Delayed Epinephrine Administration Research Articles

Managing anaphylaxis: Epinephrine, antihistamines, and corticosteroids: More than 10 years of Cross-Canada Anaphylaxis REgistry data

BackgroundEpinephrine is the first-line treatment for anaphylaxis but is often replaced with antihistamines or corticosteroids. Delayed epinephrine administration is a risk factor for fatal anaphylaxis. Convincing data on the role of antihistamines and corticosteroids in anaphylaxis management are sparse. ObjectiveTo establish the impact of prehospital treatment with epinephrine, antihistamines, and/or corticosteroids on anaphylaxis management. MethodsPatients presenting with anaphylaxis were recruited prospectively and retrospectively in 10 Canadian and 1 Israeli emergency departments (EDs) between April 2011 and August 2022, as part of the Cross-Canada Anaphylaxis REgistry. Data on anaphylaxis cases were collected using a standardized form.Primary outcomes were uncontrolled reactions (>2 doses of epinephrine in ED), no prehospital epinephrine use, use of intravenous fluids in ED, and hospital admission. Multivariate regression was used to identify factors associated with primary outcomes. ResultsAmong 5364 reactions recorded, median age was 8.8 years (IQR, 3.78-16.9); 54.9% of the patients were males, and 52.5% had a known food allergy. In the prehospital setting, 37.9% received epinephrine; 44.3% received antihistamines, and 3.15% received corticosteroids. Uncontrolled reactions happened in 250 reactions.Patients treated with prehospital epinephrine were less likely to have uncontrolled reactions (adjusted odds ratio [aOR], 0.955 [95% CI, 0.943-0.967]), receive intravenous fluids in ED (aOR, 0.976 [95% CI, 0.959-0.992]), and to be admitted after the reaction (aOR, 0.964 [95% CI, 0.949-0.980]). Patients treated with prehospital antihistamines were less likely to have uncontrolled reactions (aOR, 0.978 [95% CI, 0.967-0.989]) and to be admitted after the reaction (aOR, 0.963 [95% CI, 0.949-0.977]). Patients who received prehospital corticosteroids were more likely to require intravenous fluids in ED (aOR, 1.059 [95% CI, 1.013-1.107]) and be admitted (aOR, 1.232 [95% CI, 1.181-1.286]). ConclusionOur findings in this predominantly pediatric population support the early use of epinephrine and suggest a beneficial effect of antihistamines. Corticosteroid use in anaphylaxis should be revisited.

Delayed administration of epinephrine is associated with worse neurological outcomes in patients with out-of-hospital cardiac arrest and initial pulseless electrical activity: insight from the nationwide multicentre observational JAAM-OHCA (Japan Association for Acute Medicine) registry.

AimsThe delayed administration of epinephrine has been proven to worsen the neurological outcomes of patients with out-of-hospital cardiac arrest (OHCA) and shockable rhythm or asystole. We aimed to investigate whether the delayed administration of epinephrine might also worsen the neurological outcomes of patients with witnessed OHCA and initial pulseless electrical activity (PEA).Methods and resultsThe JAAM-OHCA Registry is a multicentre registry including OHCA patients between 2014 and 2017. Patients with emergency medical services (EMS)-treated OHCA and initial PEA rhythm were included. The primary exposure was the time from the EMS call to the administration of epinephrine. The secondary exposure was the time to epinephrine dichotomized as early (≤15 min) or delayed (>15 min). The primary outcome was the achievement of a favourable neurological outcome, defined as Cerebral Performance Categories Scale 1–2 at 30 days after OHCA. Out of 34 754 patients with OHCA, 3050 patients were included in the present study. After adjusting for potential confounders, the delayed administration of the epinephrine was associated with a lower likelihood of achieving a favourable neurological outcome [adjusted odds ratio (OR) 0.96; 95% confidence interval (CI) 0.93–0.99; P = 0.016]. The percentage of patients who achieved a favourable neurological outcome in the delayed epinephrine group was lower than that in the early epinephrine group (1.3% vs. 4.7%; adjusted OR 0.33; 95% CI 0.15–0.72; P = 0.005). A restricted cubic spline analysis demonstrated that delayed epinephrine administration could decrease the likelihood of achieving a favourable neurological outcome; this was significant within the first 10 min.ConclusionsThe delayed administration of epinephrine was associated with worse neurological outcomes in patients with witnessed OHCA patients with initial PEA.

Moving Away from Routine Emergency Department Evaluation After Treatment of Anaphylaxis – A Retrospective Review of Epinephrine Usage Among High-Risk Peanut-Allergic Children

Newly established 2020 criteria define refractory, persistent, and biphasic anaphylaxis; however, there are limited data on the incidence of these subtypes, particularly for anaphylaxis secondary to food allergy. While receipt of ≥2 epinephrine doses and delayed epinephrine administration during treatment of anaphylaxis increase risk for biphasic anaphylaxis, preliminary data indicate that a food allergy trigger decreases risk for biphasic anaphylaxis.

Biphasic anaphylaxis after first dose of messenger RNA coronavirus disease 2019 vaccine with positive polysorbate 80 skin testing result

Biphasic anaphylaxis after first dose of messenger RNA coronavirus disease 2019 vaccine with positive polysorbate 80 skin testing result

Abstract 232: Delayed Administration of Epinephrine is Associated with Worse Neurological Outcomes in Patients with Out-of-hospital Cardiac Arrest and Initial Pulseless Electrical Activity

Background: Delayed administration of epinephrine has been proven to worsen the neurological outcomes of patients with out-of-hospital cardiac arrest (OHCA) and initial shockable rhythm. We aimed to investigate whether delayed administration of epinephrine might also worsen the neurological outcomes of patients with witnessed OHCA and initial pulseless electrical activity (PEA). Methods: The Japanese Association for Acute Medicine - out-of-hospital cardiac arrest (JAAM-OHCA) Registry is a multicenter, prospective, observational registry including 34,754 OHCA patients between 2014 and 2017. The present study assessed the impact of the time to epinephrine administration on neurological outcomes in patients with witnessed non-traumatic OHCA with initial rhythm of PEA. The primary outcome was defined as Cerebral Performance Categories (CPC) Scale 1-2 at 30 days after OHCA. The association between the odds ratio for the primary outcome and the time from witnessed OHCA to epinephrine administration was assessed with a restricted cubic spline analysis. Results: Out of 34,754 patients with OHCA, 3,050 patients with OHCA and initial PEA who received epinephrine were included in the present study. Mean age was 73.7 years and 1836 (60.2%) was male. After adjusting for potential confounders, the time from witnessed OHCA to epinephrine administration was associated with lower likelihood of favorable neurological outcomes (odds ratio [OR] 0.92; 95% confidence interval [CI] 0.89-0.96; P<0.001). The restricted cubic spline analysis demonstrated that delayed epinephrine administration could decrease the likelihood of a favorable neurological outcome; this was significant within the first 10 minutes. Conclusions: Delayed administration of epinephrine was associated with worse neurological outcomes in patients with witnessed OHCA patients with initial PEA.

Global Trends in Anaphylaxis Epidemiology and Clinical Implications

The true global scale of anaphylaxis remains elusive, because many episodes occur in the community without presentation to health care facilities, and most regions have not yet developed reliable systems with which to monitor severe allergic events. The most robust data sets currently available are based largely on hospital admissions, which are limited by inherent issues of misdiagnosis, misclassification, and generalizability. Despite this, there is convincing evidence of a global increase in rates of all-cause anaphylaxis, driven largely by medication- and food-related anaphylaxis. There is no evidence of parallel increases in global all-cause anaphylaxis mortality, with surprisingly similar estimates for case-fatality rates at approximately 0.5% to 1% of fatal outcomes for hospitalizations due to anaphylaxis across several regions. Studying regional patterns of anaphylaxis to certain triggers have provided valuable insights into susceptibility and sensitizing events: for example, the link between the mAb cetuximab and allergy to mammalian meat. Likewise, data from published fatality registers can identify potentially modifiable risk factors that can be used to inform clinical practice, such as prevention of delayed epinephrine administration, correct posturing during anaphylaxis, special attention to populations at risk (such as the elderly on multiple medications), and use of venom immunotherapy in individuals at risk of insect-related anaphylaxis.

Abstract 169: Association Between Time to First Administration of Epinephrine After Defibrillation and Outcome in Out-Of-Hospital Cardiac Arrest Patients With Shockable Rhythm

Introduction: In out-of-hospital cardiac arrest (OHCA) patients during shockable rhythm, the epinephrine administration after second defibrillation is recommended by the 2015 ILCOR/CoSTR guidelines. However, there is insufficient evidence regarding the proper timing of epinephrine administration particularly in relation to defibrillation. Hypothesis: The timing of epinephrine after first defibrillation (D-E interval) was associated with clinical outcome in OHCA patients. Methods: Between 2011 and 2016, we enrolled 753,025 OHCA patients from nationwide prospective population-based registry in Japan. Following exclusion criteria, a total of 1,559 patients with witnessed by bystanders and shockable rhythm on the initial electrocardiogram who administrated epinephrine after defibrillation by emergency medical service personnel and obtained return of spontaneous circulation in prehospital setting were eligible for the study. We evaluated the association between D-E interval and favorable neurological outcome (cerebral performance category: 1 or 2) at 30 days. To evaluate predictor for better neurological outcome, study patients were categorized as every 2 minutes up to 20 minutes, and more than 20 minutes. Results: Patients with favorable neurological outcome were 22% (N=348). Patients with favorable neurological outcome had a shorter D-E interval than those with non-favorable neurological outcome (7.9±4.1vs 10.2±5.3 min, p<0.001). Multivariate logistic regression analysis showed that D-E interval at more than 10 minutes, when D-E interval at 2 to 3 minutes as defined reference, was a significant predictor for non-favorable neurological outcome ( Table ). Conclusion: Delayed epinephrine administration after first defibrillation (D-E interval >10 minutes) was significantly associated with non-favorable neurological outcome.

Biphasic Reactions in Emergency Department Anaphylaxis Patients: A Prospective Cohort Study

Biphasic reaction rates and potential associated risk factors are not well understood. To evaluate biphasic reaction rates and associated risk factors. We prospectively enrolled patients with anaphylaxis at 2 Midwestern academic emergency departments (EDs). We gathered data using patient and ED provider surveys and a structured health record review. Biphasic reaction rates and clinically significant biphasic reaction rates, defined as recurrent reactions that met anaphylaxis diagnostic criteria or were treated with epinephrine, were calculated. Characteristics associated with biphasic reactions were assessed with logistic regression and reported with odds ratios (ORs) and 95% CIs. Of 430 ED anaphylaxis visits, 31 (7.2%) patients had biphasic reactions; 22 (5.1%) had clinically significant biphasic reactions. The median time from anaphylaxis onset to first epinephrine dose was longer for patients with biphasic (78 minutes) than uniphasic courses (45 minutes) (P= .005). A biphasic course was associated with an ED setting of first epinephrine dose (OR, 3.72; 95% CI, 1.36-10.14) and a delay of more than 30 minutes from symptom onset to first epinephrine dose (OR, 3.39; 95% CI, 1.13-10.18), and was inversely associated with arrival by ambulance (OR, 0.18; 95% CI, 0.05-0.61). A clinically significant biphasic reaction was associated with an ED setting of first epinephrine dose (OR, 3.32; 95% CI, 1.08-10.25) and inversely associated with arrival by ambulance (OR, 0.08; 95% CI, 0.01-0.61). Biphasic reactions and clinically significant biphasic reactions occurred in 7.2% and 5.1% of ED anaphylaxis patients, respectively. Delayed epinephrine administration was associated with biphasic reactions.

306 Assessment of Emergency Department Anaphylaxis Patient Triage Based on the Emergency Severity Index

Early recognition and treatment of anaphylaxis is crucial. Delayed epinephrine administration for anaphylaxis allows progression of symptoms and has been associated with worse outcomes and increased mortality. Emergency department (ED) triage is a crucial step in management and ensures rapid assessment and resource allocation to the most critical patients. The Emergency Severity Index (ESI) is a common ED triage assessment tool that categorizes patients into one of five levels. Patients with the highest acuity are triaged as levels 1 and 2 while patients in levels 3, 4, and 5 are categorized based on expected resource utilization. The study objective was to assess ED triage of anaphylaxis patients and determine characteristics associated with higher versus (vs) lower triage levels. A cohort study including prospectively and retrospectively enrolled patients was conducted between 2010 and 2018 at a quaternary care academic ED with 77,000 annual patient visits. Patients were included if they met anaphylaxis diagnostic criteria for anaphylaxis. Patient health records were reviewed to evaluate patient demographics, inciting trigger, ESI triage level, out-of-hospital management, presenting signs and symptoms, ED management, and disposition. Prospectively enrolled patients and their ED providers also completed questionnaires regarding reaction characteristics and out-of-hospital treatment. Logistic regression analysis was performed to compare patient characteristics and management between patients triaged as ESI levels 1 or 2 vs levels 3 or 4. Data are summarized with descriptive statistics and corresponding odds ratios (ORs) with 95% confidence intervals (CIs). A total of 1104 patients met anaphylaxis diagnostic criteria and were eligible for study inclusion, of which 71% were enrolled retrospectively and 29% prospectively. The mean patient age was 34 years, 28% of patients were children (under 18 years of age), and 57% were female. Overall, 72% of patients received epinephrine (either prior to or after ED arrival). ESI triage levels of 1, 2, 3, 4, and 5 were assigned in 26 (2%), 517 (47%), 499 (45%), 62 (6%), and 0 (0%) of visits, respectively. There was no significant difference in ESI level assignment between prospectively and retrospectively enrolled patients. Patients assigned an ESI level of 3 or 4, compared to those with an ESI level of 1 or 2, had a longer median time from ED arrival to epinephrine administration (31 minutes [IQR 16-57] vs 13 minutes [IQR 7-13], [p < 0.01]), were more likely to be children (32% vs 24%; OR 1.50, 95% CI [1.15-1.96]), less likely to receive epinephrine in the ED (41% vs 53%; OR 0.62, 95% CI [0.49-0.78]), more likely to have an unidentified trigger (25% vs 18%; OR 1.45, 95% CI [1.08-1.93]), less likely to have angioedema (55% vs 63%; OR 0.74, 95% CI [0.58-0.94]) and less likely to report dyspnea (59% vs 66%; OR 0.74; 95% CI [0.58-0.94]), or throat tightness (45% vs 54%; OR 0.71; 95% CI [0.56-0.89]). An ESI triage level of 3 or 4 was associated with an increased time to epinephrine administration in patients presenting to the ED with anaphylaxis. Forty-one percent of patients triaged as ESI level 3 or 4 received epinephrine in the ED suggesting undertriage of a substantial proportion of anaphylaxis patients. Children and patients with an unidentified allergic trigger were more likely to be triaged as level 3 or 4.

The Association of Hospital Rate of Delayed Epinephrine Administration With Survival to Discharge for Pediatric Nonshockable In-Hospital Cardiac Arrest.

To evaluate the variation of hospital rates of delayed epinephrine administration in pediatric patients with nonshockable in-hospital cardiac arrest, and the association of those rates with event, 24-hour, and overall survival to hospital discharge. A retrospective evaluation was performed. Delayed epinephrine was defined as greater than 5 minutes between the time the need for chest compressions was identified and epinephrine was administered. The main outcome was the association of hospital rate of delayed epinephrine administration with survival to hospital discharge. Secondary outcomes were event and 24-hour survival. Evaluation used hierarchical logistic regression and included 13 patient/event-level and seven hospital-level factors. Hospitals with greater than 6 months data in the American Heart Association's Get With the Guidelines-Resuscitation registry (2000-2016) and greater than or equal to five total pediatric cardiac arrests with nonshockable rhythm. Children less than 18 years old with index nonshockable in-hospital cardiac arrest treated with greater than or equal to one epinephrine dose. None. One-thousand four-hundred sixty-two patients at 69 hospitals were included: 218 patients (14.9%) had epinephrine delay rates ranging from 0% to 80% of events (median, 15.6%; interquartile range, 7-25%). The median and interquartile range of hospital level delay was 16% (7-25%). Patient/event-level predictors of delayed epinephrine were asystole (odds ratio, 1.54 [95% CI, 1.10-2.16]) and insertion of an endotracheal tube (odds ratio, 1.86 [95% CI, 1.27-2.73]). Hospital size less than 200 compared with greater than or equal to 500 beds (odds ratio, 3.07 [95% CI, 1.22-7.73]) and ICU location (odds ratio, 0.51 [95% CI, 0.36-0.74]) were associated with epinephrine delay rates. After adjustment, increasing quartiles of epinephrine delay were associated with lower patient and hospital-level return of spontaneous circulation (p = 0.019, p = 0.006) and 24-hour survival (p = 0.018, p = 0.002) respectively, but not survival to discharge (p = 0.20, p = 0.24). Delayed epinephrine administration following pediatric nonshockable in-hospital cardiac arrest varies significantly between hospitals. Hospitals with higher rates of delayed epinephrine administration had worse patient- and hospital-level outcomes after adjusting for multiple patient- and hospital-level factors. Delayed epinephrine administration may directly contribute to increased mortality risk and/or may be a marker of unmeasured elements of hospital resuscitation performance.

Low end-tidal CO2 as a real-time severity marker of intra-anaesthetic acute hypersensitivity reactions

BackgroundPrompt diagnosis of intra-anaesthetic acute hypersensitivity reactions (AHR) is challenging because of the possible absence and/or difficulty in detecting the usual clinical signs and because of the higher prevalence of alternative diagnoses. Delayed epinephrine administration during AHR, because of incorrect/delayed diagnosis, can be associated with poor prognosis. Low end-tidal CO2 (etCO2) is known to be linked to low cardiac output. Yet, its clinical utility during suspected intra-anaesthetic AHR is not well documented. MethodsClinical data from the 86 patients of the Neutrophil Activation in Systemic Anaphylaxis (NASA) multicentre study were analysed. Consenting patients with clinical signs consistent with intra-anaesthetic AHR to a neuromuscular blocking agent were included. Severe AHR was defined as a Grade 3–4 of the Ring and Messmer classification. Causes of AHR were explored following recommended guidelines. ResultsAmong the 86 patients, 50% had severe AHR and 69% had a confirmed/suspected IgE-mediated event. Occurrence and minimum values of arterial hypotension, hypocapnia and hypoxaemia increased significantly with the severity of AHR. Low etCO2 was the only factor able to distinguish mild [median 3.5 (3.2;3.9) kPa] from severe AHR [median 2.4 (1.6;3.0) kPa], without overlap in inter-quartile range values, with an area under the receiver operator characteristic curve of 0.92 [95% confidence interval: 0.79–1.00]. Among the 41% of patients who received epinephrine, only half received it as first-line therapy despite international guidelines. ConclusionsAn etCO2 value below 2.6 kPa (20 mm Hg) could be useful for prompt diagnosis of severe intra-anaesthetic AHR, and could facilitate early treatment with titrated doses of epinephrine. Clinical trial registrationNCT01637220.

Fatal Anaphylaxis: Mortality Rate and Risk Factors

Up to 5% of the US population has suffered anaphylaxis. Fatal outcome is rare, such that even for people with known venom or food allergy, fatal anaphylaxis constitutes less than 1% of total mortality risk. The incidence of fatal anaphylaxis has not increased in line with hospital admissions for anaphylaxis. Fatal drug anaphylaxis may be increasing, but rates of fatal anaphylaxis to venom and food are stable. Risk factors for fatal anaphylaxis vary according to cause. For fatal drug anaphylaxis, previous cardiovascular morbidity and older age are risk factors, with beta-lactam antibiotics, general anesthetic agents, and radiocontrast injections the commonest triggers. Fatal food anaphylaxis most commonly occurs during the second and third decades. Delayed epinephrine administration is a risk factor; common triggers are nuts, seafood, and in children, milk. For fatal venom anaphylaxis, risk factors include middle age, male sex, white race, cardiovascular disease, and possibly mastocytosis; insect triggers vary by region. Upright posture is a feature of fatal anaphylaxis to both food and venom. The rarity of fatal anaphylaxis and the significant quality of life impact of allergic conditions suggest that quality of life impairment should be a key consideration when making treatment decisions in patients at risk for anaphylaxis.

Hospital Variation in Time to Epinephrine for Nonshockable In-Hospital Cardiac Arrest.

For patients with in-hospital cardiac arrests attributable to nonshockable rhythms, delays in epinephrine administration beyond 5 minutes is associated with worse survival. However, the extent of hospital variation in delayed epinephrine administration and its effect on hospital-level outcomes is unknown. Within Get With The Guidelines-Resuscitation, we identified 103 932 adult patients (≥18 years) at 548 hospitals with an in-hospital cardiac arrest attributable to a nonshockable rhythm who received at least 1 dose of epinephrine between 2000 and 2014. We constructed 2-level hierarchical regression models to quantify hospital variation in rates of delayed epinephrine administration (>5 minutes) and its association with hospital rates of survival to discharge and survival with functional recovery. Overall, 13 213 (12.7%) patients had delays to epinephrine, and this rate varied markedly across hospitals (range, 0%-53.8%). The odds of delay in epinephrine administration were 58% higher at 1 randomly selected hospital in comparison with a similar patient at another randomly selected hospital (median odds ratio, 1.58; 95% confidence interval, 1.51-1.64). The median risk-standardized survival rate was 12.0% (range, 5.4%-31.9%), and the risk-standardized survival with functional recovery was 7.4% (range, 0.9%-30.8%). There was an inverse correlation between a hospital's rate of delayed epinephrine administration and its risk-standardized rate of survival to discharge (ρ=-0.22, P<0.0001) and survival with functional recovery (ρ=-0.14, P=0.001). In comparison with a median survival rate of 12.9% (interquartile range, 11.1%-15.4%) at hospitals in the lowest quartile of epinephrine delay, risk-standardized survival was 16% lower at hospitals in the quartile with the highest rate of epinephrine delays (10.8%; interquartile range, 9.7%-12.7%). Delays in epinephrine administration following in-hospital cardiac arrest are common and variy across hospitals. Hospitals with high rates of delayed epinephrine administration had lower rates of overall survival for in-hospital cardiac arrest attributable to nonshockable rhythm. Further studies are needed to determine whether improving hospital performance on time to epinephrine administration, especially at hospitals with poor performance on this metric, will lead to improved outcomes.

Abstract 165: Hospital Variation in Time to Administration of Epinephrine After Cardiac Arrest With Initial Non-shockable Rhythm

Background: For patients with in-hospital cardiac arrests due to non-shockable rhythms, delays in epinephrine administration beyond 5 minutes is associated with worse survival. However, the extent of hospital variation in delayed epinephrine administration and its impact on hospital-level outcomes is unknown. Methods: Within Get with the Guidelines-Resuscitation, we identified 103,932 adult patients (&gt;18 years) at 548 hospitals with an in-hospital cardiac arrest due to a non-shockable rhythm who received at least 1 dose of epinephrine between 2000 to 2014. We constructed two-level hierarchical regression models to quantify hospital variation in rates of delayed epinephrine administration (&gt;5 minutes) and its association with hospital rates of survival to discharge. Results: Among the 548 hospitals, there was substantial variation in rates of delayed epinephrine administration (median 13.5%, range: 0%- 53.8%). The odds of delay in epinephrine administration were 61% higher at one randomly selected hospital compared to a similar patient at another randomly selected hospitals (median odds ratio [OR] 1.61; 95% C.I. 1.54 - 1.67). After adjusting for patient characteristics, the median risk-standardized survival rate for non-shockable in-hospital cardiac arrests was 12.1% and varied significantly across hospitals (range: 5.2% to 30.9%). There was an inverse correlation between a hospital’s rate of delayed epinephrine administration and its risk-standardized survival rate for cardiac arrests due to non-shockable rhythm (ρ= -0.23, P&lt;0.0001). Compared to hospitals in the best quartile, risk-standardized survival was 17.4% lower at hospitals in the worst quartile of delayed epinephrine administration (13.8% vs. 11.4%, P&lt;0.0001, Figure). Conclusions: Although delays in epinephrine administration following in-hospital cardiac arrest are common, there is substantial hospital variation in rates of delayed epinephrine administration. Hospitals with high rates of delayed epinephrine administration were found to have lower rates of risk-adjusted survival. Further studies are needed to determine if improving hospital performance on time to epinephrine administration, especially at hospitals with poor performance on this metric will lead to improvement in outcomes.

Epinephrine in Anaphylaxis: Higher Risk of Cardiovascular Complications and Overdose After Administration of Intravenous Bolus Epinephrine Compared with Intramuscular Epinephrine

Epinephrine is the drug of choice for the management of anaphylaxis, and fatal anaphylaxis is associated with delayed epinephrine administration. Data on adverse cardiovascular (CV) complications and epinephrine overdose are limited. To compare rates of CV adverse events and epinephrine overdoses associated with anaphylaxis management between various routes of epinephrine administration among patients with anaphylaxis in the emergency department. This was an observational cohort study from April 2008 to July 2012. Patients in the emergency department who met diagnostic criteria for anaphylaxis were included. We collected demographics; route of epinephrine administration; trigger; overdose; and adverse CV events, including arrhythmia, cardiac ischemia, stroke, angina, and hypertension. The study cohort included 573 patients, of whom, 301 (57.6%) received at least 1 dose of epinephrine. A total of 362 doses of epinephrine were administered to 301 patients: 67.7% intramuscular (IM) autoinjector, 19.6% IM injection, 8.3% subcutaneous injection, 3.3% intravenous (IV) bolus, and 1.1% IV continuous infusion. There were 8 CV adverse events and 4 overdoses with 8 different patients. All the overdoses occurred when epinephrine was administered IV bolus. Adverse CV events were associated with 3 of 30 doses of IV bolus epinephrine compared with 4 of 316 doses of IM epinephrine (10% vs 1.3%; odds ratio 8.7 [95% CI, 1.8-40.7], P = .006). Similarly, overdose occurred with 4 of 30 doses of IV bolus epinephrine compared with 0 of 316 doses of IM epinephrine (13.3% vs 0%; odds ratio 61.3 [95% CI, 7.5 to infinity], P < .001). The risk of overdose and adverse CV events is significantly higher with IV bolus epinephrine administration. Analysis of the data supports the safety of IM epinephrine and a need for extreme caution and further education about IV bolus epinephrine in anaphylaxis.

Anaphylaxis-related deaths in Ontario: a retrospective review of cases from 1986 to 2011.

BackgroundExamining deaths caused by anaphylaxis may help identify factors that may decrease the risk of these unfortunate events. However, information on fatal anaphylaxis is limited. The objectives of our study were to examine all cases of fatal anaphylaxis in Ontario to determine cause of death, associated features, co factors and trends in mortality. The identification of these factors is important for developing effective strategies to overcome gaps in monitoring and treatment of patients with food allergies and risk for anaphylaxis.MethodsThis was a retrospective case-series analysis of all causes of anaphylaxis-related deaths using data from the Ontario Coroner’s database between 1986 and 2011. Quantitative data (e.g. demographic) were analyzed using descriptive statistics and frequency analysis using SPSS. Qualitative data were analyzed using content analysis of grounded theory methodology.ResultsWe found 92 deaths in the last 26 years related to anaphylaxis. Causes of death, in order of decreasing frequency, included food (40 cases), insect venom (30 cases), iatrogenic (16 cases), and idiopathic (6 cases). Overall, there appears to be a decline in the frequency of food related deaths, but an increase in iatrogenic causes of fatalities. We found factors associated with fatal anaphylaxis included: delayed epinephrine administration, asthma, allergy to peanut, food ingestion outside the home, and teenagers with food allergies.ConclusionsOur findings indicate the need to improve epinephrine auto-injector use in acute reactions, particularly for teens and asthmatics with food allergies. In addition, education can be improved among food service workers and food industry in order to help food allergic patients avoid potentially fatal allergens. The increasing trend in iatrogenic related anaphylaxis is concerning, and requires monitoring and more investigation.

Epinephrine use and outcomes in anaphylaxis patients transported by emergency medical services

BackgroundAnaphylaxis is a potentially life-threatening allergic reaction that may require emergency medical system (EMS) transport. Fatal anaphylaxis is associated with delayed epinephrine administration. Patient outcome data to assess appropriateness of EMS epinephrine administration are sparse. ObjectivesThe objectives of this study are to (1) determine the frequency of epinephrine administration in EMS-transported patients with allergic complaints, (2) identify predictors of epinephrine administration, and (3) determine frequency of emergency department (ED) epinephrine administration after EMS transport. MethodsA cohort study was conducted from over 5 years. A total of 59187 EMS transports of an Advanced Life Support (ALS) ambulance service were studied. ResultsOne hundred and three patient transports for allergic complaints were analyzed. Fifteen patients received EMS epinephrine, and epinephrine was recommended for 2 additional patients who refused, for a total of 17 (17%) patients for whom epinephrine was administered or recommended. Emergency medical system epinephrine administration or recommendation was associated with venom as a trigger (29% vs 8%; odds ratio [OR], 4.70; 95% confidence interval [CI], 1.28-17.22; P = .013), respiratory symptoms (88% vs 52%; OR, 6.83; 95% CI, 1.47-31.71; P = .006), and fulfillment of anaphylaxis diagnostic criteria (82% vs 49%; OR, 3.50; 95% CI, 0.94-13.2; P = .0498). Four (4%) patients received epinephrine after ED arrival. ConclusionLow rates of epinephrine administration were observed. The association of EMS administration of epinephrine with respiratory symptoms, fulfillment of anaphylaxis diagnostic criteria, and low rate of additional epinephrine administration in the ED suggest that ALS EMS administered epinephrine based on symptom severity. Additional studies of EMS anaphylaxis management including ED management and outcomes are needed.

Intravenous versus intramuscular epinephrine administration during cardiopulmonary resuscitation – a pilot study in piglets

Early epinephrine administration in cardiac arrest seems to be advantageous to achieve return of spontaneous circulation (ROSC). Because intravenous (i.v.) or intraosseous access is not always immediately available, this study compares efficacy of early intramuscular (i.m.) epinephrine administration with early and delayed i.v. epinephrine injection in an animal cardiac arrest model. Piglets anesthetized with sevoflurane were intoxicated by an i.v. ropivacaine infusion until circulatory arrest. After 1 min basic life support (chest compression and ventilation), epinephrine i.v. (10 μg·kg(-1), group IV) or epinephrine i.m. (100 μg·kg(-1), group IM) or normal saline (group NS) was applied. Further doses of epinephrine were given in group IV every 4 min and in group IM after 10 min if required. Twenty-one minutes after circulatory arrest, i.v. epinephrine - as necessary - was given to all animals. Thus, group NS represents late epinephrine administration. Outcomes were survival and time to ROSC. Twenty-four pigs aged 19.5 (median, interquartile range 16-22) days, weighing 5.4 (5.0-5.7) kg were investigated. Total amount of ropivacaine administered was 8.9 (8.1-10.1) mg·kg(-1). Cardiac rhythm before starting CPR was pulseless electric activity and asystole in 15 and 9 pigs, respectively. Eight, seven, and four pigs survived in group IV, IM, and NS. Focusing on surviving animals, time to ROSC was 2, 4 and 19.5 min in group IV, IM, and NS. Early i.m. epinephrine provided similar survival compared with early i.v. epinephrine and was superior to delayed epinephrine administration in resuscitation of ropivacaine-induced cardiac arrest in piglets.

Food Allergy Knowledge among School Nurses in an Urban Public School District

Prior studies suggest two-thirds of fatalities from food allergy occur in school, often related to delayed epinephrine administration. School nurses must therefore have adequate food allergy knowledge to prevent and manage reactions. We evaluated knowledge among nurses in an urban school district.

Management of anaphylaxis in primary care: Canadian expert consensus recommendations

Anaphylaxis is often managed inadequately. We used findings from a systematic review of gaps in anaphylaxis management to develop evidence-based recommendations for gaps rated as clinically important by a panel of Canadian allergy experts. The nominal group technique (NGT) consensus methodology was used to develop evidence-based recommendations for the management of anaphylaxis in primary care. Physician-specific gaps from our systematic review were prioritized by consensus meeting participants in two rounds, which involved the rating, discussion, and re-rating of gaps. Using current anaphylaxis guidelines, recommendations were then developed for each category of gaps that were identified by the panel as clinically important. Thirty unique physician gaps from the systematic review were categorized according to gaps of knowledge and anaphylaxis practice behaviors. The panel rated diagnosis of anaphylaxis, and when and how to use epinephrine auto-injectors as clinically important knowledge gaps; and rated infrequent or delayed epinephrine administration, low rate of auto-injector prescription, and infrequent or no referrals to allergy specialists after a reaction as important practice behavior gaps. Evidence from four guidelines was used to support the consensus recommendation statements for three resulting categories of gap themes: anaphylaxis management, epinephrine use, and follow-up care. We used an NGT consensus methodology to develop an educational resource for primary care physicians and allergists to better understand how to manage patients with anaphylaxis. Next steps include testing our findings against observed data in primary care settings and to develop other strategies or tools to overcome gaps in anaphylaxis management.