Download More likely to own an epinephrine autoinjector

Epinephrine for rapid
treatment of anaphylaxis
– an overview
Anaphylaxis
Sudden and severe allergic reaction
Typically occurs within minutes of exposure to the
allergen and almost always within two hours
Reaction results in release of chemicals in the blood and
body tissue encouraging the dilation of blood vessels,
leading to a decrease in blood pressure and fluid leaks
(often resulting in hives and swelling)
Anaphylaxis – common causes
Foods, such as peanuts
Tree nuts, i.e. almonds, walnuts, hazel, brazil, and
cashew nuts
Shellfish, i.e. shrimp and lobster
Dairy products
Eggs
Insect stings, i.e. wasps, bees, ants
Latex
Medications
Exercise
Anaphylaxis
Signs
Rapid, weak pulse
Flushed or pale skin
Abnormal lung sounds
Loss of consciousness
Symptoms
Swelling of tissues
Hives
Itching
Nausea, vomiting,
diarrhea
Dizziness or fainting
Difficulty breathing
Diagnostic criteria
Anaphylaxis is highly likely when any ONE of the following three criteria is fulfilled:
Criterion 1 — Acute onset of an illness (minutes to several hours) involving the skin, mucosal tissue,
or both (eg, generalized hives, pruritus or flushing, swollen lips-tongue-uvula) and at least one
of the following:
• Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced peak
expiratory flow, hypoxemia).
OR
• Reduced blood pressure (BP) or associated symptoms and signs of end-organ dysfunction
(eg, hypotonia [collapse] syncope, incontinence). (See 'Criterion 3' below.)
Criterion 2 — Two or more of the following that occur rapidly after exposure to a LIKELY allergen
for that patient (minutes to several hours):
• Involvement of the skin-mucosal tissue (eg, generalized hives, itch-flush, swollen lipstongue-uvula).
• Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced peak
expiratory flow, hypoxemia).
• Reduced BP or associated symptoms and signs (eg, hypotonia [collapse], syncope,
incontinence).
• Persistent gastrointestinal symptoms and signs (eg, crampy abdominal pain, vomiting).
Criterion 3 — Reduced BP after exposure to a KNOWN allergen for that patient (minutes to several
hours)
Source: UpToDate: Anaphylaxis: Rapid recognition and treatment; Accessed 5/27/2015
Epinephrine
Drug of choice for emergency treatment of severe allergic reactions
Epinephrine acts on both alpha and beta adrenergic receptors
• Lessens vasodilation and increased vascular permeability that
occurs during anaphylaxis, which can lead to loss of intravascular
fluid volume and hypotension
• Causes bronchial smooth muscle relaxation that helps reduce
bronchospasm, wheezing and shortness of breath
• Alleviates itching, hives and angioedema (generalized swelling)
and may be effective in relieving gastrointestinal and genitourinary
symptoms associated with anaphylaxis because of relaxer effects
on smooth muscle of stomach, intestine, uterus, and urinary
bladder
Epinephrine autoinjectors in schools
Exploratory, cross-sectional, web-based survey of 6,019 U.S. schools that participated
in the EpiPen4Schools program during the 2013-2014 school year
919 anaphylactic events reported in 607 schools
852 anaphylactic events with analyzable data
• Triggers varied seasonally with food listed most frequently overall (62.5%)
• 88.8% occurred in students
• 21.9% occurred in individuals with no known allergies
74.7% were treated with epinephrine autoinjector (EAI); 8.5% received a second
epinephrine injection
Of the 204 individuals not treated with an EAI, 77.0% received antihistamines, 12.7%
received another treatment, and 8.3% received no treatment
79.6% were transported to the hospital
White MV, Hogue SL, et al. EpiPen4Schools pilot survey: occurrence of anaphylaxis, triggers, and
epinephrine administration in a U.S. school settings. Allergy Asthma Proc 2015 Apr 20.
Early epinephrine treatment for foodinduced anaphylaxis (FIA)
Chart review study – all patients who presented to the emergency department with FIA
between January 1, 2004, and December 31, 2009.
384 emergency department visits for FIA identified during the study period
234 patients (61%) received epinephrine
164 (70%) received early epinephrine treatment (before arrival to ED)
70 (30%) first received epinephrine in ED (late treatment).
Patients who received early epinephrine treatment were:
• Older (7.4 vs 4.3 years; P = .008)
• More likely to have a known food allergy (66% vs 34%; P < .001)
• More likely to own an epinephrine autoinjector (80% vs 23%; P < .001)
Patients treated early were less likely to be hospitalized (17% vs 43%; P < .001).
• After adjusting for age, sex, and race, the patients who received early
epinephrine treatment remained at significantly decreased risk of
hospitalization compared with those who received late epinephrine treatment
(odds ratio 0.25 [95% CI, 0.12-0.49])
Fleming JT, Clark S, et al. Early treatment of food-induced anaphylaxis with epinephrine is associated with a lower
risk of hospitalization. J Allergy Clin Immunol Pract 2015 Jan-Feb;3(1):57-62.
From the package insert
CONTRAINDICATIONS
There are no absolute contraindications to the use of epinephrine in a life-threatening situation
WARNINGS
Only inject into the anterolateral aspect of the thigh – do not inject into buttock
Accidental injection into the digits, hands or feet may result in loss of blood flow to the affected area
Do note inject intravenously
Administer with caution in patients who have heart disease, including patients with cardiac arrhythmias, coronary artery or organic heart disease, or
hypertension. In such patients, or in patients who are on drugs that may sensitize the heart to arrhythmias, e.g., digitalis, diuretics, or antiarrhythmics, epinephrine may precipitate or aggravate angina pectoris as well as produce ventricular arrhythmias. It should be recognized that the
presence of these conditions is not a contraindication to epinephrine administration in an acute, life-threatening situation.
Epinephrine is light sensitive and should be stored in the carrier tube provided - before using, check to make sure the solution in the auto-injector is not
discolored or contains a precipitate
PRECAUTIONS
Epinephrine autoinjectors are not intended as a substitute for immediate medical care. In conjunction with the administration of epinephrine, the patient
should seek immediate medical or hospital care. More than two sequential doses of epinephrine should only be administered under direct medical
supervision.
The effects of epinephrine may be potentiated by tricyclic antidepressants and monoamine oxidase inhibitors.
Some patients may be at greater risk of developing adverse reactions after epinephrine administration: hyperthyroid individuals, individuals with
cardiovascular disease, hypertension, or diabetes, elderly individuals, pregnant women, pediatric patients under 30 kg (66 lbs.) body weight using
adult autoinjector and pediatric patients under 15 kg (33 lbs.) body weight using child autoinjector
INFORMATION FOR PATIENTS
Epinephrine may produce symptoms and signs that include an increase in heart rate, the sensation of a more forceful heartbeat, palpitations, sweating,
nausea and vomiting, difficulty breathing, pallor, dizziness, weakness or shakiness, headache, apprehension, nervousness, or anxiety.
ADVERSE REACTIONS
Adverse reactions to epinephrine include transient, moderate anxiety; apprehensiveness; restlessness; tremor; weakness; dizziness; sweating; palpitations;
pallor; nausea and vomiting; headache; and/or respiratory difficulties. These symptoms occur in some persons receiving therapeutic doses of
epinephrine, but are more likely to occur in patients with hypertension or hyperthyroidism. Arrhythmias, including fatal ventricular fibrillation, have
been reported in patients with underlying cardiac disease or certain drugs [see PRECAUTIONS, Drug Interactions]. Rapid rises in blood pressure have
produced cerebral hemorrhage, particularly in elderly patients with cardiovascular disease. Angina may occur in patients with coronary artery
disease. The potential for epinephrine to produce these types of adverse reactions does not contraindicate its use in an acute life-threatening
allergic reaction.
Accidental injection into the digits, hands or feet may result in loss of blood flow to the affected area (see WARNINGS). Adverse events experienced as a
result of accidental injections may include increased heart rate, local reactions including injection site pallor, coldness and hypoaesthesia or injury
at the injection site resulting in bruising, bleeding, discoloration, erythema or skeletal injury.
From UpToDate
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In patients of all ages, epinephrine administered in therapeutic doses by
any route often causes mild transient pharmacologic effects, such as
anxiety, restlessness, headache, dizziness, palpitations, pallor, and
tremor. These symptoms and signs are similar to those occurring during
the physiologic "fight or flight" response due to endogenous epinephrine
that occurs normally in sudden frightening or life-threatening situations.
Anaphylaxis itself can lead to angina, myocardial infarction, and cardiac
arrhythmias in the absence of any exogenous epinephrine or before
exogenous epinephrine is administered.
“To reiterate, there are no absolute contraindications to the use of
epinephrine in the treatment of anaphylaxis. The risk of death or
serious neurologic sequelae from hypoxic-ischemic encephalopathy
due to inadequately treated anaphylaxis usually outweighs other
concerns. Existing evidence clearly favors the benefit of epinephrine
administration in anaphylaxis. Sound clinical judgment is essential.”
Source: UpToDate, Anaphylaxis: Rapid recognition and treatment, accessed 5/27/2015
Reports of adverse events and
epinephrine autoinjectors
256 reports that were submitted FDA during sample
period, October 2011-September 2012
http://www.druglib.com/reported-side-effects/epipen/ (DrugLib caveats that
information is not vetted and should not be considered as verified clinical evidence)
Reports by Reaction Type
Accidental exposure (131)
Drug ineffective (51)
Injury associated with device (44)
Expired drug administered (40)
Injection site pain (23)
Hypoesthesia (19)
Pain in extremity (16)
Contusion (13)
Injection site pallor (13)
Heart rate increased (13)
Pain (11)
Injection site discoloration (9)
Risk of cardiovascular complications
and overdose
Observational cohort study; April 2008-July 2012; patients in ED who met diagnostic
criteria for anaphylaxis. Outcomes assessed were overdose and adverse CV event,
including arrhythmia, cardiac ischemia, stroke, angina, and hypertension.
573 patients, of whom, 301 (57.6%) received at least 1 dose of epinephrine
362 doses of epinephrine were administered to 301 patients: 67.7% intramuscular (IM)
autoinjector, 19.6% IM injection, 8.3% subcutaneous injection, 3.3% intravenous (IV)
bolus, and 1.1% IV continuous infusion.
8 CV adverse events and 4 overdoses with 8 different patients.
All the overdoses occurred when epinephrine was administered IV bolus.
Adverse CV events were associated with 3 of 30 doses of IV bolus epinephrine compared
with 4 of 316 doses of IM epinephrine (10% vs 1.3%; odds ratio 8.7 [95% CI, 1.840.7], P = .006).
Risk of overdose and adverse CV events is significantly higher with IV bolus epinephrine
administration. Analysis of the data supports the safety of IM epinephrine and a
need for extreme caution and further education about IV bolus epinephrine in
anaphylaxis.
Campbell RL, Bellolio MF, et al. Epinephrine in anaphylaxis: higher risk of cardiovascular complications and overdose after
administration of intravenous bolus epinephrine compared with intramuscular epinephrine.J Allergy Clin Immunol Pract.
2015 Jan-Feb;3(1):76-80.
Unintentional injections
The rate of unintentional injections of epinephrine from
autoinjectors is increasing, with more than 15,000 such
events being reported voluntarily to the American
Association of Poison Control Centers from 1994 to
2007.
Source: UpToDate, Prescribing epinephrine for anaphylaxis self-treatment,
accessed 5/27/2015
Epinephrine digital injections
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Retrospective cohort study of cases reported to 6 poison centers during 6
years (Texas Poison Center Network database)
365 epinephrine injections to the hand identified for the 6-year period
213 were digital injections; 127 had follow-up
• All patients had complete resolution of symptoms
• None were hospitalized or received hand surgery consultation or
surgical care
• Significant systemic effects not reported
• Pharmacologic vasodilatory treatment used in 23% (29/127)
Ischemic effects documented for 4 patients; 2 had symptom resolution
within 2 hours
• All 4 patients received vasodilatory therapy and were discharged
home, with complete resolution of symptoms
Muck AE, Bebarta VS, et al. Six years of epinephrine digital injections: absence of significant local
or systemic effects. Ann Emerg Med 2010 Sep;56(3):270-4.
Reluctance to use epinephrine
In response to Campbell RL, Li JT, et al. Emergency department
diagnosis and treatment of anaphylaxis: a practice parameter. Ann
Allergy Asthma Immunol 2014 Dec;113(6):599-608.
Dr. Stadtmauer wrote “Injectable epinephrine: an epidemic of misuse”
for Medscape (accessed 2/19/2015)
• “It’s time to face the fact that there is an epidemic of
miscommunication about the use of epinephrine for allergic
emergencies”
• “It is epinephrine underuse that has consistently been shown to be the
issue in anaphylactic emergencies, and overdose is actually quite
rare”
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At rest plasma epinephrine levels are 0.035 ng/ml
Levels 10 times that amount have been measured in persons exercising, and even
higher than that in people under mental stress
The standard adult dose of self-injecting epinephrine raises the level of
epinephrine in the body about 10 times baseline