r/pharmacology Jun 14 '21

What is the reason why intravenous epinephrine must be diluted more than intramuscular in the setting of cardiac arrest?

Just curious what the physiological reason is that 1:1000 epinephrine is not to be used for cardiac arrest/active CPR.

16 Upvotes

12 comments sorted by

11

u/[deleted] Jun 14 '21

A more concentrate formulation allows for a smaller volume in muscle which is easier to administer.

A long slower infusion is required IV to reduce fatal hypertension, pulmonary and cerebral edema. For example 0.5ml of 1:10,000 IV for anaphylaxis is easier to administer safely than 0.05ml 1:1000. For cardiac events approx 10ml 1:10,000 is infused slowly which is safer and easier than 1ml 1:1000, especially when dose volume isn't a concern.

1

u/JustHere2CorrectYou Jun 14 '21

Why do you reference 0.5ml of 1:10,000 IV, which would be 50mcg, for anaphylaxis? Are you talking about it as a push dose pressor? The IM treatment dose is 0.3-0.5mg, 50mcg is off by an order of magnitude.

1

u/aswanviking Jun 14 '21

Not OP but in a patient with a pulse, 50 mcg of Epi rapid IVP is a relatively high dose.

IM doses are higher but get absorb slower and last longer.

1

u/JustHere2CorrectYou Jun 14 '21

Right, so unless they’re peri-arrest I’m not sure why we’d even give a push dose of IV epi.

If you’re going to use IV epi for anaphylaxis it will usually be as a drip. I’m just not sure where the 50mcg IV push for anaphylaxis came from. The IM dose is much larger but absorbs slower and tapers itself overtime. If you’re going to us IV epi, you need a continuous infusion.

1

u/aswanviking Jun 14 '21

Yeah fair. In theory, if you got central access, a little IV push epi (10-20 mcg) followed by drip would be quicker in onset and dose better adjusted to response.

But in non-ICU patients, just give It IM, it works surprisingly quickly.

1

u/[deleted] Jun 15 '21

IV administration of adrenaline is not recommended but can be an alternative if IM is ineffective. The recommendation is to slowly titrate 0.5mL 10,000. You are right if repeated doses are required then infusion should be performed.

https://www.medicines.org.uk/emc/product/3675/smpc#gref

1

u/JustHere2CorrectYou Jun 15 '21

Thanks for this. I’ve never seen recommendations regarding single push doses of IV epi in anaphylaxis before.

3

u/Mediocre_Doctor Jun 14 '21

I don't like this proportion nomenclature. It's better to state the concentration.

The 1 mg/mL epi has led to fatal med errors:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2826951/

During a day surgery ENT procedure, the surgeon requested local anesthetic for injection (specifically lidocaine 1% with epinephrine 1:100,000) and was handed a pre-drawn syringe. The surgeon injected the medication into the surgical site. Immediately afterward, the patient experienced a cardiac arrhythmia leading to cardiac arrest. Despite full resuscitation measures, the patient died.

Information gathered after the incident indicated that the syringe contained epinephrine 1 mg/mL (1:1,000) intended for topical use, rather than the local anesthetic for injection that was requested.

IIRC the patient recieved up to 30 mg of epinephrine.

1

u/nowlistenhereboy Jun 14 '21

Yes but my question is specifically regarding patients who are already in cardiac arrest. It is explicitly stated in protocols that the more concentrated epi cannot be substituted for use in ACLS resuscitation.

My question is if there is an actual physiological reason why the higher concentrated epi would be contraindicated in a patient who already has no heartbeat and you are doing active CPR?

2

u/pking8786 Jun 14 '21 edited Jun 14 '21

So for IM injection you need a better circulation to get it into the blood stream. Even giving IV Adrenaline (epi) you generally need to follow it with a 50ml bolus of saline to push it in during CPR (especially if using lower limb cannula).

Just read you didn't specifically mention IM, and I get that 1mg is 1mg, but dropping 1ml IV of 1 in 1000 can be damaging to blood vessels, and there's less room for error when it's concentrated, which is why our guidelines recommend an "IV expert" give IV Adrenaline in the UK resuscitation guidelines

-14

u/[deleted] Jun 14 '21

I dk whar ur talking aboit. Is this like etizplam?

1

u/hockeystar357 Jun 14 '21

It's so the full dose makes it to circulation. A few years ago there was a shortage of the premixed epinephrine syringes used during codes. Many hospitals ended up simply giving the regular concentration followed immediately by 10 mL NS. So the dilution has nothing to do with the physical aspects of the drug but rather making sure the body receives a full dose.