Anaphylaxis

Iris Rengganis
Divisi Alergi Imunologi Klinik
Departemen Ilmu Penyakit Dalam
FKUI/RSCM

Hypersensitivity Tipe I
Allergic Reaction
ALLERGEN

MAST CELL
IgE
SYNTHESIS DEGRANUL

Med. Of
Anaphyl.

LOCAL ANAPHYLAXIS
ALLERGIC
RHINITIS
ASTHMA
AT.ECZEMA
URTICARIA
FOOD ALLERGY

Roitt I, ea, Really Essential Medical Immunology, Blackwell Science, 2000; 126

Allergic Reaction
Ag

APC
AgHLA

Th2
Cell

BCell

IgE

Allergen
Ag
(subsequent
exposure)

Mast cells,
Basophils
Adapted from: The Allergy & Asthma Report 1999. p S-12

Late Fase Allergic Respons

Sneeze

IL-5

Itch
Mucus
Smooth muscle
Congestion

Histamine

EOSIN

PGD2
Tryptase
TNF

Courtesy of Dr. Raymond Mullins

Atopic dermatitis
Urticaria
Anaphylaxis

Allergic Inflammatory
allergen

IgE

B-cell switching
IgE production
IL-4
IL-13

APC

bronchial
epithelium

Th2
cell
Cytokine
mediators
IL-16+
IL-12
IL-18

inflammation, remodelling, symptoms

Holgate ea, Allergy 2nd ed, Mosby Int, 2001: 293

IL-3,-4,-5,-9
GM-CSF
eosinophil

MBP
ECP
EPO
LTC4

CD-40
CD-40L
activated
Th2 cell

mast cell
FcRI

activation
histamine,
tryptase,
PGD2,
LTC4

Anaphylaxis Reaction

Gejala & Tanda Anafilaksis Berdasarkan

Organ Sasaran
Sistem

Gejala dan Tanda

Umum/Prodromal

Lesu, lemah, rasa tak enak yang sukar dilukiskan,

rasa tak enak di dada & perut, rasa gatal di hidung
& palatum

Pernapasan
- Hidung
- Larings
- Lidah
- Bronkus

Hidung gatal, bersin, & tersumbat

Rasa tercekik, suara serak, sesak napas, stridor,
edema, spasme
Edema
Batuk, sesak, mengi, spasme

Kardiovaskular

Pingsan, sinkop, palpitasi, takikardia, hipotensi

sampai syok, aritmia. Kelainan EKG : gelombang T
datar, terbalik, atau tanda infark miokard

Gastrointestinal

Disfagia, mual, muntah, kolik, diare yang kadang

disertai darah, peristaltik usus meninggi

Kulit

Urtika, angioedema di bibir, muka atau ekstremitas

Mata

Gatal, lakrimasi

Susunan saraf pusat

Gelisah, kejang

Anaphylaxis

Manifestations of Systemic Anaphylaxis

Mekanisme & Obat Pencetus

Anafilaksis
Anafilaksis (melalui IgE)
Antibiotik (penisilin, sefalosporin)
Ekstrak alergen (bisa tawon, polen)
Obat (glukokortikoid, thiopental, suksinilkolin)
Enzim (kemopapain, tripsin)
Serum heterolog (antitoksin tetanus)
Protein manusia (insulin, vasopresin, serum)

Mekanisme & Obat Pencetus

Anafilaksis
Anafilaktoid (tidak melalui IgE)
Zat penglepas histamin secara langsung
Cairan hipertonik (media radiokontras, manitol)
Obat lain (dekstran, fluoresens)
Obat (opiat, vankomisin, kurare)
Aktivasi komplemen
Protein manusia (imunoglobulin, & produk darah lainnya)
Bahan dialisis
Modulasi metabolisme asam arakidonat
Asam asetilsalisilat
Antiinflamasi nonsteroid

Sebelum Memberikan Obat

1. Adakah indikasi memberikan obat
2. Adakah riwayat alergi obat sebelumnya
3. Apakah pasien mempunyai risiko alergi obat
4. Apakah obat tsb perlu diuji kulit dulu
5. Adakah pengobatan pencegahan untuk mengurangi
reaksi alergi

Sewaktu Minum Obat

Cara memberikan obat
Kalau mungkin obat diberikan secara oral
Hindari pemakaian intermiten
Sth mberikan suntikan, pasien harus selalu diobservasi
Beritahu pasien kemungkinan reaksi yang terjadi
Sediakan obat/alat untuk mengatasi keadaan darurat
Bila mungkin lakukan uji provokasi atau desensitisasi

Estimated Incidence or Prevalence of

Acute Anaphylactic Reactions
Cause

Incidence or prevalence

General cause

1/2700 hospitalized patients

Insect sting

0,4-0,8 % of US population

Radiographic contrast material

1/1000-14.000 procedures

Penicillin (fatal outcome)

1-7,5 per million treatments

General anesthesia

1/300 treatments

Hemodialysis

1/1000-5000 treatments

Immunotherapy (severe reaction) 0,1 per million injections

Mast Cell and Basophil Mediators of

Anaphylaxis
Primary (stored) mediators

Histamine
Chemotactic factors for neutrophils and eosinophils
Proteoglycans (eg, heparin, chondroitin sulfate)
Potent proteolytic enzymes (eg, trypsin, chymotrypsin)
Secondary (generated) mediators

Prostaglandins
Leukotrienes
Platelet-activating factor
Cytokines (interleukins and hematopoietic factors)

Management of Systemic Anaphylaxis

Initial therapy
1. Stabilize the airway. If symptoms of upper airway obstruction
develop, endotracheal intubation, puncture of the cricothyroid
membrane, or emergency tracheostomy may be required.
2. Inject epinephrine 0,3-0,5 mL of aqueous 1: 1000 solution, SK.
Dose may be repeated q15-20 min if needed.
3. Obtain venous access (with 18G or larger catheter, if possible)
for volume replacement and IV administration of medication.

Management of Systemic Anaphylaxis

Initial therapy
4. If applicable, place tourniquet above site of injection, sting,
or contact to reduce systemic absorption of the agent.
Loosen q 5 min to maintain adequate peripheral circulation.
Epinephrine may be injected into the site to induce
vasoconstriction.
5. Record vital signs often (initially, at least q 15 min).
If symptoms of severe reaction are present, admit patient to
a hospital and monitor.

Management of Systemic Anaphylaxis

Hypotension
1. Place patient in Trendelenburgs position.
2. Administer rapid fluid replacement with either saline or colloidal
solution (up to 1 L q 20-30min may be required).
3. For persistent or recurrent symptoms, administer IV epinephrine
(0,3-0,5 mL of aqueous 1: 10.000 solution) slowly into a
nonoccluded extremity or start a continuous infusion (0,025-0,1
g/kg per min). Weigh risks against possible benefits.

Management of Systemic Anaphylaxis

Hypotension
4. For hypotension not responding to the measures described,
continuous infusion of norepinephrine (0,05-0,5 g/min),
dopamine HCl (2-10 g/kg per min) or both may be needed,
titrated to maintain preanaphylaxis systolic blood pressure.
5. Severely ill or fragile patients may benefits from measurement
of central venous pressure or pulmonary arterial and capillary
wedge pressures with a flow-directed pulmonary catheter.

Management of Systemic Anaphylaxis

Hypotension
6. For cardiac patients who have received beta blockers, IV
administration of glucagon (5-15 g/min), atropine sulfate (0,3 to
0,5mg doses repeated q5-10 min as needed or until a total dose of
2 mg is reached), & isoproterenol HCl (2 g/min) may be necessary.
7. For shock, naloxone HCl 0,01 mg/kg up to a 0,4 mg dose, may be
tried with caution.
8. Military antishock trousers may be effective in increasing central volume.
9. Use antriarrhythmic agents as needed.

Management of Systemic Anaphylaxis

Bronchospasm
1. Administer oxygen by nasal catheter or face mask.
2. Mild bronchospasm : Administer a nebulized -adrenergic agonist
(eg, albuterol 0,5 mL of the 0,5% solution in 2,5 mL saline, or
metaproterenol sulfate 0,3 mL of the 0,5% solution in 2,5 mL
saline,q15-30min as needed).

Management of Systemic Anaphylaxis

Bronchospasm
Severe bronchospasm : Also administer aminophylline loading
dose of 6mg/kg IV over 30-min period (if patient has not been
taking theophylline regularly), followed by 0,3-0,9 mg/kg per hr as
maintenance dose. If necessary, terbutaline sulfate 0,25 mg, may
be injected subcutaneously & a second dose given in 15-30 min
(total dose not to exceed 0,5 mg in 4-hr period).
3. IV corticosteroid therapy (eg methylprednisolone, 1 to 2 mg/kg or
maximum of 250 mg q4-6h) may be helpful if significant symptoms
persist after 1-2 hr of vigorous therapy.

Management of Systemic Anaphylaxis

Urticaria & angioedema
1. Administer a histamine 1 (H1) blocker (eg, diphenhydramin HCl,
hydroxyzine 25-50 mg IM or PO q6-8h as needed). Nonsedating
AH1 are also effective
2. Although not proven to be of benefit in this situation or in
hypotension resulting from histamine2 (H2) receptor-induced
vasodilatation, H2 blockers (eg ranitidine 300 mg IV or PO q6-8h)
may be added.
Be cautious of possible drug interaction with theophylline
(especially with cimetidine)

Management of Systemic Anaphylaxis

Miscellaneous
If prolonged treatment has been required, send blood sample for
hemogram and electrolyte evaluation and, if indicated, order
studies for arterial blood gases and theophylline and drug levels
Order chest x-ray films in cases of poorly responsive
bronchospasm or localized abnormality on examination
Order electrocardiogram to monitor for possible myocardial
ischemia or arrhyrthmias
Consider use of corticosteroids to prevent the late recurrence of
anaphylactic symptoms

Possible Complications of Anaphylaxis

& Its Treatment
Complication
Persistent hypoperfusion leading to myocardial infarction,
cerebral ischemia, and renal failure
Respiratory failure with or without upper airway compromise
Death

Possible Complications of Anaphylaxis

& Its Treatment
Treatment
Of epinephrine, nor epinephrine, or dopamine HCl therapy
Hypertension (leading to myocardial ischemia or cerebrovascular
accident)
Cardiac arrhythmias
Tissue necrosis (extravasation into extravascular tissues)
Of vigorous intravenous fluid administration
Congestive heart failure
Pulmonary edema
Electrolyte imbalance

Possible Complications of Anaphylaxis

& Its Treatment
Side effect of treatment
Of aminophylline therapy
Gastrointestinal distress
Cardiac arrhythmias
Seizures

Of beta-adrenergic agonist therapy

Tremor, nervousness
Cardiac arrhythmias

Of antihistamine therapy
Sedation
Anticholinergic effects (acute urinary retention, blurred vision)

Diagram Anaphylaxis