Epinephrine is the most important drug in the management of anaphylaxis. It is so important because it saves lives! This is no hyperbole. This edition of the Why we do what we do series focuses on the evidence behind the use of IM Epi in Anaphylaxis.
What are the indications?
You should rapidly administer IM Epi for anyone with anaphylaxis. But how do we define anaphylaxis? Do we know it when we see it? Well, kind of. Note that 90%$ of cases have skin findings hives, itchin/flushing etc,.). Other symptoms generally come from at least oine of the following “systems;” upper airway swelling, lower respiratory tract disease, GI symptoms and cardiovascular. There is no lab test that makes the diagnosis – it’s clinical. And, based on consensus recommendation it is any of the following three criteria:
Acute onset of illness involving the skin, mucosal tissue or both plus either/both of
- Respiratory symptoms (difficulty breathing wheezing, stridor, hypoxemia)
- Hypotension or signs of reduced end organ perfusion
Two or more of the following acutely noted after exposure to a likely allergen (the first time eating fish):
- Skin-mucosal involvement including hives, swollen lips, tongue and/or soft palate
- Respiratory symptoms
- Persistent GI symptoms (abdominal pain, vomiting)
Hypotension after exposure to a known allergen for the patient
- Adults: systolic BP <90 mmHg
- Babies <12 months: <70 mmHg
- 1-10 years < (70 + age x2)mmHg
The individual patient response to Anaphylaxis varies. It can actually resolve spontaneously (we make our own epinephrine naturally) or it could progress to cardiovascular collapse within minutes. Death is from upper or lower airway obstruction or cardiovascular collapse. In general it is very hard to predict who will progress and how rapidly they will. So when in doubt…
Administer Epinephrine ASAP!
What is the dose?
In adult sized patients (>30kg):
- 0.3 to 0.5 mg/dose IM in the anterolateral thigh (you choose the leg)
- Epi-Pen and Auvi-Q autoinjectors are 0.3mg
In children (<30kg):
- 0.01 mg/kg IM in the anterolateral thigh
- The “Junior” autoinjectors have a dose of 0.15 mg
The dose should be repeated every 5 to 15 minutes as clinically warranted
Why IM instead of subcutaneous or IV?
IM is preferred over subcutaneous injection because it leads to a more rapid rise in plasma concentration. Simons et al demonstrated as such in a small RCT in healthy adults that received either an IM or subQ injection and in a prospective study of children with anaphylaxis noting that the mean maximum plasma epi concentration in epi was at least 10% greater and achieved faster 8 +/- minutes.
Only use IV if the patient has circulatory collapse – the infusion rate of 2-10 mcg/min is listed in adults and 0.1 to 1 mcg/kg/min in children. This can be done peripherally for a short time period if necessary.
How does it work?
Epi has numerous adrenergic effects. In short, the alpha-1 agonist leads to vasoconstriction, increased peripheral vascular resistance (thus increasing afterload and BP) as well as decreasing mucosal edeam (especially important in the upper airway). The beta-1 adrenergic agonism head cardiac effects on inotropy and chronotropy. And the beta-2 adrenergic agonist effects lead to bronchodilation and decreased release of inflammatory cytokines from mast cells/basophils.
What’s the evidence?
A case series of patients with anaphylaxis that suggested that though symptom onset was rapid (<5 minutes) in the 6 fatalities, epinephrine was not administered until a mean of 93 minutes (range 25-180) after onset.
A series of deaths from anaphylaxis in 24 patients from when I was in high school and college. Only 5 (20%) received Epi at any point. Admittedly, this was 1992-98 and Epi wasn’t as “popular” back then.
In 164 deceased patients with anaphylaxis only 14% received Epi before they had respiratory or cardiac arrest. 62% did get it overall, but once the patient was in arrest there was no reversal of the course towards mortalityland.
So, sure, there are no RCTs for anaphylaxis. It would be hard to ethically withhold it. Ultimately, though the evidence remains limited s is a first line treatment as recommended by experts in the field. Despite this, prescription and administration rates in the ED, thoguh improving are still unacceptably low.
Are there any contraindications?
With Epi you get activation of the “fight or flight” response – anxiety, headache, restlessness/jittery, palpitations, and tremor. These are short lived and preferable to airway or circulatory collapse. The risk of causing ventricular arrhythmias, MI or pulmonary edema as well as increased BP leading to intracranial hemorrhage is theoretical and only really an issue if you give the wrong concentration (1:1000 IV for instance). It is then more likely that anaphylaxis itself would lead to these bad things rather than the Epi you just gave.
So, in summary – there are NO real contraindications to giving IM Epi.