Dr. Zohair Al aseri

1
Anaphylaxis

• Dr. Zohair Al aseri
• FRCPC Emergency Medicine
• FRCPC Critical Care Medicine
• Assistant Professor
• Chairman Dept. of Emergency Medicine
• College of Medicine
• King Saud University Hospitals

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52 y o m pt presented to er c/o
CASE 1

• Vomiting blood 2 times _at_ home
• NO other complaints
• PMH PUD 10 y ago, HTN
• Med ACEI metoprolol
• V/S tachy
• CNS, CHEST HEART exam were normal
• Hg 50 ,
• blood transfusion started

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52 y o m pt presented to ER c/o vomiting blood
CASE 1

• GI consulted _at_ 1.00 am , came decided to do
  endoscope in ER

Procedure started by sedation propafol iv
lidocain spray
Pt became hypotensive , itching all over ,a/w
swelling
GI staff decided to leave come back again If
the pt became more stable.
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52 y o m pt presented to ER c/o vomiting blood
CASE 1

• What is your diagnosis?

• What is your 1st line treatment ?

• What is your plan if your pt remain
  hypotesive after resuscitation?

• What are the indications of intubation in this
  pt?

• What are your choice of medication for
  induction paralysis ?

• What about post intubation sedation pain
  control ?

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Anaphylaxis

• Definition
• Anaphylaxis is derived from the Greek word ana
  meaning backward or against and phylaxis meaning
  protection
• There is no universally accepted clinical
  definition of anaphylaxis

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Epidemiology in SA
Anaphylaxis

• Data regarding the incidence and prevalence of
  anaphylaxis and the number of deaths caused by it
  are limited.

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Etiology
Anaphylactic (IgE dependent)
Foods
Medications (eg, antibiotics)   Aspirin
NSAID Venoms Latex
Allergen vaccines Animal or human
proteins Polysaccharids
Exercise
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Anaphylaxis
Etiology
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Anaphylaxis
Etiology
Cytotoxic Transfusion reactions to cellular
elements (IgG,Igm)
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Etiology
Anaphylaxis

• Idiopathic anaphylaxis is one of the most common
  causes, accounting for approximately one third of
  cases in retrospective studies
• Its a diagnosis of exclusion.

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Pathophysiology
Anaphylaxis

• Some authors reserve the term anaphylaxis only
  for IgE-dependent events and the term
  anaphylactoid to describe IgE-independent
  reactions that otherwise are clinically
  indistinguishable.

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Anaphylaxis
Pathophysiology
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Pathophysiology
Biochemical mediators

• Histamine
• Tryptase
• Platelet-activating factor
• Heparin

• PGD
• Leukotriene
• Histamine-releasing factor
• Chymase

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Pathophysiology
Anaphylaxis
?

• Postmortem serum tryptase might be useful in
  establishing anaphylaxis as the cause of death in
  subjects experiencing sudden death.
• Increased postmortem tryptase levels have been
  reported
• 12 of healthy adults with sudden death
• 40 of victims of (SIDS)

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Anaphylactic transfusion reactions

• Recent findings Anti-IgA is not responsible for
  most reactions.
• Anti-haptoglobin antibodies are responsible for
  more reactions than anti-IgA in Japan.
• The cause of most reactions is still not known.
• The incidence of reactions to platelets is the
  highest compared with fresh frozen plasma and red
  blood cells.

• Anaphylactic transfusion reactions. Current
  Opinion in Hematology. 10(6)419-423, November
  2003.Gilstad, Colleen W.

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14100 14100 11,000 15,000 112,000 1100,000
1150,000
Febrile (FNHTR) Allergic Delayed
hemolytic TRALI Acute hemolytic Fatal
hemolytic Anaphylactic
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Risks associated with transfusion of cellular
blood components in Canada

• The most frequent potentially severe outcomes for
  red cell transfusion were hemolytic reactions and
  volume overload
• for platelet transfusion were major allergic
  reactions and bacterial contamination

Comprehensive review of risks associated with
allogeneic red blood cell and platelet
transfusions in Canada.
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Domen RE, Hoeltge GA Allergic transfusion
reactions. Arch Pathol Lab Med 2003, 127316-320.
Nine-year retrospective review of all transfusion
reactions reported to the Cleveland Clinic
transfusion service

• A 9-year retrospective review
• "severe allergic" reactions occurred in 153,612
  blood components
• 19630 platelets
• 128,831 FFP
• 157,869 RBC transfusions

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Manifestations
SKIN

• Generalized urticaria and angioedema are the
  most common manifestations .
• Cutaneous manifestations might be delayed or
  absent in rapidly progressive anaphylaxis.

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Manifestations
SKIN

• Periorbital edema
• Perioral edema
• Diaphoresis
• Itching
• Burning

• Increased skin temperature (redistribution of
  blood)
• Urticaria (hives)
• Flushing

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Anaphylaxis
Manifestations

• The next most common manifestations are The
  respiratory symptoms

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Manifestations
Respiratory

• SIGNS
• Increased RR
• Stridor (laryngeal edema)
• Wheezing (bronchospasm)
• Decreased pulmonary compliance
• Pulmonary edema
• Respiratory failure

• SYMPTOMS
• Dyspnea
• Chest discomfort
• Coughing
• Sneezing

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Manifestations
CVS

• Hypotension
• Increased HR
• Decreased svr
• Dysrhythmias

• Retrosternal pain
• MI
• Cardiac arrest
• ECG Changes

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Manifestations
Anaphylaxis

• CNS
• Non-specific
• Disorientation
• LOC
• Dizziness
• Light-headedness
• Malaise

• GI
• Non-specific
• Vomiting
• Diarrhea
• Nausea
• Abdominal pain

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ED Anaphylaxis
A review of 142 patients in a single year

• Laryngeal edema 15 (10.6)
• Hoarseness 14 (9.9)
• SBP lt90 mmHg 13 (9.2)
• GCS lt15 4(2.8)
• Loc 3 (2.1)
• Stridor 2 (1.4)
• Cyanosis 2 (1.4)

• Dyspnoea 61 (43)
• Wheeze 50 (35.2)
• Vomiting 27 (19.0)
• B.spasm 26 (18.3)
• Syncope
• dizziness 21 (14.8)
• R. rate 25 19 (13.4)

133 (94) of the 142 patients had cutaneous
features.
Anthony F. T. Brown MB Brisbane, Australia (J
Allergy Clin Immunol 2001
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Transfusion Reaction
Signs

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Transfusion Reaction
Symptoms

• Feeling of apprehension or something wrong
• Agitation
• Flushing
• Pain at venepuncture site
• Pain (abdomen , flank or chest )

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TREATMENT
Anaphylaxis

• Stop Administration of Antigen (blood)
• Establish and maintain a/w
• 100 oxygen administration,
• intravascular volume expansion.
• Epinephrine
• Systemic glucocorticosteroid

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AIR WAY
TREATMENT

• Low Threshold
• Tube Size?
• Induction Agent?
• paralytic agent?

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Bronchospasm
Anaphylaxis

• For bronchospasm resistant to epinephrine

• Give Nebulized (albuterol, salbutamol)
• repeated doses

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Persistent Bronchospasm
Anaphylaxis

• Aminophylline, a phosphodiesterase inhibitor,
  weak bronchodilator that also increases RL
  ventricular contractility and decreases pulmonary
  VR.
• An IV loading dose of 5 to 6 mg/kg of
  aminophylline given over 20 m. should be followed
  by an infusion of 0.5 to 0.9 mg/kg /h

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Anaphylaxis IVIA
IV Induction agent
Etomidate
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Anaphylaxis IVIA
IV Induction agent
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Volume Expansion
Anaphylaxis

• Volume expansion is important
• Initially, 1 to 3 L of RL ,NS

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Catecholamines
Anaphylaxis

• Life-saving
• First-line catecholamines include epinephrine
• Dopamine????

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EPINEPHRINE
Anaphylaxis

• a1 -adrenergic
• Vasoconstriction
• ß1 -adrenergic
• Vasoconstriction
• Increased peripheral vascular resistance
• Increases myocardial contractility
• Decreased mucosal edema)

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EPINEPHRINE
Anaphylaxis

• ß2 -adrenergic effects are of primary importance
• Bronchodilation
• Release of histamine, tryptase, and other
  chemical mediators of inflammation from mast
  cells and basophils by cAMP production)

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EPINEPHRINE
Contraindication

• There are no absolute contraindications to
  epinephrine administration in anaphylaxis

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HOW DO YOU GIVE IT?
EPINEPHRINE

• The UK consensus panel on emergency guidelines
  states that the subcutaneous route of
  administration for epinephrine has no role in
  anaphylaxis

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Epinephrine absorption in adults

• IM versus SQ injection
• Prospective, randomized, blinded placebo-
  controlled 6-way crossover study in healthy
  allergic men age 18 to 35 y
• CONCLUSION
• IM injection of epinephrine into the thigh is
  the preferred method of administration in the
  initial treatment of anaphylaxis

F. Estelle R. Simons MD (Journal of Allergy and
Clinical Immunology 2001)
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Epinephrine absorption in children
Anaphylaxis

• Prospective, randomized, blinded, study in 17
  children with a history of anaphylaxis
• SQ V/S IM from autoinjector.
• Plasma epinephrine concentrations, HR, BP, and
  adverse effects were monitored.

F. Estelle R. Simons MD Winnipeg, Manitoba,
Canada Allergy and Clinical Immunology 
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Epinephrine absorption in children
The IM route of injection is preferable.
Epinephrine SQ
0.27 0.04 Epinephrine IM
0.3
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IM Epinephrine

• The IM route has several benefits
• There is a greater margin of safety.
• It does not require intravenous access.
• The IM route is easier to learn.
• The best site for IM injection is the
  anterolateral aspect of the middle third of the
  thigh.

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IM Epinephrine
Adrenaline IM dose adults 0.5 mg IM ( 500
micrograms 0.5 mL of 11000) adrenaline Adrenal
ine IM dose children gt 12 years 500 micrograms
IM (0.5 mL) i.e. same as adult 300 micrograms
(0.3 mL) if child is small or prepubertal gt 6
12 years 300 micrograms IM (0.3 mL) gt 6 months
6 years 150 micrograms IM (0.15 mL) lt 6 months
150 micrograms IM (0.15 mL)
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IV EPINEPHRIN

• IV Epiniphrine
• Indications
• 1) Shock
• 2) Coma hypotension
• 3) Stridor a/w edema
• 4) No response to I/M epiniphrine

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Anaphylaxis
IV EPINEPHRIN
0.1 mg (0.1 ml) of 11,000 with 10 ml of n/s.
This is equivalent to a 100 mcg bolus given at
10 mcg/min. Once therapy has begun, a
continuous infusion could be delivered with 0.5
to 5 mcg/min titrated to clinical response.
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Epinephrine infusions
Anaphylaxis

• Useful in patients with persistent hypotension or
  bronchospasm after initial resuscitation
• Infusions should be started at 5 to 10 µg/min
  (approximately 0.050.1 µg/kg per minute) and
  titrated to correct hypotension.

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Catecholamine Infusions
Anaphylaxis

• Norepinephrine infusions may be required
• 5 to 10 µg/min (0.050.1 µg/kg per mi)
• and titrated to correct hypotension.

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Anaphylaxis
Steroid
Inject hydrocortisone slowly intravenously or
intramuscularly, The dose of hydrocortisone for
adults and children depends on age gt12 years and
adults 200 mg IM or IV slowly gt6 12 years 100
mg IM or IV slowly gt6 months 6 years 50 mg IM
or IV slowly lt6 months 25 mg IM or IV slowly
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Antihistamine
Anaphylaxis

• Ranitidine
• 50 mg in adults (1 mg/kg) in children, diluted in
  5 dextrose to a total volume of 20 mL and
  injected IV over 5 minutes.
• Cimetidine
• (4 mg/kg) may be administered to adults, but no
  pediatric dosage in anaphylaxis has been
  established.

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H1 and H2 antagonists

• Improve outcomes???
• a randomized, double-blind, 91 adult patients
  with acute allergic syndromes were treated with
• 50 mg of diphenhydramine and Placepo
• 50 mg of diphenhydramine and 50 mg of ranitidine

Lin RYAnn Emerg Med. November 2000
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Antihistamine
H1 and H2 antagonists
Lin RYAnn Emerg Med. November 2000
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Antihistamine
Anaphylaxis

• Conclusion
• These findings favour the recommendation for
  using combined H1 and H2 antihistamines in acute
  allergic syndromes.
• Lin RYAnn Emerg Med. November 2000

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Anaphylaxis
Antihistamine

• Unlikely to be lifesaving in a true anaphylaxis
• Inject chlorphenamine slowly IV or IM
• The dose of chlorphenamine depends on age
• gt12 years and adults 10 mg IM or IV slowly
• gt6 12 years 5 mg IM or IV slowly
• gt6 months 6 years 2.5 mg IM or IV slowly
• lt6 months 250 micrograms/kg IM or IV slowly

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Biphasic Anaphylaxis
Anaphylaxis

• Rare.
• Rates between 5 to 20.
• Recurrence Ranging from mild to sever
  life-threats
• TTT
• Prolonged observation is required.

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Risk Of Biphasic Anaphylaxis

• Biphasic Anaphylactic Reactions in
  Paediatrics
• Iincidence 6
• Delayed epinephrine injection
• Steroids do not prevent biphasic reactions
• The time from the onset of symptoms to the
  reaction

Joyce M. Lee MD Children's Hospital, Harvard
Medical School
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Anaphylaxis in Pregnancy
Anaphylaxis

• The management of anaphylaxis in pregnancy
  consists of
• Maternal Resuscitation
• Close monitoring of the fetal status
• Iimmediate delivery of the fetus if compromised.

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Anaphylaxis in Pregnancy
Anaphylaxis

• Treatment depends on the severity of the reaction
  and consists of
• Fluid resuscitation
• Oxygen
• Epinephrine
• H1 and H2 blockers
• Corticosteroids.

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• What are the bad prognostic signs of anaphylaxis?

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ß-Adrenergic blockade
Anaphylaxis

• Paradoxical bradycardia
• Profound hypotension
• Severe bronchospasm.
• These agents might impede treatment effectiveness
  with epinephrine.

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ß-Adrenergic blockade
TTT

• Glucagon, 1-5 mg (20-30 µg/kg
• maximum, 1 mg in children), IV over 5
  minutes, followed by an infusion of 5-15 µg/min.
• (Aspiration precautions should be observed
  because glucagon may cause n v.)

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ANAPHYLAXIS and ACE
Persons taking ACEI and/or angiotensin II
antagonists will have a diminished compensatory
response
Hypotension
release of ACE leading to the production of
angiotensin 2, a potent vasocontrictor
release of epinephrine from the adrenal cortex
Site of action of ACE inhibitors angiotensin
2 antagonist
Vasocontriction Decreased Vascular
Permeability
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The heart in anaphylaxis
Anaphylaxis

• High-dose epinephrine administered iv (ie, rapid
  progression to high dose).
• 1-3 mg (110,000 dilution) slowly administered
  iv over 3 minutes
• 3-5 mg administered iv over 3 minutes
• 4-10 µg/min infusion.

1
2
3
3
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Anaphylaxis
OUTCOME    

a)RESPIRATORY b)LOC
c)CVS
What is the NO. 1 cause of death in anaphylaxis?
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Anaphylaxis
Causes of Death In Anaphylaxis
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(No Transcript)
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PROGNOSIS

• Bad prognostic signs
• A/W
• B.Asthma
• Rapid manifestations after exposure
• Late epi inj.
• epi requirement
• CAD
• B.B
• ACEI

be aware prepared
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Anaphylaxis

• Questions

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Anaphylaxis Algorithm
(Hypotension due to Antigen )
Check ABCs in Monitored bed
Low threshold for Intubaion if any one of the
following present Persistent airway and/or sever
tongue swelling Respiratory Failure Respiratory
Distress Hypoxia
Stop Administration of Antigen (i.e. blood)

• 100 oxygen administration, establish and
  maintain a/w

0.3 mL Epinephrine 11,000 IM in lateral aspect
of the thigh Repeated dose if still hypotensive
in 3-4 minutes
Start Glucagon, 1-5 mg (20-30 µg/kg (maximum,
1 mg in children), iv bolus over 5 minutes
followed by infusion of 515 µg/min.
For bronchospasm resistant to epinephrine give
nebulized (salbutamol)
Reassess ABCs
IV N/S 5001000ccBolus
Yes
Diphenhydramine 50 mg of IV/IM
D/C Home with prednisone 50 mg once per day for 5
days , diphenhydramine 25 50 mg po Q 68 h for
2 days and consider 0.3 mg epi pen prescription
in food allergy induced anaphylaxis
Is the patient on B. Blockers?
Methylprednisolone (Solu-Medrol) 125 mg IV
NO
Yes
Ranitidine 50 mg in adults (1 mg/kg) in children,
diluted in 5 dextrose to a total volume of 20 mL
and injected IV over 5 minutes
Still Hypotension
NO
Stable
Reassess ABCs
Observe for 6 hours
Reassess ABCs
NO
Unstable
IV Epinephrine
NO
High Risk Patient
Hypotension
Yes
ICU Admission
Yes

• Airway compromise
• Requirement of high doses of epinephrine
• History of Cornary Artery Disease
• History of B.Asthma
• Patient on B.Blockers or ACEI

High Risk Patient
IV Epinephrine 0.1 mg (0.1 ml) of 11,000 with
10 ml of n/s. this is equivalent to a 100 mcg
bolus given at 10 mcg/min. a continuous infusion
of 0.5 to 5 mcg/min titrated to clinical
response. Epinephrine should not be administered
IV to patients with normal BP
Prepare for difficult air way and call
anaesthesia for back up
Prepared by Dr Zohair Alaseri Feb 2006