Pathophysiology & ManagementScott Cooper B.Sc. (Hons.) Dip. Paramedical Science
Understanding the terminologyPathophysiologySigns and SymptomsClinical Management
Between 1996 and 2007 there where 112 anaphylaxis fatalities in Australia During those 9 years, food induced anaphylaxis admissions increase by350% Globally, the incidence of allergic related medical conditions related tofood 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 inthe last decade in the UK
AnaphylaxisCan be defined as “An exaggerated immune response toa foreign antigen or protein resulting in severe lifethreatening condition”Refers to the physiological events regardless ofactivation mechanism.The term was first used by a couple of FRENCHscientists who where abusing dogs by testing seaanemone antivenin on cute little beagle puppies withsad eyes. It was noted that one of the dogs died withouta perceived reason.
Anaphylaxis continuedAetiologies are grouped into either:Allergic Mediated by Immunoglobulin E (Ig-E) Require previous exposure and sensitization The most common trigger of anaphylaxisNon allergic or anaphylactoid Conflicting evidence as to whether these reaction are activatedby IgE response or not No previous exposure or sensitization required
Anaphylactic ShockShock can be defined as a state of poor systemicperfusionAnaphylactic shock is a state of poor end organperfusion as a direct result of the anaphylacticreactionIn summary anaphylactic shock is just one ofmany possible clinical manifestations resultingfrom a severe allergic reaction.
BasophilsA type of granulocytic white blood cellMake up <1% of WBC countAlthough able to initiate release of chemicalweapons, also possess the ability to initiate mastcells to triggerPredominantly secrete histamine whentriggered.ARE MOBILE!
Mast CellsSimilar to basophils, these cells are locatedthroughout the body bound in connective tissue.Concentrated beneath the skin and the mucousmembranes of the respiratory and digestive tractsCan be considered as storage points for chemicalWMD’sWhen activated, release a multitude of chemicalinflammatory mediators
SensitisationJoe Boggs aged 2 eats his first ever peanut. Certaincells called blah blah blah cells, for some reason,believe this protein to be foreign and dangerousBlah blah blah cells take photographs of the proteinand take it to the bling bling cells who producemassive quantities of an antibody type, IgE. Thisantibody is specific to these proteins.The IgE antibodies bind to mast cells and basophils,ready to attack if this protein shows up again
Stage OneJoe 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 thisrecognised foreign antigen invader.All hell breaks loose and a cascade of highly complexbiochemical pathways result in the basophils screaming“CODE RED!!” The basophils flow throughout the blood stream, releasing theirchemical weapons as they go, if they havent already been triggered bythe same protein, they also get their bigger mates, the Mast Cells tofire their weaponry as well
Stage TwoBasophils now initiate what is known as a ‘Mastcell-leukocyte-cytokine-cascadeIn normal people, this reaction is controlled bya feedback system ensuring the cascade doesnot get out of hand.In persons with a SAR, this process becomesuncontrolled and results in the release ofmultiple chemical mediators over seconds,minutes and hours
Stage FourThe patient begins to feel unwell as theinflammatory mediators act on the target tissuesThe integumentary, cardiovascular, respiratory,gastro intestinal and central nervous systems canall be affected.If the patient has integumentary involvement(Urticaria, erythema, swelling or pruritis(itching)) AND Respiratory compromise ORhypotension, the patient is said to be inanaphylaxis
Integumentary SystemDue to the high concentration of mast cellsunder the skin, this is often the first sign of animpending reactionHistamine causes vasodilatation of themicorcapillaries resulting in a flushedappearanceAs the capillaries become more permeable,plasma leaks into the interstitial space resultingin urticaria and pruritis due to the irritation ofplasma being outside of the vessel wall
Cardiovascular SystemInflammatory mediators including histamine,Leukotriens and kinins now cause widespreadvasodilatation and vessel wall permeability,As much as 35% of circulating fluid volume canbe lost to the interstitial space, this coupledwith the massive vasodilatation causes a rapiddrop in blood pressure, anaphylactic shock.Baroreceptors in the aortic arch and carotidbulb detect this pressure drop and heart rateincreases.
Cardiovascular System (cont’d)As the blood pressure drops, pre load and afterload decrease, resulting in a potential for poorcardiac perfusion, this is of particular concern inthe elderly or patients with cardiac disease.As the fluid builds up in the interstitial spaces,angioedema begins to cause swelling, particularlyto the eyes, ears, mouth and tongue, throat andlungsThe patient begins to complain of a lump oritching in throat, dysphagia and dyspnoea as theupper airway / tongue swells.
Severe Glossal Oedema
Angelina Jolie or Angiodema…..
Laryngoscope View of Laryngeal oedema
Respiratory SystemAs well as previously discussed upper respiratorytract inflammation due to angioedema, thesmooth muscle of the distal bronchi alsoconstrict, causing a reduction in the lumendiameter, resulting in further airflow resistance.This is a futile protection mechanism to limit theexposure to the antigenAs the patient becomes hypoxaemic, therespiratory rate increases dramaticallyHypoxaemia leads to further vasodilatation andtachycardia, placing more strain on the heart.
GastrointestinalMost gastrointestinal symptoms are due to therelease of serotonin during the reaction, this thebowel to spasm, causing abdominal cramping,induces nausea and diarrhoea.This is an attempt by the body to rid itself of theantagonist, by increasing bowel transit andinducing vomiting.Strong GI symptoms have been associated withan increase in severity and incidence ofanaphylaxis.
Central Nervous SystemMost CNS symptoms are due to hypotensionExpect anxiety, dizziness, confusion, and oftencombative behavior as cerebral blood flow iscompromisedANY GCS less than 15 indicates poor cerebralperfusion and is time critical.Most patients experiencing hypotensiongenuinely believe they are dying, rest andreassurance is an essential aspect of patientmanagement
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 toneTreatment depends on the symptomsPrepare for the worst i.e. cardiac arrest
It should be remembered that anaphylaxis can beMonophasic, Biphasic or multiphasicMost people recover immediately after aggressiveintervention without experiencing furthersymptoms, some however do, as much as 24 hourslater.Always transport patient for physicianassessment, never leave a patient at homefollowing anaphylaxis, even if asymptomatic
ADRENALINEAdrenaline is a naturally occurring catecholamine which primarilyacts on Alpha1 and Beta1 & 2 adrenergic receptors, locatedmainly 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
ADRENALINE (cont’d)There is also anecdotal evidence that adrenaline assists instabilising the mast cells from degranulatingThe 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 forpatients 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 beallergic 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 ofreaction Nebulised = 5mg, single dosePAEDIATRIC I.M.I. = 10mcg / kg (Max 250mcg) every 5 minutes until Ptstabilises for patients equal to or >1 years of age I.M.I. = 100mcg every 5 minutes until Pt stabilises for patientsequal to or <1 years of age Nebulised = 5mg, Single dose
ADRENALINE (cont’d) EpiPen Most people identified as having high risk to anaphylaxis are providedwith an EpiPen If already administered, dose should be taken into account Below table shows the standard dose of EpiPen in AustraliaWeightWeight EpiPen DoseEpiPen DoseChildren < 10kgChildren < 10kg Not usually RecommendedNot usually RecommendedChildren 10-20kgChildren 10-20kg EpiPen Jr. 150mcgEpiPen Jr. 150mcgChildren & Adults >20kgChildren & Adults >20kg EpiPen 300mcgEpiPen 300mcg
FluidsSeverely shocked patient require large volumes of asuitable crystalloid solution to maintain organ perfusion!Adrenaline is the first line drug but fluids also have a vitalrole to play, and may in fact be the only and / or saferintervention required2-3 litres rapid infusion through at least a 16g isrecommended for hypotensive patients, consider
Bronchodilators e.g. SalbutamolThe respiratory symptoms exhibited by patients in anaphylaxisare very similar to those exhibited by asthmatics.Smooth muscle constriction may be relieved bybronchodilators such as salbutamolSalbutamol sulphate is a direct acting sympathomimetic agentwhich mainly effects β2 receptors. As a predominantly β2adrenoreceptor stimulant, Salbutamol bronchodilating action isrelatively more prominent than its cardiac effects
Anti Histamines Generally not recommended for serve allergic reactions Histamine is just one of the many inflammatory mediatorsresponsible for initiating anaphylaxis and is more of an initialmediator than a protracted one. Histamine has been shown to peak early and then return to normaldespite the persistence of severe physiological compromise The main issue of concern is that the major antihistaminepromethazine (phenergan) is a vasodilator and may in fact worsenthe patients outcome. It would therefore seem prudent that phenergan be restricted to thetreatment of skin symptoms and not in patients with realised orpotential 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 mansadrenaline in beta blocked patients! If a patient is beta blocked the efficacy of adrenaline may be severelyreduced due to it’s inability to bind to the beta receptor sites Glucagon works by binding to a different receptor site but still elicitssimilar 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 allergiesRemember these patient groups are statistically more likely toexperience and anaphylactic reactionAre 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 itAlthough anaphylaxis is rare, you never knowwhen 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!!!!!!!