Michael Langan, MD Geriatrician, MGH Senior Health September 10, 2012 Epi-Port (cartridge housing, portable, fashionable, easy to use) Epi-Pod (cartridge, removable, replaceable) A new drug delivery system for treatment of anaphylactic shock Twist, Turn, Push (TTP) From concept to patent to market 1:30P.M.-2:30P.M. Fox Hill Village Auditorium Sponsored by the MGH Wellness Center *************************

1. {
Anaphylaxis Management: Problems
with the Current System
The EpiPort® Epinephrine Auto-Injector
Michael Langan, M.D.

2.  1st recorded 2640BC in hieroglyphics
 bee sting of a pharoah
 First described Portier and Richet 1902
 “Without protection”
 “ana” - against
 “prophylaxis” - protection
 Profound shock & subsequent death in
dogs after 2nd challenge with a foreign
antige
 Characterized by explosive release of
mediators by mast cells mediated by IgE
Anaphylaxis

3. Anaphylaxis
An acute systemic allergic
reaction
The result of a re-exposure to an
antigen that elicits an IgE
mediated ic response
Usually caused by a common
environmental protein that is not
intrinsically harmful
Often caused by medications,
foods, and insect stings
It is a Type I hypersensitivity

4.  Allergic Reaction
 An exaggerated response by the immune system to a foreign
substance
 Anaphylaxis
 An unusual or exaggerated allergic reaction
 A life-threatening emergency
Allergies and Anaphylaxis

5. {
ANAPHYLAXIS
Common Causes
•Foods, such as Peanut
•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

6. Frequency of symptoms in
Anaphylaxis
Urticaria/angioedema 88%
Upper airway edema 56%
Dyspnea or wheeze 47%
Flush 46%
Dizziness,
hypotension, syncope
33%
Gastrointestinal sx 30%
Rhinitis 16%

8. Anaphylaxis- is an acute life-threatening reaction caused by an
IgE-mediated reaction and results from the sudden systemic
release of mast cells and basophil mediators .

9. Clinical Manifestations of
Anaphylaxis
 Skin: Flushing, pruritus,
urticaria, angioedema
 Upper respiratory:
Congestion, rhinorrhea
 Lower respiratory:
Bronchospasm, throat or
chest tightness, hoarseness,
wheezing, shortness of
breath, cough

10. Symptoms that can occur during an
Allergic or Anaphylactic Reaction
 Skin: Hives, swelling, itchy red rash
 Gut:Cramps, nausea, vomiting,
diarrhea, gas
 Neuro: Weakness, impending doom
feeling
 Respiratory: Itchy, watery eyes;
runny nose; stuffy nose; sneezing;
cough; itching or swelling of lips,
tongue or throat; changes in voice;
difficulty swallowing; tightness in
chest; wheezing; shortness of
breath; repetitive throat clearing.
 Cardiovascular: reduced blood
pressure, increased heart rate,
shock, pale and sweaty.
Common sites for
allergic reactions
Mouth (swelling of the
lips, tongue, itching
lips)
Airways (wheezing or
breathing problems
Digestive tract
(stomach cramps,
vomiting, diarrhea)
Skin (hives, rashes, or
eczema)

11. -Sudden, rapid, and unexpected
-historically occurred in health care setting
-76% of food related deaths due to foods outside
the home
-foods, medications, insect stings
 150-200 fatalities
 Death caused by respiratory compromise or
cardiovascular collapse
Under-recognized
Underreported
Undertreated
Poorly Understood

13. Its typical explosive onset and unforeseen
nature of severity is frightening

14. Anaphylaxis Fatalities
 Estimated 500–1000 deaths annually
 1% risk
 Risk factors:
 Failure to administer epinephrine immediately
 Peanut, Soy & tree nut allergy (foods in general)
 Beta blocker, ACEI therapy
 Asthma
 Cardiac disease
 Rapid IV allergen
 Atopic dermatitis (eczema)

15. The first documented case of a
food fatal reaction was described
in 1926 by a pediatrician. A 1 -year-
old boy with atopic eczema
experienced three episodes of
generalized allergic reactions at
home after intake of a few spoons
of mashed peas. In the hospital
setting an oral challenge with
carrots/mashed peas was
performed under the supervision
of a chief nurse. Immediately after
the intake of the test meal the child
developed angioedema, cyanosis
and collapsed. He died despite
emergency treatment.

16.  Most knew they were allergic to causative food
 Peanuts and tree nuts most common foods (90%)
 Individual did not ask about ingredients, were misinformed or
incorrect labeling of product
 Most patients had a diagnosis of asthma even if well controlled
 Injectable epinephrine was not carried or administered in a
timely fashion
 Skin reactions (hives, swelling) mainly absent in these severe
reactions
Fatal anaphylaxis

17. Epinephrine = The only medication
that can stop the progression of
anaphylaxis and reverse the
symptoms.
Effect immediate
.

18. The events leading up to
fatal anaphylaxis are unseen
and unpredictable.
1. Occurs in the absence of medical professionals (school, restaurant)
2. Interval between exposure to allergen and death 10-15 minutes for
insect stings and 25-30 minutes for food induced.
3. Most fatalities in teenagers and young adults
4. Can occur on first exposure
5. IM epinephrine drug of choice. No alternative.

19.  Epinephrine (adrenaline) is the drug of choice in the
treatment of anaphylaxis.
 There is no other medication with a similar effect on
the many body systems that are potentially involved
in anaphylaxis.
 Epinephrine narrows blood vessels and opens
airways in the lungs. These effects can reverse severe
low blood pressure, wheezing, severe skin itching,
hives, and other symptoms of an allergic reaction.
 The first step in the management of anaphylaxis is
the subcutaneous or intramuscular injection of 0.01
ml/kg of aqueous epinephrine 1:1000 (maximal dose
0.3 to 0.5 ml or 0.3-05 mg).

20. Epinephrine is the medication of choice for treating an
anaphylactic episode .
The recommended dose of epinephrine is 0.01 mg/kg I.M to as much as 0.3 mg-in
children, and it may be repeated within 5 minutes if symptoms worsen or severe
symptoms persist. (1:1,000 aqueous solution (1 mg/mL) ).
The lateral aspect of the thigh appears to be the optimal location of
administration.
There are 2 doses of self –injectable epinephrine : Epipen jr 0.15mg , Epipen 0.3mg.
Use of I.V should be reserved for the most extreme conditions ( more adverse
reaction).
The more advanced the anaphylactic reaction- development of hypotension- the
less likely epinephrine is to reverse the reaction.

21.  Treats all symptoms of anaphylaxis and prevents
progression
 Intramuscular injection in lateral thigh produces
most rapid rise in blood level
 0.01 mg/kg in children, 0.3-0.5 mg in adults
 Patients who receive epinephrine and have
symptoms other than hives should be lying down
with feet elevated (empty heart syndrome)
 Up to 20% of time, more than one dose needed
 New recommendations: have 2 or more devices
Epinephrine

22. Epipen
The epinephrine auto-injector was
introduced in 1980.
Epinephrine auto-injectors such as
EpiPen and EpiPen Jr. contain 0.3 and
0.15 mg of epinephrine respectively
and are designed for single dose
intramuscular injection for
emergency treatment of anaphylaxis.

24. {
EpiPen and Twinject
How to Administer
EpiPenTwinject

26. Epinephrine
Allows time to safely transport the
patient to a medical facility.
The risk to benefit ratio is
overwhelmingly favorable.
In the year 2000 there were only 7 states
that allowed first responders to carry
and administer epinephrine.

27. VASTUS LATERALIS

29. Vastus Lateralius

31. {
Intramuscular injection of epinephrine is
preferable to subcutaneous administration I
because of the faster and higher rate of
absorption in the muscle.

32. Fear of needles may
also play a role

34. {
EpiPen and Twinject
How to Administer
EpiPenTwinject

35. {
EpiPen and Twinject
How to Administer
EpiPen & Twinject
1.Obtain patient’s prescribed auto-injector Esure:
a. Prescription is written for the patient who is experiencing the severe allergic reaction or
your protocols permit carrying the auto-injector on the ambulance.
b. Medication is not discolored (if visible)
2.Obtain order from medical direction, either on-line or offline.
3.Remove safety cap(s) from auto-injector
4.Place tip of auto-injector against patient’s thigh.
a. Lateral portion of the thigh
b. Midway between waist and knee
5.Push the injector firmly against the thigh until the injector activates.
6.Hold the injector in place until the medication is injected (at least 10 seconds).
7.Record activity and time.
8.Dispose of a single-dose injector, such as the EpiPen, in a biohazard container. Save a two-dose
injector, such as Twinject, and transport it with the patient in case the second dose is later required.

36.  Can deliver only a single dose –One chance
 Accidental misfires common (digital auto-injection)
 Poor compliance (not carried, fear of using)
 Counterintuitive design
 Complex instructions
 Needle length inadequate in up to 1/3 of patients
 May require second dose (probable secondary to needle length)
 Inconvenient portability, unappealing, not designed for active
lifestyle
Problems with current
Auto-Injector technology

37. No Feedback Loops

38. Patient-Doctor Relationship minimal
Not amenable to EBM
Faulty Mental Models
Does not conform to acute or chronic
disease
History, treatment, and outcome are binary
options.

39. No evidence based
studies (logistical
and ethical
reasons)
Lack of feedback

40. Something you buy but
hope you never have to
use (airbag, smoke
detector)
No positive or negative
feedback

42. Digital Auto-injection
Counter-intuitive Design

46. In teenagers, failure to carry epinephrine varied
1.perceived risk of reactions
2. social circumstances
3. convenience of carrying.
Many teenagers expressed desire for a less bulky design
in a 2011 study looking at adolescents attitudes towards
and experience with epinephrine auto-injectors.

47.  Risk-taking behaviors varied by
social circumstances, convenience,
and perceived risks. Compliance
with carrying an epinephrine auto-
injector was poor.
 61% reported that they “always” carry
frequencies varied with activity
 : traveling (94%)
 restaurants (81%)
 friends’ homes 67%),
 school dance (61%),
 wearing tight clothes (53%), and
 sports (43%).45
Survey:
Adolescents and
young adults at
high risk for
fatal
anaphylaxis due
to food
allergens

48. Myth:
Epinephrine is Dangerous
REALITY:
 Risks of anaphylaxis far outweigh risks
of epinephrine administration
 Minimal cardiovascular effects in children
(Simons et al, 1998)
 Caution when administering epinephrine in
elderly patients or those with known cardiac
disease

49. Twist, Turn, Push
TTP