Anaphylaxis: Rapid recognition and treatment

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Anaphylaxis Rapid recognition and treatmentDR
jarahzadehIntensivist
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ANAPHYLAXIS

• In a few seconds it was extremely ill
• breathing became distressful and panting
• it could scarcely drag itself along, lay on
  its side, was seized with diarrhea, vomited blood
  and died in twenty five minutes.
• Charles
  Richet 1902
  
• 
  

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ANAPHYLAXIS

• Instead of inducing tolerance ( prophylaxis),
• Richets experiments in dogs injected with
• sea anemone toxin resulted in lethal
• responses to doses previously tolerated.
• He coined the word ana (without) phylaxis
• (protection). He won the Nobel prize for this
• work.

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Definition of Anaphylaxis

• Definition in common use with various versions
  but may be supplanted
• An acute allergic reaction resulting in
  widespread allergic symptoms which involves two
  or more organ systems, and is potentially
  life-threatening, often resulting from an
  IgE-mediated mechanism.
• Anaphylactoid term falling into disuse but
  meant to describe anaphylaxis without IgE
  involvement ie a non-allergic mechanism.
• Anaphylaxis now describes a clinical event,
  regardless of mechanism

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Current Definition of Anaphylaxis

• Short practical form Anaphylaxis is a serious
  allergic reaction that is rapid in onset and may
  cause death
• (Sampson et al. Second symposium on the
  definition and management of anaphylaxisJ
  Allergy Clin Immunol 2006117391-7)
• More detailed diagnostic criteria are presented
  in slides at end of workshop

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• Anaphylaxis is highly likely when any ONE of the
  following 3 criteria is fulfilled
• 1. Acute onset of an illness (minutes to several
  hours) with involvement of the skin, mucosal
  tissue, or both (eg, generalized hives, pruritus
  or flushing, swollen lips-tongue-uvula)
• AND AT LEAST ONE OF THE FOLLOWING
• A. Respiratory compromise (eg, dyspnea,
  wheeze-bronchospasm, reduced PEF in older
  children and adults, stridor, hypoxemia)
• B. Reduced BP or associated symptoms of
  end-organ dysfunction (eg, hypotonia, collapse,
  syncope, incontinence)
•  

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• 2. TWO OR MORE OF THE FOLLOWING that occur
  rapidly after exposure to a likely allergen for
  that patient (minutes to several hours)
• A. Involvement of the skin-mucosal tissue (eg,
  generalized hives, itch-flush, swollen
  lips-tongue-uvula)
• B. Respiratory compromise (eg, dyspnea,
  wheeze-bronchospasm, stridor, reduced PEF in
  older children and adults, hypoxemia)
• C. Reduced BP or associated symptoms (eg,
  hypotonia, collapse, syncope, incontinence)
• D. Persistent gastrointestinal symptoms (eg,
  crampy abdominal pain, vomiting)
•  

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• 3. Reduced BP after exposure to a known allergen
  for that patient (minutes to several hours)
• A. Infants and children low systolic BP (age
  specific) or greater than 30 percent decrease in
  systolic BP
• B. Adults systolic BP of less than 90 mm Hg or
  greater than 30 percent decrease from that
  person's baseline

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IgE Mediated Allergic Reactions

• Allergen bridges 2 molecules of IgE causing
  mediator release
• Early phase manifestations are due to release of
  preformed mediators , histamine tryptase, and
  newly generated leukotrienes, which cause
• vasodilation and increased vascular
  permeability,itch , sneeze and bronchospasm
• Late phase manifestations are due to recruitment
  of eosinophils, neutrophils TH2 cells and other
  inflammatory cells 4-12 hrs later due to
  cytokines released in the early phase eg platelet
  activating factor, TNFa, eosinophil chemotactic
  factor, IL 3-5 etc
• As well , interleukin 4 formed by mast cells can
  stimulate further production of IgE and
  potentiate other allergic reactions

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EARLY LATE PHASE
Immediate symptoms (mins to few hrs) due to mediator release Begins 4-12 hrs after allergen exposure due to inflammatory cell influx
Allergic rhinitis rhinorrhea, sneeze, itch Asthma bronchospasm, wheeze, dyspnea Urticaria short lived lesions lt 24 hrs, responds well to antihistamines Anaphylaxis occurs Allergic rhinitis nasal congestion Asthma increased bronchial irritability and inflammation with increased tendency to asthma flareups and increased severity Urticaria-lesions last gt24 hrs, poor response to antihistamines Anaphylaxis -No late phase

• .

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EARLY LATE PHASE
Responds to symptom-relief therapy antihistamines for urticaria and rhinitis bronchodilators for bronchospasm Limited response to symptom-relief therapy
Response to steroids minimal for acute relief but symptoms subside with control of late phase reaction and its effects on target cells Responds to steroids

• .

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ACTIONS OF HISTAMINE

• Peripheral vasodilation
• Increased vascular permeability
• Altered cardiac conduction
• Bronchial/intestinal smooth muscle contraction
• Nerve stimulation-Cutaneous pruritus/pain
• Increased glandular mucus secretions

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CLINICAL MANIFESTATIONS OF ALLERGY

• Knowing the actions of histamine and other
  mediators , what would you predict to be the
  clinical effects on the body?

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CLINICAL MANIFESTATIONS OF ALLERGY

• Vasodilation erythema, nasal congeston,
  hypotension, anaphylaxis
• Increased vascular permeability urticaria,
  hypotension, anaphylaxis
• Smooth muscle spasm asthma, intestinal cramps,
  diarrhea, anaphylaxis
• Mucus secretion allergic rhinitis, asthma
• Nerve stimulation-itch, sneeze

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URTICARIA

• Raised central white or red wheals
• Surrounding erythema or flare, with itch or
  burning
• Histamine mediated
• Varies in shape size circular, gyrate,
  linear, isolated or coalescent
• Well demarcated, blanch with pressure
• Predisposition to warm areas, pressure sites
• Lasts hours, max 24 - 48

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ANGIOEDEMA

• Diffuse skin colored subcutaneous swelling
• Pathology similar to urticaria except it occurs
  in deeper subcutaneous tissues
• Not itchy or painful, unless in confined site
• Can be histamine, bradykinin etc mediated
• Can last hours or days
• Not very responsive to antihistamines
• Often found in 40 of urticaria cases

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ANAPHYLAXIS OVERVIEW

• Anaphylaxis is a severe, potentially fatal
  systemic allergic reaction that occurs suddenly
  (minutes to hours) after contact with an
  allergy-causing substance
• Death can occur in minutes, usually due to
  closure of airways
• Allergic reaction affects many body systems
  rash swelling, breathing difficulties, vomiting
  diarrhoea, heart failure low blood pressure
  ?
  ANAPHYLACTIC SHOCK

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Anaphylaxis Rapid recognition and treatment
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Fatal anaphylaxis
Minutes to cardiac arrest Minutes to cardiac arrest
Median Range
55 iatrogenic 5 1 80
37 food 30 6 360
32 venom 15 4 120
Pumphrey RSH, Clinical and experimental allergy,
2000
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Anaphylaxis Rapid recognition and treatment
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recognition

• Underrecognized, undertreated
• Most important diagnosis marker is trigger
• Over 40 symptoms and signs described

cutaneuos gt80
respiratory up to 70
gastrointestinal up to 40
cardiovascular up to 35
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CLINICAL MANIFESTATIONS OF ANAPHYLAXIS

• SKIN- urticaria, angioedema, pruritus, erythema
• RESPIRATORY- rhinitis, conjunctivitis, cough,
  dyspnea, wheeze, stridor, voice change
• GI throat swelling or tightness, dysphagia,
  vomiting, diarrhea, cramps
• CVS hypotension, dizziness, syncope, cyanosis,
  secondary myocardial infarction
• CNS hypoxic seizures

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Anaphylaxis clinical features

• Skin 85
• Upper respiratory 56
• Lower respiratory 47
• Cardiovascular 33
• (30of adults, 5 of children)
• Gastrointestinal 30
• Rhinitis 16
• BIPHASIC ANAPHYLAXIS 5 - 8

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Anaphylaxis Causes of Death

• Upper and/or Lower Airway Obstruction (70)
• Cardiac Dysfunction (24)

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Diagnostic criteria

• Criterion 1 acute onset (minutes hours)
  involving skin and/or mucosa at least one
• Respiratory compromise
• Reduced blood pressure
• Criterion 2 At least 2 of the following, minutes
  hours after exposure TO A LIKELY ALLERGEN FOR
  THAT PATIENT
• Skin/mucosal involvement
• Respiratory compromise
• Reduced blood pressure
• Gastrointestinal symptoms
• . Criterion 3 Reduced blood pressure minutes
  hours after exposure TO A KNOWN ALLERGEN FOR THAT
  PATIENT

J Allergy Clin Immunol, 2006
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BIPHASIC ANAPHYLAXIS

• What is the importance?

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BIPHASIC ANAPHYLAXIS

• Early signs may be deceptively mild, resolves
  with or without treatment the biphasic phase
  then occurs and may lead to fatal outcome
• Delayed epinephrine treatment or inadequate dose
  are risk factors
• Severe initial phase may predispose to biphasic
• Important to monitor in ER for 4-6 hrs after an
  anaphylactic reaction
• Steroids may not prevent it, but often used

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Potentional pitfalls in recognition of anaphylaxis

• Absent / missed skin symptoms
• Non-specific signs of hypotension (confusion,
  collapse, incontinence...)
• Certain conditions (surgery)
• DD asthma exacerbation
• Lab tets to support Diagnosis (tryptase)

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Causes of Anaphylaxis

• Food allergy
• Medication allergy
• Insect (hymenoptera) sting allergy
• Physical eg exercise, cold,
• Latex allergy
• Allergy to vaccines, hormones, seminal fluid
• Allergic reactions to immunotherapy, skin tests
• Idiopathic

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Most common food causes of anaphylaxis in North
America

• Common (Anaphylaxis) Less Common
• Peanut ) ????? ????? (
  Soy(?????)
• Tree Nuts ) (???? ?????? Wheat(????)
• Fish
• Shellfish Crustaceans Shellfish
  Mollusks
• Cows Milk Sulfites
• Egg
• Sesame(????)

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IMMUNOLOGICAL MECHANISMS OF ANAPHYLAXIS

• .

IgE-mediated Foods, some drugs eg penicillin, insulin, insect venom, latex, biologicals eg allergy serum
Direct mast cell degranulation Radiocontrast material, tubocurarine, dextran, opiates eg codeine
Complement activation Incompatible drug transfusion ( type II hypersensitivity), tissue plasminogen activator
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IMMUNOLOGICAL MECHANISMS OF ANAPHYLAXIS

• .

COX-1 (cyclooxygenase1 ) inhibition ASA Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
Unknown (yes, this is considered a mechanism) Idiopathic anaphylaxis Local anaesthetics Physical (Exercise, Cold-induced anaphylaxis) Sulfites
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Anaphylaxis Rapid recognition and treatment
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GENERAL MANAGEMENT OF ANAPHYLAXIS

• Airway
• Breathing
• Circulation
• But use epinephrine promptly

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Fatal anaphylaxis risk factors

• Concomitant asthma
• No epinephrine
• Non effective epinephrine
• Upright posture
• Other cardiopulmonary disease

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Fatal anaphylaxis risk factors

• Concomitant asthma
• No epinephrine
• Non effective epinephrine
• Upright posture
• Other cardiopulmonary disease

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Initial AnaphylaxisTreatment

• Epinephrine (adrenaline) is first line treatment
• Epinephrine preferably given IM
• Antihistamines bronchodilators are not first
  line treatment but may be given after
  epinephrine.
• Transportation to hospital should not be delayed
  to administer these once epinephrine has been
  given.

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Management of anaphylaxis Initial

• Epinephrine 0.01mg/kg (max 0.5mg) IM X3, every
  5-20min as needed. In severe cases epinephrine IV
• H1 antagonists eg Diphenhydramine (Benadryl)
  25-100mg
• H2 antagonists eg cimetidine
• IV fluids to maintain venous access and
  circulation
• Oxygen
• Corticosteroids

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Management of anaphylaxis Bronchospasm

• Inhaled bronchodilators eg salbutamol. IV if
  unresponsive to inhaled
• Oxygen
• Intubation and ventilation if needed

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Management of anaphylaxis Laryngeal edema

• Racemic epinephrine via nebulizer
• Intubation or cricothyrotomy or tracheostomy

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Management of anaphylaxis Hypotension

• Trendelenberg position
• Volume expansion with crystalloid
• Vasopressors eg dopamine, norepinephrine,
  metaraminol, vasopressin
• Glucagon esp if on beta-blocker

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Treatment of Anaphylaxis in Beta Blocked Patients

• Give epinephrine initially.
• If patient does not respond to epinephrine and
  other usual therapy
• Glucagon 1 mg IV over 2 minutes
• Isoproterenol (a pure beta-agonist ß1ß2 agonist)
• 1 mg in 500 ml D5W starting at 0.1
  mcg/kg/min

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EFFECTS OF EPINEPHRINE

• Increases BP, reverses peripheral vasodilation ,
  ( alpha-adrenergic activity)
• Reduces urticaria and angioedema by
  vasoconstriction (alpha)
• Bronchodilation relaxes bronchial smooth muscle
  (beta-2 adrenergic activity)
• Increases cardiac contractility force and
  volume, increasing heart rate BP (beta-1)
• Prevents further mast cell degranulation (beta)

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SIDE EFFECTS OF EPINEPHRINE

• Based on the effects of epinephrine, what would
  you predict as the possible side effects?
• What conditions or factors would you consider as
  higher risk for side effects of epinephrine use?

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SIDE EFFECTS OF EPINEPHRINE

• Increased heart rate, shakiness, dizziness,
  headache, anxiety, fear
• Hypertension and intracranial bleed
• Myocardial ischemia, infarction, arrythmia

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Epinephrine Auto-injectors

• Epipen
• Epipen Jr. (0.15 mg)
• Epipen (0.30 mg)
• One dose auto-injection
• Twinject
• Twinject 0.15
• Twinject 0.30
• Two doses first is an auto-injection, second
  dose is manual

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Treatment

• Removal of the causing agent
• Epinephrine
• 0.3 0.5 mg (0.01mg/kg) i.m. (vastus lateralis),
  repeat 5 15 minutes
• i.v. titrate the dose
• Oxygen
• Intubate, if stridor or arrest
• Trendelenburg position
• i. v. Fluids (cristalloids vs. colloids?)
• Steroides, antihistamines, inhaled beta agonists,
  glucagon of secondary (and questionable)
  importance

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Questions? Thank you for attention !