Adrenaline and anaphylaxis: could we inject it better?

#Anaphylaxis #Allergy #Adrenaline #AAI  


Anaphylaxis is a rapid-onset, potentially fatal systemic hypersensitivity reaction triggered by allergens such as foods (peanuts, tree nuts, shellfish, milk, egg), drugs, or insect venoms. Symptoms can appear within seconds and progress to airway obstruction or cardiovascular collapse.  

Although intramuscular (IM) adrenaline is the first-line treatment recommended by scientific societies, its use remains insufficient, often delayed, and marred by dosing or route-of-administration errors. Antihistamines and corticosteroids are only second- or third-line treatments and have no effect on the immediate life-threatening symptoms. Rapid recognition of anaphylaxis is also challenging, especially in children and infants. Barriers include under-prescription of adrenaline auto-injectors (AAIs), fear of adverse effects, lack of training for patients and healthcare providers, and limited AAI availability in some countries.  

In this context, the study was initiated to provide an overview of clinical guidelines, pharmacokinetic/pharmacodynamic data, and safety considerations related to AAI use in anaphylaxis, with the goal of optimizing adrenaline administration and reducing risks.    

AAI: the ultimate weapon against anaphylaxis?

Intramuscular adrenaline delivered via an auto-injector ensures faster and more effective delivery of the therapeutic dose than a manual syringe, achieving higher and more stable plasma concentrations. Recommended doses vary by age and weight, with devices ranging from 0.1 mg to 0.5 mg. Adverse effects following intramuscular injection are rare and generally mild, usually limited to tremors, palpitations, or feelings of anxiety.

Severe cardiovascular complications mainly occur with intravenous bolus use, often linked to overdose. Some specific risks persist, such as overdose, needle-related injuries—especially in agitated children—or accidental finger injections, which can be reduced through user education and training. Pharmacokinetic and pharmacodynamic profiles vary by device: EpiPen offers rapid absorption, Emerade has a longer onset but delivers a higher dose, and Anapen achieves marked absorption even with a shorter needle. Adrenaline is chemically unstable with a limited shelf life, though it retains more than 90% of its concentration for several months after expiry. However, out-of-date use is discouraged.    

Adrenaline: fast, safe… and essential!

Anaphylaxis is a life-threatening emergency requiring prompt adrenaline administration. However, the effectiveness of this intervention is still compromised by injection delays, underuse of auto-injectors, and limited access, compounded by a lack of training for patients and healthcare professionals. The aim of this study was to optimize the clinical use of AAIs, ensure their availability, and promote their safe and appropriate use. Data confirm that intramuscular adrenaline administered via AAI is both safe and effective when delivered at the correct dose, and that potential adverse effects should never deter its administration in critical situations.

The study’s conclusions remain limited by the quality and heterogeneity of available data. Future directions include enhancing training for patients, healthcare providers, and first responders; improving global AAI accessibility; and exploring new administration routes, such as nasal sprays, as well as innovative injection technologies.

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