1. Pathophysiology & Management
Scott Cooper B.Sc. (Hons.) Dip. Paramedical Science

2. Understanding the terminology
Pathophysiology
Signs and Symptoms
Clinical Management

3.  Between 1996 and 2007 there where 112 anaphylaxis fatalities in Australia
 During those 9 years, food induced anaphylaxis admissions increase by
350%
 Globally, the incidence of allergic related medical conditions related to
food allergies is on the rise
 In the US there are approximately 150-200 anaphylaxis death annually
 Hospital admission for anaphylaxis management have increased 7 x in
the last decade in the UK

4. Anaphylaxis
Can be defined as “An exaggerated immune response to
a foreign antigen or protein resulting in severe life
threatening condition”
Refers to the physiological events regardless of
activation mechanism.
The term was first used by a couple of FRENCH
scientists who where abusing dogs by testing sea
anemone antivenin on cute little beagle puppies with
sad eyes. It was noted that one of the dogs died without
a perceived reason.

5. Anaphylaxis continued
Aetiologies are grouped into either:
Allergic
 Mediated by Immunoglobulin E (Ig-E)
 Require previous exposure and sensitization
 The most common trigger of anaphylaxis
Non allergic or anaphylactoid
 Conflicting evidence as to whether these reaction are activated
by IgE response or not
 No previous exposure or sensitization required

6. Anaphylactic Shock
Shock can be defined as a state of poor systemic
perfusion
Anaphylactic shock is a state of poor end organ
perfusion as a direct result of the anaphylactic
reaction
In summary anaphylactic shock is just one of
many possible clinical manifestations resulting
from a severe allergic reaction.

7. Basophils
A type of granulocytic white blood cell
Make up <1% of WBC count
Although able to initiate release of chemical
weapons, also possess the ability to initiate mast
cells to trigger
Predominantly secrete histamine when
triggered.
ARE MOBILE!

8. Mast Cells
Similar to basophils, these cells are located
throughout the body bound in connective tissue.
Concentrated beneath the skin and the mucous
membranes of the respiratory and digestive tracts
Can be considered as storage points for chemical
WMD’s
When activated, release a multitude of chemical
inflammatory mediators

9. Sensitisation
Joe Boggs aged 2 eats his first ever peanut. Certain
cells called blah blah blah cells, for some reason,
believe this protein to be foreign and dangerous
Blah blah blah cells take photographs of the protein
and take it to the bling bling cells who produce
massive quantities of an antibody type, IgE. This
antibody is specific to these proteins.
The IgE antibodies bind to mast cells and basophils,
ready to attack if this protein shows up again

10. Stage One
Joe Boggs aged 2 and 26 days eats his second ever peanut.
As soon as the protein is absorbed into the blood stream,
circulating basophils detect the presence of this
recognised foreign antigen invader.
All hell breaks loose and a cascade of highly complex
biochemical pathways result in the basophils screaming
“CODE RED!!”
 The basophils flow throughout the blood stream, releasing their
chemical weapons as they go, if they haven't already been triggered by
the same protein, they also get their bigger mates, the Mast Cells to
fire their weaponry as well

11. Stage Two
Basophils now initiate what is known as a ‘Mast
cell-leukocyte-cytokine-cascade
In normal people, this reaction is controlled by
a feedback system ensuring the cascade does
not get out of hand.
In persons with a SAR, this process becomes
uncontrolled and results in the release of
multiple chemical mediators over seconds,
minutes and hours

12. Stage Three
Disseminated mast cell activation release a
variety of noxious mediators including:
Histamines
Prostaglandins
Leukotriens
Chemokines
Cytokines
These rapidly synthesized toxic compounds elicit a
widespread increase in vascular permeability and
vasodilatation

13. Stage Four
The patient begins to feel unwell as the
inflammatory mediators act on the target tissues
The integumentary, cardiovascular, respiratory,
gastro intestinal and central nervous systems can
all be affected.
If the patient has integumentary involvement
(Urticaria, erythema, swelling or pruritis
(itching)) AND Respiratory compromise OR
hypotension, the patient is said to be in
anaphylaxis

14. Integumentary System
Due to the high concentration of mast cells
under the skin, this is often the first sign of an
impending reaction
Histamine causes vasodilatation of the
micorcapillaries resulting in a flushed
appearance
As the capillaries become more permeable,
plasma leaks into the interstitial space resulting
in urticaria and pruritis due to the irritation of
plasma being outside of the vessel wall

16. Cardiovascular System
Inflammatory mediators including histamine,
Leukotriens and kinins now cause widespread
vasodilatation and vessel wall permeability,
As much as 35% of circulating fluid volume can
be lost to the interstitial space, this coupled
with the massive vasodilatation causes a rapid
drop in blood pressure, anaphylactic shock.
Baroreceptors in the aortic arch and carotid
bulb detect this pressure drop and heart rate
increases.

17. Cardiovascular System (cont’d)
As the blood pressure drops, pre load and after
load decrease, resulting in a potential for poor
cardiac perfusion, this is of particular concern in
the elderly or patients with cardiac disease.
As the fluid builds up in the interstitial spaces,
angioedema begins to cause swelling, particularly
to the eyes, ears, mouth and tongue, throat and
lungs
The patient begins to complain of a lump or
itching in throat, dysphagia and dyspnoea as the
upper airway / tongue swells.

18. Severe Glossal Oedema

19. Angelina Jolie or Angiodema…..

20. Laryngoscope View of Laryngeal oedema

21. Respiratory System
As well as previously discussed upper respiratory
tract inflammation due to angioedema, the
smooth muscle of the distal bronchi also
constrict, causing a reduction in the lumen
diameter, resulting in further airflow resistance.
This is a futile protection mechanism to limit the
exposure to the antigen
As the patient becomes hypoxaemic, the
respiratory rate increases dramatically
Hypoxaemia leads to further vasodilatation and
tachycardia, placing more strain on the heart.

22. Gastrointestinal
Most gastrointestinal symptoms are due to the
release of serotonin during the reaction, this the
bowel to spasm, causing abdominal cramping,
induces nausea and diarrhoea.
This is an attempt by the body to rid itself of the
antagonist, by increasing bowel transit and
inducing vomiting.
Strong GI symptoms have been associated with
an increase in severity and incidence of
anaphylaxis.

23. Central Nervous System
Most CNS symptoms are due to hypotension
Expect anxiety, dizziness, confusion, and often
combative behavior as cerebral blood flow is
compromised
ANY GCS less than 15 indicates poor cerebral
perfusion and is time critical.
Most patients experiencing hypotension
genuinely believe they are dying, rest and
reassurance is an essential aspect of patient
management

24. Primary Survey DRABC find and fix
 Airway
 Adrenaline to reduce and arrest the laryngeal / glossal oedema
 Breathing
 High flow Oxygen, slow gentle IPPV if required
 Bronchodilators to assist with bronchospasm
 Circulation
 RAISE THE LEGS! Simple but highly effective
 Fluids to maintain end organ perfusion
 Adrenaline to increase vascular tone
Treatment depends on the symptoms
Prepare for the worst i.e. cardiac arrest

25. It should be remembered that anaphylaxis can be
Monophasic, Biphasic or multiphasic
Most people recover immediately after aggressive
intervention without experiencing further
symptoms, some however do, as much as 24 hours
later.
Always transport patient for physician
assessment, never leave a patient at home
following anaphylaxis, even if asymptomatic

26. ADRENALINE
Adrenaline is a naturally occurring catecholamine which primarily
acts on Alpha1 and Beta1 & 2 adrenergic receptors, located
mainly in tissues innervated by sympathetic nerves.
(β1)
 increases heart rate
 Increases the force of myocardial contraction
 Increases the irritability of the ventricles
(β 2)
 Bronchodilation
(α 1)
 Peripheral vasoconstriction

27. ADRENALINE (cont’d)
There is also anecdotal evidence that adrenaline assists in
stabilising the mast cells from degranulating
The net results of adrenaline are:
 Increase in vascular tone
 Increase in BP
 Increase in preload and afterload
 Decrease in vascular permeability
 Decrease in swelling
 Acts as a bronchodilator

28. ADRENALINE (cont’d)
 Whilst it is important adrenaline is administered in a timely fashion for
patients in anaphylaxis, it is also prudent to consider the following:
 Adrenaline can be a dangerous drug!
 Is this a genuine anaphylaxis (Vasovagal? or anxiety??)
 Consider age and cardiac health of patient in dosing
 Best Route
 IMI (vastus lateralus as more reliable absorption profile)
 Nebulised (for isolated minor facial and/or tongue swelling thought to be
allergic in origin – IMI if stridor present)
 Ensure adequate monitoring of patient post administration

29. ADRENALINE (cont’d)
ADULT
 I.M.I. = 250 - 500mcg every 5 minutes until Pt stabilises
 Consider age of patient, medical condition of patient and severity of
reaction
 Nebulised = 5mg, single dose
PAEDIATRIC
 I.M.I. = 10mcg / kg (Max 250mcg) every 5 minutes until Pt
stabilises for patients equal to or >1 years of age
 I.M.I. = 100mcg every 5 minutes until Pt stabilises for patients
equal to or <1 years of age
 Nebulised = 5mg, Single dose

30. ADRENALINE (cont’d)
 EpiPen
 Most people identified as having high risk to anaphylaxis are provided
with an EpiPen
 If already administered, dose should be taken into account
 Below table shows the standard dose of EpiPen in Australia
WeightWeight EpiPen DoseEpiPen Dose
Children < 10kgChildren < 10kg Not usually RecommendedNot usually Recommended
Children 10-20kgChildren 10-20kg EpiPen Jr. 150mcgEpiPen Jr. 150mcg
Children & Adults >20kgChildren & Adults >20kg EpiPen 300mcgEpiPen 300mcg

31. Fluids
Severely shocked patient require large volumes of a
suitable crystalloid solution to maintain organ perfusion!
Adrenaline is the first line drug but fluids also have a vital
role to play, and may in fact be the only and / or safer
intervention required
2-3 litres rapid infusion through at least a 16g is
recommended for hypotensive patients, consider

32. Bronchodilators e.g. Salbutamol
The respiratory symptoms exhibited by patients in anaphylaxis
are very similar to those exhibited by asthmatics.
Smooth muscle constriction may be relieved by
bronchodilators such as salbutamol
Salbutamol sulphate is a direct acting sympathomimetic agent
which mainly effects β2 receptors. As a predominantly β2
adrenoreceptor stimulant, Salbutamol bronchodilating action is
relatively more prominent than its cardiac effects

33. Anti Histamines
 Generally not recommended for serve allergic reactions
 Histamine is just one of the many inflammatory mediators
responsible for initiating anaphylaxis and is more of an initial
mediator than a protracted one.
 Histamine has been shown to peak early and then return to normal
despite the persistence of severe physiological compromise
 The main issue of concern is that the major antihistamine
promethazine (phenergan) is a vasodilator and may in fact worsen
the patients outcome.
 It would therefore seem prudent that phenergan be restricted to the
treatment of skin symptoms and not in patients with realised or
potential haemodynamic compromise

34. Steroids
 Inhibit the accumulation of inflammatory cells at inflammation sites
 Inhibits the release and synthesis of inflammatory mediators
 Plays a part in suppressing cell mediated immune reactions

35. Glucagon
 Glucagon is a hyperglycemic agent but it also acts as a poor mans
adrenaline in beta blocked patients!
 If a patient is beta blocked the efficacy of adrenaline may be severely
reduced due to it’s inability to bind to the beta receptor sites
 Glucagon works by binding to a different receptor site but still elicits
similar effects as adrenaline within the cell.
 Recommended dose = initial load of 1-5mg I.V.I. over 5 minutes
 NOT RECOGNISED QAS MANAGEMENT, JUST FOR INTEREST

36. Useful questions to ask your patient:
Do you suffer from any of the following?
Asthma
Bad hay fever
Severe allergies
Remember these patient groups are statistically more likely to
experience and anaphylactic reaction
Are you taking beta blockers?
May explain why adrenaline isn’t working!

37. Familiarise yourself with adrenaline regularly:
When to give it
Dosages
How to draw that dose up,
How to administer it safely IMI (aspirate)
The risks associated with it
Although anaphylaxis is rare, you never know
when you might need it!

38.  Journal of Emergency medicine July 2002
 Anaphylaxis
 Emergency Medicine Australia 2006
 Anaphylaxis: Clinical concepts and research priorities
 Allergy Notes August 2008
 Anaphylactoid Reactions to Intravenous Contrast media
 New England Journal of Medicine November 2006
 Anaphylaxis Prevention via pretreatment
 Emergency Care in the Streets
 Nancy Caroline
 Queensland Ambulance Service
 Clinical Protocol Manual
 Drug Therapy protocols
 Ultravist Drug information Guide
 And many more!!!!!!!