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Take home messages

  • Anaphylaxis is terrifying but manageable, if you spot it early
  • Have a differential of what else could be going on, but don't delay treatment
  • Follow up is really important

I can almost guarantee that at some point during your FRCA exam journey, be it primary or final level, you are going to be tested on your knowledge of anaphylaxis.

You need to know it inside out.

Our hope is that this post and podcast contains everything you could possibly need to know and more to ace your exams, and more importantly save someone's life.

Anaphylaxis is bonkers.

After a second exposure to an allergen, the entire immune system throws its toys out the pram and assumes there's bad guys everywhere, with widespread angioedema, bronchospasm and cardiovascular collapse.

Fortunately, it's not particularly difficult to treat:

Adrenaline 500 micrograms IM

The key is spotting it in a timely fashion, and then supporting the cardiovascular and respiratory systems long enough for the adrenaline to do its job.

Some not-so-fun history

In 2640 BC pharaoh Menes probably died of anaphylaxis after being stung by a wasp, and this is considered the first documented case, albeit in heiroglyphs.

The term is from the Greek άνά-, ana- (against), and φύλαξις, phylaxis, (protection).

In 1902, two French physiologists on an expedition, Charles Richet and Paul Portier, decided it would be sensible to try and induce immunity to a variety of sea-creature toxins in the ship's dog.

To do this they injected a little bit, which the dog didn't mind all that much, followed by a little bit more three weeks later, which the dog very much did mind, because it promptly died.

Instead of achieving protection, (prophylaxis) they did the opposite (anaphylaxis) and sensitised the poor mutt to the poison.

What exactly happens?

Anaphylaxis is a Type I hypersensitivity reaction, meaning it is a true allergic reaction mediated via IgE by mast cells, resulting in release of histamine.

What is anaphylaxis?

Anaphylaxis is a life-threatening systemic allergic reaction

  • It is a type 1 immediate hypersensitivity reaction induced by IgE antibodies
  • The trigger cross-links IgE on mast cells, causing degranulation and release of histamine and other eicosanoids and cytokines

What is the triad of anaphylaxis?

  • Cardiovascular collapse
  • Bronchospasm
  • Angioedema, flushing or rash affecting skin and mucosa

Anaphylaxis in 60 seconds

Note that the newest Resus council guidelines reduce the emphasis on hydrocortisone and chlorphenamine to ensure that adrenaline is given as the main priority, however they are unlikely to do harm and are probably worth giving to prevent recurrence of the reaction.

What else could it be?

Anaphylaxis is one of those 'until proven otherwise' diagnoses, because it's far safer to assume it is anaphylaxis and be wrong, than the other way round. But it is good to consider what else could be causing the clinical picture in front of you.

Other causes of tachycardia

Tachycardia can be direct or indirect.

Direct causes include:

  • Pain or inadequate depth of anaesthesia
  • Drug induced by atropine or glycopyrrolate, or high partial pressures of desflurane

Indirect causes include:

  • Compensation for hypotension
  • Hypovolaemic shock
  • Haemorrhage
  • Septic shock
  • Cardiogenic shock
  • Obstructive shock
  • Pulmonary embolism
  • Fat, air, amniotic fluid, bone cement

Other causes of high airway pressures

High airway pressures may be caused by any obstruction to fresh gas flow either in the breathing system, or in the patient's own respiratory system, such as:

  • Bronchospasm
  • Asthma
  • Endobronchial intubation
  • Tension pneumothorax
  • Pneumoperitoneum causing diaphragmatic splinting
  • A full review of high airway pressure management can be found on our Critical Incidents page

How to manage anaphylaxis

What is the immediate management of anaphylaxis?

  • Stop the administration of all agents likely to have caused the anaphylaxis
  • Call for help
  • Maintain the airway and give 100% oxygen
  • Lie the patient flat with the legs elevated 
  • Give adrenaline*
  • IV crystalloid boluses fluid, understanding that adult patients may require up to 2–4 litres

*This may be given:

  • IM 0.5–1 mg (0.5–1 ml of 1:1000) - repeated every 10 min as required
  • IV 50–100 µg i.v. (0.5–1 ml of 1:10 000) over 1 min 

Why do we use adrenaline?

This is a classic FRCA Primary SOE or OSCE question, because it tests your understanding of how adrenaline works, and what effects it has on the body.

Adrenaline is an α-receptor agonist

This means it has powerful vasopressive activity, counteracting the histamine-induced vasodilatation responsible for the profound distributive shock that leads to the cardiovascular collapse seen in anaphylaxis.

It also helps to reduce the widespread oedema, particularly of the airway which is of primary concern to the anaesthetist.

It is also a β-receptor agonist

The almost equal β1 and β2 activity gives adrenaline three powerful actions against anaphylaxis that make it invaluable as a first line therapy.

  • It induces bronchodilation, thereby counteracting the bronchospasm induced by histamine release
  • It acts directly on the heart, and improves cardiac output via both chronotropy and inotropy
  • Reduces histamine release by acting on Mast Cell β2 receptors and stabilising their membrane

So what causes it?

Anaphylaxis occurs when a trigger, to which IgE antibodies have already been produced from a previous exposure, is recognised as being present in the body. Food allergens such as nuts, soy and egg are common, as well as a host of drugs and chemicals found around the hospital.

What are the common causes of anaphylaxis in theatre?

The sixth national audit project (NAP6) identified the four most common triggers of anaphylaxis as:

Antibiotics 47%

  • Teicoplanin comprised only 12% of antibiotic exposures, but caused 38% of antibiotic-induced anaphylaxis

Neuromuscular blocking agents 33%

  • Suxamethonium-induced anaphylaxis, mainly presenting with bronchospasm, was twice as likely as with other NMBAs
  • Atracurium-anaphylaxis mainly presented with hypotension. Non-depolarising NMBAs had similar incidences to each other.

Chlorhexidine 9%

  • May be detected by development of a rash during prepping and draping
  • Often overlooked as the trigger is usually assumed to be one of the drugs given during induction of anaesthesia

Patent Blue dye 4.5%

  • Commonly used in breast surgery

Can you test for anaphylaxis?

Yes, and it's important that this is done whenever a suspected anaphylactic reaction occurs, as it allows us to differentiate true anaphylaxis from anaphylactoid reactions, which can look very similar.

  • The key protein released from mast cells is tryptase

Levels generally peak after 90 minutes from onset of the reaction, and rapidly normalises within eight hours.

Samples should be taken at the following times:

  • As soon as the patient is stable
  • One to two hours after (testing for peak levels)
  • Twenty-four hours after (testing for baseline)

Referral should then be made to the allergy clinic and the reaction should be reported via the Yellow Card Scheme to the Medicines and Healthcare products Regulatory Agency (MHRA)

What is a biphasic reaction?

  • The recurrence of  symptoms soon after the initial episode
  • They can occur in up to 5% of cases of anaphylaxis
  • Sometimes more than 24 hours after the first reaction
  • Generally less severe than the initial reaction

There's substantial debate as to whether patients with anaphylactic reactions should be observed in hospital for extended periods of time to ensure they don't suffer a severe biphasic reaction, but in general patients are often monitored for around 6-12 hours before being allowed home, assuming someone is able to keep an eye on them.

For intraoperative anaphylaxis, however, your patient is most likely headed to ICU, so you don't really need to worry about this.

The Resus Council guidelines - updated May 2021

References and Further Reading

Emergency treatment of anaphylactic reactions: Guidelines for healthcare providers
Guidance for healthcare providers who may deal with an anaphylactic reaction. It describes the recognition and treatment of an anaphylactic reaction including the delivery of drugs for treatment.
Abstract. Owing to the nature of their work, anaesthetists are involved in adverse drug reactions more commonly than most other clinicians. These adverse reacti

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