Pharmacology
Respiratory
A 14 year old patient, with a history of asthma and atopy, is given penicillin in hospital. He immediately develops an itchy rash, angioedema and worsening stridor and wheeze. What is the most appropriate dose of adrenaline for this patient:
Answer:
| Age group | IM adrenaline (1:1000) |
|---|---|
| Adult | 500 mcg (0.5 mL) |
| Child > 12 years | 500 mcg (0.5 mL) |
| Child 6 - 12 years | 300 mcg (0.3 mL) |
| Child 6 months - 6 years | 150 mcg (0.15 mL) |
| Child < 6 months | 100-150 mcg (0.1 - 0.15 mL) |
Management of Anaphylaxis
Pharmacology / Respiratory
Last Updated: 8th November 2021
Pathophysiology
Anaphylaxis is a severe, potentially life-threatening, generalised type I hypersensitivity reaction. It occurs when an antigen binds to specific IgE immunoglobulins on mast cells triggering degranulation and release of inflammatory mediators (e.g. histamine, prostaglandins, and leukotrienes). Patients with pre-existing asthma, especially poorly controlled asthma, are at particular risk of life-threatening reactions.
Anaphylaxis can be triggered by any of a very broad range of triggers, but those most commonly identified include food, drugs, latex and venom. Of foods, nuts are the most common cause; muscle relaxants, antibiotics, NSAIDs and aspirin are the most commonly implicated drugs. Food is the commonest trigger in children and drugs the commonest in adults. A significant number of cases are idiopathic.
Clinical Features
Severe anaphylaxis is characterised by sudden onset and rapidly developing, life-threatening airway, breathing and circulation problems associated with skin and/or mucosal changes.
- Airway
- Pharyngeal or laryngeal oedema with hoarseness and stridor
- Breathing
- Bronchospasm with tachypnoea, dyspnoea, wheeze, hypoxia, cyanosis, respiratory arrest
- Circulation
- Peripheral vasodilation with hypotension, tachycardia, signs of peripheral shut-down (e.g. pale, clammy), shock, cardiac arrest
- Disability
- Decreased brain perfusion leads to confusion, agitation and loss of consciousness
- Exposure
- In about 80% of cases there are associated skin and mucosal changes such as flushing, pruritus, urticaria and angioedema; skin and/or mucosal changes can be absent or subtle in up to 20% of reactions
- Gastrointestinal symptoms
- Nausea, vomiting, abdominal pain, diarrhoea, incontinence
Most reactions occur over several minutes; rarely, reactions may be slower in onset. The speed of onset of the reaction depends on the trigger e.g. intravenous medications will cause a more rapid onset than stings which in turn will cause a more rapid onset than ingestion of food.
Reactions can vary greatly, from hypotension alone, to reactions with predominantly asthmatic features, to cardiac/respiratory arrest. Skin or mucosal changes alone are not a sign of an anaphylactic reaction.
Immediate Drug Treatment
- Oxygen
- Initially give 100% high flow oxygen using a mask with an oxygen reservoir
- Once pulse oximetry is feasible target an SpO2 of 94 - 98%
- Adrenaline
- This is the most important drug for treatment of anaphylaxis and works best when given as early as possible after the onset of the reaction:
- The intramuscular route is best for most individuals; the best site for IM injection is the anterolateral aspect of the middle third of the thigh.
- As an alpha-receptor agonist, it reverses peripheral vasodilation and reduces oedema. As a beta-receptor agonist it dilates bronchial airways, increases the force of myocardial contraction, and suppresses histamine and leukotriene release.
- For adults, the initial dose is 0.5 mg = 500 micrograms = 0.5 mL of 1:1000 adrenaline. After the initial dose of adrenaline, further doses can be given at about 5 min intervals according to the patient's response.
- If features of anaphylaxis persist despite 2 doses of IM adrenaline, the refractory anaphylaxis algorithm should be followed, and an adrenaline infusion started with expert support.
- Nebulised adrenaline may be effective as an adjunct to treat upper airway obstruction caused by laryngeal oedema, but only after treatment with IM (or IV) adrenaline and not as an alternative. Recommended doses are 5 mL of 1 mg ML (1:1000) adrenaline.
- Adrenaline remains the first line vasopressor for treatment of anaphylaxis. Consider other vasopressors and inotropes (e.g. noradrenaline, vasopressin, metaraminol and glucagon) when initial resuscitation with adrenaline and fluids has not been successful. Only use these drugs in specialist settings where there is experience in their use.
- Intravenous fluid
- A rapid IV fluid challenge (crystalloid 10 mL/kg in a child or 500 - 1000 mL in an adult) should be administered and the response monitored; further doses can be given if necessary.
- There is no evidence to support the use of colloid over crystalloid fluid in resuscitation, therefore crystalloid fluid (Hartmann's solution or 0.9% saline) should be given as colloids have a higher risk of hypersensitivity reactions.
- Updates in ALS 12th edition (2021):
- Antihistamines
- Antihistamines are not recommended for the treatment of anaphylaxis. They are of no benefit in treating life-threatening symptoms of anaphylaxis and their use may delay more appropriate treatment. Antihistamines may be helpful in alleviating cutaneous symptoms but should only be given after the patient has been stabilised. In this context, use a non-sedating oral antihistamine, such as cetirizine.
- Corticosteroids
- The routine administration of corticosteroids is not advised. Consider giving steroids after initial resuscitation for refractory reactions or ongoing asthma/resistant shock. Steroids should not be given preferentially to adrenaline. The evidence that corticosteroids help shorten protracted symptoms or prevent biphasic reactions is very weak. Oral corticosteroids may be indicated where an acute asthma exacerbation may have contributed to the severity of the anaphylaxis. Steroids should be given via the oral route where possible.
- Antihistamines
| Age group | IM adrenaline (1:1000) |
|---|---|
| Adult | 500 mcg (0.5 mL) |
| Child > 12 years | 500 mcg (0.5 mL) |
| Child 6 - 12 years | 300 mcg (0.3 mL) |
| Child 6 months - 6 years | 150 mcg (0.15 mL) |
| Child < 6 months | 100-150 mcg (0.1 - 0.15 mL) |
Investigations
Emergency treatment should not be delayed and should be based on a clinical diagnosis of anaphylaxis. In addition to the usual investigations appropriate for a medical emergency, the specific test to help confirm the diagnosis of anaphylaxis is measurement of mast cell tryptase. Tryptase is a major component of mast cell granules, therefore in anaphylaxis mast cell degranulation leads to markedly increased blood tryptase concentration.
Tryptase concentration in the blood may not increase significantly until 30 minutes or more after the onset of symptoms and peaks 1 - 2 hours after onset. Ideally three timed samples are taken, the initial sample as soon as feasible after resuscitation has started, the second sample 1 - 2 hours (but no later than 4 h) after the start of the symptoms and the third sample either at 24 h or in convalescence (for baseline levels).
Discharge and Follow-Up
All patients should be reviewed by a senior clinician and a decision made about the need for further treatment and duration of observation. There is no reliable way of predicting who will have a biphasic reaction so decisions about discharge must be made for each patient by an experienced clinician. Prior to discharge, a healthcare with the appropriate skills should offer people the following:
- Information about anaphylaxis, including the signs and symptoms, and the risk of a biphasic reaction (with clear instructions about returning to hospital if symptoms return)
- Information about what to do if anaphylaxis occurs
- Consideration of an adrenaline auto-injector or a replacement
- Advice about how to avoid the suspected trigger
- Information about the need for referrals to specialist allergy service
- Information about patient support groups
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
