A retrospective audit of adult and paediatric anaphylaxis management from two Australian metropolitan mixed emergency departments.

BACKGROUND: Anaphylaxis is a potentially life-threatening allergic reaction, with presentations to emergency departments (EDs) increasing across Australia. Understanding the features of those presenting with anaphylaxis and aspects related to its optimal clinical management across the admission, treatment and discharge settings is needed to minimise its impact. We aimed to evaluate the nature and management of presentations related to anaphylaxis across two Australian EDs. METHODS: Retrospective audit of paediatric and adult patients presenting to a community or tertiary level ED with anaphylaxis from 1 May 2018 to 30 April 2019. Data extracted from medical records included demographic characteristics, causative agents, clinical features, treatments administered across community, ambulance or ED settings, as well as post-discharge care arrangements including provision of Adrenaline Auto-Injector (AAI) and Allergy/Anaphylaxis Action Plan (AAP). RESULTS: A total of 369 (107 paediatric and 262 adult) ED presentations were identified. A total of 94 (36%) adult and 46 (43%) paediatric patients received pre-hospital adrenaline, with a further 91 (35%) adult and 29 (27%) paediatric patients receiving a dose of adrenaline in the ED. The most commonly administered treatment in ED were corticosteroids, given to 157 (60%) adult and 55 (51%) paediatric patients. Among those requiring an AAI for discharge, 123/210 (59%) adult and 57/91 (63%) of paediatric patients left hospital with an AAI. In contrast, among those requiring an allergy/anaphylaxis action plan (AAP) on discharge, 61/206 (30%) adult and 30/90 (33%) of paediatric patients left hospital with one. Factors associated with an increased likelihood of receiving AAI on discharge in paediatric and adult patients included receipt of any adrenaline, receipt of two or more doses of adrenaline, and longer duration of hospital stay. Adults presenting within business hours were more likely to be discharged with AAI, but no such difference was observed for paediatric patients. Similar findings were evident for provision of AAP on discharge. CONCLUSION: These findings demonstrate the need to improve assessment and treatment in the ED. In particular, the observed large variability in provision of AAI and AAP on discharge presents opportunities to explore strategies to improve awareness and provision of these critical components of post-discharge care.

The Pharmacologic Management of Cardiac Arrest.

The effectiveness of pharmacologic management of cardiac arrest patients is widely debated; however, several studies published in the past 5 years have begun to clarify some of these issues. This article covers the current state of evidence for the effectiveness of the vasopressor epinephrine and the combination of vasopressin-steroids-epinephrine and antiarrhythmic medications amiodarone and lidocaine and reviews the role of other medications such as calcium, sodium bicarbonate, magnesium, and atropine in cardiac arrest care. We additionally review the role of ß-blockers for refractory pulseless ventricular tachycardia/ventricular fibrillation and thrombolytics in undifferentiated cardiac arrest and suspected fatal pulmonary embolism.

Detecting epinephrine auto-injector shortages in Finland 2016-2022: Log-data analysis of online information seeking.

INTRODUCTION: Medicine shortages prevail as a worldwide problem causing life-threatening situations for adults and children. Epinephrine auto-injectors are used for serious allergic reactions called anaphylaxis, and alternative auto-injectors are not always available in pharmacies. Healthcare professionals in Finland use the dedicated internet source, Physician's Database (PD), when seeking medical information in practice, while Health Library (HL) provides health information for citizens (S1 Data). The objectives were to assess whether (1) professionals' searches for epinephrine auto-injectors and (2) citizens' anaphylaxis article openings relate to epinephrine shortages in Finland. METHODS: Monthly log data on epinephrine auto-injectors (EpiPen®, Jext®, Emerade®) from PD and on openings of anaphylaxis articles from HL were collected during 2016-2022. Professionals' searches of seven auto-injectors and citizens' openings of four anaphylaxis articles were compared to information on epinephrine shortages reported by Finnish Medicines Agency. Professionals' auto-injector prescriptions provided by Social Insurance Institution were also assessed. RESULTS: Total searches in EpiPen® (N = 111,740), Jext® (N = 25,631), and Emerade® (N = 18,329) could be analyzed during 2016-2022. EpiPen® only could visually show seasonal patterns during summertime, peaking vigorously in the summer of 2018 when the major EpiPen® shortage appeared worldwide. Anaphylaxis articles equaled 2,030,855 openings altogether. Openings of one anaphylaxis article ("Bites and Stings") peaked during summertime, while another article ("Anaphylactic Reaction") peaked only once (three-fold increase) at the end of 2020 when COVID-19 vaccinations started, and auto-injector prescriptions were lowest. Fifty EpiPen®, one Jext®, and twelve Emerade® shortages were reported. Almost a two-fold increase in peaks of auto-injector prescriptions was found during summertime. CONCLUSION: This study shows that (1) epinephrine shortages related to professionals' searching for auto-injectors, and (2) citizens' information seeking on anaphylaxis related to summertime and shortages with lesser prescriptions. Therefore, the dedicated internet databases aimed at professionals and citizens could be used as additional information sources to detect anaphylactic reactions and auto-injector shortages.

Level of Awareness of Certified Non-critical Care Physicians in Diagnosing, Managing, and Disposing Anaphylactic Cases.

Background: Anaphylaxis is known as an acute, severe hypersensitivity reaction that rapidly initiates after exposure to a triggering agent. It is a life-threatening condition, and early recognition and swift intervention are crucial to saving patients' lives. Objective: The objective of this study is to assess the ability of certified non-critical care physicians to recognize, manage, and dispose cases of anaphylaxis. Methods: A survey consisting of 19 questions was developed by expert emergency consultants to evaluate physicians' knowledge regarding the recognition, management, and disposition of anaphylactic episodes. Responses were collected through in-person surveys conducted with physicians from various specialties and varying clinical experience levels at a tertiary care center in the Eastern Province of Saudi Arabia. Results: In this cross-sectional study, a total of 173 physicians completed the survey, with 81.5% being consultants and 18.5% specialists. Only 5.2% correctly identified all three proposed anaphylaxis clinical scenarios, 16.8% identified two scenarios correctly, and 51.4% identified only one scenario. While 42.8% recognized the first-line management of anaphylaxis, only 24.3% and 24.9% knew the correct epinephrine dose and route, respectively. Regarding the disposition of patients experiencing an anaphylactic episode, 61.9% of responders opted to dispose the case to the emergency department. Conclusion: Our study reveals a knowledge gap among non-critical care physicians practicing in a tertiary care center concerning the identification and management of anaphylaxis. Raising awareness of this life-threatening condition is imperative to address this serious issue.

Trends in Incidence and Drug Prescriptions for Croup in Children Under 5 Years of Age: A 2002-2019 Population-Based Study.

BACKGROUND: Tracking national croup trends can provide important insights for childhood health management. This study aimed to analyze the incidence and drug prescription trends in Korean children over a two-decade period. METHODS: This population-based study encompassed 479,783 children aged < 5 years from 2002-2019, utilizing the National Health Insurance Service-National Sample Cohort. We identified participants with a primary croup diagnosis who were admitted to or visited the emergency room. Age-specific and age-adjusted incidence rates/10,000 person-years were calculated. We assessed using orthogonal polynomial contrasts and stratified by various factors (sex, age, residential area, economic status, comorbidities, and healthcare facility types). We observed changes in the use of five medications: inhaled steroids, systemic steroids, inhaled epinephrine, antibiotics, and short-acting bronchodilators. Generalized binomial logistic regression was used to analyze factors influencing prescription strategies. RESULTS: In 2002, the croup-related visits were 16.1/10,000 person-years, increasing to 98.3 in 2019 (P for trend < 0.001). This trend persisted, regardless of age, sex, region, and economic status. Children with comorbid atopic dermatitis or asthma maintained consistent croup rates, while those without comorbidities increased. Treatment trends showed decreasing antibiotic (73-47%) and oxygen use (21.3-3.4%), with increasing nebulized epinephrine (9.3-41.5%) and multiple drug prescriptions (67.8-80.3%). Primary care centers exhibited a greater increase in prescription usage and hospitalization duration than did tertiary healthcare institutions. CONCLUSION: Over the past two decades, croup incidence has risen, accompanied by increased epinephrine use and decreased antibiotic prescriptions. Longer hospitalization and higher medication use were mainly observed in primary care facilities.

El pediatra de Atención Primaria y la anafilaxia / The primary care pediatrician and anaphylaxis

La anafilaxia es una reacción alérgica grave de instauración rápida y potencialmente mortal. El diagnóstico de anafilaxia es clínico y debe realizarse de manera precoz. Aparece en las 2 primeras horas tras exposición al alérgeno, en los primeros 30 minutos en alergia alimentaria y más precozmente con medicamentos intravenosos o picaduras de himenópteros. Los síntomas cutáneos suelen ser los primeros en manifestarse y están presentes en la mayoría de los casos, más de un 80%. Pueden ser leves o transitorios e incluso no estar presentes en un 18% de los casos. Si se afecta el sistema cardiocirculatorio estaríamos ante un shock anafiláctico. La causa más frecuente en Pediatría son los alimentos. Existen cofactores cuya presencia aumenta la probabilidad de anafilaxia; los más importantes son: el ejercicio, los fármacos, la fiebre y el estrés. El tratamiento de elección es la adrenalina intramuscular. Tanto los padres como los niños deben saber identificar los signos y/o síntomas del inicio de la anafilaxia para instaurar el tratamiento pautado en el plan de acción escrito.

Anaphylaxis is a severe, rapid and potentially fatal allergic reaction. The diagnosis of anaphylaxis is clinical and must be early. It appears in the first 2 hours after exposure to the allergen, in the first 30 minutes in food allergy and earlier with intravenous drugs or hymenoptera stings. Cutaneous symptoms are generally the first to appear and are present in most cases, more than 80%. They may be mild or transitory, or absent in 18% of cases. If the cardio-circulatory system is affected, an anaphylactic shock occurs. The most frequent cause in pediatrics is nutrition. There are several cofactors whose presence increases the likelihood of anaphylaxis; the most important are: exercise, medication, fever and stress. The treatment of choice is intramuscular adrenaline. Parents and children should be able to identify the signs and/or symptoms of anaphylaxis in order to implement the treatment prescribed in the written action plan. (AU)

Tranexamic acid versus adrenaline-soaked pledgets for the reduction of intraoperative bleeding in functional endoscopic sinus surgery.

OBJECTIVE: Aim: To examine the impact of locally applied tranexamic acid and adrenaline, separately and in combination, on intraoperative blood loss and surgical field quality during functional endoscopic sinus surgery. PATIENTS AND METHODS: Materials and Methods: The study involved 40 patients with chronic rhinosinusitis. They were divided into two groups. Group I received adrenaline alone in one side and a mixture of adrenaline and tranexamic acid in the other side. Group II received adrenaline alone in one side and tranexamic acid in the otherside. Parameters like surgery time, blood loss, and surgical field quality were studied. RESULTS: Results: In Group I, the combination of adrenaline and tranexamic acid significantly reduced blood loss and enhanced surgical field quality compared to adrenaline alone. In Group II, adrenaline outperformed tranexamic acid in shortening surgery duration and improving surgical field quality. However, there was no significant difference in blood loss reduction between adrenaline and tranexamic acid. CONCLUSION: Conclusions: The study concluded that tranexamic acid is less effective than adrenaline when introduced as topical intranasal pledgets in both decreasing the time needed for the surgery and improving the subjective satisfaction of the surgeon while there is no significant difference regarding decreasing intraoperative blood loss. The mixture of adrenaline and tranexamic acid pledgets are more effective than adrenaline-only pledgets in terms of decreasing the intraoperative blood loss and improving the surgeon's satisfaction with no significant difference regarding the time needed for the surgery.

Fatal food anaphylaxis in adults and children.

Anaphylaxis is a life-threatening reaction characterized by the acute onset of symptoms involving different organ systems and requiring immediate medical intervention. The incidence of fatal food anaphylaxis is 0.03 to 0.3 million/people/year. Most fatal food-induced anaphylaxis occurs in the second and third decades of life. The identified risk factors include the delayed use of epinephrine, the presence of asthma, the use of recreational drugs (alcohol, nicotine, cannabis, etc.), and an upright position. In the United Kingdom (UK) and Canada, the reported leading causal foods are peanuts and tree nuts. In Italy, milk seems to be the most common cause of fatal anaphylaxis in children < 18 years. Fatal food anaphylaxis in Italian children and adolescents almost always occurs outside and is characterized by cardiorespiratory arrest; auto-injectable adrenaline intramuscular was available in few cases. Mortality from food anaphylaxis, especially in children, is a very rare event with stable incidence, but its risk deeply impacts the quality of life of patients with food allergy and their families. Prevention of fatal food anaphylaxis must involve patients and their families, as well as the general public, public authorities, and patients' associations.

Sequence of Epinephrine and Advanced Airway Placement After Out-of-Hospital Cardiac Arrest.

Importance: While epinephrine and advanced airway management (AAM) (supraglottic airway insertion and endotracheal intubation) are commonly used for out-of-hospital cardiac arrest (OHCA), the optimal sequence of these interventions remains unclear. Objective: To evaluate the association of the sequence of epinephrine administration and AAM with patient outcomes after OHCA. Design, Setting, and Participants: This cohort study analyzed the nationwide, population-based OHCA registry in Japan and included adults (aged ≥18 years) with OHCA for whom emergency medical services personnel administered epinephrine and/or placed an advanced airway between January 1, 2014, and December 31, 2019. The data analysis was performed between October 1, 2022, and May 12, 2023. Exposure: The sequence of intravenous epinephrine administration and AAM. Main Outcomes and Measures: The primary outcome was 1-month survival. Secondary outcomes were 1-month survival with favorable functional status and prehospital return of spontaneous circulation. To control imbalances in measured patient demographics, cardiac arrest characteristics, and bystander and prehospital interventions, propensity scores and inverse probability of treatment weighting (IPTW) were performed for shockable and nonshockable initial rhythm subcohorts. Results: Of 259 237 eligible patients (median [IQR] age, 79 [69-86] years), 152 289 (58.7%) were male. A total of 21 592 patients (8.3%) had an initial shockable rhythm, and 237 645 (91.7%) had an initial nonshockable rhythm. Using IPTW, all covariates between the epinephrine-first and AAM-first groups were well balanced, with all standardized mean differences less than 0.100. After IPTW, the epinephrine-first group had a higher likelihood of 1-month survival for both shockable (odds ratio [OR], 1.19; 95% CI, 1.09-1.30) and nonshockable (OR, 1.28; 95% CI, 1.19-1.37) rhythms compared with the AAM-first group. For the secondary outcomes, the epinephrine-first group experienced an increased likelihood of favorable functional status and prehospital return of spontaneous circulation for both shockable and nonshockable rhythms compared with the AAM-first group. Conclusions and Relevance: These findings suggest that for patients with OHCA, administration of epinephrine before placement of an advanced airway may be the optimal treatment sequence for improved patient outcomes.

Endoscopic Treatment of Small Bowel Bleeding.

Approximately 5% of all gastrointestinal (GI) bleeding originates from the small bowel. Endoscopic therapy of small bowel bleeding should only be undertaken after consideration of the different options, and the risks, benefits, and alternatives of each option. Endoscopic therapy options for small bowel bleeding are like those treatments used for other forms of bleeding in the upper and lower GI tract. Available endoscopic treatment options include thermal therapy (eg, argon plasma coagulation and bipolar cautery), mechanical therapy (eg, hemoclips), and medical therapy (eg, diluted epinephrine injection). Patients with complicated comorbidities would benefit from evaluation and planning of available treatment options, including conservative and/or medical treatments, beyond endoscopic therapy.

Resuscitation With Early Adrenaline Infusion for Children With Septic Shock: A Randomized Pilot Trial.

OBJECTIVES: In children with septic shock, guidelines recommend resuscitation with 40-60 mL/kg of fluid boluses, yet there is a lack of evidence to support this practice. We aimed to determine the feasibility of a randomized trial comparing early adrenaline infusion with standard fluid resuscitation in children with septic shock. DESIGN: Open-label parallel randomized controlled, multicenter pilot study. The primary end point was feasibility; the exploratory clinical endpoint was survival free of organ dysfunction by 28 days. SETTING: Four pediatric Emergency Departments in Queensland, Australia. PATIENTS: Children between 28 days and 18 years old with septic shock. INTERVENTIONS: Patients were assigned 1:1 to receive a continuous adrenaline infusion after 20 mL/kg fluid bolus resuscitation (n = 17), or standard care fluid resuscitation defined as delivery of 40 to 60 mL/kg fluid bolus resuscitation prior to inotrope commencement (n = 23). MEASUREMENTS AND MAIN RESULTS: Forty of 58 eligible patients (69%) were consented with a median age of 3.7 years (interquartile range [IQR], 0.9-12.1 yr). The median time from randomization to inotropes was 16 minutes (IQR, 12-26 min) in the intervention group, and 49 minutes (IQR, 29-63 min) in the standard care group. The median amount of fluid delivered during the first 24 hours was 0 mL/kg (IQR, 0-10.0 mL/kg) in the intervention group, and 20.0 mL/kg (14.6-28.6 mL/kg) in the standard group (difference, -20.0; 95% CI, -28.0 to -12.0). The number of days alive and free of organ dysfunction did not differ between the intervention and standard care groups, with a median of 27 days (IQR, 26-27 d) versus 26 days (IQR, 25-27 d). There were no adverse events reported associated with the intervention. CONCLUSIONS: In children with septic shock, a protocol comparing early administration of adrenaline versus standard care achieved separation between the study arms in relation to inotrope and fluid bolus use.

Role of catecholamine synthases in the maintenance of cancer stem-like cells in malignant peripheral nerve sheath tumors.

Malignant peripheral nerve sheath tumors (MPNSTs) are malignant tumors that are derived from Schwann cell lineage around peripheral nerves. As in many other cancer types, cancer stem cells (CSCs) have been identified in MPNSTs, and they are considered the cause of treatment resistance, recurrence, and metastasis. As an element defining the cancer stemness of MPNSTs, we previously reported a molecular mechanism by which exogenous adrenaline activates a core cancer stemness factor, YAP/TAZ, through ß2 adrenoceptor (ADRB2). In this study, we found that MPNST cells express catecholamine synthases and that these enzymes are essential for maintaining cancer stemness, such as the ability to self-renew and maintain an undifferentiated state. Through gene knockdown and inhibition of these enzymes, we confirmed that catecholamines are indeed synthesized in MPNST cells. The results confirmed that catecholamine synthase knockdown in MPNST cells reduces the activity of YAP/TAZ. These data suggest that a mechanism of YAP/TAZ activation by de novo synthesized adrenaline, as well as exogenous adrenaline, may exist in the maintenance of cancer stemness of MPNST cells. This mechanism not only helps to understand the pathology of MPNST, but could also contribute to the development of therapeutic strategies for MPNST.

Emergency treatment of peri-operative anaphylaxis: Resuscitation Council UK algorithm for anaesthetists.

Peri-operative anaphylaxis is a rare but potentially catastrophic event which must be considered whenever unexpected and significant cardiovascular or respiratory compromise occurs during anaesthesia. The Resuscitation Council UK algorithm for peri-operative anaphylaxis highlights the importance of early intravenous adrenaline and fluid resuscitation and provides guidance on the treatment of refractory anaphylaxis and immediate follow-up. This algorithm is endorsed by the Royal College of Anaesthetists, Association of Anaesthetists, British Society of Allergy and Clinical Immunology and Clinical Immunology Professional Network of the British Society for Immunology. This document was produced by the Perioperative Allergy Network steering committee in collaboration with the Resuscitation Council UK.

Food Allergy Reaction Severity and Management in a Diverse Population.

BACKGROUND: Definitive treatment for food allergy reactions including anaphylaxis varies widely by reaction severity and socioeconomic status, but little data exist to characterize the relationship between severity, management, and race and ethnicity. OBJECTIVE: To analyze the differences in reaction severity, epinephrine use, and emergency room (ER) use by race and ethnicity in a large, diverse, food-allergic cohort. METHODS: We analyzed intake data from participants in the Food Allergy Outcomes Related to White and African-American Racial Differences cohort on the history of food allergy reactions, severity of the reactions, and management associated with each reaction. We used descriptive statistics as well as mixed-effects logistic and Poisson models to describe the differences in reaction severity, ER visits, and total lifetime epinephrine use by race and ethnicity. RESULTS: A total of 784 children were included in the analysis: 425 (54.2%) were non-Hispanic White, 282 (36.0%) were non-Hispanic Black, and 77 (9.8%) were Hispanic/Latino. Non-Hispanic Black children had increased odds of more severe reactions (odds ratio, 1.7; 95% CI, 1.2-2.3) and higher odds of going to the ER (odds ratio, 2.8; 95% CI, 1.4-5.4). Both non-Hispanic Black (incidence rate ratio, 0.4; 95% CI, 0.3-0.5) and Hispanic/Latino (incidence rate ratio, 0.3; 95% CI, 0.2-0.5) children had lower rates of total lifetime epinephrine use. CONCLUSIONS: There are significant disparities in the severity and treatment of food allergy reactions by race and ethnicity, resulting in increased ER use and decreased total lifetime epinephrine use. Equipping parents with resources and tools on management of food allergy reactions may result in decreased disparity in access to definitive care.

Outcomes with intracoronary vs. intravenous epinephrine in cardiac arrest.

BACKGROUND: Advanced Cardiovascular Life Support (ACLS) guidelines recommend intravenous (IV) and intraosseous (IO) epinephrine as a basic cornerstone in the resuscitation process. Data about the efficacy and safety of intracoronary (IC) epinephrine during cardiac arrest in the catheterization laboratory are lacking. OBJECTIVE: To examine the efficacy and safety of IC vs. IV epinephrine for resuscitation during cardiac arrest in the catheterization laboratory. METHODS AND RESULTS: This is a prospective observational study that included all patients who experienced cardiac arrest in the cath lab at two tertiary centres in Egypt from January 2015 to July 2022. Patients were divided into two groups according to the route of epinephrine given; IC vs. IV. The primary outcome was survival to hospital discharge. Secondary outcomes included rate of return of spontaneous circulation (ROSC), time-to-ROSC, and favourable neurological outcome at discharge defined as modified Rankin Scale (MRS) <3. A total of 162 patients met our inclusion criteria, mean age (60.69 ± 9.61), 34.6% women. Of them, 52 patients received IC epinephrine, and 110 patients received IV epinephrine as part of the resuscitation. Survival to hospital discharge was significantly higher in the IC epinephrine group (84.62% vs. 53.64%, P < 0.001) compared with the IV epinephrine group. The rate of ROSC was higher in the IC epinephrine group (94.23% vs. 70%, P < 0.001) and achieved in a shorter time (2.6 ± 1.97 min vs. 6.8 ± 2.11 min, P < 0.0001) compared with the IV group. Similarly, favourable neurological outcomes were more common in the IC epinephrine group (76.92% vs. 47.27%, P < 0.001) compared with the IV epinephrine group. CONCLUSION: In this observational study, IC epinephrine during cardiac arrest in the cath lab appeared to be safe and may be associated with improved outcomes compared with the IV route. Larger randomized studies are encouraged to confirm these results.

Real-Life Adherence to Venom Immunotherapy and Adrenaline Autoinjector.

INTRODUCTION: Venom immunotherapy (VIT) and adrenaline autoinjector (AAI) are important therapies in venom anaphylaxis. Adherence to VIT and AAI in patients with venom allergy has been evaluated in a few studies; however, solid data are lacking. This study aimed to evaluate VIT and AAI retrieval rates in patients with venom allergy with a special focus on adherence to treatment. Adherence was compared to subcutaneous immunotherapy (SCIT) with inhalant allergens. METHODS: This was a retrospective study among patients registered for allergen immunotherapy at the Allergy Center, Odense University Hospital, Denmark, from January 1, 2010, to December 31, 2014. Data on purchased immunotherapy and AAI were obtained from the Danish National Health Service Prescription Database. Multivariable logistic regression was used to analyze if allergen, age, sex, mastocytosis, and treatment site affected adherence. RESULTS: The 3-year adherence to VIT was 92.4% (244/264) compared to 87.4% (215/246) in SCIT with inhalant allergens, and the 5-year adherence to VIT was 84.1% (222/264) compared to 74.8% (184/246) in SCIT with inhalant allergens (p = 0.045). Females treated with VIT were more adherent than males (p = 0.45 [3-year], p = 0.008 [5-year]), whereas allergen, age, mastocytosis, or treatment site did not significantly affect adherence. Only 28.6% of patients (12/42) purchased an AAI after premature termination of VIT. CONCLUSION: In this register-based study, we found that the 3- and 5-year adherences to VIT and SCIT with inhalant allergens are at the upper end of the spectrum hitherto reported. Patients' 5-year adherence to VIT was higher than patients' 5-year adherence to SCIT with inhalant allergens. If VIT was prematurely terminated, less than 1/3 would have purchased an AAI.