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.
Management of Systemic Anaphylaxis
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.
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
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.
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 ormaximum of 250 mg q4-6h) may be helpful if significant symptomspersist 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 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
Possible Complications of Anaphylaxis & Its Treatment
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
Possible Complications of Anaphylaxis & Its Treatment
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