Anaphylaxis, Anaphylactoid reaction


It is a serious allergic reaction, rapid in onset, caused by release of the mediators from certain type of white blood cells triggered by either immunologic or non-immunologic mechanisms. In most severe cases, there is bronchospasm, upper airway angioedema and hypotensive shock. It is an IgE mediated type 1 hypersensitivity reaction that results in mast cell activation and release of multiple mediators like histamine, leukotriene, TNF and various other cytokines. Common causes include insect bites/ stings, foods and medication.

Epidemiology and problem statement-

The number of people who get anaphylaxis is 4–5 per 100,000 persons per year, with a lifetime risk of 0.05–2%. Rates appear to be increasing: with the numbers in the 1980s being approximately 20 per 100,000 per year, while in the 1990s it was 50 per 100,000 per year. There is an increase in the rate of anaphylaxis in last 2-3 decades particularly food-induced anaphylaxis. The risk is greatest in young people and females. Currently, anaphylaxis leads to 500–1,000 deaths per year (2.4 per million) in the United States, 20 deaths per year in the United Kingdom (0.33 per million), and 15 deaths per year in Australia (0.64 per million).


The common causes of anaphylaxis include:
• Insect bites or stings (common in older patients): venom from stinging or biting insects such as Hymenoptera or Triatominae
• Foods (common in young patients): peanuts, wheat, nuts, shellfish, milk, eggs, seasame, chickpeas
• Medication: β lactam antibiotics (penicillin), cephalosporins, aspirin, NSAIDs, chemotharpy, vaccines, protamine and herbal preperation
• Physical factors like exercise or temperature (hot or cold)
• Biological agents like semen, latex, hormonal changes
• Fodd additives like monosodium glutamate
• During anesthesia, neuromuscular blocking agents, antibiotics and latex
• Vaccines (MMR, varicella, influenza, hepatitis B, tetanus, meningococcal, HPV)
• Idiopathic (32-50%)

Risk factors:

Patients with atopic diseases like asthma, eczema, or allergic rhinitis are at high risk of anaphylaxis from food, latex and radiocontrast. Those with mastocytosis or belonging to higher socioeconomic status are at high risk.

Causes of life-threatening allergic reaction during anesthesia:

  1. Neuromuscular blocking agents (70%)
    • Steroid based compounds (vecuronium and pancuronium) cause anaphylactic reaction
    • Benzylisoquinoliniums (mivacurium and atracurium) tends to cause anaphylactoid reaction
    • Drug reactions caused by neuromuscular blocking agents, 43% are caused by succinylcholine, 37% vecuronium and 7% atracurium.
  2. Latex (12.6%)
    • It is increasingly been recognized as the cause particularly in abdominal and gynaecological surgery.
    • There is recognized cross reactivity between latex sensitivity and certain foods like banana, chestnuts and avocado.
  3. Colloids (4.7%)
    • Fluids used for resuscitation after anaphylaxis may themselves cause histamine release and worsen the reaction
    • The risk is greatest with gelatin solution
    • All hyperosmolar solutions can release histamine directly. These solutions, example mannitol, should be infused slowly.
  4. Induction agents (3.6%)
    • The incidence of severe reactions to thiopental is reported in 1 in 14,000
    • Reaction to propofol are less common and are least common to etomidate
  5. Antibiotics (2.6%)
    • Penicillins are most frequently implicated in hypersensitivity reaction
    • The incidence of cross reactivity with cephalosporins is about 8%.
  6. Benzodiazepines (2%)
    • BZDs occasionally cause allergic reactions.
  7. Opioids (1.7%)
    • Opioids usually cause anaphylactic reactions
    • Morphine is implicated most commonly
    • Morphine, codeine and meperidine can cause dose dependent, non immunological cutaneous histamine release
  8. Other agents
    • Radio contrast media can produce hypersensitivity reactions in up to 3% of the patients
    • Other agents that can cause severe reaction during the perioperative period include protamine, aprotonin, atropine and bone cement
    Source: Sally Ann Rider, Carl Waldmann. Anaphylaxis. Contin Educ Anaesth Crit Care Pain 2004; 4(4): 111-113.
  9. Pathophysiology
    Anaphylaxis is a severe allergic reaction of rapid onset affecting many body systems. It is due to release of inflammatory mediators and cytokines from mast cells and basophills, particularly due to immunologic reaction but sometimes due to non-immunologic reaction
    • Immunologic reaction
    In this reaction, immunoglobin (IgE) binds to the antigen (the foreign material). Antigen bound IgE then activates FcRI receptors on the mast cells and basophills. This leads to release of histamine, leukotriene, TNF and various other cytokines. The chemical mediators that are released from the mast cells and basophils affect blood vessels, pulmonary bronchioles and other organs, leading to an increased vascular permeability, peripheral vasodilation, coronary vasoconstriction and smooth muscle contraction, especially in the bronchioles.

• Non immunologic reaction
It involves substances that directly cause the degranulation of the mast cells and basophills. These include agents like contrast medium, opioids, temperature (hot and cold) and vibration.

Signs and symptoms-

Anaphylaxis typically presents with different symptoms over minutes or hours, with an average onset of 5-30 min is exposure is intravenous and 2 hours for food. The most common affected areas are:
• Skin (80-90%)
o Generalized hives, itchiness, flushing or swelling (angioedema) of the afflicted tissues.
o Burning sensation of the skin
o Swelling of tongue or throat in about 20% of the cases
o Runny nose
o Swelling of the conjunctiva
o Skin may become blue tinged due to lack of oxygen

• Respiratory (70%)
o Shortness of breath, wheezes and stridor
o Spasms of bronchial muscles
o Hoarseness, pain with swallowing
o Cough

• Gastrointestinal (30-45%)
o Crampy abdominal pain
o Diarrhea and vomiting
o Loss of bladder control and pelvic pain

• Heart and vasculature (10-45%)
o Coronary artery spasm causing myocardial infarction
o Dyrrhythmias and cardiac arrest
o Fast heart rate caused by low blood pressure is common, a Bezold Jarisch reflex is seen in 10% cases where slow heart rate is seen with low blood pressure
o A drop in blood pressure or shock may cause feeling of lightheadedness or loss of consciousness

• Central nervous system (10-15%)
o Dilatation of blood vessels around brain causing headache
o A feeling of anxiety or impending doom


ECG changes
Cardiac arrest
Vascular headache
Feeling of doom
N & V


• Abdominal pain
• Abnormal (high pitched) breathing sound
• Anxiety
• Chest discomfort or tightness
• Cough
• Diarrhea
• Difficulty breathing
• Difficulty swallowing
• Dizziness or light headedness
• Hives, itches
• Nasal congestion
• Nausea or vomiting
• Palpitation
• Skin redness
• Slurred speech
• Swelling of face, eyes and tongues
• Unconsciousness
• Wheezing
• Abnormal heart rhythm (arrhythmia)
• Pulmonary edema
• Hives
• Hypotension
• Mental confusion
• Rapid pulse
• Skin is blue from lack of oxygen or pale from shock
• Swelling (angioedema) in the throat
• Swelling of eyes and face
• Weakness
• Wheezing


• Airway blockage
• Cardiac arrest
• Respiratory arrest
• Shock


There are 3 types of anaphylaxis:

  1. Anaphylactic shock
    • It is associated with systemic vasodilation that causes low blood pressure
  2. Biphasic anaphylaxis
    • Recurrence of symptoms within 1-72 hours with no further exposure to the allergen
    • Recurrence typically occur within 8 hours
  3. Pseudoanaphylaxis or anaphylactoid reaction
    • It is the anaphylaxis which does not involve an allergic reaction but is due to mast cell degranulation
    • It is non IgE mediated
    • Anaphylactoid reaction does not require prior sensitization and may produce anaphylaxis like reaction in a dose dependent manner.

Diagnostic criteria-

Anaphylaxis is diagnosed any of the following three signs and symptoms within minutes or hours of exposure to an allergen:

  1. Involvement of the skin or mucosal tissue plus either respiratory difficulty or low blood pressure
  2. Two or more of the following symptoms after the contact with the allergen:
    a. Involvement of skin or mucosa
    b. Respiratory difficulties
    c. Low blood pressure
    d. Gastrointestinal symptoms
  3. Low blood pressure after exposure to a known allergen
    During an attack, blood tests for tryptase or histamine is used for diagnosing anaphylaxis due to insect stings or medication
    Allergy testing
    • Skin allergy testing (patch testing) for certain foods and venoms
    • Blood testing for specific IgE is useful to confirm milk, egg, peanut, tree nut and fish allergies
    • Skin testing for penicillin allergies
    Anaphylaxis is a medical emergency. Following treatment is recommended:
    • Epinephrine (adrenaline) is the primary treatment, should be given intramuscularly in the anterolateral thigh as soon as diagnosis is made. The injection may be repeated every 5-15 minutes if there is insufficient response.
    • Epinephrine can also be given intravenously but is associated with dysrrhythmias and myocardial infarction
    • Airway management
    • Supplemental oxygen
    • Large volumes of intravenous fluids
    • Adjuncts
    o Antihistamines (both H1 and H2)
    o Corticosteroids used to decrease the risk of biphasic anaphylaxis
    o Nebulized salbutamol is effective for bronchospasm that does not resolve with epinephrine
    o Methylene blue is used in those not responsive to other measures due to its effect of relaxing smooth muscle.
    • Close monitoring
    DO NOT
    • It should not be assumed that any prior allergy shots received by the patient provides complete protection
    • Pillow should not be placed under the patient head if he is having trouble breathing. This can block the airway.
    • Nothing should be given to the patiet by mouth, if he is having trouble breathing

Anaphylaxis Drill

Immediate management
• Stop the administration of all agents likely to have caused anaphylaxis
• Call for help
• Maintain the airway, give 100% oxygen and lie the patient flat with the legs elevated
• Give epinephrine im in a dose of 0.5-1 mg (0.5-1 ml of 1:1000) and may be repeated every 10 min according to the arterial pressure and pulse until improvement occurs
• Alternatively, 50-100 mcg iv (0.5-1 ml of 1:10000) over 1 min in patients with cardiovascular collapse, with titration of further dose. This should be given at a rate of 0.1 mg/min stopping when a response has been obtained
• Give iv fluids with colloid or crystalloid (avoiding colloids that have higher incidence of allergy). Adult patient may require 2-4 litre

Subsequent management-

• Give antihistamines (chlorpheniramine 10-20 mg by slow iv infusion). Use of H2 receptor antagonists remain unproven
• Ranitidine 50 mg is usually administered by slow iv infusion
• Give corticosteroids (100-500 mg hydrocortisone slowly iv)
• Bronchodilators may be required for persistent bronchospasm
• Catecholamine infusion as CVS instability may last several hours
• Epinephrine 0.05-0.1 mg/kg/min (4 ml/hr of 1:10000 for 70 kg adult)
• Check ABGs for acidosis and consider bicarbonate 0.5-1.0 mmol/kg (8.4% solution= 1 mmol/ml)

Source: Sally Ann Rider, Carl Waldmann. Anaphylaxis. Contin Educ Anaesth Crit Care Pain 2004; 4(4): 111-113.

Differential diagnosis-

The differential diagnosis includes:
• Asthma
• Syncope
• Panic attacks
• Scrombroidosis
• Anisakiasis


• Avoid triggers such as foods and medications that have caused an allergic reaction in the past.
• If the child is allergic to certain foods, one new food is introduced at a time in small amounts.
• People who have had serious allergic reactions should wear a medical ID tag.
• If there is a history of serious allergic reactions, the patient should carry emergency medications (such as a chewable form of diphenhydramine and injectable epinephrine or a bee sting kit).
• Injectable epinephrine should not be used on anyone else. They may have a condition (such as a heart problem) that could be negatively affected by this drug.