A 2020 Chinese guideline on the emergency management of anaphylactic reactions aimed to provide evidence-based recommendations for the emergency management of anaphylaxis. The recommended dose of intramuscular (IM) epinephrine is 0.01 mg/kg, with a maximum dose of 0.5 mg for patients aged 14 years and older, and a maximum of 0.3 mg for patients under 14 years. The concentration used should be 1 mg/mL (1:1000), consistent with commercial preparations. If there is no response, repeat dosing is suggested every 5 to 15 minutes, as strongly recommended by clinical guidelines. A systematic review did not find any randomized controlled trials (RCTs) evaluating different doses of epinephrine, but four clinical guidelines support the recommended dosage and concentration. Additionally, six guidelines advise on the 5 to 15-minute intervals for repeated doses. This dosing protocol has been longstanding, supported by safety data, with the Tmax for IM epinephrine reported as 8 ± 2 minutes, which aligns with the recommended re-dosing interval. It is crucial to closely observe the patient's response, establish venous access, and be ready to administer a second dose if necessary. [1]
The panel also stated that IM epinephrine should be administered in the mid-anterolateral thigh, according to a strong recommendation. This preference is based on evidence suggesting that administering epinephrine at this site results in a higher maximum plasma concentration (Cmax) compared to injections in the upper arm, as demonstrated in a randomized cross-over trial. Although the trial presented low-quality evidence and indicated uncertain evidence of a potential for mild transient adverse effects when injecting into the thigh, no other comparative studies were found to challenge these findings. Clinical guidelines consistently recommend the mid-anterolateral thigh as the optimal injection site, as it facilitates better drug delivery without serious safety concerns. This recommendation persists despite some healthcare providers being more familiar with using the upper arm for IM injections. [1]
The 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care emphasize prompt IM administration as lifesaving, with the anterolateral thigh preferred due to faster and higher peak plasma concentrations. Standard dosing endorsed across guidelines includes 0.3 to 0.5 mg IM for adults and 0.01 mg/kg for pediatric patients until the adult dose is reached, with repeat doses every 5 to 15 minutes as needed and no cumulative maximum dose. Pediatric dosing recommendations are supported by organizations including the American Academy of Pediatrics (AAP) and the American Academy of Allergy, Asthma & Immunology, which recognize fixed autoinjector doses of 0.15 mg for smaller children and support transition to 0.3 mg at lower weight thresholds to reduce underdosing. [2], [3], [4]
A 2017 clinical report from the AAP discussed the use of epinephrine for first-aid management of anaphylaxis. Upon recognition of an anaphylactic event, prompt administration of epinephrine by the IM route can be life-saving. In healthcare settings, traditionally an epinephrine dose of 0.01 mg/kg is injected IM to a maximum of 0.3 mg in a prepubertal child and up to 0.5 mg in a teenager. Epinephrine autoinjectors can also be administered at a dose of 0.15 mg in a young child and 0.3 mg in a child or teenager. In regards to the safety of epinephrine, IM injection of epinephrine was found to achieve peak concentrations faster than that given by subcutaneous (SC) injection (Table 1). Additionally, IM epinephrine generally poses a low risk of serious adverse effects. [5]
Consistent with guideline recommendations, available review articles likewise support prompt IM epinephrine at the earliest signs of anaphylaxis, administered into the mid anterolateral thigh with immediate transport to an emergency department. Recommended dosing is 0.01 mg/kg using the 1 mg/mL concentration, up to a maximum of 0.5 mg in adults and 0.3 mg in children, with some sources specifying 0.5 mg IM for adults and adolescents and 0.01 mg/kg in children weighing 30 kg or less to a maximum of 0.3 mg in prepubertal children and 0.5 mg in adolescents. Repeat dosing every 5 to 15 minutes is advised for persistent, refractory, or recurrent symptoms, although most patients require only one or two doses. There are no contraindications to epinephrine in the treatment of anaphylaxis, including in patients with cardiovascular disease, hypertension, or those receiving beta blockers, and delays in administration have been associated with more severe reactions and increased mortality. Autoinjectors provide fixed doses of 0.3 mg for adults and children or adolescents weighing more than 30 kg and 0.15 mg for children weighing 15 to 30 kg, with brief pressure against the skin after activation to ensure full delivery. [6], [7]