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Anafilassi:gestione dell’evento e terapia Filippo Fassio SOD Immunologia e Terapie Cellulari– AOU Careggi (Direttore Prof. E. Maggi)
Anafilassi: linee guida…
Anafilassi: linee guida… The evidence base for the assessment and management of patients with anaphylaxis is weak in comparison to, for example, the evidence base for the assessment and management of patients with asthma or allergic rhinitis.  It is likely to remain so in the absence of randomized, controlled studies of therapeutic interventions performed during an anaphylactic episode. =
Anafilassi: diagnosi…
Anafilassi: introduzione…                         (2) The Guidelines focus on the supreme importance of making a prompt clinical diagnosis and on the basic initial treatment that is urgently needed and should be possible even in a low resource environment.
Anafilassi: introduzione…                         (3) Cabinadi un aereo Zone non accessibiliaisoccorsi
Anafilassi: gestione e terapia…               (1) { “Action plan” o protocollod’emergenzascritto Rimuovereil trigger posizionamento chiamare aiuto adrenalina CCS fluidi ossigeno Anti-H1 { Iniziare RCP se indicato Rivalutareperiodicamente
Anafilassi: gestione e terapia…               (3) { “Action plan” o protocollod’emergenzascritto ? { Iniziare RCP se indicato Rivalutareperiodicamente
Anafilassi: gestione e terapia…               (4)
Anafilassi: gestione e terapia…               (5) ,[object Object]
 Call for Help
 Inject Epinephrine(0,01 mg/Kg IM up to 0,5 mg in adults; 0,01 mg/Kg IM, up to 0,3 mg in children) ,[object Object],(not if respiratory distress or vomiting) ,[object Object]
Estabilish IV access
Whenindicated, 1-2 l of 0.9% NaCl,[object Object]
Anafilassi: adrenalina…                             (1) ,[object Object],The WHO classifies epinephrine as an essential medication for the treatment of anaphylaxis. Previous WAO publications and anaphylaxis guidelines published in indexed, peer-reviewed journals consistently emphasize prompt injection of epinephrine as the first-line medication of choice in anaphylaxis. The evidence base for prompt epinephrine injection in the initial treatment of anaphylaxis (B) is stronger than the evidence base for the use of antihistamines and glucocorticoids (C) in anaphylaxis.  It consists of observational studies performed in anaphylaxis, RC clinical pharmacology studies in patients at risk for anaphylaxis but not experiencing it at the time of the investigation, studies in animal models of anaphylaxis, in vitro studies, and retrospective studies, including epidemiologic studies and fatality studies.
Anafilassi: adrenalina…                             (2) ,[object Object],Epinephrine should be injected by the intramuscular route in the mid-anterolateral thigh as soon as anaphylaxis is diagnosed or strongly suspected 1:1000 solution (1 mg/mL) 0,01 mg/Kg IM up to 0,5 mg in adults;  0,01 mg/Kg IM,  up to 0,3 mg in children Record the time of the dose and repeat it in 5-15 minutes Most patients respond to 1 or 2 doses of epinephrine injected intramuscularly promptly; however, more than 2 doses are occasionally required
Anafilassi: adrenalina…                             (3) ,[object Object],Transient pharmacologic effects after a recommended dose of epinephrine by any route of administration include pallor, tremor, anxiety, palpitations, dizziness, and headache.  These symptoms indicate that a therapeutic dose has been given.  Serious adverse effects such as ventricular arrhythmias, hypertensive crisis, and pulmonary edema potentially occur after an overdose of epinephrine by any route of administration.
Anafilassi: Terapia Farmacologica…
Anafilassi: ossigenoterapia… Supplemental oxygen should be administered by facemask or by oropharyngeal airway at a flowrate of 6-8 L/min to all patients with respiratory distress and those receiving repeated doses of epinephrine.  It should also be considered for any patient with anaphylaxis who has concomitant asthma, other chronic respiratory disease, or cardiovascular disease.  Continuous monitoring of oxygenation by pulse oximetry is desirable, if possible
Anafilassi: Terapia Farmacologica…
Anafilassi: riempimento volemico… During anaphylaxis, large volumes of fluids potentially leave the patient’s circulation and enter the interstitial tissue; therefore, rapid intravenous infusion of 0.9% saline (isotonic saline or normal saline) should be commenced as soon as the need for it is recognized.  The rate of administration should be titrated according to the blood pressure, cardiac rate and function, and urine output.  All patients receiving such treatment should be monitored for volume overload
Anafilassi: CPR e Rivalutare! When indicated at any time, prepare to initiate cardiopulmonary resuscitation with continuous chest compressions. At frequent and regular intervals, monitor patient’s blood pressure, cardiac rate and function, respiratory status and oxygenation and obtain electro- cardiograms; start continuous non-invasive monitoring, if possible
Anafilassi: Altre terapie…                         (1)
Anafilassi: Altre terapie…                         (2) Anaphylaxis guidelines published to date in indexed, peer- reviewed journals differ in their recommendations for administration of second-line medications such as antihistamines, beta-2 adrenergic agonists, and glucocorticoids. The evidence base for use of these medications in the initial management of anaphylaxis, including doses and dose regimens, is extrapolated mainly from their use in treatment of other diseases such as urticaria (antihistamines) or acute asthma (beta-2 adrenergic agonists and glucocorticoids). Concerns have been raised that administering one or more second-line medications potentially delays prompt injection of epinephrine, the first-line treatment.
Anafilassi: Dopo la dimissione…
Anafilassi: Autoiniettore…                        (1) Educazione!!! Quandousarlo? Come usarlo? I pazienti lo portano con sé? Lo sannousare? Lo usano? Perchè non lo usano?
Anafilassi: Autoiniettore…                        (2) They should be taught why, when, and how to inject epinephrine and equipped with a personalized written anaphylaxis emergency action plan that helps them to recognize anaphylaxis symptoms, and instructs them to inject epinephrine promptly, then seek medical assistance. Currently available epinephrine auto-injectors also have some limitations. These include the lack of an optimal range of doses; for example, a 0.1 mg dose for use in infants and young children weighing less than 15 kg, uncertainties about appropriate needle length required for intramuscular dosing in patients who are overweight or obese, intrinsic safety hazards, and limited shelf- life of only 12-18 months.
Anafilassi: Autoiniettore…                        (3)
Anafilassi: Autoiniettore…                        (4) ? Interventieducazionali “avanzati”
L’Autoiniettore di Adrenalina nell’AnafilassiCorso di simulazione avanzata su manichino full-scale.Filippo Fassio– SOD Immunologia e Terapie Cellulari, AOU CareggiFilippo Bressan– UO Anestesia e Rianimazione, ASL4 Prato                 Chiara Gasperini– UO Anestesia e Rianimazione, ASL3 Pistoia
  STRUTTURA DEL CORSO 8:30 –  9:00	Presentazione del corso e pre-test 9:15 – 10:15    Parte Teorica e test in itinere 10:15 – 10:30  Pausa caffè 10:30 – 11:15  Familiarizzare con il manichino 11:15 – 12:30  Simulazioni 12:30 – 12:45  Post-test e conclusione del corso
Anafilassi: Autoiniettore…                        (7)
Anafilassi: Autoiniettore…                        (8) 1,7 3,0 4,5 +164%
Anafilassi: Autoiniettore…                        (6) ? Singoloautoiniettore o doppioautoiniettore? Cosaconsigliareai bambini con peso > 15 kg? Ago standard vabene per tutti?
Grazie!
TERAPIA DELL’ANAFILASSI Adrenalina 1/1000 (i.m. coscia):  Adulti0.5 ml;Bambini0.3 ml) O2 terapia (6-8 l/min) Fisiologica 0.9% e.v. 5-10ml/kg /5-10min Steroidi e.v.(idrocort*metilpred**):      * Adulti 200 mg; Bambini 1 mg/kg      **Adulti 50-100 mg, Bambini1 mg/kg Antistaminici H1 e.v.(clorfeniramina): Adulti25-50 mg/e.v.; Bambini1mg/kg Antistaminici H2 e.v.(ranitidina): Adulti50 mg;Bambini 1 mg/Kg Broncodilatatori (salbutamolo): Adulti5 mg/3 ml; Bambini2.5 mg/3 ml Adrenalina endovena:10-20 g/min, max. 0.75-1.5 g/Kg/ in fis.100 ml:10-20 gtt/min
ADRENALINA: effetti Inibisce il rilascio dei mediatori da mastociti e basofili Antagonizza gli effetti dei mediatori sugli organi bersaglio:  -adrenergico: vasocostrizione arteriole pre-capillari di cute, mucose,rene  pressione sanguigna 					  permeabilità vascolare  1-adrenergico:  frequenza e contrazione cardiaca  2-adrenergico: broncodilatazione  AMPc mastociti e basofili  capacità di sintesi e liberazione dei mediatori dell’anafilassi

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Terapia dello Shock Anafilattico - Adrenalina

  • 1. Anafilassi:gestione dell’evento e terapia Filippo Fassio SOD Immunologia e Terapie Cellulari– AOU Careggi (Direttore Prof. E. Maggi)
  • 3. Anafilassi: linee guida… The evidence base for the assessment and management of patients with anaphylaxis is weak in comparison to, for example, the evidence base for the assessment and management of patients with asthma or allergic rhinitis. It is likely to remain so in the absence of randomized, controlled studies of therapeutic interventions performed during an anaphylactic episode. =
  • 5. Anafilassi: introduzione… (2) The Guidelines focus on the supreme importance of making a prompt clinical diagnosis and on the basic initial treatment that is urgently needed and should be possible even in a low resource environment.
  • 6. Anafilassi: introduzione… (3) Cabinadi un aereo Zone non accessibiliaisoccorsi
  • 7. Anafilassi: gestione e terapia… (1) { “Action plan” o protocollod’emergenzascritto Rimuovereil trigger posizionamento chiamare aiuto adrenalina CCS fluidi ossigeno Anti-H1 { Iniziare RCP se indicato Rivalutareperiodicamente
  • 8. Anafilassi: gestione e terapia… (3) { “Action plan” o protocollod’emergenzascritto ? { Iniziare RCP se indicato Rivalutareperiodicamente
  • 9. Anafilassi: gestione e terapia… (4)
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  • 19. Anafilassi: ossigenoterapia… Supplemental oxygen should be administered by facemask or by oropharyngeal airway at a flowrate of 6-8 L/min to all patients with respiratory distress and those receiving repeated doses of epinephrine. It should also be considered for any patient with anaphylaxis who has concomitant asthma, other chronic respiratory disease, or cardiovascular disease. Continuous monitoring of oxygenation by pulse oximetry is desirable, if possible
  • 21. Anafilassi: riempimento volemico… During anaphylaxis, large volumes of fluids potentially leave the patient’s circulation and enter the interstitial tissue; therefore, rapid intravenous infusion of 0.9% saline (isotonic saline or normal saline) should be commenced as soon as the need for it is recognized. The rate of administration should be titrated according to the blood pressure, cardiac rate and function, and urine output. All patients receiving such treatment should be monitored for volume overload
  • 22. Anafilassi: CPR e Rivalutare! When indicated at any time, prepare to initiate cardiopulmonary resuscitation with continuous chest compressions. At frequent and regular intervals, monitor patient’s blood pressure, cardiac rate and function, respiratory status and oxygenation and obtain electro- cardiograms; start continuous non-invasive monitoring, if possible
  • 24. Anafilassi: Altre terapie… (2) Anaphylaxis guidelines published to date in indexed, peer- reviewed journals differ in their recommendations for administration of second-line medications such as antihistamines, beta-2 adrenergic agonists, and glucocorticoids. The evidence base for use of these medications in the initial management of anaphylaxis, including doses and dose regimens, is extrapolated mainly from their use in treatment of other diseases such as urticaria (antihistamines) or acute asthma (beta-2 adrenergic agonists and glucocorticoids). Concerns have been raised that administering one or more second-line medications potentially delays prompt injection of epinephrine, the first-line treatment.
  • 25. Anafilassi: Dopo la dimissione…
  • 26. Anafilassi: Autoiniettore… (1) Educazione!!! Quandousarlo? Come usarlo? I pazienti lo portano con sé? Lo sannousare? Lo usano? Perchè non lo usano?
  • 27. Anafilassi: Autoiniettore… (2) They should be taught why, when, and how to inject epinephrine and equipped with a personalized written anaphylaxis emergency action plan that helps them to recognize anaphylaxis symptoms, and instructs them to inject epinephrine promptly, then seek medical assistance. Currently available epinephrine auto-injectors also have some limitations. These include the lack of an optimal range of doses; for example, a 0.1 mg dose for use in infants and young children weighing less than 15 kg, uncertainties about appropriate needle length required for intramuscular dosing in patients who are overweight or obese, intrinsic safety hazards, and limited shelf- life of only 12-18 months.
  • 29. Anafilassi: Autoiniettore… (4) ? Interventieducazionali “avanzati”
  • 30. L’Autoiniettore di Adrenalina nell’AnafilassiCorso di simulazione avanzata su manichino full-scale.Filippo Fassio– SOD Immunologia e Terapie Cellulari, AOU CareggiFilippo Bressan– UO Anestesia e Rianimazione, ASL4 Prato Chiara Gasperini– UO Anestesia e Rianimazione, ASL3 Pistoia
  • 31. STRUTTURA DEL CORSO 8:30 – 9:00 Presentazione del corso e pre-test 9:15 – 10:15 Parte Teorica e test in itinere 10:15 – 10:30 Pausa caffè 10:30 – 11:15 Familiarizzare con il manichino 11:15 – 12:30 Simulazioni 12:30 – 12:45 Post-test e conclusione del corso
  • 33. Anafilassi: Autoiniettore… (8) 1,7 3,0 4,5 +164%
  • 34. Anafilassi: Autoiniettore… (6) ? Singoloautoiniettore o doppioautoiniettore? Cosaconsigliareai bambini con peso > 15 kg? Ago standard vabene per tutti?
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  • 38. TERAPIA DELL’ANAFILASSI Adrenalina 1/1000 (i.m. coscia): Adulti0.5 ml;Bambini0.3 ml) O2 terapia (6-8 l/min) Fisiologica 0.9% e.v. 5-10ml/kg /5-10min Steroidi e.v.(idrocort*metilpred**): * Adulti 200 mg; Bambini 1 mg/kg **Adulti 50-100 mg, Bambini1 mg/kg Antistaminici H1 e.v.(clorfeniramina): Adulti25-50 mg/e.v.; Bambini1mg/kg Antistaminici H2 e.v.(ranitidina): Adulti50 mg;Bambini 1 mg/Kg Broncodilatatori (salbutamolo): Adulti5 mg/3 ml; Bambini2.5 mg/3 ml Adrenalina endovena:10-20 g/min, max. 0.75-1.5 g/Kg/ in fis.100 ml:10-20 gtt/min
  • 39. ADRENALINA: effetti Inibisce il rilascio dei mediatori da mastociti e basofili Antagonizza gli effetti dei mediatori sugli organi bersaglio:  -adrenergico: vasocostrizione arteriole pre-capillari di cute, mucose,rene  pressione sanguigna  permeabilità vascolare  1-adrenergico:  frequenza e contrazione cardiaca  2-adrenergico: broncodilatazione  AMPc mastociti e basofili  capacità di sintesi e liberazione dei mediatori dell’anafilassi
  • 40. ADRENALINA α1 β2 β1 α2 VASOCOSTRIZIONE  RESISTENZE PERIF. EDEMA MUCOSA EFFETTO INOTROPO POS. CRONOTROPO POS. RILASCIO INSULINA  RILASCIO NORADREN BRONCODILATAZIONE  VASODILATAZIONE  GLICOGENOLISI  RILASCIO MEDIATORI
  • 41. ADRENALINA: effetti collaterali Ansietà,paura,agitazione,cefalea, vertigini, tremori,pallore, tachicardia. Effetti alfa e beta adrenergici:     PA sistolica e diastolica     consumo di O2 miocardico per effetto inotropo e cronotropo positivoeffetto pro-aritmico BENEFICI RISCHI
  • 42. ADRENALINA: eventi avversi Aritmie, crisi ipertensiva, edema polmonare acuto sono generalmente indotti da overdose, soprattutto per rapida infusione e.v.  diluire la soluzione base (1 mg/ml) a 1/10000 (0.1 mg/ml) o 1/100000 (0.01 mg/ml) NB: Se usata correttamente, non è controindicata nei pazienti cardiopatici o anziani.