Anaphylaxis is defined as a severe, life threatening, generalised or systemic hypersensitivity reaction. It is characterised by rapid onset of life threatening compromise of:
often alongside skin and mucosal changes
It is estimated that around 1 in 300 people will experience anaphylaxis in their lifetime. The reported incidence of anaphylaxis is around 1-3 events per 10,000 population per year. Some details about the epidemiology are hard to unpick, and this is a major focus of the most recent RCOA audit, NAP-6. Anaphylaxis may be fatal in 3-6% of cases, with another 2% having a poor neurological outcomes.
Anaphylaxis is a type 1 hypersensitivity reaction. Exposure to a foreign protein (antigen) results in production of IgE, which binds to mast cells (and basophils) throughout the body. Repeat exposure to this antigen, via binding to this IgE, results in massive release of the vasoactive components of the mast cells. These include histamine, prostaglandins, tryptase, substance A, leukotrienes. Despite the pathophysiology involving previous sensitisation, direct previous exposure to the specific drug is not necessary, for example with muscle relaxants. Daily life provides a source of these antigens in sources such as food and cosmetics which can provide the sensitisation.
Anaphylactoid reactions are clinically indistinguishable from anaphylactic ones. The pathophysiology is slightly different, as the vasoactive substance release is not mediated via IgE, but via another mechanism. Contrast media is the most common cause of this. Less severe reactions are much more commonly seen with drugs causing direct histamine release e.g. morphine, atracurium, mivacurium.
The most common causes in perioperative anaphylaxis are:
Muscle relaxants (70%)
The aminosteroid agents are a more common cause of anaphylaxis, whilst the benzylisoquinoliniums often have an anaphylactoid basis.
Suxamethonium is the most common cause
Induction agents (4%)
Thiopentone is the agent with apparently to greatest association
Penicillins are the most commonly indicated
Other, less common causes include bone cement, atropine, protamine, and contrast media.
There are a number of other triggers that may occur in the non-theatre environment.
Drugs (including those above)
The route of administration may impact on the speed of onset of symptoms:
IV - onset in 5 mins
Stings - 10-15mins
Oral - 30-35 mins
Anaphylaxis is likely if the following 3 criteria are met:
Sudden onset with rapid progression
Life threatening airway and/or breathing and/or circulatory compromise
Skin and/or mucosal changes
In more detail, these may be:
Bronchospasm, with wheeze
Shortness of breath
Skin or mucosal changes can be absent or very difficult to spot in around 20% of cases. Conversely, they can very commonly be present without anaphylaxis e.g. histamine release from direct drug interaction.
The NAP-6 defined 5 different grades of severity of anaphylaxis:
Unexpected severe hypotension +/- severe bronchospasm +/- airway swelling +/- grade 1 features
Guidance on management has been provided by the Resuscitation Council (UK) and by the AAGBI. As with urgent acute medical conditions, an ABC approach is appropriate.
Stop any possible precipitating agent
Inform the team of the suspected anaphylaxis
Call for help
Ensure airway is secure. Intubation may be needed if not already the case
Increase FiO2 to 100%
Focused respiratory assessment
Elevate legs if hypotensive
Treat with adrenaline IV
50 mcg - adult dose (0.5ml of 1:10,000 solution)
1 mcg/kg - paediatric dose
0.5mg in the IM dose
Doses may need to be repeated
An infusion may be needed if significant ongoing compromise
Give a crystalloid fluid bolus (500-1000ml)
Ensure adequate anaesthesia if surgery is in progress
Assess conscious level if not anaesthetised
Look for evidence of rash or mucosal changes
Consider whether there is less obvious ongoing allergen exposure e.g. CVC, latex, colloid
Adult - 10mg
6-12 years - 5mg
6m-6 years - 2.5mg
<6m - 250mcg/kg
Adults - 200mg
6-12 years - 100mg
6m-6 years - 50mg
<6m - 25mg
Treat ongoing bronchospasm if present:
Take investigations - see below
Finish surgery as soon as possible
Inform critical care and prepare for transfer
In the event of cardiac arrest, then normal ALS algorithms should be followed. This will likely involve the non-shockable algorithm and involve early administration of adrenaline.
Investigation of the cause of the episode is important to optimise the patient’s future care. This includes:
Identifying the responsible agent
Mast Cell Tryptase Mast cell tryptase is the initial investigation of choice to confirm diagnosis. Tryptase is a protease almost exclusively found in mast cells which has a more useful plasma profile than some of the other agents e.g. histamine. Its plasma half life is around 3 hours, with a peak level at 1 hour. Multiple measurements of serum tryptase levels are taken to try and provide a profile that confirms anaphylaxis:
At 1 hour
At 24 hours (assumed to represent baseline levels)
In anaphylaxis, the levels will peak at the 1 hour measurement, before returning back to baseline levels at the 24 hour test. Normal levels are 0.8-1.5 ng/ml, with peaks of over 20 ng/ml in anaphylaxis, and slightly lower (but still notably raised) in anaphylactoid reactions. Samples are taken in a clotted serum tube and require refrigeration.
Allergen Identification Identification of the specific causative agent can be undertaken at a later time. This will involve referral to the regional allergy centre. Here there will be specialist review of the notes (e.g. timeframe of events compared to drug administration) and allergen testing. The options for allergen testing include:
Skin prick testing
Skin prick testing is perhaps the most common, but is relatively insensitive for some drug classes e.g. opioids, benzodiazepines. Intradermal testing is more sensitive but less specific than skin prick testing. Challenge testing has the clear disadvantage of the risk of precipitating a further anaphylaxis episode.
As part of their follow up, patients will be given a self administration adrenaline device e.g. Epipen. This contains 300 mcg of adrenaline (for adults).
There are a number of life threatening and non life threatening conditions that may imitate anaphylaxis, especially in the early stages.
The 6th national audit project (NAP-6) from the Royal College of Anaesthetists was into perioperative anaphylaxis. This aimed to provide more detailed information on this condition. The results from this should be available soon.