Management of the Anaphylactic ShockManagement of the Anaphylactic Shock

Eric Revue1, MD

Pr A. Bellou2, MD

Eric Revue1, MD

Pr A. Bellou2, MD

Emergency Medicine Symposium Hué March 2012

2 President of European Society for Emergency MedicineHead of Emergency Medicine Department

Director of Emergency Medicine Training Program University Hospital, Faculty of Medicine, Rennes, France

1 European Society for Emergency MedicineHead of Emergency Medicine Department

Director of Prehospital Emergency Medicine (SMUR)Louis Pasteur ‘s Hospital, Chartres, France

What is anaphylaxis?What is anaphylaxis?

An acute systemic allergic reaction The result of a re-exposure to an antigen that

elicits an IgE mediated response Usually caused by a common environmental

protein that is not intrinsically harmful Often caused by medications, foods, and insect

stings It is a Type I hypersensitivity

HistoryHistory 1st recorded 2640 BC in

hieroglyphics– bee sting of a pharoah

Richet & Portier– South Seas– Man-o-war– coined term anaphylaxis

IgE

Binds irreversible to FcεRI receptors on mast cells, basophils, and eosinophils Is usually for parasitic infections E heavy chain

REVISED NOMENCLATURE FOR ANAPHYLAXISREVISED NOMENCLATURE FOR ANAPHYLAXIS

Anaphylaxis

Allergic anaphylaxis

Non-allergic anaphylaxis

IgE- mediated anaphylaxis

Immunologic,

non-IgE-mediated anaphylaxis

Johansson SGO et al JACI 2004,113:832-6

J Allergy Clin Immunol 2007;120:506-15

Anaphylaxis

MEDIATORS

Mast CellMast Cell

Has high affinity for IgE molecules (105 IgE/cell) Originates in the bone marrow, reside in

connective tissues Increases host response to parasitic infections Contain immunological mediators in granules ie.

Histamine, ECF-A, HMW-NCF 2 populations that vary in granule content and

activity Connective tissue Mucosal

What is happening?What is happening? Initial exposure sensitizes mast cells. Antigen specific IgE molecules attach to high affinity Fc

receptors on the mast cell surface. Cross linking of IgE molecules on surface causes

intracellular signaling pathway– Inflammatory mediators are released upon degranulation

Mediators InvolvedMediators Involved

Include histamine, proteases, chemotactic factors, leukotrienes, prostaglandin D, and cytokines

Primary: released before degranulation– Interleukin 4 used by T cells

induces B cell maturation– IL-3 and IL-5 released by T

and mast cells are chemo attractants for eosinophils

Secondary: come from granules

Diagnostic of AnaphylaxisDiagnostic of Anaphylaxis

• Anaphylaxis network symposium:

J Allergy Clin Immunol 2006 ;117 : 391-7

Definition : severe allergic reaction with sudden onset and risk of death

Diagnostic of AnaphylaxisDiagnostic of Anaphylaxis

Criteria 1 : skin lesions and/or mucosa lesions (urticaria, itching or erythema, lips oedema or tongue-uvula edema). With one or mors following signs :

Respiratory troubles (dyspnea, bronchospasm, stridor, decreased of peak flow, hypoxia)

Systolic BP<90 mmHg) ou organ dysfunction (hypotonia, syncope, incontinence)

Diagnostic of AnaphylaxisDiagnostic of Anaphylaxis

Criteria 2 : 2 or more signs after exposition to a probable allergen:

skin lesions and/or mucosa lesions (urticaria, itching or erythema, lips oedema or tongue-uvula edema). With one or mors following signs :

Respiratory troubles (dyspnea, bronchospasm, stridor, decreased of peak flow, hypoxia)

Systolic BP<90 mmHg) ou organ dysfunction (hypotonia, syncope, incontinence)

Persistant gastrointestinal troubles (abdominal pain, vomiting)

Diagnostic of AnaphylaxisDiagnostic of Anaphylaxis

Criteria 3: Decrease of SBP< 90mmHg or more than 30% compared to basal in adults* after exposition to known allergen.

*In child decrease of SBP is defined as: SBP < 70 mmHg from 1 month to 1 year, below (70 mmHg + [2 x age]) from 1 to 10 years, <90mmHg from 11 to 17 years.

TriggersCommon causes:

• Foods• Bee and wasp stings• Drugs• Latex rubber

Foods reported as triggers

• Peanuts 8

• Fish• Shellfish• Eggs• Milk• Sesame, Pulses etc• Others

Note:Anaphylaxis may be worse in those on beta blockers

Drugs causing anaphylaxis

• Antibiotics (especially penicillin)• Anaesthetic agents• Aspirin• NSAID’S• IV Contrast media• Opioid analgesics

Rare Causes:

• Exercise• Semen• Vaccines

The Big Eight/Most Common Food AllergensThe Big Eight/Most Common Food Allergens

SHELLFISH FISH COWS MILK EGGS

SOYA WHEAT PEANUTS TREE NUTS

International Food Allergen ListInternational Food Allergen List

U.S. TOP “8”•Fish•Crustacean Shellfish•Egg•Milk•Peanuts•Tree-nuts•Soy•Wheat

•Gluten ?

+Sesame+Molluscs+Sulfites +Gluten

CanadaTop 8 Plus

+ Sesame+ Molluscs+ Sulfites+ Gluten + Celery+ Mustard+ Lupin

E.U.Top 8 Plus

+Buckwheat

+ Another 20 allergens are recommended

Japan4 of Top 8*Milk*Egg*Peanuts*WheatPlus+ Buckwheat

+Sesame+Molluscs+Sulfites+Gluten

Australia/NZ Top 8 Plus

+ Gluten (in place of wheat)+ Sulfites

CodexTop 7 Plus

+Sulfites+Gluten (in place of wheat)

Hong Kong Top 7 Plus

INCIDENCE and PREVALENCEINCIDENCE and PREVALENCE

• Indicators:

- prevalence of all suspected allergic reaction with medical assistance

- prevalence of severe reactions

- prevalence of severe anaphylaxis complicated by death

• Results from different ways: registres, allergy network, hospitals, ED, Schools

Prevalence in Emergency Departments

Prevalence in Emergency Departments

Gaeta, 2007-Ann Allergy

12 millions allergic reactions over 12 years (1993 à 2004) in US

1% of all ED visits

1 million per year

12,400 anaphylaxis per year in ED

2000 : 2831 cases2004 : 3573 cases22% increase

French Allergy Vigilance Network

Clin Exp Allergy, 2010

Allergy Network Clinical AspectsAllergy Network Clinical Aspects

Children: 34% Adults: 66%

ED visits: 80.5%

Epinephrine: 44.5%

Hospitalisation rate : 59.3%

Moneret-Vautrin et al Rev Méd Int 2006;120:S70-72

Allergy Network Clinical AspectsAllergy Network Clinical Aspects

Anaphylactic Shock: 47.6%

Severe systemic reactions: 36.7%

Laryngeal Angio-Edema: 12.4%

Severe asthma: 4.4%

Moneret-Vautrin et al Rev Méd Int 2006;120:S70-72

Clinical SignsClinical Signs

Shock

Myocardial infarction

Cardiac arrest

Cardiac anaphylaxis

SymptomsSymptoms

Peripheral vasodilation– vascular permeablility (edema)

Bronchospasm Cardiac arrhythmias Smooth muscle contractions

Laryngeal AngioedemaLaryngeal Angioedema

MortalityMortality Review: 4 for 20,381 cases of anaphylaxis

cared in ED=2 for 10,000

Moneret-Vautrin, 2005-Allergy

0.65 to 2%=1 to 3 for 1 million in Europe

Neugut, 2001-Arch Int Med : 20 for 1 million in US

• Risk Factors:– Delayed adrenalin

administration– Beta blokers, AC Inhibitors– Asthma, co-morbidity– Allergen introduced IV90% of died patients had

dyspnea before then cardiac arrest

Drug allergy=Shock is the main symptom

MortalityMortality

Anaphylaxis and Food AllergyAnaphylaxis and Food Allergy

32 deaths in patients with

age between 2 to 32 ans - peannut >90% of reations - history of asthma - majority didn’t receive

epinephrine

Bock SA et al. J Allergy Clin Immunol 2001;107:191-3

Uniphasic AnaphylaxisUniphasic Anaphylaxis

Antigen Exposure

Treatment

Initial Symptoms

0 Time

Biphasic ReactionBiphasic Reaction

Allergen contact

Treatment Treatment

1 to 38 hours

Initial phase Recurrent phase

Time (h)

Ellis AK, Day JH, Can Med Ass,2003

Meta-analysisMeta-analysis

1995 to 2001 : 5

1- Schwartz, 1995-Allergy Proc : US

2- Klein, 1995-JACI US

3- Stewart, 1995-Q J Med UK

4- Pastorello, 2001-J Chrom Biomed Sc ApplItaly

5- Brown, 2001-JACI Australia

2003 to 2008 : 12

6- Bellou, 2003-Emerg Med J, France7- Brown, 2004-JACI, Australia8- Clarck, 2004-JACI, USA9- Clarck, 2005-JACI, USA10- Haymore, 2005-JACI, USA11- De Villiers Smit, 2005-J Emerg

MedHong Kong12- Luke, 2006-Ann Emerg Med, USA13- Braganza, 2006-Arch Dis Child

Australia14- Gaeta, 2007-Ann Allergy, USA15- Melville N, 2008-Emerg Med J, UK16- De Silva IL, 2008-Allergy, Australia17- Ross MP, 2008-JACI, USA

Type of AllergenType of Allergen

Food : 33%

Hymenoptera Venom : 28%

Drugs : 26%

Epinephrin Administration in EDEpinephrin Administration in ED

15-Ross MP, USA: 19%17-Melville N, UK: 5%

Epinephrin Self-injectedEpinephrin Self-injected

Allergist Follow-upAllergist Follow-up

Hospitalisation after ED CareHospitalisation after ED Care

SUMMARYSUMMARY

• 75 to 85% of anaphylaxis are cared in EDs +++• 4 guideline recommendations not fully respected:

(1) adrenaline at the acute phase,

(2) prescription of self-injected adrenaline,

(3) education of patient,

(4) follow-up by allergist

GuidelinesGuidelines Anaphylaxis network symposium :

J Allergy Clin Immunol 2006 ;117 : 391-7

Self-injected Adrenaline: cardiovascular or respiratory signs and know allergen

Information of patient

Allergy follow-up after ED visit

Monitoring in ED: 8 to 24 h, hospitalisation for severe or recurrent anaphylaxis, asthmatic patient

Guidelines for ED Treatment

Guidelines for ED Treatment

• Suspicion of severe anaphylaxis• ABC• Diagnostic (definition)• 1e line : Adrenaline + Fluid resuscitation:

crystalloïds or saline 0.9%, adult 500 ml to1000 ml ( up to 4000ml), children 20ml/Kg

Jasmeet S. Resuscitation 2008;77:157-169.

A U T H O R S ’ C O N C L U S I O N S• Implications for practice

We found no relevant evidence for adrenaline use in the treatment of anaphylaxis. We are, therefore, unable to make any new recommendations based on the findings of this review. Guidelines on the management of anaphylaxis need to be more explicit about the basis of their recommendations regarding the use of adrenaline.

Adrenaline (epinephrine) for the treatment of anaphylaxiswith and without shock (Review)Sheikh A, Shehata YA, Brown SGA, Simons FERThis is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library2010, Issue 10http://www.thecochranelibrary.com

A U T H O R S ’ C O N C L U S I O N S• Implications for research

Although placebo-controlled trials of adrenaline in anaphylaxis would be unethical, it might be possible to conduct randomized controlled trials comparing two different doses of adrenaline, or two different routes of administration of adrenaline, in addition to other standard-of-care treatments (Simons 2008).

Adrenaline (epinephrine) for the treatment of anaphylaxiswith and without shock (Review)Sheikh A, Shehata YA, Brown SGA, Simons FERThis is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library2010, Issue 10http://www.thecochranelibrary.com

Epinephrine Injection: IM vs. SQEpinephrine Injection: IM vs. SQ

Prospective, randomized, blinded study in childrenT-max was 8 ± 2 minutes after injection of epinephrine 0.3 mg from an EpiPen IM in the vastus lateralis vs. 34 ± 14 minutes (range, 5 to 120) after injection of epinephrine 0.01 mg/kg SQ in the deltoid region.

Simons FER, Gu X, Simons KJ. Epinephrine absorption in adults: intramuscular versus subcutaneous injection. The Journal of Allergy and Clinical Immunology 2001;108:871–3.

Adrenaline I.MAdrenaline I.M

• Adrenaline IM: dilution 1/1000

- Adult : 500 microgramms (0,5ml)- Child > 12 years: 500 microgrammes (0,5ml)- Child 6 to 12 years: 300 microgrammes

(0,3ml)- Child < 6 years: 150 microgrammes (0,15ml)

Jasmeet S. Resuscitation 2008;77:157-169.

Self-injected epinephrine

Self-injected epinephrine

Self-injected epinephrine

Adrenaline I.VAdrenaline I.V• Intravenous adrenaline has been associated with fatal

cardiac arrythmias and myocardial infarction, these cases have been associated with too rapid injection, undiluted doses, or excessive doses (Fischer, 1995; Pumphrey, 2000; Brown, 2001; Montanaro and Bardana, 2002).

• To minimise these adverse effects, the use of intravenous adrenaline is now recommended at a dilution of 1:10,000 (Project Team of the Resuscitation council, UK, 2005).

Adrenaline I.VAdrenaline I.V

• IV: dilution 1/10000 (10 ml with 100 microgrammes/ml adrenaline), routinely used by EPs:

- Adult: bolus of 50 microgrammes (0.5ml)- Child: bolus of 1 microgramme/Kg- If repeated administration=perfusion by pump (1 to

4 microgrammes/min)

Jasmeet S. Resuscitation 2008;77:157-169.

Can epinephrine inhalations be substituted for epinephrine injection in children at risk for systemic anaphylaxis?Simons FE, Gu X, Johnston LM, Simons KJ.Pediatrics. 2000 Nov;106(5):1040-4.

Can epinephrine inhalations be substituted for epinephrine injection in children at risk for systemic anaphylaxis?Simons FE, Gu X, Johnston LM, Simons KJ.Pediatrics. 2000 Nov;106(5):1040-4.

• NO• In a study in children, those treated with

adrenaline inhalers had blood adrenaline levels no higher than a control group treated with placebos.

A U T H O R S ’ C O N C L U S I O N S• Implications for practice

We found no relevant evidence for the use of glucocorticoids in the treatment of an acute episode of anaphylaxis. We are, therefore, unable to make any new recommendations based on the findings of this review. While we do not necessarily suggest that anaphylaxis guidelines no longer recommend glucocorticoids, these guidelines need to be more explicit about the basis of their recommendations regarding the use of these agents (Alrasbi M, Sheikh A. Comparison of international guidelines for the emergency medical management of anaphylaxis. Allergy 2007; 62:838–41.).

Glucocorticoids for the treatment of anaphylaxis (Review)Choo KJL, Simons FER, Sheikh AThis This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library2010, Issue 10http://www.thecochranelibrary.com

Second line treatmentSecond line treatment

• Histamine antagonists

Dexchlorpheniramine=against itching• Corticosteroids

Hydrocortisone-Methylprednisolone=prevent recurrent anaphylaxis

Jasmeet S. Resuscitation 2008;77:157-169.

Guidelines for ED TreatmentGuidelines for ED Treatment

Specific situations

Glucagon : 1-2 mg every 5 min, resistance to adrenaline, patient treaed by β blokers

Cardiac arrest :

follow current guidelines

fluid resuscitation=4 to 8l

adrenaline : 1 to 3 mg IV (3min), 3 to 5 mg (3min),

4 to 10 microg/min pump perfusion

Positive Diagnosis in EDPositive Diagnosis in ED

Medical history to identify allergen

Tryptase

- Specific for mast cells degranulation, confirm

anaphylactic reaction

- Still increased at 6th hour

Lieberman PL et al, J Allergy Clin Immunol 2005;115:S483-523

Biologic tests in anaphylaxisBiologic tests in anaphylaxis

0 30 60 90 120 150 180 210 240 270 300 330

Plasma histamine

Serum tryptase

24-hr Urinary histamine metabolite

T1 = after emergency treatment start, T2 = 1 to 2 h after T1 et T3 at 24 h in the ward. Put serum at -20°C.

Anaphylactic ShockAnaphylactic Shock

020406080

100120140160180

T0 T3 T5 T15 T30 T60

BA

MP

(mm

Hg)

Time (min)

RT

R0

Bellou A. Shock, 2003

Vasodilatation

Effect of NO Synthase, Histamine and Serotonine Inhibition Pathways

Effect of NO Synthase, Histamine and Serotonine Inhibition Pathways

0

100

200

300

400

500

HR

(bea

ts/m

inut

e)

Time (minutes)

NIR

IR

IR+L-NAME+DPH+CIM+DHE

Bellou A. Shock, 2003

New treatments of Anaphylactic ShockVasopressin?

Anesthesiology, V 106, No 5, May 2007

Management of the Anaphylactic shock

Management of the Anaphylactic shockManagement of the Anaphylactic shock

Position: Place victims in a position of comfort. If hypotension is present, elevate the legs until replacement fluids and vasopressors restore the blood pressure

Oxygen. Administer oxygen at high flow rates. Epinephrine. Administer epinephrine to all patients with clinical

signs of shock, airway swelling, or definite breathing difficulty Antihistamines. Administer antihistamines slowly intravenously or

intramuscularly (eg, 25 mg of diphenhydramine). H2 blockers. Administer H2 blockers, such as cimetidine(300 mg

PO, IM, or IV) Inhaled b-adrenergic agents. Provide inhaled albuterol if

bronchospasm is a major feature. If hypotension is present,administer parenteral epinephrine before inhaled albuterol to prevent a possible further decrease in blood pressure.Inhaled ipratropium may be especially useful for treatment of bronchospasm in patients on b-blockers.

Management of Anaphylactic ShockManagement of Anaphylactic Shock

Position:Oxygen. Epinephrine.Antihistamines. H2 blockers. Inhaled b-adrenergic agents.

Management of the Anaphylactic shockManagement of the Anaphylactic shock

Corticosteroids. Infuse high-dose intravenous corticosteroids slowly or administer intramuscularly after severe attacks, especially for asthmatic patients and those already receiving steroids. The beneficial effects are delayed at least 4 to 6 hours

Envenomation. Rarely insect envenomation by bees, but not wasps, leaves a venom sac. Immediately scrape away any insect parts at the site of the sting.Squeezing is alleged to increase envenomation. Judicious local application of ice may also slow antigen absorption. The application of papain (available in meat tenderizers) to the stinger site is a common home remedy that appears to have no therapeutic value.

Glucagon. For patients unresponsive to epinephrine, especially those receiving b-blockers, glucagon may be effective.This agent is short-acting (1 to 2 mg every 5 minutes IM or IV). Nausea, vomiting, and hyperglycemia are common side effects.

Observation. Observe closely up to 24 hours. Many patients do not respond promptly to therapy, and symptoms may recur in some patients (up to 20%) within 1 to 8 hours despite an intervening asymptomatic period

Rapid Progression to Lethal Airway ObstructionRapid Progression to Lethal Airway Obstruction

Close observation is required during conventional therapy Early, elective intubation is indicated for patients with hoarseness, lingual edema, and posterior or oropharyngeal swelling. If respiratory function deteriorates, perform semi elective (awake, sedated) tracheal intubation without paralytic agents

Angioedema. Patients are at high risk for rapid deterioration. Most will present with some degree of labial or facial swelling. Patients with hoarseness, lingual edema, and posterior or oropharyngeal swelling are at particular risk for respiratory compromise

Early tracheal intubation. If intubation is delayed, patients can deteriorate over a brief period of time (0.5 to 3 hours),with development of progressive stridor, severe dysphonia oraphonia, laryngeal edema, massive lingual swelling, facial and neck swelling, and hypoxemia. At this point both tracheal intubation and cricothyrotomy may be difficult or impossible.

During Cardiac Arrest: Key Interventions and Modifications of BLS/ALS Therapy During Cardiac Arrest: Key Interventions and Modifications of BLS/ALS Therapy

Airway, Oxygenation, and Ventilation Death may result from angioedema and upper or lower airway obstruction. Bag-mask

ventilation and tracheal intubation may fail. Cricothyrotomy may be difficult or impossible because severe swelling will obliterate landmarks.

In desperate circumstances, consider the other airway techniques: Fiber optic tracheal intubation Digital tracheal intubation, in which the fingers are used to guide insertion of

a small (#7 mm) tracheal tube Needle cricothyrotomy followed by transtracheal ventilation Cricothyrotomy as described for the patient with massive neck swelling

Support of Circulation : rapid volume resuscitation and administration of vasopressors to support blood pressure. Epinephrine is the drug of choice for treatment of both vasodilation/hypotension and cardiac arrest.

Rapid volume expansion is an absolute requirement.—When anaphylaxis occurs, it can produce profound vasodilation that significantly increases intravascular capacity. Very large volumes should be administered over very short periods; typically 2 to 4 L of isotonic crystalloid should be given

During Cardiac Arrest: Key Interventions and Modifications of BLS/ALS Therapy During Cardiac Arrest: Key Interventions and Modifications of BLS/ALS Therapy

High-dose epinephrine IV (ie, rapid progression to high dose) should be used without hesitation in patients in full cardiac arrest.—A commonly used sequence: 1 to 3 mg IV (3 minutes),3 to 5 mg IV (3 minutes), then 4 to 10 mg/min.

Antihistamines IV. There is little data about the value of antihistamines in anaphylactic cardiac arrest, but it is reasonable to assume that little additional harm could result.

Steroid therapy. Although steroids should have no effect if given during a cardiac arrest, they may be of value in the post resuscitation period.

Asystole/PEA Algorithms. Because the arrest rhythm in anaphylaxis is often PEA or asystole, the ILCOR panel recommended adding the other steps in the Asystole and PEA Algorithms: Administration of atropine—Transcutaneous pacing

Prolonged CPR. Cardiac arrest associated with anaphylaxis may respond to longer therapy than usual.—In these circumstances the patient is often a young person with a healthy heart and cardiovascular system.Rapid correction of vasodilation and low blood volume is required.—Effective CPR may maintain sufficient oxygen delivery until the catastrophic effects of the anaphylactic reaction resolve

CONCLUSIONCONCLUSION

• EPs : critical role=first line• Improve knowledge in Allergy• Use Adrenaline even without hypotension• Collaboration with allergist is essential

• Develop research in anaphylaxis

Càm on !abdelouahab.bellou@chu-rennes.frerevue@ch-chartres.fr