A consensus parameter for the evaluation and management of angioedema in the emergency department

Despite its relatively common occurrence and life-threatening potential, the management of angioedema in the emergency department (ED) is lacking in terms of a structured approach. It is paramount to distinguish the different etiologies of angioedema from one another and more specifically differentiate histaminergic-mediated angioedema from bradykinin-mediated angioedema, especially in lieu of the more novel treatments that have recently become available for bradykinin-mediated angioedema. With this background in mind, this consensus parameter for the evaluation and management of angioedema attempts to provide a working framework for emergency physicians (EPs) in approaching the patient with angioedema in terms of diagnosis and management in the ED. This consensus parameter was developed from a collaborative effort among a group of EPs and leading allergists with expertise in angioedema. After rigorous debate, review of the literature, and expert opinion, the following consensus guideline document was created. The document has been endorsed by the American College of Allergy, Asthma & Immunology (ACAAI) and the Society for Academic Emergency Medicine (SAEM)

Intravenous Cetirizine Versus Intravenous Diphenhydramine for the Treatment of Acute Urticaria: A Phase III Randomized Controlled Noninferiority Trial

STUDY OBJECTIVE: Acute urticaria is a frequent presentation in emergency departments (EDs), urgent care centers, and other clinical arenas. Treatment options are limited if diphenhydramine is the only intravenous antihistamine offered because of its short duration of action and well-known adverse effects. We evaluate cetirizine injection, the first second-generation injectable antihistamine, for acute urticaria in this multicenter, randomized, noninferiority, phase 3 clinical trial. METHODS: Adult patients presenting to EDs and urgent care centers with acute urticaria requiring an intravenous antihistamine were randomized to either intravenous cetirizine 10 mg or intravenous diphenhydramine 50 mg. The primary endpoint was the 2-hour pruritus score change from baseline, with time spent in treatment center and rate of return to treatment centers as key secondary endpoints. Frequency of sedation and anticholinergic adverse effects were also recorded. RESULTS: Among 262 enrolled patients, the 2-hour pruritus score change from baseline for intravenous cetirizine was statistically noninferior to that for intravenous diphenhydramine (-1.6 versus -1.5; 95% confidence interval -0.1 to 0.3), and in favor of cetirizine. Treatment differences also favored cetirizine for mean time spent in treatment center (1.7 versus 2.1 hours; P=.005), return to treatment center (5.5% versus 14.1%; P=.02), lower change from baseline sedation score at 2 hours (0.1 versus 0.5; P=.03), and adverse event rate (3.9% versus 13.3%). CONCLUSION: Intravenous cetirizine is an effective alternative to intravenous diphenhydramine for treating acute urticaria, with benefits of less sedation, fewer adverse events, shorter time spent in treatment center, and lower rates of revisit to treatment center

Clinical severity classes in COVID-19 pneumonia have distinct immunological profiles, facilitating risk stratification by machine learning

ObjectiveClinical triage in coronavirus disease 2019 (COVID-19) places a heavy burden on senior clinicians during a pandemic situation. However, risk stratification based on serum biomarker bioprofiling could be implemented by a larger, nonspecialist workforce.MethodMeasures of Complement Activation and inflammation in patientS with CoronAvirus DisEase 2019 (CASCADE) patients (n = 72), (clinicaltrials.gov: NCT04453527), classified as mild, moderate, or severe (by support needed to maintain SpO2 > 93%), and healthy controls (HC, n = 20), were bioprofiled using 76 immunological biomarkers and compared using ANOVA. Spearman correlation analysis on biomarker pairs was visualised via heatmaps. Linear Discriminant Analysis (LDA) models were generated to identify patients likely to deteriorate. An X-Gradient-boost (XGB) model trained on CASCADE data to triage patients as mild, moderate, and severe was retrospectively employed to classify COROnavirus Nomacopan Emergency Treatment for covid 19 infected patients with early signs of respiratory distress (CORONET) patients (n = 7) treated with nomacopan.ResultsThe LDA models distinctly discriminated between deteriorators, nondeteriorators, and HC, with IL-27, IP-10, MDC, ferritin, C5, and sC5b-9 among the key predictor variables during deterioration. C3a and C5 were elevated in all severity classes vs. HC (p < 0.05). sC5b-9 was elevated in the “moderate” and “severe” categories vs. HC (p < 0.001). Heatmap analysis shows a pairwise increase of negatively correlated pairs with IL-27. The XGB model indicated sC5b-9, IL-8, MCP1, and prothrombin F1 and F2 were key discriminators in nomacopan-treated patients (CORONET study).ConclusionDistinct immunological fingerprints from serum biomarkers exist within different severity classes of COVID-19, and harnessing them using machine learning enabled the development of clinically useful triage and prognostic tools. Complement-mediated lung injury plays a key role in COVID-19 pneumonia, and preliminary results hint at the usefulness of a C5 inhibitor in COVID-19 recovery

310 IV Cetirizine Versus IV Diphenhydramine in Treatment of Acute Urticaria

Study Objectives: Acute urticaria, the most common symptom of acute allergic reactions, is a frequent presentation in the emergency department (ED). Diphenhydramine injection, the only available antihistamine injection, is sedating, short in duration with anticholinergic side effects. Cetirizine injection 10 mg/mL, a recent innovation in antihistamine pharmacology, may minimize these problems. A multicenter phase III randomized trial was conducted, in which a newly developed IV cetirizine was compared to IV diphenhydramine in treatment of acute urticaria. Methods: Adult subjects who presented to 19 EDs and urgent care centers (UCCs) with acute urticaria requiring IV antihistamine injections were randomized to either IV cetirizine 10 mg or IV diphenhydramine 50 mg. Primary endpoint was the 2-h pruritus score change from baseline, using a previously validated scoring scale. Key secondary endpoints were time spent in treatment center and need to return to ED/clinic. Patient sedation was scored at 1 h, 2 h, and discharge. Other secondary endpoints (rescue drugs, symptom recurrence, etc) were also measured. Results: Adult subjects (n=262) were enrolled from March 2017 to April 2018. The 2-hour pruritus score change from baseline from IV cetirizine was demonstrated to be statistically non-inferior to IV diphenhydramine (change from baseline in diphenhydramine group, -1.50 (SD 0.984); change from baseline in cetirizine group, -1.61 (SD 0.944); p=NS). Time spent in treatment center was 2.1 h in the diphenhydramine group vs 1.7 h in the cetirizine group (p=0.0024). Return to ED/Clinic was 14.0% in the diphenhydramine group and 5.5% in the cetirizine group (p=0.0232). There was significantly less sedation in the cetirizine group at 1h (p=0.0034), 2 h (p=0.0292), and at discharge (p=0.0443) compared to diphenhydramine. There were significantly fewer adverse events (p=0.0083) and fewer rescue drug usages (p=0.0159) reported in subjects treated with cetirizine compared to diphenhydramine. Conclusion: This study demonstrates IV cetirizine as an effective alternative to IV diphenhydramine in the treatment of acute urticaria with less sedation, fewer adverse events, less symptom recurrence, less rescue drug use, shorter time to discharge and lower readmission to EDs and UCCs

Intravenous injection cetirizine vs intravenous injection diphenhydramine in treatment of acute urticaria

Background: Acute urticaria, the most common symptom of acute allergic reactions, is a frequent presentation in the Emergency Department (ED). Diphenhydramine injection, the only available antihistamine injection, is sedating, short in duration with anticholinergic side effects. Cetirizine injection 10 mg/ mL, a recent innovation in antihistamine pharmacology, minimizes these problems. A phase III clinical trial using a newly developed IV cetirizine was compared to IV diphenhydramine in treatment of acute urticaria. Methods: Adult subjects who presented to EDs and Urgent Care Centers with acute urticaria and in need of IV antihistamine injections were randomized to either IV cetirizine 10 mg or IV diphenhydramine 50 mg. Primary endpoint was the 2-h pruritus score change from baseline. Key secondary endpoints were time spent in treatment center and need to return to ED/clinic. Patient sedation was scored at 1 h, 2 h, and discharge. Other secondary endpoints (rescue drugs, symptom recurrence, etc.) were also measured. Results: Adult subjects (n=262) were enrolled from March 2017 to April 2018. The 2-hour pruritus score change from baseline from IV cetirizine was demonstrated to be statistically non-inferior to IV diphenhydramine, and in favor of cetirizine. Time spent in treatment center was 2.1 h in the diphenhydramine group vs 1.7 h in cetirizine (per protocol p=0.0024). Return to ED/Clinic was 14.0% in the diphenhydramine group and 5.5% in cetirizine (p=0.0232). There was significantly less sedation in the cetirizine group at 1h (p=0.0034), 2 h (p=0.0292), and at discharge (p=0.0443) compared to diphenhydramine. There were significantly fewer adverse events (AEs) (p=0.0083) and fewer rescue drug usages (p=0.0159) reported in subjects treated with cetirizine compared to diphenhydramine. Conclusion: This study demonstrates IV cetirizine as an effective alternative to IV diphenhydramine in the treatment of acute urticaria with benefits of less sedation, less AEs, less symptom recurrence, less rescue drug use, shorter time spent in treatment center and less return to treatment center