CMP1 Anaphylaxis

3.3.2 ACCS Major Presentations CT1&2

CMP1 Anaphylaxis The trainee will be able to identify patients with anaphylactic shock, assess their clinical state, produce a list of appropriate differential diagnoses, initiate immediate resuscitation and management and organise further investigations


Assessment Methods GMP Domains
Identify physiological perturbations causing anaphylactic shock E, C, Mi, ACAT 1
Recognise clinical manifestations of anaphylactic shock E, C, Mi, ACAT 1
Elucidate causes of anaphylactic shock E, C, Mi, ACAT 1
Know anaphylaxis guidelines E, C, Mi, ACAT 1
Define follow-up pathways after acute resuscitation E, C, Mi, ACAT 1


Recognise clinical consequences of acute anaphylaxis Mi, C, S 1
Perform immediate physical assessment (laryngeal oedema, bronchospasm, hypotension) Mi, C, D, S 1
Institute resuscitation (adrenaline/epinephrine), oxygen, IV access, fluids) Mi, C, D, S 1
Arrange monitoring of relevant indices Mi, C, S 1
Order, interpret and act on initial investigations (tryptase, C1 esterase inhibitor etc.) Mi, C 1
Be an ALS provider L 1


Exhibit a calm and methodical approach ACAT, C, Mi, S 3
Adopt leadership role where appropriate ACAT, C, Mi, S 2,4
Involve senior and specialist allergy services promptly ACAT, C, Mi, S 2, 3



The purpose of these notes is to provide a practical minded but detailed background to the vague and wishy washy curriculum.  I am only including information that I think is relevant to either a) treating anaphylaxis, or b) passing a question on anaphylaxis in the MCEM.

 Key points

  • If YOU decide this is anaphylaxis or might be anaphylaxis give your patient IM adrenaline.
  • See first key point.


Anaphylaxis is a systemic allergic reaction mediated by massive histamine release triggering haemodynamic instability, airway or breathing compromise and death.  Defining it in such terms doesn’t actually help us diagnose it, so we have a set of clinical criteria to remember.

Anaphylaxis was defined at the World Allergy Organization in May 20103.  My god that must have been a fun party, though I doubt they served peanuts, or shellfish.  Those clever, clever people decided to go for the following:

  1. Involvement of Skin or mucosal tissue plus respiratory difficulty or a low BP
  2. 2 of the following
    1. Involvement of the skin or mucosa
    2. Respiratory difficulties
    3. Low BP
    4. GI symptoms
  3. Low blood pressure after exposure to allergen

NB I don’t know why low BP is in twice.  I think the important thing is the exposure to allergen part.

Or if you have started thinking in medical nomenclature

ANAPHYLAXIS = ?allergen + 2(skin/resp/CVS/GI)

Risk of having an anaphylactic reaction in your lifetime 1 in 1300

Risk of having another anaphylactic reaction again if you’ve already had one:  1 in 12 per year.


Our immune system contains mast cells, which are full to the brim of histamine, and other mediators.  On their cell surface membranes antibodies are stuck [IgE].  If you are unlucky enough to ingest/come into contact with something that fits that particular lock and key mechanism, you cause degranulation.

Degranulation releases a cocktail of vasoactive mediators into the local area, they have a myriad of effects, but the key one to remember is that they vastly increase vascular permeability and vasodilatation.  If this response goes systemic you can dump up to 50% of your circulatory volume into the extravascular compartment in minutes.  Prostaglandins and leukotrienes effect on smooth muscle causes bronchospasm (in lungs), uterine contraction (in uterus), stomach cramps, vomit or diarrhoea (in GI tract).

NB – NSAIDs and other drugs can also trigger mast cells, not through direct allergy but through the complement system.  This is why “immune mediated” and “non-immune mediated” anaphylaxis classification is needed.

How do we become allergic? A process of sensitisation has been inferred to occur.  Some form of prior exposure is required for the immune system to produce antibodies to that antigen and stick them to mast cells.  T helper cells and Antigen presenting cells are implicated here.

Onset time, features and progression are largely thought to be due to how the allergen has been encountered (an injected allergen is going to cause an immediate response, an ingested allergen one a little later).


Foods are more important triggers in children, in the geriatric population it seems to be drugs.

The best data from the UK that the resus council is relying on seems to be from a discussion at a Novartis symposium, I can’t find the original, but I can show you what the resus council think the causes of fatal anaphylaxis are.

Stings 47 29 wasp 4 bee 14 unknown
Nuts 32 10 peanut, 6 walnut, 2 almond, 2 brazil, 1 hazel, 11 mixed or unknown
Food 13 5 milk, 2 fish, 2 chickpea, 2 crustacean, 1 banana, 1 snail
Maybe food 17 5 during meal, 3 mil 3 nut 1 of each – fish, yeast, sherbert, nectarine, grape, strawberry
Antibiotics 27 11 penicillin, 12 cephalosporin, 2 amphotericin, 1 ciprofloxacin, 1 vancomycin
Anaesthetic Drugs 39 16 suxamethonium, 7 vecuronium, 6 atracurium, 7 at induction
Other Drugs 24 6 NSAIDS, 3 ACEI, 5 gelatins, 2 protamin, 2 vit K 1 each etoposide, acetazolamide, pethidine, local anaesthetic, diamorphine, streptokinase
Contrast Media 11 9 iodinated 1 technetium 1 fluroescin
Other 3 1 latex, 1 hair dye, 1 hydatid

Suspected Triggers for fatal anaphylactic reactions in the UK between 1992 and 2001.2

If you think about this table a bit it’s a little bit stupid.  After all nuts are a food (I’m not sure snails are).  So with a bit of judicious thinking we can produce a simpler table, which shows that drugs are the biggest culprit by far.

Food 62
Drugs 101
Other 3
Stings 47




Timing for fatal anaphylaxis


As you can see from this piece of research, injected drugs if they are going to cause fatal anaphylaxis tend to cause problems within 20 minutes of being injected2.  Food takes up to one hour to cause symptoms.


Biphasic Reactions

Occurs 1-72 hours [usually within 1-4 hours] after initial symptoms8.

23% of adults and 11% of children

Your local department will have “rules” governing how long patients are kept in after anaphylaxsis.  Most departments I have worked in have a 6-8 hour rule.  Biphasic reactions are one of the rationales for steroids post event.

Recognition, and Treatment

The history, signs and symptoms of anaphylaxis are broad, vague and difficult to pin down.  Its one of those things that some older (or ‘more experienced’ if within earshot) doctors talk about ‘knowing it when they see it’.

Key points from the history:

  • Exposure to allergen
  • Patient tells you that they feel itchy, or unwell
  • Sudden onset (mins – hours) of symptoms

Key points from examination

  • Upper airway swelling
  • Oedema of lips/tongue
  • Hives/urticaria/flushed
  • Wheeze/SOB/Low sats
  • Presyncopal/syncopal/confusion/low SBP

Other signs

  • Sudden GI upset
  • Incontinence




You should know this, all the doses, all the ranges, and all of the routes.  There is no excuse for an ACCS trainee not to be able to regurgitate this information.

Luckily it’s pretty straightforward.

The Resus council, World Allergy Organization, and the BMJ all emphasise the adrenaline as a first line measure.  Get it into your patient as soon as you have made the diagnosis.  Do not pussy foot around giving some steroids, and some nebs and hoping!

If you think it is anaphylaxis.  GIVE ADRENALINE IM.

If you have even a hint of airway compromise get all of the help in the world into the Resus room.  Anaphylactic patients who have airway compromise can end up in a can’t ventilate, can’t intubate situation.

Things not on the algorithm that you should have in the back of your mind:

  • If the patient is on beta blockers you may need to give them glucagon as well.
  • If the patient is beta blocked and has persistent bradycardia or bronchospasm consider anticholinergic (atropine for the heart, ipratropium for the lungs).

Post-resuscitation Management

Once you’ve cured your patient you need to arrange for a period of observation (NICE currently recommend 6-12 hours)4.  However there is evidence from observational studies in Canada that you can cut this down to between 4 and 6 hours8.

Make sure your documentation is going to be useful for the immunologist that will see them in clinic.  So you’ll need to document potential triggers, time of onset, and clinical manifestations.

Take a serum tryptase level as soon as possible after emergency treatment, and a second sample 2 hours after that (but no more than 4 hours from the onset of symptoms).  Tryptase is released by mast cell degranulation (it makes up the structure of the granules).  It acts as a biochemical marker for allergic anaphylaxis.

People who have had anaphylaxis need to referring to an allergy service, a prescription for an epipen, and education on its use.

Reproduced with the kind permission of the resuscitation council



Why Adrenaline?

Adrenaline is a sympathomimetic catecholamine.  It acts on both alpha and beta adrenoreceptors equally.  It’s actions effectively oppose the actions of the histamine release.

CVS – positive inotrope, and chronotrope, increases cardiac output, coronary blood flow, increases systemic vascular resistance,

RS – potent bronchodilator

There are also beta2 receptors on the cell surface membranes of mast cells which are inhibitory.

The IM route is preferred because it is EASIER, QUICKER, AND SAFER

NB:  A note on IV Adrenaline for Anaphylaxis

This is potentially dangerous and should only be done by someone experienced in its use.  It tends to be given IV for anaphylaxis in theatre, or in refractory cases.  ALS Guidance suggests using 0.5ml of 1 in 10 000 concentration.  That’s 50mcg IV bolus (of the pre-prepared arrest dose syringes), and titrating to response.  In kids they suggest 1mcg/kg.



Why Anti-histamines?

There isn’t much evidence that these help, but it makes sense, and it’s certainly not going to do much harm.  Chlorphenamine is a first choice in the UK (weirdly they don’t have it in New Zealand).  H2 receptor antagonists such as ranitidine or cimetidine have even less evidence than Chlorphenamine.


Why steroids?

There is no evidence for their benefit (there’s a Cochranre review to back me up here5), but it’s thought that there may be role in relieving protracted anaphylaxis or protect people from biphasic reactions.


How much fluid??!

Large volumes may be required.  It’s not unheard of to need to give 2-3 Litres to adults, and often need more.  Use Crystalloid, don’t use colloids3,4,6.



Adrenaline autoinjectors come in two strengths 150mcg and 300mcg.  Note that’s less than you’ll be giving to your patients.  It depends on your local department, but if it’s genuine anaphylaxis it’s reasonable (and recommended) to prescribe an autoinjector to take home.



For refractory anaphylaxsis in patients who are beta-blocked.  A second agent is thought to be needed to increase the contractility of the heart, via the cAMP system rather than through adrenoreceptors.  Use is only through anecdotal case reports.  Dose is thought to be 1-2mg IV every 5 minutes.


Anaphylactic Mimics

Angioedema – rapid swelling of dermis, mucosa, and subcutaneous tissues.  We often think of this as only occurring around the mouth, face and lips.  Actually it can occur anywhere, but normally it doesn’t matter.  There are 2 broad types – acquired (allergic, or idiopathic), and Hereditary.  Hereditary angioedema is divided into 3.  Types 1 and 2 are caused by autosomal dominant mutations that stop you producing or using c1 inhibitor.  Type 3 is due to a mutation in the gene that encodes clotting factor XII.  The pathogenesis of both boils down to an inappropriately jittery complement system.  Attacks can be idiopathic or caused by local trauma (intubation, dental procedures etc).

Incidence is estimated at 1:50 0007, [anaphylaxis is 1 in 1300].

The treatment is with c1-esterase inhibitor concentrate (very expensive from £1000 per treatment).

Blood tests to diagnose are C4 level, C1INH level, and C1INH function.

Type C1 INH C1 INH function C4
HAE 1 Low Low
HAE 2 Normal/High Reduced Low
HAE 3 Normal Normal Normal

Need to be interpreted with clinical picture, and most need to be repeated more than once to be sure.

Emergency Treatment

Consider HAE in patients with anaphylaxis that isn’t getting better, with a slightly slower onset time.


If you don’t have C1INH to give consider FFP, or transexamic acid.  C1INH is expensive, and getting it sometimes results in a fight between blood bank and pharmacy (I have worked in places where pharmacy keeps it, and where blood bank keeps it).


Awesome further reading/resources

Resus council guidelines – available at:

WAO guidelines – available at:

NICE guidelines for anaphylaxis –

#FOAMed content:

  • EM Basic podcast on Anaphylaxis
  • SGEM post on Biphasic reactions and length of stay in department
  • EMlitofnote review of Grunau paper.



  1. Pumphrey RS. Lessons for management of anaphylaxis from a study of fatal reactions. Clin Exp Allergy 2000;30(8):1144-50.
  2. Gupta R, Sheikh A, Strachan DP, Anderson HR. Burden of allergic disease in the UK: secondary analyses of national databases. Clin Exp Allergy 2004;34(4):520-6.
  3. World Allergy Organization Guidelines for the Assessment and Management of Anaphylaxis, World Allergy Organization Journal 2011;4(2):13-37
  4. NICE clinical guideline 134 Anaphylaxis CG 134. National Institute of Clinical Excellence.
  5. Choo KJ, Simons E, et al. Glucocorticoids for the treatment of anaphylaxis: Cochrane systematic review.  Allergy 2010.  Oct 65(10): 120-5-11
  6. Working Group of the Resuscitation Council UK. Jan 2008.  Emergency Treatment of Anaphylactic Reactions
  7. Hereditary Angioedema Consensus 2010.  Allergy, Asthma & Clinical Immunology 2010, 6:13.
  8. Schellenberg, R. Robert, and Frank Xavier Scheuermeyer. “Incidence of Clinically Important Biphasic Reactions in Emergency Department Patients With Allergic Reactions or Anaphylaxis.” (2013).



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