Food-Induced Anaphylaxis among Children Weighing <15 kg: A Single-Center Case Series of the Pediatric Emergency Department

<b><i>Introduction:</i></b> Food-induced anaphylaxis among infants shows an increasing prevalence; however, the prescription of epinephrine auto-injectors (EAIs) for children weighing &#x3c;15 kg is associated with issues of the needle length and the epinephrine dose. Several studies have shown age-related differences in food-induced anaphylaxis, although little is known about the weight-related differences in food-induced anaphylaxis. This study aimed to reveal the incidence, clinical characteristics, and management of food-induced anaphylaxis in children weighing &#x3c;15 kg. <b><i>Methods:</i></b> This chart review included children who visited the pediatric emergency department (ED) of the National Center for Child Health and Development (Tokyo, Japan) from January 2014 to December 2016 and were diagnosed with food-induced anaphylaxis. The severity of anaphylaxis was evaluated using the Sampson Grading Scale. <b><i>Results:</i></b> Of 89,232 ED visits, 444 visits included patients with food-induced anaphylaxis, after excluding cases of food-induced anaphylaxis related to oral desensitization therapy. The incidence was 4.98 per 1,000 visits. More than half of the children (<i>n</i> = 247/444, 55.6%) weighed &#x3c;15 kg. The proportion of grade 3 and higher severity anaphylactic symptoms was 74.5% (184/247) in children weighing &#x3c;15 kg and 79.2% (156/197) in children weighing 15 kg or more. The recurrence rate of food-induced anaphylaxis was 22.3% (55/247) in children weighing &#x3c;15 kg and 48.7% (96/197) in children weighing 15 kg or more. Among the children weighing &#x3c;15 kg, the proportion of those with recurrent food-induced anaphylaxis was 4 times higher in children weighing 10–15 kg than in those weighing &#x3c;10 kg (32.2% [47/146] vs. 7.9% [8/101]). The proportion of patients who were prescribed EAIs before each visit was 25.5% (14/55) in children weighing &#x3c;15 kg with a history of food-induced anaphylaxis. <b><i>Conclusion:</i></b> Food-induced anaphylaxis among children weighing &#x3c;15 kg occurred as frequently and was as severe as that among children weighing 15 kg or more. However, the proportion of patients prescribed EAIs was very low in children weighing &#x3c;15 kg with food-induced anaphylaxis. The potential need for EAIs is suggested among children weighing &#x3c;15 kg, especially among children weighing 10 kg or more but &#x3c;15 kg.

CSACI position statement: transition recommendations on existing epinephrine autoinjectors

Epinephrine is the first line treatment for anaphylaxis, an acute potentially life-threatening allergic reaction. It is typically administered intramuscularly in the anterolateral thigh at a dose of 0.01 mg/kg of 1:1000 (1 mg/ml) solution to a maximum initial dose of 0.5 mg. Currently in Canada, epinephrine autoinjectors (EAI) are available in three doses, 0.15 mg, 0.30 mg, and 0.50 mg. There are currently no published studies comparing 0.3 mg and 0.5 mg EAIs in the paediatric or adult populations to compare clinical effectiveness. However, as weight increases above 30 kg, the percentage of the recommended 0.01 mg/kg epinephrine dose from an existing 0.3 mg EAI decreases resulting in potential underdosing. As such, The Canadian Society of Allergy and Immunology (CSACI) recommends that for those who weigh ≥ 45 kg, physicians could consider prescribing the 0.50 mg EAI based on shared decision making with patients.

Abstract 13761: Does Targeted Temperature Management Modify the Association Between Increasing Epinephrine Dose and Survival Outcomes Following Out-of-Hospital Cardiac Arrest?

Introduction: Epinephrine (EPI) improves return of circulation after out of hospital cardiac arrest (OHCA). These beneficial cardiac effects are not accompanied by improved neurological survival possibly due to EPI induced microvascular effects and critical brain ischemia. We hypothesized that these dose-dependent adverse EPI effects may be mitigated by targeted temperature management (TTM) such that the relative benefit of TTM is greater at higher EPI doses. Methods: This was a retrospective cohort study of adult non-traumatic OHCA patients in Seattle and King County, Washington from 2008-2018, who were unconscious at hospital admission. We used logistic regression to assess the relationship among EPI dose, TTM, and survival to hospital discharge, and survival with favorable neurological status (Cerebral Performance Category (CPC) 1 or 2). The model evaluated whether TTM modified the association of increasing EPI dose using an interaction term between TTM and EPI dose. Results were stratified by initial shockable vs non-shockable rhythm. Results: Of 5254 eligible patients, the median EPI dose was 2.0 mg (IQR 1.0 - 3.0); 3052 (58%) received TTM. In all, 2177 (41%) survived to discharge, and 1889 (36%) survived with CPC 1-2. Increasing dose of EPI was associated with a decreasing likelihood of survival (OR 0.58, [95% CI 0.55-0.61] for each additional mg of EPI) and CPC 1-2 (OR 0.56, [0.53-0.59]). The dose-dependent EPI association was modified by TTM. After adjustment for Utstein covariates, for each additional mg of EPI, TTM was associated with a relative stepwise improvement in odds of survival (interaction OR 1.35, [1.23, 1.49]) and CPC 1-2 (OR 1.34, [1.21, 1.50]) (Figure). This interaction was consistent among shockable and non-shockable OHCA (Figure). Conclusions: We observed an interaction between TTM and EPI dose such that the beneficial association of TTM increased with increasing EPI dose, suggesting TTM may attenuate the adverse effects of higher dose EPI.

Impact of Total Epinephrine Dose on Long Term Neurological Outcome for Cardiac Arrest Patients: A Cohort Study

Introduction: Although epinephrine is universally acknowledged to increase return of spontaneous circulation (ROSC) after cardiac arrest, its balanced effects on later outcomes remain uncertain, causing potential harm during post-resuscitation phase. Recent studies have questioned the efficacy and potential deleterious effects of epinephrine on long-term survival and neurological outcomes, despite that the adverse relationship between epinephrine dose and outcome can be partially biased by longer CPR duration and underlying comorbidities. This study explored the long-term effect of epinephrine when used in a cohort of patients that underwent cardiac arrest during cardiopulmonary resuscitation.Methods: The data were originally collected from a retrospective institutional database from January 2007 to December 2015 and are now available on Dryad (via: https://doi.org/10.5061/dryad.qv6fp83). Use of epinephrine was coded by dose (&lt;2 mg, 2 mg, 3–4 mg, ≥5 mg). A favorable neurological outcome was defined using a Cerebral Performance Category (CPC) 1 or 2. The association between epinephrine dosing and 3-months neurological outcome was analyzed by univariate analysis and multivariate logistic regression.Results: Univariate and multivariate analysis demonstrated a negative association between total epinephrine dose and neurological outcome. Of the 373 eligible patients, 92 received less than 2 mg of epinephrine, 60 received 2 mg, 97 received 3–4 mg and 124 received more than 5 mg. Compared to patients who received less than 2 mg of epinephrine, the adjusted odds ratio (OR) of a favorable neurological outcome was 0.8 (95% confidence interval [CI]: 0.38–1.68) for 2 mg of epinephrine, 0.43 (95% confidence interval [CI]: 0.21–0.89) for 3–4 mg of epinephrine and 0.40 (95% confidence interval [CI]: 0.17–0.96) for more than 5 mg of epinephrine.Conclusion: In this cohort of patients who achieved ROSC, total epinephrine dosing during resuscitation was associated with a worse neurological outcome three months after cardiac arrest, after adjusting other confounding factors. Further researches are needed to investigate the long-term effect of epinephrine on cardiac arrest patients.

Randomised trial of epinephrine dose and flush volume in term newborn lambs

ObjectivesNeonatal resuscitation guidelines recommend 0.5–1 mL saline flush following 0.01–0.03 mg/kg of epinephrine via low umbilical venous catheter for persistent bradycardia despite effective positive pressure ventilation (PPV) and chest compressions (CC). We evaluated the effects of 1 mL vs 3 mL/kg flush volumes and 0.01 vs 0.03 mg/kg doses on return of spontaneous circulation (ROSC) and epinephrine pharmacokinetics in lambs with cardiac arrest.DesignForty term lambs in cardiac arrest were randomised to receive 0.01 or 0.03 mg/kg epinephrine followed by 1 mL or 3 mL/kg flush after effective PPV and CC. Epinephrine (with 1 mL flush) was repeated every 3 min until ROSC or until 20 min. Haemodynamics, blood gases and plasma epinephrine concentrations were monitored.ResultsTen lambs had ROSC before epinephrine administration and 2 died during instrumentation. Among 28 lambs that received epinephrine, 2/6 in 0.01 mg/kg-1 mL flush, 3/6 in 0.01 mg/kg-3 mL/kg flush, 5/7 in 0.03 mg/kg-1 mL flush and 9/9 in 0.03 mg/kg-3 mL/kg flush achieved ROSC (p=0.02). ROSC was five times faster with 0.03 mg/kg epinephrine compared with 0.01 mg/kg (adjusted HR (95% CI) 5.08 (1.7 to 15.25)) and three times faster with 3 mL/kg flush compared with 1 mL flush (3.5 (1.27 to 9.71)). Plasma epinephrine concentrations were higher with 0.01 mg/kg-3 mL/kg flush (adjusted geometric mean ratio 6.0 (1.4 to 25.7)), 0.03 mg/kg-1 mL flush (11.3 (2.1 to 60.3)) and 0.03 mg/kg-3 mL/kg flush (11.0 (2.2 to 55.3)) compared with 0.01 mg/kg-1 mL flush.Conclusions0.03 mg/kg epinephrine dose with 3 mL/kg flush volume is associated with the highest ROSC rate, increases peak plasma epinephrine concentrations and hastens time to ROSC. Clinical trials evaluating optimal epinephrine dose and flush volume are warranted.

Immediate Intravenous Epinephrine Versus Early Intravenous Epinephrine for In-Hospital Cardiopulmonary Arrest

Background intravenous epinephrine has been a key treatment for cardiopulmonary arrest since the early 1960s. Although, many studies have questioned neurological outcome benefit, it remains to be recommended in international guidelines for its benefit on return of spontaneous circulation (ROSC). The ideal timing for the first epinephrine dose is uncertain. We aimed to look at the association of immediate epinephrine administration (within 1-minute of cardiac arrest recognition) with return of spontaneous circulation (ROSC) up to 24-hours and beyond 24-hours. Methods this was a multicenter retrospective chart review of patients undergoing cardiopulmonary resuscitation. Descriptive statistics were used to characterize study population, while t-test and chi-square were used to compare groups and outcomes. Results immediate epinephrine administration (within 1-minute) is associated with higher rates of ROSC up to 24-hours (OR = 2.36, 95% CI; [1.46–3.81]) and beyond 24-hours (OR = 2.26, 95% CI; [1.06–4.83]). Conclusions we encourage immediate administration of epinephrine in conjunction with high-quality CPR, as this is associated with higher rates of ROSC.

Immediate Intravenous Epinephrine (Within 1-minute) Versus Early Intravenous Epinephrine (After 1-minute) for In-Hospital Cardiopulmonary Arrest: A Multicenter Retrospective Review

Background: intravenous epinephrine has been a key treatment for cardiopulmonary arrest since the early 1960s. Although, many studies have questioned neurological outcome benefit, it remains to be recommended in international guidelines for its benefit on return of spontaneous circulation (ROSC). The ideal timing for the first epinephrine dose is uncertain. We aimed to look at the association of immediate epinephrine administration (within 1-minute of cardiac arrest recognition) with return of spontaneous circulation (ROSC) up to 24-hours and beyond 24-hours.Methods: this was a multicenter retrospective chart review of patients undergoing cardiopulmonary resuscitation.Results: immediate epinephrine administration (within 1-minute) is associated with higher rates of ROSC up to 24-hours (OR=2.36, 95% CI; [1.46-3.81]) and beyond 24-hours (OR=2.26, 95% CI; [1.06-4.83]).Conclusions: we encourage immediate administration of epinephrine in conjunction with high-quality CPR, as this is associated with higher rates of ROSC.

Effect of prehospital intraosseous combined with in-hospital intravenous access in out-of-hospital cardiac arrest

Objective: Obtaining vascular access during out-of-hospital cardiac arrest (OHCA) is challenging. The aim of this study was to compare the effectiveness of prehospital intraosseous infusion (IO) combined with in-hospital intravenous (IV) (pre-IO + in-IV) access versus the simple IV (pre-IV + in-IV) access in adult OHCA patients who do not achieve prehospital return of spontaneous circulation (ROSC). Methods: This retrospective observational study included adults with OHCA of presumed cardiac etiology between October 1, 2017-October 1, 2020 at an academic emergency department in China. All of the OHCA patients included within the study had Emergency Medical Services cardiopulmonary resuscitation and received prehospital epinephrine administration, but did not achieve prehospital ROSC. The study population were classified as either pre-IO + in-IV or IV (pre-IV + in-IV) based on their epinephrine administration route. The prehospital epinephrine routes were the first and only attempted route. The primary outcome investigated was sustained ROSC following arrival at the emergency department. The secondary outcome considered was the time from dispatch to the first epinephrine dose. Results: Of 193 included adult OHCA subjects who did not have prehospital ROSC, 128 received IV access only. The 65 pre-IO + in-IV-treated patients received epinephrine faster compared to IV-treated patients in terms of the median time from dispatch to the first injection of epinephrine (14.5 vs. 16.0 min, P = 0.001). In the pre-IO + in-IV group, 34 of 65 patients (52.3%) achieved sustained ROSC compared with 65 of 128 (50.8%) patients in the IV group (χ2 = 0.031, P = 0.841). There was no significant difference in sustained ROSC (adjusted OR1.049, 95% CI: 0.425-2.591, P = 0.918) between the two groups. Conclusion: A similar sustained ROSC rate was achieved for both the pre-IO + in-IV access group and the simple IV access group. Our results suggested that an IV route should be established quickly for prehospital IO-treated OHCA patients who do not achieve prehospital ROSC.

Neonatal resuscitation guideline adherence: simulation study and framework for improvement

We wanted to assess newborn life support (NLS) knowledge and guideline adherence, and provide strategies to improve (neonatal) resuscitation guideline adherence. Pediatricians completed 17 multiple-choice questions (MCQ). They performed a simulated NLS scenario, using a high-fidelity manikin. The literature was systematically searched for publications regarding guideline adherence. Forty-six pediatricians participated: 45 completed the MCQ, 34 performed the scenario. Seventy-one percent (median, IQR 56–82) of the MCQ were answered correctly. Fifty-six percent performed inflation breaths ≤ 60 s, 24% delivered inflation breaths of 2–3 s, and 85% used adequate inspiratory pressures. Airway patency was ensured 83% (IQR 76–92) of the time. Median events/min, compression rate, and percentage of effective compressions were 138/min (IQR 130–145), 120/min (IQR 114–120), and 38% (IQR 24–48), respectively. Other adherence percentages were temperature management 50%, auscultation of initial heart rate 100%, pulse oximeter use 94%, oxygen increase 74%, and correct epinephrine dose 82%. Ten publications were identified and used for our framework. The framework may inspire clinicians, educators, researchers, and guideline developers in their attempt to improve resuscitation guideline adherence. It contains many feasible strategies to enhance professionals’ knowledge, skills, self-efficacy, and team performance, as well as recommendations regarding equipment, environment, and guideline development/dissemination. Conclusion: NLS guideline adherence among pediatricians needs improvement. Our framework is meant to promote resuscitation guideline adherence. What is Known:• Inadequate newborn life support (NLS) may contribute to (long-term) pulmonary and cerebral damage.• Video-based assessment of neonatal resuscitations has shown that deviations from the NLS guideline occur frequently; this assessment method has its audiovisual shortcomings. What is New:• The resuscitation quality metrics provided by our high-fidelity manikin suggest that the adherence of Dutch general pediatricians to the NLS guideline is suboptimal.• We constructed a comprehensive framework, containing multiple strategies to improve (neonatal) resuscitation guideline adherence.