Anaphylaxis

Anaphylaxis is an acute, life-threatening, IgE-mediated allergic reaction that occurs in previously sensitized patients upon re-exposure to a familiar antigen. Symptoms include stridor, wheezing, dyspnea, and hypotension. Diagnosis is clinical. Bronchospasm and upper airway edema are life-threatening and require inhalation or injection of beta-agonists and sometimes endotracheal intubation. Hypotension is treated with intravenous fluids and vasopressors.

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What causes anaphylaxis?

Anaphylaxis is commonly caused by drugs (eg, beta-lactam antibiotics, insulin, streptokinase, allergen extracts), foods (nuts, eggs, seafood), proteins (tetanus antitoxin, blood products from blood transfusions), animal venom, and latex. Peanut and latex allergens can be spread through the air. A history of atopy does not increase the risk of anaphylaxis, but it does increase the risk of death if anaphylaxis occurs.

Interaction of antigens with IgE on the surface of basophils or mast cells causes the release of histamine, leukotrienes and other mediators that cause smooth muscle contraction (bronchoconstriction, vomiting, diarrhea) and vasodilation with the release of plasma from the bloodstream.

Anaphylactoid reactions are clinically indistinguishable from anaphylaxis, but they are not mediated by IgE and do not require prior sensitization. They are caused by direct stimulation of mast cells or immune complexes that activate the complement system. Common triggers include iodinated radiographic and radiocontrast agents, aspirin, other NSAIDs, opioids, blood transfusions, Ig, and exercise.

Symptoms of anaphylaxis

The main symptoms of anaphylaxis involve the skin, upper and lower respiratory tract, cardiovascular system, and gastrointestinal tract. One or more organ systems may be involved, symptoms do not necessarily progress, and each patient usually experiences repeated anaphylaxis upon re-exposure to the antigen.

• Typical symptoms of anaphylaxis include stridor, rales, desaturation, respiratory distress, ECG changes, cardiovascular collapse, and clinical features of shock.
• Less typical symptoms of anaphylaxis include swelling, rash, and urticaria.

It should be suspected if there is a history of similar episodes of severe allergic-type reactions with respiratory problems and/or hypotension, especially if there were cutaneous manifestations.

Symptoms vary from mild to severe and include fever, itching, sneezing, rhinorrhea, nausea, intestinal spasms, diarrhea, a feeling of suffocation or dyspnea, palpitations, and dizziness. The main objective signs are decreased blood pressure, tachycardia, urticaria, angioedema, dyspnea, cyanosis, and fainting. Shock can develop within minutes, the patient is lethargic, unresponsive to stimuli, and death is possible. Respiratory and other symptoms may be absent in collapse.

The diagnosis of anaphylaxis is made clinically. The risk of rapid progression to shock leaves no time for investigations, although mild equivocal cases may allow time for 24-hour urinary N-methylhistamine or serum tryptase levels.

What diseases is anaphylaxis differentiated from?

• Primary disease of the cardiovascular system (eg, congenital heart defect in a newborn).
• Sepsis (with rash).
• Latex allergy.
• Tension pneumothorax.
• Acute severe asthma (history of asthma, with hospitalizations).
• Airway obstruction (eg, foreign body aspiration).

Treatment of anaphylaxis

Adrenaline is the mainstay of treatment and should be given promptly. It is given subcutaneously or intramuscularly (usual dose 0.3-0.5 ml 1:1000 for adults and 0.01 ml/kg for children; repeat after 10-30 minutes); maximum absorption is achieved with intramuscular administration. Patients with collapse or severe airway obstruction may be given adrenaline intravenously at a dose of 3-5 ml 1:10,000 over 5 minutes or by drip [1 mg in 250 ml 5% distilled water to achieve a concentration of 4 mcg/ml, starting with 1 mcg/min to 4 mcg/min (15-60 ml/h)]. Epinephrine can be given by sublingual injection (0.5 ml in a 1:1000 solution) or endotracheally (3 to 5 ml in a 1:10,000 solution diluted in 10 ml of saline). A second subcutaneous injection of epinephrine may be necessary.

A 1 mg tablet of glucagon may be used following a 1 mg/hour infusion in patients receiving oral beta-blockers, which blunt the effect of epinephrine.

Patients with stridor and dyspnea who do not respond to epinephrine should be given oxygen and intubated. Early intubation is recommended because waiting for a response to epinephrine may result in airway edema so severe that endotracheal intubation is impossible and cricothyrotomy is required.

To increase blood pressure, 1-2 liters (20-40 ml/kg for children) of isotonic fluid (0.9% saline) is administered intravenously. Hypotension refractory to fluid administration and intravenous injection of adrenaline is treated with vasoconstrictors [e.g., dopamine 5 mcg/(kg x min)].

Antihistamines - both H2 _blockers (eg, diphenhydramine 50-100 mg IV) and H2 _blockers (eg, cimetidine 300 mg IV) - should be given every 6 hours until symptoms resolve. Inhaled beta-agonists are useful for relieving bronchoconstriction; inhaled albuterol 5-10 mg is used long-term. The role of glucocorticoids is unproven but may help prevent late reactions at 4-8 hours; initial dose of methylprednisolone is 125 mg IV.

What should be done first if there is anaphylaxis?

Oxygen therapy.

Adrenaline intravenously slowly 1 mcg/kg given in divided doses under ECG monitoring until hypotension resolves (solution 1:10,000):

• 12 years: 50 mcg (0.5 ml);
• 6-12 years: 25 mcg (0.25 ml);
• >6 months - 6 years: 12 mcg (0.12 ml);
• <6 months: 5 mcg (0.05 ml).

If there is no venous access, adrenaline is administered intramuscularly (1:1000 solution):

• 12 years: 500 mcg (0.5 ml);
• 6-12 years: 250 mcg (0.25 ml);
• >6 months - 6 years: 120 mcg (0.12 ml);
• <6 months: 50 mcg (0.05 ml).

Antihistamines - chlorphenamine (chlorpheniramine):

• 12 years: intravenously or intramuscularly 10-20 mg;
• 6-12 years: intravenously or intramuscularly 5-10 mg;
• 1-6 years: intravenously or intramuscularly 2.5-5 mg.

In all cases of severe or recurrent reaction, and in patients with asthma, administer hydrocortisone intravenously 4 mg/kg:

• 12 years: intramuscularly or slowly intravenously 100-500 mg;
• 6-12 years: intramuscularly or slowly intravenously 100 mg
• 1-6 years: intramuscularly or slowly intravenously 50 mg.

If the clinical picture of shock has not improved under the influence of drug therapy, administer intravenous fluid 20 ml/kg of body weight. If necessary, repeat.

Further management

• If accompanied by severe bronchospasm and no response to adrenaline - bronchodilators, eg salbutamol by dose/inhaler, according to the protocol for acute severe asthma.
• Infusion of catecholamines, as in cardiovascular instability, can last several hours - adrenaline or noradrenaline 0.05-0.1 mcg/kg/min.
• Blood gas monitoring to decide on the use of bicarbonate - up to 1 mmol/kg 8.4% sodium bicarbonate (1 mmol = 1 ml) if the pH is below 7.1.

How is anaphylaxis prevented?

Anaphylaxis is prevented by avoiding exposure to known triggers. Desensitization is used when exposure to allergens cannot be avoided (eg, insect bites). Patients with a late reaction to radiocontrast agents should avoid repeated exposure; if their use is absolutely necessary, prednisolone 50 mg orally every 6 hours for 3 times 18 hours before the procedure and diphenhydramine 50 mg orally 1 hour before the procedure are given; however, there is no evidence to support the effectiveness of this approach.

Patients with anaphylactic reactions to insect venom, food products and other known substances are advised to wear an “alarm” bracelet and carry a syringe with adrenaline (0.3 mg for adults and 0.15 mg for children) for self-help after contact with the allergen.