Pathophysiology & Management

Scott Cooper B.Sc. (Hons.) Dip. Paramedical Science

Understanding the terminology

Pathophysiology

Signs and Symptoms

Clinical Management

Understanding the terminology

Pathophysiology

Signs and Symptoms

Clinical Management

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

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

AnaphylaxisCan 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.

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

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.

Basophils

A type of granulocytic white blood cellMake up <1% of WBC countAlthough able to initiate release of

chemical weapons, also possess the ability to initiate mast cells to trigger

Predominantly secrete histamine when triggered.

ARE MOBILE!

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

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

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

Stage TwoBasophils 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

Stage ThreeDisseminated mast cell activation

release a variety of noxious mediators including:HistaminesProstaglandinsLeukotriensChemokinesCytokines

These rapidly synthesized toxic compounds elicit a widespread increase in vascular permeability and vasodilatation

Stage FourThe 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

Integumentary SystemDue 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

Cardiovascular SystemInflammatory 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.

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.

Severe Glossal Oedema

Angelina Jolie or Angiodema…..

Laryngoscope View of Laryngeal oedema

Respiratory SystemAs 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.

GastrointestinalMost 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.

Central Nervous SystemMost CNS symptoms are due to

hypotensionExpect 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

Primary Survey DRABC find and fix Airway

Adrenaline to reduce and arrest the laryngeal / glossal oedema

BreathingHigh flow Oxygen, slow gentle IPPV if requiredBronchodilators to assist with bronchospasm

CirculationRAISE THE LEGS! Simple but highly effectiveFluids to maintain end organ perfusionAdrenaline to increase vascular tone

Treatment depends on the symptomsPrepare for the worst i.e. cardiac arrest

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

ADRENALINEAdrenaline is a naturally occurring catecholamine which primarily

acts on Alpha1 and Beta1 & 2 adrenergic receptors, located mainly in tissues innervated by sympathetic nerves.

(1) increases heart rate Increases the force of myocardial contraction Increases the irritability of the ventricles

(2) Bronchodilation

(1) Peripheral vasoconstriction

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

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

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

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 DoseChildren < 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

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

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

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

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

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

Useful questions to ask your patient:Do you suffer from any of the following?

AsthmaBad hay feverSevere 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!

Familiarise yourself with adrenaline regularly: When to give itDosagesHow 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!

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!!!!!!!