Download Anaphylaxis - SDACEP Conference

Brook Eide MD, MS FACEP
Objectives
 Prevalence of allergies
 Pathophysiology of allergic reactions
 Recognition of reactions
 Common allergens
 When is a reaction anaphylaxis
 Appropriate treatment of allergies and anaphylaxis
Anaphylaxis – The Numbers
 The lifetime prevalence of anaphylaxis is 2%
 The median time between the onset of symptoms and
respiratory or cardiac arrest was 5 minutes in
iatrogenic anaphylaxis, 15 minutes in stinging insect
venom-induced anaphylaxis, and 30 minutes in food
induced anaphylaxis
 Foods are the most common cause in children
 Medications and insect stings are more common in
adults
Anaphylaxis
 Acute, potentially fatal, multi-organ system reaction
caused by the release of chemical mediators from mast
cells and basophils
 Classic form involves prior sensitization to an allergen
with later re-exposure, producing symptoms via an
immunologic mechanism
Laboratory Studies
 Anaphylaxis is a clinical diagnosis and treatment




cannot await laboratory confirmation
Tryptase:
Needs to be obtained within 3 hours of symptom onset
More likely to be elevated with anaphylaxis from
stinging insect venom or medication
A normal tryptase does not rule out a diagnosis of
anaphylaxis
Lab Studies
 Plasma Histamine:
 Peak within 5 to 15 minutes and decline to baseline
within 60 minutes
 More likely to increase than the tryptase
 Helpful in hospitalized patients when blood samples
can be collected immediately
 By the time community based patients make it to the
ED levels have usually returned to baseline
Diagnosis
 Primarily a clinical diagnosis
 Patients are commonly restless and anxious
 Multiple organ systems involved
 Laboratory studies are not usually required and rarely
helpful
Signs and Symptoms
 Anaphylaxis may present with various combinations of
approximately 40 potential symptoms and signs
 Most commonly affects the cutaneous, respiratory,
cardiovascular, and gastrointestinal systems
 Skin or mucous membranes are involved in around
80%
 ***Skin symptoms are absent or unrecognized in 20%
of all episodes***
Signs and Symptoms
 Majority of adults have urticaria, erythema, pruritus,
or angioedema
 Children (poorly understood reasons) present more
commonly with respiratory symptoms followed by
cutaneous
 Some of the most severe cases present in the absence
of skin findings
 Dermatologic: Flushing, Urticaria, Angioedema,





Cutaneous or Conjunctival Injection, Pruritus,
Warmth, Swelling
Respiratory: Nasal Congestion, Choryza, Rhinorrhea,
Sneezing, Throat Tightness, Wheezing, Shortness of
Breath, Cough, Hoarseness, Dyspnea
Cardiovascular: Dizziness, Weakness, Syncope, Chest
Pain, Palpitations
Gastrointestinal: Dysphagia, Nausea, Vomiting,
Diarrhea, Bloating, Cramps
Neurologic: Headache, Dizziness, Blurred Vision,
Seizure
Other: Metallic Taste, Sense of Impending Doom
Time Course of anaphylaxis
 Usual course is rapid onset, evolution, and resolution of





symptoms within seconds to hours
Anaphylaxis is UNPREDICTABLE
It may be mild and resolve spontaneously due to
endogenous production of compensatory mediators
It may be severe and progress within minutes to respiratory
or cardiovascular compromise and death
At the onset of an anaphylactic episode it is not possible to
predict how severe it will become, how rapidly it will
progress, and whether it will resolve promptly and
completely or become biphasic or protracted
The factors that determine the course of anaphylaxis in an
individual patient are not fully understood
Anaphylactic Disease Course
 The time course of an anaphylactic reaction:
 A uniphasic reaction occurs immediately after exposure
and resolves with or without treatment within the first
minutes to hours, and then does not recur during that
anaphylactic episode.
 A biphasic reaction includes a recurrence of symptoms
that develops after apparent resolution of the initial
reaction. Biphasic reactions have been reported to occur in
1% to 20% of anaphylaxis episodes and typically occur
about 8 hours after the first reaction, although recurrences
have been reported up to 72 hours later
 A protracted reaction is any anaphylaxis episode that
lasts for hours or days following the initial reaction
 New diagnostic criteria for anaphylaxis were
published in 2006 to help health care
professionals both recognize the spectrum of signs
and symptoms that constitute anaphylaxis and
establish a more systematic approach to its
diagnosis and management
12
 Reduced BP after exposure to a known allergen for that
patient (minutes to several hours).
 Reduced BP is defined:
 In adults, as a systolic BP of less than 90 mm Hg or greater
than 30% decrease from that person's baseline
 In infants and children, as a low systolic BP (age-specific)
or greater than 30% decrease in systolic BP. Low systolic BP
is defined as:
 Less than 70 mm Hg for ages 1 month to 1 year
 Less than (70 mm Hg plus twice the age) for ages 1 to 10 years
 Less than 90 mm Hg for ages 11 to 17 years
 Note: In infants and young children, hypotension may
be a late manifestation of hypovolemic shock.
Tachycardia, in the absence of hypotension, also may
indicate shock.
259
Anaphylactic Disease Course
 The time course of an anaphylactic reaction may be uniphasic,
biphasic, or protracted
 A uniphasic reaction occurs immediately after exposure and
resolves with or without treatment within the first minutes to
hours, and then does not recur during that anaphylactic episode
 A biphasic reaction includes a recurrence of symptoms that
develops after apparent resolution of the initial reaction.
Biphasic reactions have been reported to occur in 1% to 20% of
anaphylaxis episodes and typically occur about 8 hours after the
first reaction, although recurrences have been reported up to 72
hours later
 A protracted reaction is any anaphylaxis episode that lasts for
hours or days following the initial reaction
Food Allergy
 15 million Americans with food allergies
 A food allergy can begin at any age
 Affects 1 in 13 children in the United States
 Roughly 2 in every classroom
 Economic cost of children’s food allergies is nearly $25
billion per year.
 In the U.S., food allergy is the leading cause of
anaphylaxis outside the hospital setting.
Food Allergy
 Food allergies among children increased approximately
50% between 1997 and 2011
 The number of people who have a food allergy is
growing, but there is no clear answer as to why
 More than 17 million Europeans have a food allergy,
and hospital admissions for severe reactions in
children have risen seven-fold over the past decade,
according to the European Academy of Allergy and
Clinical Immunology (EAACI)
Food Allergy
 Every 3 minutes, a food allergy reaction sends
someone to the emergency department – that is more
than 200,000 emergency department visits per year.
 The U.S. Centers for Disease Control reported that
food allergies result in more than 300,000 ambulatorycare visits a year among children under the age of 18.
 Food allergy is the leading cause of anaphylaxis
outside the hospital setting.
Food Allergy
 Eight foods account for 90% of all reactions: milk,
eggs, peanuts, tree nuts, soy, wheat, fish and shellfish.
 Even trace amounts of a food allergen can cause a
reaction
 Studies show the number of children living with
peanut allergy appears to have tripled between 1997
and 2008
Food Allergies
 The foods most associated with food allergy in children are:
 Milk
 Eggs
 Peanuts
 Children may outgrow their allergic reactions to milk and
to eggs. Peanut and tree nut allergies are likely to persist.
 The most common food allergens in adults are:
 Fruit and vegetable pollen (oral allergy syndrome)
 Peanuts and tree nuts
 Fish and shellfish
Food Allergies
 Symptoms caused by a food allergy can range from
mild to life-threatening
 The severity of each reaction is unpredictable
 People who have previously experienced only mild
symptoms may suddenly experience a life-threatening
reaction
 This is why allergists do not like to classify someone as
“mildly” or “severely” food allergic - there is just no
way to tell what may happen with the next reaction
Food Allergies
 Anyone with a food allergy should always have his or
her auto-injector close at hand
 Be sure to have two doses available, as the severe
reaction can recur in about 20% of individuals
 There are no data to help predict who may need a
second dose of epinephrine, so this recommendation
applies to all patients with a food allergy
 If you are uncertain whether a reaction warrants
epinephrine, use it right away; the benefits of
epinephrine far outweigh the risk that a dose may not
have been necessary
Food Allergies
 Fatalities associated with food-induced anaphylaxis are
most commonly associated with peanut or tree nut
ingestion
 Such fatalities are associated with delayed use or lack of
proper epinephrine dosing
 The highest risk groups for fatal anaphylaxis associated
with food ingestion are:
 Adolescents and young adults
 Individuals with known FA and with a prior history of
anaphylaxis
 Individuals with asthma, especially those with poor control
(although fatal reactions may occur even in individuals with
mild asthma)
Exercise-Induced Anaphylaxis
 Exercise-induced anaphylaxis in adults is triggered by foods in about one




third of patients
It has a natural history marked by frequent recurrence of the episodes
37% of the patients reported a food trigger, most commonly crustacean
shellfish (16%), alcohol (11%), tomatoes (8%), cheese (8%), and celery
(7%)
All patients met criteria for exercise-induced anaphylaxis (anaphylactic
symptoms, urticaria, or angioedema with symptoms consistent with
upper respiratory obstruction) or had cardiovascular collapse during
exercise
75% of the patients were female
 The average number of episodes per year at the time of initial presentation
was 14.5, but this frequency decreased to 8.3 at the time of the survey
Exercise-Induced Anaphylaxis
 The most frequently occurring symptoms were
pruritus (92%), urticaria (86%), angioedema (72%),
flushing (70%), and shortness of breath (51%)
 About 50% of the patients reported seasonal rhinitis or
dust allergies, 19% also reported having asthma, and
10% had eczema
 Most cases of exercise-induced anaphylaxis are
associated with food, the food can be ingested without
symptoms in the absence of exercise
Exercise-Induced Anaphylaxis
 Cessation of physical activity usually results in
immediate improvement of symptoms
 Exercise-induced anaphylaxis attacks are not
consistently elicited by the same type and intensity of
physical activity in a given patient
 Co-factors such as foods, alcohol, temperature, drugs
(ie. aspirin and other nonsteroidal anti-inflammatory
drugs), humidity, seasonal changes, and hormonal
changes are important in the precipitation of attacks
Exercise-Induced Anaphylaxis
 A distinct subset of exercise-induced anaphylaxis is
food-dependent exercise-induced anaphylaxis
(FDEIA), in which anaphylaxis develops only if
physical activity occurs within a few hours after eating
a specific food
 Neither food intake nor physical activity by itself
produces anaphylaxis
 The foods most commonly implicated in fooddependent exercise-induced anaphylaxis are wheat,
shellfish, tomatoes, peanuts, and corn
Medication
 Approximately 10% of all US patients report having
had an allergic reaction to a penicillin-class antibiotic
in the past
 However, less than 1% of the population has an
immunoglobulin E (IgE)–mediated reaction to
penicillin, indicating a true drug allergy
 They may have had side effects or a symptom of the
underlying illness that was interpreted as an allergy,
such as a viral exanthema or rash in a child on
amoxicillin
Medication
 Furthermore, even patients with true penicillin
allergies may lose the allergy over time
 About 80% of patients with an IgE-mediated penicillin
allergy lose their sensitivity by 10 years after their
reaction
 1 in 5000 exposures to penicillin or cephalosporin
causes anaphylaxis`
Drug Allergies
 Onset of hives within a few hours of taking a new
medication is easily recognized
 Many clinical presentations are complex or take place
in the setting of illness and/or polypharmacotherapy
 ie. ICU patient taking multiple medications
Drug Allergies
 Risk factors for the development of drug allergy
include female sex, prior history of drug allergic
reaction, recurrent drug exposure, genetic factors, and
certain disease states
 Reactions to ampicillin occur more commonly in
patients with atypical or abnormal lymphocytes (EBV,
leukemia)
 Patients with AIDS have a very high rate of
dermatologic reactions
 Generalized herpes virus also has high rate of skin
reactions
Non allergic Rash
 A common problem is exanthematous skin reactions
in small children treated with antibiotics, usually
penicillins
 These mostly mild and transient skin reactions appear
to be due to a combined effect of the drug use and
various viral infections causing immune stimulation
 The vast majority of children will tolerate penicillins if
given them again later
Insect
 Hymenoptera stings account for more deaths in the




United States than any other envenomation
Most deaths result from immunologic mechanisms,
some are from direct toxicity
Ants sting 9.3 million people each year
Other Hymenoptera species account for more than 1
million stings annually
Anaphylaxis secondary to Hymenoptera envenomation
affects roughly 3% of the general population
Hymenoptera Reactions
 Hymenoptera stings of all types are more common in
males than in females, probably because of more
frequent exposure
 Most deaths were in older (>50 years) and younger (<
10 years) males
 Individuals with large local reactions have a 5-10% risk
of subsequent development of a severe systemic
reaction if re-stung
Hymenoptera Reactions
 Rapid onset of symptoms is the rule; 50% of deaths
occur within 30 minutes of the sting, and 75% occur
within 4 hours
 Fatal allergic reactions can occur as the first
generalized reaction
 Far more common, however, is a fatal reaction
following a previous, milder generalized reaction
 The shorter the interval since the last sting, the more
likely it is that a severe reaction will take place
Hymenoptera Reactions
 Venom load may be sufficient to cause fatal injury
without the added effects of the endogenous system
 This may result from as few as 30 vespid stings or 200
honeybee stings
 Since the compounds are similar in anaphylactic and
toxic reactions, pathology and treatment also are
similar
Hymenoptera Reactions
 People who have been stung should remove the bee
stinger as quickly as possible
 Removal method is not as important as rapidity
because the stinging apparatus actively injects venom
into the wound for 1 minute after the sting, even if the
bee has been killed or knocked away from the site
Hymenoptera Reactions
 Most endangered patients die within 30 minutes of a
sting
 Increased vascular permeability in anaphylaxis may
result in transfer of 50% of the intravascular fluid into
the extravascular space within 10 minutes
 Check airway and ventilatory status
 Treatment should include an initial intravenous (IV)
bolus of 10-20 mL/kg isotonic crystalloids in addition
to diphenhydramine and epinephrine
 Observe for sufficient duration to ensure symptoms do
not rebound after initial treatment
 Rebound phenomena may occur up to 12 hours after
sting
IV Contrast
 Immediate Hypersensitivity Reaction
 Symptoms develop within one hour of adminstration
and many begin within 5 minutes
 Signs and symptoms are similar to those of anaphylaxis
 Flushing, Pruritis, Urticaria, Angioedema,
Bronchospasm, Wheezing, Laryngeal Edema, Stridor,
Hypotension, Shock, Loss of Consciousness
IV Contrast
 Test dosing is not recommended
 Severe and fatal reactions to usual doses of Contrast
Medium have occurred in patients who tolerated test
doses of the agent
 Fatalities have resulted from the test doses themselves,
even to amounts as small as 1-2 mL
Premedication
 Administer 13 hours prior:
 Prednisone – Orally 13 hours prior, 7 hours prior, and 1
hour prior at 50 mg per dose
 Children are on the same time scale at a dose of 0.5 to
0.7 mg/kg per dose
 Diphenhydramine – Oral or parenteral 1 hour before at a
50 mg dose in adults and 1.25mg/kg in children up to 50
mg
IV Contrast
 Pretreatment reduces the rate of breakthrough
reactions from 17-60% down to 9%
 Premedication was effective regardless of the severity
of the initial reaction
 It is very likely that the most severe reactors were not
entered into this protocol
 This was done with hyperosmolal contrast agents
which are associated with a higher rate of reaction
IV Contrast
 To avoid further reactions, the patient should never
receive same agent that caused the initial reaction
 If the reaction was to high osmolal contrast material,
use either nonionic low osmolal contrast or an isoosmolal agent in combination with premedications
 If the reaction was to low osmolal contrast, use an isoosmolal agent in combination with premedications
 Low osmolal agents cause significantly fewer reactions
compared to high osmolal contrast, and non-ionic low
osmolal agents are recommended for any patient with
a previous anaphylactic reaction
IV Contrast
 Factors associated with recurrent reaction despite
premedication include: prior severe allergic reaction to
any substance, one or more drug allergies, chronic oral
glucocorticoid use, allergy to four or more allergens
IV Contrast
 The incidence of any adverse reaction to ICM is about
15%. Most of these reactions are mild and require no
treatment
 The overall risk of any adverse reaction was 12.66%
with ionic ICM and 3.13% with nonionic ICM
 The risk of death was 1 death in 100,000 patients with
either type of agent
IV Contrast
 The reason that low-osmolality ICM have not completely
replaced the older high-osmolality ICM is the higher cost
of the low-osmolality agents
 Professional organizations have formulated guidelines
regarding the selective use of low-osmolality ICM for
certain high-risk patients
 However, with the selective use of nonionic ICM, severe
adverse contrast reactions are 3 times as likely in low-risk
patients who receive conventional ionic agents (0.09%)
than in high-risk patients who receive nonionic agents
(0.03%)
 Thus, the single most important risk factor for an adverse
reaction is the type of contrast agent that is chosen for
injection
IV Contrast
 Idiosyncratic reactions may occur in people with a previous
reaction to ionic or nonionic ICM, asthma, and/or food or
medication allergies
 Previous reactions to ionic or nonionic ICM increase the
relative risk of a repeat reaction 3.3- to 6.9-fold compared
with the risk in the general population
 Approximately 60% of patients who had hives after ICM
administration in the past have hives with a repeat
exposure
 Similarly, facial edema has a recurrence rate in 68% of
patients; difficulty breathing, 59%; and bronchospasm,
38%.
IV Contrast
 People with asthma have 1.2-2.5 times the risk of such




reactions than the general population
In addition, when the reactions occur, they are more likely
to be severe
Severe reactions are 5-9 times more common in people
with asthma than in others
Patients with allergies, including hay fever, are 1.5-3 times
more likely to have an adverse reaction to ICM than other
people
However, no consistent data warrant the use of any unique
precautions in patients who have seafood or shellfish
allergies
IV Contrast
 No intervention completely eliminates the risk of a
breakthrough immediate hypersensitivity reaction
 In an uncontrolled study, patients with previous
hypersensitivity reactions to conventional contrast
medium, pretreatment with prednisone and
diphenhydramine combined with the use of a nonionic
low osmolar agent, reduced the rate of reactions to
0.7%
Management
 Anaphylaxis is a medical emergency that requires
immediate recognition and intervention
 Management depends on the severity of initial
reaction
 Purely local reactions do not require much
intervention
 Severe or refractory anaphylaxis will require admission
and a longer treatment and observation
ManagementNonpharmacotherapy
 Supportive care
 Airway management
 High-flow oxygen
 Cardiac monitoring and pulse oximetry
 IV access
 Fluid resuscitation with isotonic crystalloid solution
 Supine position with legs elevated
Management- Pharmacotherapy
 Adrenergic agonists (epinephrine)
 Antihistamines
 H2 receptor antagonists
 Bronchodilators
 Corticosteroids
 Positive inotropic agents
 Vasopressors
Initial Management
 Elimination of additional allergen exposure
 IM injection of epinephrine
 These actions should be quickly followed by these
additional steps
 Placement of the patient in a recumbent position (if
tolerated), with the lower extremities elevated
 Provision of supplemental oxygen
 Administration of intravenous (IV) fluid (volume
resuscitation)
Life Saving Epi
 Administer epinephrine as soon as possible once anaphylaxis




is recognized, and transport the patient to the nearest
emergency facility
Delayed administration of epinephrine has been implicated
in contributing to fatalities.
In a study of 13 fatal or near-fatal food-induced anaphylactic
reactions in children, 6 of the 7 children who survived
received epinephrine within 30 minutes of ingesting the
food, whereas only 2 of the 6 children who died received
epinephrine within the first hour
Epinephrine, therefore, should be available at all times to
patients at risk
A recent study in schools also highlights the fact that
children with FA often do not have ready access to
epinephrine at school, thus placing them at increased risk
Life Saving Epi
 Experts in the field agree that epinephrine is the only first-
line treatment for anaphylaxis.
 There is no substitute for epinephrine, thus all other
treatments are adjunctive.
 In the treatment of anaphylaxis, H1 and H2 antihistamines
and corticosteroids are commonly used, but little or no
data exist demonstrating their functional role or
effectiveness.
 The use of antihistamines is the most common reason
reported for not using epinephrine and may place a
patient at significantly increased risk for progression
toward a life-threatening reaction.
Life Saving Epi
 In August 2015, the recommendation for epinephrine…
 Do not hesitate to use epinephrine for possible
anaphylaxis, even in the absence of proof that patients'
symptoms are the result of an allergic reaction
 Epinephrine in appropriate doses is safe, and there are
no absolute contraindications for its use in treating
anaphylaxis, according to a consensus statement
prepared by an expert panel of emergency physicians
and allergists
Life Saving Epi
 Delay in administration of epinephrine may lead to
more severe and treatment resistant anaphylaxis
 It is not necessary for the [National Institute of Allergy
and Infectious Disease and the Food Allergy and
Anaphylaxis Network] criteria to be met to administer
epinephrine
 Antihistamines and glucocorticoids do not work fast
enough to be an appropriate first-line treatment for a
severe reaction, but they may be administered after
epinephrine at the discretion of the treating physicians
Life Saving Epi
 There are no absolute contraindications to
epinephrine use in anaphylaxis
 However, there are subgroups of patients who might
theoretically be at higher risk for adverse effects during
epinephrine therapy
 Because the risk of death or serious disability from
anaphylaxis itself usually outweighs other concerns,
existing evidence clearly favors the benefit of
epinephrine administration in most situations
Sept 2014 Study Results
 Epinephrine is the first-line treatment for anaphylaxis,
but at the ED, steroids were the most common
medication given (69%), followed by antihistamines
(66%), epinephrine (42%) and Albuterol (28%)
 ED intake procedures for allergic emergencies show
quick processing, with the majority of patients (69%)
seen immediately or within five minutes of arriving at
the ED
 However, discharge procedures demonstrate that the
majority of patients are not receiving critical
information needed for effective ongoing management
of severe allergies
Sept 2014 Study Results
 While 64% of respondents received advice to continue
steroids/antihistamines upon discharge from the ED, only
36% were given a prescription for epinephrine, and less
than a quarter of respondents (24% and 18%, respectively),
were given information about food allergies or a referral to
an allergist
 When looking at only those patients who experienced firsttime reactions, the numbers improved, but only slightly:
41% were given a prescription for epinephrine, 31% were
given information about food allergies and 32% were given
a referral to an allergist
Epi Administration
 IV epinephrine (1:10,000 solution) is recommended
for patients who do not respond to an initial (or
repeated) IM injection of epinephrine and fluid
resuscitation and may not be adequately perfusing
muscle tissue
 Endotracheal or intra-osseous epinephrine can be
delivered if IV access cannot be obtained immediately
 The efficacy of this delivery method is based on a
single study of a small number of patients
experiencing cardiac arrest
Life Saving Epi
 Epinephrine is the drug of choice for anaphylaxis and




should be administered as first-line therapy
The pharmacologic actions of this agent address the
pathophysiologic changes that occur in anaphylaxis
better than any other single drug
Failure to administer epinephrine early in the course of
treatment has been repeatedly implicated in
anaphylaxis fatalities
Despite this fact, physicians often fail to prescribe
epinephrine
In addition, the timing of emergency responses can
determine when epinephrine is injected
Life Saving Epi
 The therapeutic actions of epinephrine, which
encompass a broad range of effects germane to the
mechanisms of anaphylaxis, include the following:
 Increased vasoconstriction, increased peripheral
vascular resistance, and decreased mucosal edema via
α1-adrenergic agonist receptor effects
 Increased inotropy and increased chronotropy via β1adrenergic receptor agonist effects
 Bronchodilation and decreased release of mediators of
inflammation from mast cells and basophils via β2adrenergic receptor agonist effects
Life Saving Epi
 In therapeutic doses and by any route, epinephrine
frequently causes mild transient adverse effects in
individuals of all ages
 These include anxiety, fear, restlessness, headache,
dizziness, palpitations, pallor, and tremor
 Rarely, epinephrine may lead to ventricular arrhythmias,
angina, myocardial infarction, pulmonary edema, sudden
sharp increase in BP, and intracranial hemorrhage
 These severe adverse effects are more likely to occur when
epinephrine is given in overdose by any route
 for example, after an intravenous bolus injection or
intravenous injection of a 1:1,000 epinephrine solution instead
of a 1:10,000 epinephrine solution.
Life Saving Epi
 Epinephrine has an onset of action within minutes but is





rapidly metabolized
Therefore, the effect is often short-lived and repeated doses
may be necessary
If a patient responds poorly to the initial dose or has ongoing
or progressive symptoms despite initial dosing, repeated
dosing may be required after 5 to 15 minutes
Reports of patients receiving epinephrine for food-induced or
nonfood-induced anaphylaxis note that as high as 10% to 20%
of individuals who receive epinephrine will require more than
1 dose before recovery of symptoms
In many of the cases, the subsequent doses of epinephrine
were given more than 15 minutes after the first dose (some
more than 1 hour), despite recommendations to repeat dosing
as frequently as every 5 to 15 minutes
The optimal dosing interval for repeated dosing has not been
studied prospectively
 Epinephrine can be delivered through a variety of routes, including IM, IV, and
endotracheal or intraosseous
 IM epinephrine is recommended over subcutaneous injection because it







provides a more rapid increase in plasma and tissue concentrations of
epinephrine
The IM dose should be given in the anterolateral thigh in the vastus lateralis
muscle
The needle used should be of adequate length to reach the muscle beneath the
subcutaneous adipose tissue over the vastus lateralis muscle
IM injection into the thigh may be impossible in overweight or obese
individuals, especially women who have thicker subcutaneous fat tissue
In the circumstance of inadequate IM dosing, subcutaneous dosing will
provide some benefit but will be less effective than IM dosing
When an epinephrine auto-injector is used, children weighing less than 25 kg
should receive the 0.15 mg dose
Children over 25 kg through adults should receive the 0.3 mg dose autoinjector
When a 1:1,000 epinephrine solution is used, patients should receive a dose of
0.01 mg/kg with a maximum dose of 0.5 mg
Life Saving Epi
 Some level of decision making regarding the risk-to-benefit ratio





may be warranted, and especially for patients:
Who have cardiovascular disease and are reluctant to receive
epinephrine due to fear of adverse cardiac effects
These patients should be made aware that myocardial ischemia
and dysrhythmias can occur in untreated anaphylaxis
Receiving monoamine oxidase inhibitors (which block
epinephrine metabolism) or tricyclic antidepressants (which
prolong epinephrine duration of action)
Receiving stimulant medications (for example, amphetamines or
methylphenidate used in the treatment of attention-deficithyperactivity disorder) or abusing cocaine
With certain pre-existing conditions, such as recent intracranial
surgery, aortic aneurysm, uncontrolled hyperthyroidism, or
hypertension
Meds affection Epi
 Certain medications also may affect symptom severity and
treatment response in patients with food-induced
anaphylaxis, for example:
 β-adrenergic antagonists may decrease the response to
epinephrine therapy in patients undergoing anaphylaxis
 Angiotensin-converting enzyme inhibitors and, to a lesser
extent, angiotensin II receptor blockers may interfere with
endogenous compensatory mechanisms, resulting in more
severe or prolonged symptoms
 α-adrenergic blockers may decrease the effects of endogenous
or exogenous epinephrine at α-adrenergic receptors,
rendering patients less responsive to epinephrine
Adjuvant Medications
 Glucagon
 Treatment of anaphylaxis may be complicated by concomitant





use of β-adrenergic receptor antagonists
When administered orally, parenterally, or topically (for example,
eye drops), these antagonists may decrease the effects of
endogenous or exogenous epinephrine at β-adrenergic receptors
and render patients less responsive to epinephrine
This class of drugs may cause patients to be resistant to
treatment with epinephrine, and they can develop refractory
hypotension and bradycardia
Glucagon should be administered in this setting because it has
inotropic and chronotropic effects that are not mediated through
β-receptors
A single dose of 1-5 mg in adults (in children, 20-30 μg/kg, to a
maximum of 1 mg) administered intravenously over 5 minutes is
recommended, which may be repeated or followed by an
infusion of 5-15 μg/minute
Rapid administration of glucagon can induce vomiting
Adjuvant Medications
 H1 antihistamines. In contrast to epinephrine, very limited
scientific evidence supports the use of H1antihistamines in
the emergency treatment of anaphylaxis
 H1 antihistamines are useful only for relieving itching and
urticaria
 They do not relieve stridor, shortness of breath, wheezing,
GI symptoms, or shock
 Therefore, they should be considered adjunctive therapy
and should not be substituted for epinephrine
Adjuvant Medications
 For oral and IV dosing, first-generation H1 antihistamines
such as diphenhydramine 25-50 mg are used
 Sedation and cognitive and psychomotor impairment are
recognized side effects of the first-generation
H1 antihistamines, and these may contribute to decreased
awareness of anaphylaxis symptoms
 Alternative oral dosing with a less-sedating, secondgeneration H1 antihistamine (such as cetirizine 10 mg) may
be used because it has a relatively rapid onset of action
compared with other second-generation H1 antihistamines
and is available in generic formulations
Adjuvant Medications
 Bronchodilator medications
 For the treatment of bronchospasm not responsive to IM epinephrine,




inhaled bronchodilators such as albuterol should be used as needed
and should be considered to be adjunctive therapy to the
administration of epinephrine
Albuterol does not relieve airway edema (for example, laryngeal
edema) and should not be substituted for IM epinephrine dosing in the
treatment of anaphylaxis
In most emergency care settings, nebulized therapy may be more
practical than metered-dose inhalers (MDIs) (with spacers) for
patients with respiratory distress, but MDIs also can be helpful when
the respiratory distress is mild or when nebulized therapy is not
available
Moreover, the effectiveness of albuterol delivery via nebulizer vs MDI
(with spacer) remains uncertain for patients with severe respiratory
distress
Therefore, albuterol administration via nebulizer (if available) is
recommended in this setting
Adjuvant Medications
 H2 antihistamines
 Minimal evidence supports the use of
H2 antihistamines in the emergency treatment of
anaphylaxis
 Some health care professionals use these medications
concurrently with H1 antihistamines for relief of
symptoms; however, rigorous studies in anaphylaxis
that support this idea are lacking
Adjuvant Medications
 Corticosteroids
 Very little information is available to support or refute the use of




corticosteroids for the treatment of acute anaphylaxis
However, their empiric use is prevalent and supported by many
health care professionals
Corticosteroids are not helpful in the treatment of acute
anaphylaxis due to their slow onset of action (4 to 6 hours)
These agents often are given because of their anti-inflammatory
properties that benefit allergic and inflammatory disease and
also because they may help prevent biphasic or protracted
reactions, which occur in up to 20% of individuals
Treatment should be stopped within 2 to 3 days, since all
biphasic reactions reported to date have occurred within 3 days
Adjuvant Medications
 Vasopressors
 Patients who have persistent hypotension despite the
administration of epinephrine and IV fluids should receive
vasopressor medications titrated to the desired effect of
restoring BP
 Ideally, continuous non-invasive monitoring of blood
pressure and heart rate should be performed
 Due to the narrow risk-to-benefit ratio of these
medications, patients requiring vasopressors should be
transferred to a hospital setting for acute care
 No compelling evidence exists to support one vasopressor
over another in this clinical scenario
Adjuvant Medications
 Atropine
 Consider intravenously administered atropine for
patients with bradycardia
 Supplemental oxygen therapy
 Oxygen should be administered initially to all patients
experiencing anaphylaxis, especially those with
evidence of hypoxia or respiratory distress
 Supplemental oxygen helps not only with optimization
of oxygen delivery and organ perfusion, but also with
bronchodilation
Adjuvant Medications
 IV fluids
 Many patients with anaphylaxis require IV fluids
 Massive fluid shifts can occur rapidly in anaphylaxis due to
increased vascular permeability, with transfer of up to 35% of the
intravascular volume into the extravascular space within
minutes
 Any patient who does not respond promptly and completely to
injected epinephrine should be assumed to have intravascular
volume depletion causing persistent hypotension despite
maximum vasoconstriction
 These patients should receive large-volume fluid resuscitation,
with normal saline being the preferred treatment
 Large-volume fluid resuscitation should be initiated
immediately in patients who present with orthostasis,
hypotension, or incomplete response to IM epinephrine.
Supportive Measures
 Patient positioning
 The patient should be placed in a recumbent position
(when tolerated) with the lower extremities elevated to
maximize perfusion of vital organs
 This also helps prevent empty ventricle syndrome, in
which severe hypotension leads to inadequate cardiac
filling and electrical cardiac activity without a pulse
 Individuals with respiratory distress or vomiting may
not tolerate a recumbent position
Treatment Course Review
 Dosing with IM epinephrine followed by transfer to an emergency
facility for observation and possible further treatment
 Observation for 4 to 6 hours or longer based on severity of the reaction
 Education for patient and family on:
 Allergen avoidance
 Early recognition of signs and symptoms of anaphylaxis
 Anaphylaxis emergency action plan implementation
 Appropriate IM epinephrine administration
 Medical identification jewelry or an anaphylaxis wallet card
Treatment Course Review
 Epinephrine auto-injector prescription and training





provided at the time of discharge
Continuation of adjunctive treatment after patient
discharge:
H1 antihistamine: diphenhydramine every 6 hours for 2-3
days; alternative dosing with a non-sedating second
generation antihistamine
H2 antihistamine: ranitidine twice daily for 2-3 days
Corticosteroid: prednisone daily for 2-3 days
Follow-up appointment with primary health care
professional (after the food-induced anaphylactic
reaction), with consideration for additional follow-up with
a clinical specialist such as an allergist/immunologist
Take Home points
 Allergic Reactions are common and becoming more




common
1 in 50 people will have an anaphylactic reaction in
there life
Take Food and insect sting reactions seriously
Inappropriate antibiotics have individual
consequences
You don’t have to have a rash to have anaphylaxis
Take Home
 Epi…. Epi…. Epi
 Epinephrine is the ONLY first line treatment for




anaphylaxis
There is no real contraindication to giving epi
Think about glucagon if now responding to epi
Add oxygen to you steroid antihistamine regiment
DC with an epi pen