Severe allergic reaction refers to a sudden, severe, potentially life-threatening systemic allergic reaction in the body after contact with an allergen. It is characterized by fatal respiratory and/or circulatory disorders, with some patients having no typical skin symptoms or circulatory shock.
I. Clinical Diagnostic Criteria for Severe Allergic Reaction
Severe allergic reaction is strongly suspected when any one of the following three criteria is met:
- Acute onset (within minutes to hours) with symptoms affecting the skin and/or skin mucosal tissue, such as generalized rash, itching or flushing, swelling of the lips, tongue, or uvula, and at least one of the following conditions:a. Respiratory symptoms, such as hoarseness, coughing, chest tightness, dyspnea, bronchospasm, wheezing, cyanosis, decreased peak expiratory flow (PEF), hypoxemia.b. Blood pressure drop or symptoms related to end-organ dysfunction, such as hypotonia, syncope, incontinence.
- Rapid onset of 2 or more of the following symptoms within minutes to hours after the patient’s exposure to a suspected allergen:a. Skin and mucosal tissue symptoms, such as generalized rash, itching or flushing, swelling of the lips, tongue, uvula;b. Respiratory symptoms, such as hoarseness, coughing, chest tightness, dyspnea, bronchospasm, wheezing, cyanosis, decreased PEF, hypoxemia;c. Blood pressure drop or symptoms related to end-organ dysfunction (e.g., hypotonia, syncope, incontinence);d. Persistent gastrointestinal symptoms, such as abdominal pain, vomiting.
- Blood pressure drop within minutes to hours after the patient’s exposure to a known allergen.
II. Grading of Severe Allergic Reaction
- Grade I: Only skin and mucosal system symptoms and gastrointestinal system symptoms, stable hemodynamics, stable respiratory system function.
- Skin and mucosal system symptoms: rash, itching or flushing, redness and/or numbness of lips and tongue, etc.
- Gastrointestinal system symptoms: abdominal pain, nausea, vomiting.
- Grade II: Significant respiratory symptoms or blood pressure drop appear.
- Respiratory system symptoms: chest tightness, shortness of breath, dyspnea, wheezing, bronchospasm, cyanosis, decreased peak expiratory flow, hypoxemia, etc.
- Blood pressure drop: adult systolic blood pressure 80~90mmHg or 30%~40% decrease from baseline; infants and children: <1 year, systolic blood pressure <70mmHg; 1~10 years: systolic blood pressure <(70mmHg + 2 × age); 11~17 years: systolic blood pressure <90mmHg or 30%~40% decrease from baseline.
- Grade III: Any of the following symptoms appear: Confusion, somnolence, loss of consciousness, severe bronchospasm and/or laryngeal edema, cyanosis, severe blood pressure drop (systolic blood pressure <80mmHg or >40% decrease from baseline), incontinence, etc.
- Grade IV: Cardiac arrest and/or respiratory arrest occurs.
III. Management of Severe Allergic Reaction
- Rapid and timely intramuscular injection of epinephrine into the mid-thigh is the first-line treatment for severe allergy.
- During the management of severe allergic reactions, close monitoring of heart, blood pressure, respiration, and blood oxygen saturation should be implemented.
- When airway edema or bronchospasm leads to severe respiratory distress, tracheal intubation or tracheostomy should be considered; in an emergency, cricothyrotomy can be performed.
International guidelines on severe allergic reactions consistently agree that epinephrine is the drug of choice for anaphylaxis and is also the only drug that reduces hospitalizations and deaths, used as first-line treatment for anaphylaxis. Epinephrine acts by stimulating α1 receptors, constricting peripheral blood vessels, reversing hypotension and mucosal edema; stimulating β1 receptors, enhancing myocardial contractility, reversing hypotension; stimulating β2 receptors, reversing bronchoconstriction and reducing inflammatory mediator release.
IV. Epinephrine Dosing Regimen
1. Timing of Epinephrine Use Use as early as possible when the patient is diagnosed with a severe allergic reaction of Grade II or above.
2. Administration Method and Dose Concentration of Epinephrine (1) Intramuscular Injection For patients with Grade II or III reactions, intramuscular epinephrine is the first choice; intramuscular injection can also be considered for patients with Grade I reactions whose gastrointestinal symptoms are difficult to relieve.
- Dosage: Epinephrine dosage is 0.01mg/kg;
- ≥14 years old, single maximum dose not exceeding 0.5mg; <14 years old, single maximum dose not exceeding 0.3mg, concentration 1mg/ml (1:1000). If symptoms do not improve, repeat administration once every 5-15 minutes.
- Site: Mid-lateral thigh.
(2) Intravenous Injection For patients with Grade IV reactions who have experienced or are about to experience cardiac and/or respiratory arrest, intravenous epinephrine should be administered; for patients with Grade III reactions who have established intravenous access and are monitored in the ICU/during surgery, intravenous epinephrine can be administered.
- Dosage: Single intravenous dose of epinephrine
- Grade III reaction: children >14 years old and adults, 0.1~0.2mg; children ≤14 years old, 2~10μg/kg;
- Grade IV: children >14 years old and adults, 0.5~1mg; children ≤14 years old, 0.01~0.02mg/kg; concentration 0.1mg/ml (1:10000), which means diluting the existing 1ml:1mg epinephrine injection 10 times; if symptoms do not improve, repeat administration once every 3-5 minutes.
(3) Intravenous Infusion For patients with Grade II or III reactions, after 2-3 times of intravenous/intramuscular epinephrine injection, or after intravenous access has been established and monitored in the ICU/during surgery, intravenous epinephrine infusion can be performed; for patients with Grade IV reactions, when symptoms improve but are not completely relieved, intravenous epinephrine infusion can be considered.
- Dosage: 3~20μg/(kg·h); concentration 0.1~0.004mg/ml (1:10000~1:250000), which means diluting the existing 1ml:1mg epinephrine injection 10~250 times.
(4) Subcutaneous Injection Subcutaneous injection of epinephrine is not recommended for emergency management of severe allergic reactions.
The European Academy of Allergy and Clinical Immunology Anaphylaxis Guidelines (EAACI guidelines) state that intramuscular epinephrine is well-tolerated, and studies indicate that intramuscular injection can achieve higher plasma epinephrine levels; subcutaneous or inhaled epinephrine is not recommended for anaphylaxis patients. The World Allergy Organization Anaphylaxis Guidance 2020 (2020 WAO guidelines) does not recommend the intravenous route for initial anaphylaxis treatment; if the intravenous route is necessary, intravenous infusion should be performed using an infusion pump. Although international guidelines recommend intramuscular epinephrine as first-line treatment for anaphylaxis in all situations, the latest advanced life support guidelines for anaphylaxis-related cardiac arrest indicate that if cardiac arrest is imminent or has occurred, intravenous push of epinephrine is required.
V. Contraindications and Precautions for Epinephrine Use In the emergency management of life-threatening severe allergic reactions, there are no absolute contraindications to the use of epinephrine; however, it should be used cautiously in patients with a history of cardiovascular disease and elderly patients, weighing the benefits against the risks.
- To prevent adverse reactions from epinephrine use, unnecessary intravenous administration should be avoided as much as possible;
- When using intravenous epinephrine, attention should be paid to concentration control and continuous monitoring of heart, blood pressure, respiration, and blood oxygen saturation;
- If local adverse reactions to epinephrine occur, phentolamine local infiltration injection can be used.
The WAO guidelines emphasize the necessity of long-term management after emergency treatment for severe allergic reactions, educating patients about the risks of severe allergic reactions and self-treatment upon recurrence, and prescribing epinephrine autoinjectors (EAI) for individuals at risk of recurrence. Currently, EAI is not widely used in China. Based on the recommendations of international guidelines, the promotion of EAI use in China can be considered to improve the timeliness of anaphylaxis treatment.
References:
[1] Vc A , Ija B , Me C , et al. World allergy organization anaphylaxis guidance 2020 – ScienceDirect[J]. World Allergy Organization Journal, 13( 10).