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Anaphylaxis

Iris RengganisDivisi Alergi Imunologi Klinik

Departemen Ilmu Penyakit DalamFKUI/RSCM

Hypersensitivity Tipe IAllergic Reaction

ALLERGEN IgESYNTHESISMAST CELLDEGRANUL

Med. OfAnaphyl. LOCAL ANAPHYLAXIS

ALLERGIC RHINITIS

ASTHMAAT.ECZEMAURTICARIAFOOD ALLERGY

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

Allergic Reaction

Ag

APCAg-HLA

Th2Cell

B-Cell IgE

Allergen

(subsequent exposure)

Ag

Mast cells,Basophils

Adapted from: The Allergy & Asthma Report 1999. p S-12

Histamine

PGD2

Tryptase

TNF

IL-5

EOSIN

Late Fase Allergic Respons

SneezeItchMucusSmooth muscleCongestionAtopic dermatitisUrticariaAnaphylaxis

Courtesy of Dr. Raymond Mullins

CytokinemediatorsIL-16+IL-12IL-18bronchial

epithelium

inflammation, remodelling, symptoms

MBPECPEPOLTC4

activationhistamine, tryptase,PGD2,LTC4

eosinophil mast cell

FcRI

activatedTh2 cell

IL-4

B-cell switchingIgE production

IL-13CD-40CD-40L

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

IgE

APC Th2cell

allergen

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

Allergic Inflammatory

Anaphylaxis Reaction

Gejala & Tanda Anafilaksis Berdasarkan Organ Sasaran

SistemUmum/Prodromal

Pernapasan- Hidung- Larings

- Lidah- Bronkus

Kardiovaskular

Gastrointestinal

Kulit

Mata

Susunan saraf pusat

Gejala dan Tanda

Lesu, lemah, rasa tak enak yang sukar dilukiskan,rasa tak enak di dada & perut, rasa gatal di hidung& palatum

Hidung gatal, bersin, & tersumbatRasa tercekik, suara serak, sesak napas, stridor, edema, spasmeEdemaBatuk, sesak, mengi, spasme

Pingsan, sinkop, palpitasi, takikardia, hipotensisampai syok, aritmia. Kelainan EKG : gelombang T datar, terbalik, atau tanda infark miokard

Disfagia, mual, muntah, kolik, diare yang kadang disertai darah, peristaltik usus meninggi

Urtika, angioedema di bibir, muka atau ekstremitas

Gatal, lakrimasi

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

Kalau mungkin obat diberikan secara oralHindari pemakaian intermitenSth mberikan suntikan, pasien harus selalu diobservasiBeritahu pasien kemungkinan reaksi yang terjadiSediakan obat/alat untuk mengatasi keadaan daruratBila mungkin lakukan uji provokasi atau desensitisasi

Cara memberikan obat

Estimated Incidence or Prevalence of Acute Anaphylactic Reactions

Cause

General cause

Insect sting

Radiographic contrast material

Penicillin (fatal outcome)

General anesthesia

Hemodialysis

Immunotherapy (severe reaction)

Incidence or prevalence

1/2700 hospitalized patients

0,4-0,8 % of US population

1/1000-14.000 procedures

1-7,5 per million treatments

1/300 treatments

1/1000-5000 treatments

0,1 per million injections

Mast Cell and Basophil Mediators of Anaphylaxis

Primary (stored) mediatorsHistamineChemotactic factors for neutrophils and eosinophilsProteoglycans (eg, heparin, chondroitin sulfate)Potent proteolytic enzymes (eg, trypsin, chymotrypsin)

Secondary (generated) mediatorsProstaglandinsLeukotrienesPlatelet-activating factorCytokines (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.


Initial therapy4. 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.


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.


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.


Hypotension6. 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 of2 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.


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).


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 ormaximum of 250 mg q4-6h) may be helpful if significant symptomspersist after 1-2 hr of vigorous therapy.


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)


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 levelsOrder chest x-ray films in cases of poorly responsive bronchospasm or localized abnormality on examinationOrder electrocardiogram to monitor for possible myocardial ischemia or arrhyrthmiasConsider 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


Treatment

Of epinephrine, nor epinephrine, or dopamine HCl therapyHypertension (leading to myocardial ischemia or cerebrovascular accident)Cardiac arrhythmiasTissue necrosis (extravasation into extravascular tissues)

Of vigorous intravenous fluid administrationCongestive heart failurePulmonary edemaElectrolyte imbalance


Side effect of treatment

Of aminophylline therapyGastrointestinal distressCardiac arrhythmiasSeizures

Of antihistamine therapySedationAnticholinergic effects (acute urinary retention, blurred vision)

Of beta-adrenergic agonist therapy Tremor, nervousnessCardiac arrhythmias

Diagram Anaphylaxis

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