timepoints. Results: Rates of successful ROSC (n=21(96%) vs. n=14(82%), P=0.18) and survival to recovery (n=11(50%) vs. n=12(71%),P=0.19) were similar in CA treated with (CA+EPI) and without (CA-Epi) EPI, respectively. Greater myocardial injury occurred in CA+EPI, compared to CA-Epi, with increased Hs-Troponin levels measured at 24- (26.0±0.9ng/mL vs. 9.4±5.3,P=0.015) and 72-hours (20.9±8.3ng/mL vs. 5.0±2.4,P=0.012) (Fig B). To examine mRNA expression in cardiac tissue, rt-PCR was performed. At 72-hours, CA+EPI, compared to CA-EPI, was associated with significantly increased expression of inflammatory (TNF-α, IL1β, IL10, F4-80 and CD68) and fibrotic (TGFβ, Col1 and Col3) genes. There was no difference between SHAM-EPI and SHAM+EPI at 72-hours (Fig C). Conclusion: In a mouse model of cardiac arrest, the use of epinephrine did not improve rates of ROSC and survival. However, epinephrine exposure was associated with increased biomarkers of myocardial injury, end-organ inflammation, and fibrosis. These findings underscore the need for further pre-clinical studies to assess alternate agents that confer protection to vital organs and improve rates of survival.

Abstract 305: Effect Of Initial Epinephrine Administration Time On Cerebral Perfusion In A Porcine Experimental Model Of Cardiac Arrest

Background: The effect of initial epinephrine administration time from cardiac arrest on cerebral perfusion pressure (CePP) during CPR is controversial. The purpose of this study was to evaluate the association between initial epinephrine administration time and CePP in a porcine cardiac arrest model. Methods: Initial administration time of epinephrine was divided into 3 groups based on time after inducing ventricular fibrillation (VF): 5 minutes (early group), 10 minutes (intermediate group), and 15 minutes (delayed group). Twenty-four pigs were randomly assigned to each group. After 4 minutes of untreated ventricular fibrillation, 2 cycles of BLS (BLS1 and BLS2 phase) and 10 cycles of ACLS (ACLS1~10 phase) were conducted. Macrovascular circulation (CePP) and microvascular circulation using laser doppler flowmetry presented as a fraction of the baseline flow (f-LDF) were measured. Linear mixed model was used to measure median difference in CePP and f-LDF between groups. Results: A total of 22 pigs were analyzed. Early group showed higher and earlier peak of CePP and f-LDF compared to those of intermediate or delayed groups. There was a significant group by phase interaction in CePP where the early group showed a higher CePP on earlier phase. (Early group: median 38.2 [95% confidence intervals 30.7-50.5] mmHg at BLS 2 phase, intermediate group: 27.1 [14.1-35.7] mmHg at ACLS1 phase, late group: 12.2 [2.2-34.9] mmHg at ACLS 4 phase), p< 0.001). There was no significant group by phase interaction in f-LDF; however, there was a tendency of decreased peak and delayed reach to peak with time. (Early group: median 5.7 [95% confidence interval 3.5-7.8] at ACLS 2 phase, intermediate group: 3.6 [1.5-5.1] at ACLS 4 phase, late group: 2.2 [0.9-3.3] at ACLS 6 phase, p =0.93). Conclusion: In this VF cardiac arrest porcine study, the early administration of epinephrine group showed higher and earlier peak of CePP and f-LDF compared to those of the intermediate and delayed groups.

Abstract 274: Identifying Target Populations For Extracorporeal Cardiopulmonary Resuscitation Among Patients With Refractory Out-of-hospital Cardiac Arrest Using Machine Learning

Introduction: Extracorporeal cardiopulmonary resuscitation (ECPR) can be used on patients with out-of-hospital cardiac arrest (OHCA) when the cause is potentially reversible. However, little is known about the optimal target populations for ECPR among those with refractory OHCA. Methods: We retrospectively analyzed nationwide OHCA registry data on 57,754 patients from 93 hospitals in Japan, 2014-2019. We identified 1,273 patients having a witness or initially shockable rhythms with refractory OHCA of presumed cardiac origin without return of spontaneous circulation after >3 doses of adrenaline administration and defibrillations when necessary at the emergency department (ED). We used the causal forest—a machine learning method to estimate heterogeneous treatment effects—to determine individual treatment effects of ECPR on a favorable 30-day neurologic outcome defined as the Cerebral Performance Category scale of 1 or 2, adjusting for confounders (e.g., age, sex, initial cardiac rhythms, and laboratory data). We compared patient characteristics in each quintile of individual ECPR effects to identify potential determinants of ECPR effects in patients with refractory OHCA. Finally, to determine optimal targets of ECPR, we evaluated how ECPR effects could vary depending on patient characteristics. Results: We found that the treatment effects of ECPR on a favorable neurologic outcome were heterogeneous (top 20% vs. others, 0.15 vs. 0.00; p<0.001) ( Figure 1 ). The key determinants of ECPR effects were initial cardiac rhythms on the emergency medical service (EMS) and at ED arrival, regardless of EMS transport time or laboratory data. In addition, ECPR effects varied depending on the information on ED arrival (i.e., witness, bystander CPR, and initial cardiac rhythms) ( Figure 2 ). Conclusion: Among patients with refractory OHCA, information available on arrival at the ED could effectively identify patients who may particularly benefit from ECPR.

ORAL FOOD CHALLENGE OUTCOMES AT 1 YEAR, 2 YEARS, AND 3 YEARS OF ORAL IMMUNOTHERAPY

<h3>Introduction</h3> While the efficacy of single-food oral immunotherapy (OIT), especially peanut, have been extensively studied, analyses on the efficacy of multi-food OIT and less common OIT foods are limited. We aimed to summarize the efficacy of OIT (single-food OIT and multi-food OIT) in our large pediatric cohort. <h3>Methods</h3> A retrospective review of patients undergoing OIT between September 1, 2019 and June 6, 2022 was performed. For peanut, tree nuts, and sesame, patients were eligible for an OIT milestone food challenge after completing 1 year, 2 years, and 3 years of maintenance OIT. For milk, egg, soy, and wheat, patients were eligible for an OIT milestone challenge after completing 6 months of OIT maintenance. <h3>Results</h3> Seventy patients underwent a total of 109 OIT milestone food challenges. Twenty-four patients underwent multiple challenges to different foods. Of the 109 milestone challenges, 104 (95.5%) passed, 5 (4.6%) failed, and 3 (2.8%) required epinephrine administration. Most of the challenges were to peanut (51.4%), followed by milk (11%) and cashew/pistachio (10%). Milk resulted in the most milestone challenge failures (n=2) and reactions resulting in epinephrine administration (n=2). Five patients underwent and passed a 3-year milestone challenge. <h3>Conclusion</h3> There was a high pass rate for OIT milestone challenges and a low epinephrine administration rate. Patients who tolerate maintenance dosing of OIT for at least 6 months for milk, egg, or wheat or 1 year for peanut, tree nuts, or sesame have shown potential for tolerating higher amounts of food allergen protein up to a full challenge.

TYPE II AND III KOUNIS SYNDROME AFTER PEANUT ANAPHYLAXIS

<h3>Introduction</h3> Acute coronary syndrome (ACS) associated with allergic or anaphylactic reactions, described in 1991 as "allergic angina", is known as Kounis syndrome (KS). Triggers include food, drugs, and coronary stents. This case highlights ACS following peanut anaphylaxis. <h3>Case Description</h3> A 61 year-old smoker with peanut allergy and diabetes presented with pruritus and urticaria following accidental peanut ingestion. He was treated with diphenhydramine, famotidine, methylprednisolone, and epinephrine with symptomatic improvement. He experienced sudden hypotension and pruritus and received additional epinephrine. EKG revealed inferolateral ST elevations with reciprocal depressions. He underwent catheterization with stents to LAD and RCA and received clopidogrel. After intervention, he developed chest pain with recurrent inferolateral ST elevations; progressed to pulseless ventricular tachycardia requiring CPR, revascularization, balloon pump placement, and CVICU transfer. Ultimately, he discharged on prasugrel. <h3>Discussion</h3> KS has three variants: type I and II are defined by absence or presence of coronary artery disease, respectively. Type III describes DES thrombosis. Our patient had evidence of underlying CAD. Anaphylaxis-induced coronary vasospasm was further exacerbated by epinephrine administration, likely resulting in plaque rupture, consistent with Type II KS. Ruptured plaques increase mast cells, histamine, and other cytokines. Histamine is well-described in coronary vasoconstriction. Non-allergic ischemia patients are shown to have increased histamine. Stent thrombosis is a multifactorial process; with common causes ruled out, Type III KS became more plausible. Treatment includes offending-agent removal, corticosteroids, antihistamines, and revascularization. KS management requires detailed history, cardiovascular and anaphylactic pathophysiology focus, mast cell degranulation inhibiting agents, and allergy desensitization.

A NEWLY DEVELOPED WEB BASED ANAPHYLAXIS CURRICULUM IMPROVES THE EFFECTIVENESS OF UNASSIGNED EPINEPHRINE ADMINISTRATORS

<h3>Introduction</h3> Anaphylaxis is a severe, life-threatening allergic reaction. Children can suffer from anaphylactic reactions at school. In 2014, Pennsylvania Legislature passed Act 195, which allows individuals to administer unassigned epinephrine in an emergency. This allows school staff to serve as unassigned epinephrine administrators (UEA's) during anaphylactic reactions. We developed an online training program which aims to help Pennsylvania school staff identify at risk children, manage, and treat anaphylaxis. This study measured the effectiveness of our online curriculum. <h3>Methods</h3> A newly developed web-based curriculum was distributed to UEA's within various Pennsylvania schools. An anonymous pre/post online survey (20-item survey) was administered to participants (UEA's) (n = 170). <h3>Results</h3> UEA's were identified as teachers (57%), administrators (15%), nurses (2%), and "other staff" (26%). Epinephrine was administered by ‘‘other staff'' most frequently (55%) followed by teachers (30%) and school nurses (15%). Prior to the integration of our standardized online curriculum training, 24% of UEA's were aware of the general signs/symptoms of anaphylaxis. 28% knew the first line treatment for anaphylaxis, and only 17% had correctly identified the 4 essential steps of epinephrine administration. Following the implementation of our online curriculum, follow up surveys revealed significant improvement in anaphylaxis assessment scores. 88% of UEA's were aware of signs/symptoms of anaphylaxis, 92% cited epinephrine as first-line therapy for anaphylaxis, and 79% had correctly identified the 4 essential steps of treatment compared with 12% before the training course. <h3>Conclusion</h3> Provision of online training for school staff increases availability and effectiveness of UEA's.

OPEN-LABEL SAFETY TRIAL OF HOUSE DUST MITE SUBLINGUAL IMMUNOTHERAPY TABLET IN ADOLESCENTS WITH ALLERGIC RHINITIS/RHINOCONJUNCTIVITIS

<h3>Introduction</h3> The HDM sublingual immunotherapy (SLIT) tablet is a treatment option for allergic rhinitis with/without conjunctivitis (AR/C) approved in adults worldwide and in adolescents in some countries. The MT-18 trial was conducted specifically in adolescents per FDA request to supplement existing adolescent safety data of the HDM SLIT tablet. <h3>Methods</h3> MT-18 (EudraCT:2020-000446-34) was a phase 3, open-label, single-arm, multi-center, 28-day safety trial of daily HDM SLIT tablet (12 SQ-HDM dose) conducted in European adolescents (12-17 y; N=253) with HDM-associated AR/C, with or without asthma. The primary endpoint was at least 1 treatment-emergent adverse event (TEAE). Secondary endpoints were at least 1 solicited TEAE, at least 1 treatment-related adverse event (TRAE), and at least 1 serious TEAE. <h3>Results</h3> The percentage of adolescents reporting any TEAE was 88%, the percentage reporting any TRAE was 86%, and there were no serious TEAEs. Two subjects (1%) discontinued due to AEs. The most common TRAEs were local application site reactions. Most TRAEs were mild in severity and were typically experienced during the first 1-2 days of treatment. The most common TRAEs recurred for <10 days in MT-18. No treatment-related anaphylaxis, epinephrine administrations, severe local swellings, severe mouth or throat edema, or eosinophilic esophagitis occurred in the trial. <h3>Conclusions</h3> There were no new or unexpected safety findings in MT-18 compared with previous safety data. The HDM SLIT tablet was well tolerated in European adolescents with HDM AR/C, similar to previous data in North American adolescents.

TriService Nursing Research Program: A critical component to support military nursing science

TriService Nursing Research Program: A critical component to support military nursing science