Epinefrina: ¿Cómo, cuándo y dónde)

Dr. Noel Rodríguez Pérez. Conferencia dictada en el XVII Congreso Latinoamericano de Alergia, Asma e Inmunología, Cartagena, 2012

1. Dr. Noel Rodríguez Perez,
Alergólogo-Pediatra
Profesor de Pediatría y Alergia Universidad Autónoma de Tamaulipas
[email protected]; www.alergia.ws
XVII Congreso
Latinoamericano de Asma,
Alergia e inmunología

2. Escolar de 6 años de
edad acude a
urgencias por
picadura de abeja
EF. Edema facial,
urticaria, disnea,
sibilancias, T/A en
limite normal. Estable

3. Difenhidramina?
Hidrocortisona?
Rehidratación?
Epinefrina?
Intubación?
SABA nebulizado?

4. 1.-Anaphylaxis. J Allergy Clin Immunol 2008;121:S402-7.
2.-Second Symposium on the Definition and Management of
Anaphylaxis: Summary Report—Second National Institute of
Allergy and Infectious Disease/Food Allergy and Anaphylaxis
Network Symposium Ann Emerg Med. 2006;47:373-380.

Anafilaxia, es una
reacción alérgica
sistémica, de inicio
agudo y
potencialmente fatal,
que ocurre de manera
súbita posterior al
contacto con una
causa conocida de
alergia.

5. Simons RE. J Allergy Clin Immunol 2009;124:625-36.

6. 3 to 6 hours

(CysLTs, PAF,
IL-5)
Mast cell
Allergen
Cellular infiltrates: 3 to 6 hours (LPR)
PGs
Return
of
Symptoms
Histamine IL-4, IL-6
Eosinophil
CysLTs, GM-CSF,
TNF-, IL-1, IL-3, PAF,
ECP, MBP
Proteases
CysLTs
Basophil
Histamine,
CysLTs,
TNF-, IL-4, IL-5, IL-
6
Monocyte
CysLTs, TNF-,
PAF, IL-1
Lymphocyte
IL-4, IL-13, IL-5,
IL-3, GM-CSF
EPR 15 min
(Early-Phase Reaction)

7. Simons RE. J Allergy Clin Immunol 2009;124:625-36.

8. Difenhidramina?
Hidrocortisona
Rehidratación?
Adrenalina!
Intubación?
SABA nebulizado?

9. Adrenalina es el fármaco más eficaz para el tratamiento de
la anafilaxia (A)
Aplicar adrenalina ante el primer signo o síntoma de
anafilaxia
A-Adrenalina
B-Braething (respiración)
C-Circulación



Mclean-Tooke AP, Bethune CA, Fay AC, Spickett GP. Adrenaline in the treatment of anaphylaxis: what is the evidence?
BMJ 2003; 327:1332-5.

10. Multicenter study of emergency department visits for food
allergies. Clark S. et al. J Allergy Clin Immunol 2004;113:347-52.
 Objetivo: Describir el manejo de reacciones alérgicas agudas por alimentos
Métodos: Revisión de expedientes de 21 departamentos de urgencias EU.
Resultados: 678 expedientes, ~29 años, 57% mujeres, 43% hombres
Tratamiento:
Antihistamínicos: 72%
Corticoesteroides sistémicos: 48%
Epinefrina: 16% (12% referido a alergólogo)

11. Pumphrey RS. Lessons for management of
anaphylaxis from a study of fatal reactions.
Clin Exp Allergy. 2000 Aug;30(8):1144-50.
Objetivo: Entender las circunstancias que llevan a una
anafilaxia fatal
Métodos. Revisión del registro de todos los casos de
anafilaxia fatal desde 1992.
Expedientes con Información detallada para dar
seguimiento de casos, reacción, necropsia .

12. Lessons for management of anaphylaxis from a
study of fatal reactions.
Pumphrey RS. Clin Exp Allergy. 2000 Aug;30(8):1144-50.
Hallazgos
~20 muertes registradas por año
~50% iatrogénicas, 25% alimentos, 25% veneno de insectos
~50% murieron por asfixia (alimentos) y 50% por choque
(iatrogénico, veneno)
Media tiempo de muerte. 5 min iatrogénico, 15 min veneno, 30
min alimentos
28% resucitados pero murieron 3 horas a 30 días (hipoxia)
La adrenalina se uso en 62%, solo 14% antes del paro cardiaco

13. Bock SA et al. J Allergy Clin Immunol 2001;107:191-3

14. 80.5
70.2
37.3
12.9
0
10
20
30
40
50
60
70
80
90
Corticosteroids Antihistamines Epinephrine Resuscitation

15. 67.3
18.6
15.2
5.8
0
10
20
30
40
50
60
70
80
Discharged to home Symptomatic/medic Hospitalization Return within 24hs

16. Muerte por anafilaxia correlaciona con retraso en aplicación de epinefrina.
Debe de administrarse de inmediato ante síntomas respiratorios ó
cardiovasculares.
El uso temprano esta justificado en pacientes con antecedente de asma y
especialmente en aquellos que requieren de medicación frecuente
Epinefrina mantiene T/A, Antagoniza efectos de mediadores, e inhibe
liberación posterior.
No contraindicaciones absolutas
Es la droga de primera elección, es bien tolerada y es potencialmente salva
vidas.
Kemp SF, Lockey RF, Simons RE Allergy 2008: 63: 1061–1070

17. Intramuscular (IM). (B)
Concentraciones plasmáticas mayores y
más rápidas la vía subcutánea.
Mayor margen de seguridad que la
administración intravenosa.
El mejor sitio de administración es la cara
anterolateral del muslo (B).

Simons FER, Gu X, Simons KJ. J Allergy Clin Immunol 2001; 108:871-3.
Simons FER, Roberts JR, Gu X, Simons KJ. J Allergy Clin Immunol 1998; 101:33-7.

18. Adultos (1mg = 1ml
1/1.000) 0.3 a 0.5. Repetir
cada 5 a 15 minutos
según la gravedad y
tolerancia del paciente.
Lactantes y niños, 0.01
mg por kilogramo,
máximo 0.3 mg, repetir en
5 a 15 minutos en caso
necesario.
Liberman P, et. al. J Allergy Clin Immunol 2010;126:477-80.

19. Simons FER. J Allergy Clin Immunol. 2004;113:837-44.
Tiempo para C
max después de la inyección (minutos)
5 10 15 20 25 30 35
Epinefrina
IM

Epinefrina
Subcutánea

34 ± 14(5-120)
minutos
8 ± 2 min
p<0.05

20. Simons FR, et al. J Allergy Clin Immunol 2001;108:871-3.

21. Mutasem M. et al. J Allergy Clin Immunol 2006;117: 398-403.

22. Potencial de Arritmia letal: Hipotension profunda,
Insuficiencia C-R. Pobre respuesta a dosis repetidas de
epinefrina IM o SC. En UCI/Urgencias
No dosis o rigimen establecio
1:100,000 (1mg [1mL de 1:1000 en 100mL sol. Salina])
Infusion continua de 30 a 100mL/hora (5 a 15mL/minuto): 0.5 a
0.1µg/kg/hora
Niños. Regla de los “6”: 0.6/peso (Kgs) = mcg + cbp 100mL sol.
Sal. (100µg/10ml). Infusion continua a 0.l - 1µg/kg/minuto
IV/intraosea.
Lieberman P. Et al. Allergy Clin Immunol 2010;126:477-80.
Davis JE, et al. Ped Emergency Med 2007;4:1-28

23. GALAXIA. Med Clin (Barc). 2011 Mar 26;136(8):349-55.

24. …Sin embargo, no siempre es efectiva:
Administración tardía
Dosis inadecuada
Vía de administración inapropiada
Epinefrina caducada
Enfermedades subyacentes: Asma no controlada,
Enfermedad cardiovascular, Mastocitos

25. 1042Sim ons et al J ALLERGY CLIN IM M UNOL
DECEM BER 2001
picking up the syringe to injecting the epinephrine dose
into the vial were as follows:parents,142 ±13 seconds
(range,83-248); physicians,52 ±3 seconds (range,30-
83); general duty nurses,40 ±2 seconds (range,26-71);
and emergency department nurses,29 ±0.09 seconds
(range,27-33). The control groups did not differ signifi-
cantly from each other with regard to speed (P> .05).
The mean (±SEM) volume of epinephrine drawn up by
the parents was 0.07 ±0.01 mL (range,0.004-0.151); this
compared with volumes of 0.085 ±0.01 mL (range,0.03-
0.19) for the physicians,0.098 ±0.01 mL (range,0.04-
0.13) for the general duty nurses,and 0.099 ±0.01 mL
(range,0.07-0.15) for the emergency department nurses.
The mean (±SEM) value for epinephrine content of
the parents’doses (73 ±11 mg; range,4-151) did not dif-
fer significantly from those of the physicians (86 ±10
mg; range,25-193),the general duty nurses (98 ±7 mg;
range,44-133),or the emergency department nurses (99
±6 mg; range 72-145; P> .05; Fig 2). There was an
almost 40-fold range of epinephrine content of the doses
drawn up by the parents; this was in contrast to a 7- to 8-
fold range in the physician group,a 3-fold range in the
general duty nurse group,and a 2-fold range in the emer-
gency department nurse group.
There was no correlation between the time that it took
to draw up the epinephrine doses and the amount of the
epinephrine (in micrograms) contained in the doses (Fig
3). The parents’comments about the technique included
the following:
“It takes too long.”
“The components are small and easy to lose.”
“The amount is tiny,impossible to remember,and
difficult to measure.”
“It is very easy to give an overdose or no dose at all.”
“The removal of the air is the hardest part.”
“This is way too much to ask of a parent.”
“In a real-life emergency,an anxious parent could not
do this.”
“This is far too hard,too complicated,and too difficult
for a parent to do.”
“Babysitters and daycare staff would refuse to do this.”
DISCUSSION
The available options for administration of an accurate
epinephrine dose to infants experiencing anaphylaxis out-
side the hospital setting vary considerably in ease of use
and in cost,and each has advantages and disadvantages.
The EpiPen Jr and EpiPen auto-injectors currently
represent the most user-friendly method of giving an epi-
nephrine injection,but they are also associated with the
greatest expense ($50.00 US or more for a single dose)
and are not available in many countries. They have the
additional disadvantage that neither of the 2 doses avail-
able (0.15 mg for the EpiPen Jr and 0.3 mg for the
EpiPen) is suitable for infants,given that even by the age
of 24 months only 3% of infants will have achieved a
weight of 15 kg.
15
The Ana-Kit was intermediate
between the EpiPen Jr and EpiPen auto-injectors and the
FIG 1.The length of tim e needed for participants to draw up the
epinephrine dose is show n by group. The parents w ere signifi-
cantly slow er (P£.05) than the controls. During treatm ent of actu-
al anaphylaxis, w hen seconds count, this difference m ight be clin-
ically relevant. The controls did not differ significantly from each
other (P> .05). GD, General duty; ED, em ergency departm ent.
FIG 2.The epinephrine content (in m icrogram s) of the dose draw n
up by the participants is show n by group. Wide variances w ere
found, from a 40-fold range in epinephrine content of parents’
doses (w orst) to a 2-fold range of epinephrine content of em er-
gency departm ent nurses’ doses (best). The m ean epinephrine
doses draw n up by each group did not differ significantly (P> .05).
GD, General duty; ED, em ergency departm ent.
FIG 3.There w as no correlation betw een the accuracy of the epi-
nephrine dose and the speed w ith w hich the dose w as draw n up.
It is a concern that som e doses fell outside the potential 50%
underdosing (45 mg) and 50% overdosing (135 mg) broad lim its
indicated by the shaded areas. MD, Physician; GDN, general duty
nurse; EDN, em ergency departm ent nurse. Tiempo necesario para cargar dosis
correcta de epinefrina.
Padres significativamente lentos VS
control.
Dosis de epinefrina en jeringa.
Rango de ±40 veces en padres VS
±2 en enfermeras

26. Simons FER, et al. J Allergy Clin Immunol 2000;105:1025-30.

27. GALAXIA. Med Clin (Barc). 2011 Mar 26;136(8):349-55.
Efectos frecuentes, transitorios:
Ansiedad, miedo, inquietud, mareos, cefalea,
palpitaciones, palidez, temblor.
Poco frecuentes, asociados a dosis:
Arritmias ventriculares, isquemia miocárdica, edema
pulmonar, crisis de hipertensión, hemorragia
intracraneal.
Riesgo aumentado:
Ancianos, morbilidad asociada, MAO, Antidepresivos,
Beta bloqueadores, intoxicación cocaína

28. Aplique epinefrina al inicio de cualquier signo o síntoma
de anafilaxia
Simons FER, et al. Curr Opin Allergy Clin Immunol. 2012;12(4):389-399.