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37697239
37697239
Review Article
DOI: 10.1111/j.1610-0387.2008.06938.x
Keywords
Summary
epinephrine
inhalation
subcutaneous
anaphylaxis
emergency set
Introduction
Epinephrine (adrenalin), along with
norepinephrine (noradrenalin) and dopamine, is one of the bodys own catecholamines. The effects of epinephrine
are mediated by adrenergic receptors
(adrenoceptors) on target cells. When
analyzing their expression it must be recalled that there is variation between the
species with regard to distribution of adrenoceptors, and thus the results from
animal experiments are not entirely applicable to humans [1]. Via reversible
agonist-receptor binding, epinephrine
stimulates adrenoceptors which are cou-
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The Authors Journal compilation Blackwell Verlag GmbH, Berlin JDDG 1610-0379/2009/0705
autoinjector can lead to necrosis of the distal phalanges from severe vasospasm. The
EpiPen, an epinephrine autoinjector, is
not approved in Germany. In general,
concomitant use of other sympathomimetic drugs (such as 2-receptor agonists
for broncholysis) warrants caution given
the risk of life-threatening disruption of
heart rhythm (lengthening of the QT interval) [11, 12].
The main requirement for use of an autoinjector is proper patient education.
Studies have shown, however, that despite patient education, many remain reluctant to use an autoinjector. Although
the majority of patients reportedly agree
on the necessity of carrying an epinephrine autoinjector in their emergency
kits, only a portion of them actually have
a functioning epinephrine autoinjector
on them, and many patients would not
use it in an emergency [1315].
There are as yet no studies available that
apply the criteria of evidence-based medicine to the effectiveness of various
therapeutic procedures in allergy emergencies [1518]. Epinephrine, given
subcutaneously, intramuscularly, or intravenously, is the initial treatment of
choice in anaphylaxis. H1 and H2 antihistamines (H1-AH), as well as glucocorticoids, are given as adjuvant therapies, although there are no randomized
controlled studies on their use.
Inhalable epinephrine formulations
Examples of inhalable epinephrine formulations are Primatene MistTM and InfectoKrupp Inhal. The Primatene Mist
inhaler is also available as spray foam,
with the added chlorofluorocarbons as foaming agents. InfectoKrupp Inhal is
available as a solution with a pump or
drop applicator for use in a nebulizer. A
pump/nebulizer/spray chamber system is
available separately. This allows it to be
used as a spray (Figure 1). InfectoKrupp
Inhal, made by Infectopharm, was approved for use as a nebulizer in November
2005 as adjuvant therapy in acute respiratory distress arising in acute stenosing
laryngo-tracheitis and allergic reactions.
10 ml of InfectoKrupp Inhal contain
40 mg of epinephrine; 1 puff contains
0.56 mg of epinephrine; the recommended standard dose, which is merely applicable to use in the nebulizer, is 714 puffs.
The larger the particle size, the greater is
the amount of purely oropharyngeal deposition of the drug: at a particle size
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thyrotoxicosis,
pheochromocytoma,
narrow angle glaucoma, abnormal urinary excretion, and cor pulmonale,
heart rhythm disorders (tachycardia),
and coronary heart disease. The preference for inhalable epinephrine preparations results from reluctance on the part
of patients and doctors to use or prescribe autoinjectors [13, 14], potential
cardiac side effects of parenteral administration [28], and injury due to improper
injection [810].
In addition, studies have shown that 69 %
of parents of children with a history of
food-induced anaphylactic reactions were
not able to use an autoinjector (EpiPen)
[29]. This means that compliance is worse
for autoinjectors than for epinephrine inhalers [13, 14, 29]. Thus it may become
a matter of the use of an inhaler versus
non-treatment. Also, there is a recognized need for epinephrine inhalers as
emergency treatment for asthmatic reactions [30].
With regard to study methods, in all studies mentioned here on inhalation of
epinephrine, healthy subjects used careful inhalation technique. The subjects
were thoroughly instructed in the use of
the aerosol, and there was no prior physical exertion [20, 26]. There are no
comparative studies available on inhaled
versus subcutaneous/intramuscular/oral
epinephrine administration in patients
actually undergoing an anaphylactic
event [27]. Given that during an anaphylactic reaction patients often have
difficulty breathing (due to bronchospasm or laryngeal edema) [27], bioavailability would presumably be more limited than in healthy people. In order to
reach systemically effective plasma concentrations of epinephrine, 2040 inhalations are recommended. At such high
concentrations, considerable gastrointestinal effects such as nausea and vomiting can occur. In 2 out of 8 patients, [23]
20 inhalations (0.15 mg epinephrine per
inhalation) caused mild nausea, in another 2 patients severe nausea, and in one
patient vomiting occurred. One person
with severe nausea complained of symptoms lasting for hours, while in the remainder of patients symptoms subsided
within 80 minutes. It is not conceivable
that in an emergency situation a continued laminar flow of the inhaled preparation could be achieved.
Epinephrine inhalers may be recommended for swelling of the upper airways and
adequate inhalers also for broncho construction, but not for circulatory shock.
In a child with asthma, urticaria, and
food allergy, such a preparation is worth
discussing, but not in a patient with a
wasp venom allergy and circulatory
collapse. When prescribing Primatene
Mist (inhaler) and InfectoKrupp
Inhal for emergency sets for patients
with immediate hypersensitivity, doctors
should thus keep in mind that in most
instances, hemodynamic stabilization
cannot be achieved. There is an indication for Primatene Mist in patients
with bronchial asthma and laryngeal
edema (off-label use), because inhalation
of epinephrine has been shown to be effective in laryngeal edema and bronchospasm [31, 32].
For treatment of patients with anaphylaxis, the required plasma epinephrine
concentrations for 1-receptor-mediated
circulatory effects are not reliably achieved
with aerosols. They depend on various influences, mainly inhalation technique, and
at high doses (up to 40 puffs) are accompanied by severe gastrointestinal side
effects and the risk of hyperventilation.
To treat anaphylaxis with circulatory
compromise, emergency sets for patients
with a history of immediate hypersensitivity should include an epinephrine injector (Fastjekt or Anapen). Prior to
using the autoinjector, it is essential that
the patient be thoroughly and repeatedly
educated in its use in order to ensure
compliance and correct use [15].
<<<
Conflict of interest
None.
Correspondence to
Prof. Dr. med. Tilo Biedermann
Universitts-Hautklinik
Liebermeisterstrae 25
Tel.: +49-7071-29-80836
Fax: +49-7071-29-4117
D-72076 Tbingen
E-mail: tilo.biedermann@med.
uni-tuebingen.de
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