In the largest randomized, placebo-controlled trial of its kind, use of epinephrine (adrenaline) for out-of-hospital cardiac arrest was associated with a small increase in survival at 30 days, but at the expense of worse neurological impairment.
The findings call into question a drug that has been a mainstay for resuscitation outside of hospitals for more than 50 years and should prompt some soul-searching among policy makers around the globe in terms of which outcomes are most valued, investigators say.
Has alpha and beta1/2 effects so it is an inopressor
Do not give cardiac arrest doses (1 mg) to patients with a pulse
• Take a 10 ml syringe with 9 ml of normal saline
• Into this syringe, draw up 1 ml of epinephrine from the cardiac amp (Cardiac amp contains Epinephrine 100 mcg/ml)
• Now you have 10 mls of Epinephrine 10 mcg/ml
Dose-0.5-2 ml every 2-5 minutes (5-20 mcg)
Inject 1 mg of epinephrine 1:10,000 (one amp of crash cart epi) into a 1L bag of normal saline. Draw up 10mL from the 1L bag in a 10mL syringe (The concentration of epinephrine in the syringe is now 1 mcg/mL). Push Dose: 10 mL every 2-5 minutes (10 mcg) note that the onset = 1 minute and duration = 5-10 minutes. Dose of epinephrine given via infusion: 1mL/min (1 mcg/min) and titrate to a maximum of 20mL/min.
ONE LINER: NOT AS GOOD AS NOREPI, MAY HELP A DYING HEART
- Mechanism: β/⍺ agonism
- Dose: Initial dose 5mcg/min (0.05mcg/kg/min)
- Indication: Hypotension + bad heart – hypotension AND bradycardia; hypotension with poor contractility (titrate epi for heart function on
POCUS + titrate norepi for BP); Periarrest phase (push-dose epi)
- Good/bad: (+) Give a dying heart a better chance (maybe); (+) Can be used in push dose; (-) Lactate no longer reliable for monitoring shock;
(-) Increased arrhythmias; (-) Limited evidence that epi is superior to norepi in most situations.
“Don’t be afraid of epinephrine. It is unfortunately so hard for so many people to get past the mental idea of giving themselves [or a child] a shot, but it invariably makes you feel so much better when you’re having an allergic reaction,” says Dr. Brown. “It only does good things, it only keeps you safe. It really is a wonder drug in anaphylaxis.”
People may wonder if they should administer epinephrine if they suspect — but aren’t sure — that they are having an anaphylactic reaction. The answer is yes. Epinephrine should be administered without delay if there is any concern or suspicion of anaphylaxis, because the risk of an untreated severe allergic reaction outweighs the risk of inappropriately receiving epinephrine.
This is a very pragmatic, large and well-delivered trial that poses a lot more clinical and moral questions
Epinephrine can increase ROSC, but it may worsen neurologic outcome and survival upon discharge.
In adults with out-of-hospital cardiac arrest, the use of epinephrine resulted in a significantly higher rate of 30-day survival than the use of placebo, but there was no significant between-group difference in the rate of a favorable neurologic outcome because more survivors had severe neurologic impairment in the epinephrine group.
Adrenaline improved the return of spontaneous circulation and likelihood of survival to reach hospital but only slightly increased survival rates at 30 days. More of those survivors had severe neurological problems.
It remains unclear if out of hospital protocols should change as a result of this trial. The findings are also not able to inform hospital cardiac arrest protocols, as use of adrenaline typically occurs within three minutes of cardiac arrest.
PDP-E provided a greater increase in SBP compared to PDP-PE. However, dosing errors occurred more frequently in those receiving PDP-E. Larger head-to-head studies are necessary to further evaluate the efficacy and safety of PDP-E and PDP-PE.
The release of norepinephrine and epinephrine provides an immediate jumpstart to the stress response, while stimulation of the HPA axis and the release of cortisol provides fuel to sustain the response until the stressor is resolved.
Epinephrine (adrenaline) remains a central part of management of OHCA in ACLS guidelines. Recent studies (i.e. PARAMEDIC-2) have raised concerns about the efficacy and possible deleterious effects of epinephrine on both overall survival and long-term neurological outcomes.
Epinephrine is a double-edged sword (Save the Heart at the Expense of the Brain):
Alpha-agonist – improves coronary perfusion and aortic diastolic pressures
Beta-agonist – increases myocardial work, promotes dysrhythmias, and increases platelet activation and clot formation causing potential adverse effects on neurologic injury and recovery.
The data before PARAMEDIC2, although fundamentally flawed because it is almost all observational, is pretty easy to summarize, and is very consistent with the results we saw in PARAMEDIC2: using epinephrine results in higher rates of ROSC and more patients being admitted to hospital. It is unclear if more patients leave the hospital alive, but if they do, there is no increase in the truly important outcome of neurologically intact survival.
Epinephrine is currently recommended in the management of out-of-hospital cardiac arrest (OHCA) by both the American Heart Association and the European Resuscitation Council despite a paucity of clear evidence that it improves patient-centered outcomes.
Is epinephrine the ideal drug? There is a sizeable body of research on alternative or adjunctive drug therapies for cardiac
Compared with the IO approach, the IV approach appears to be the optimal route for adrenaline administration in advanced life support for OHCA during prehospital resuscitation.”
Clinical Take Home Point: This study should not change your practice of IV vs IO access in OHCA. Future randomized trials of access are needed to clarify this situation. If you are using IO access in cardiac arrest you want to go as proximal to the central circulation as possible, which is most commonly the humeral IO.
Be safe. Never push IV epinephrine 1:1,000 or 1:10,000 to a patient with a pulse. Use the “Dirty Epi Drip” trick as a temporizing measure until a pharmacy-made drip is available.
After injecting a dose of epinephrine, some solution will remain in the injection device. This is normal and does not mean that you did not receive the full dose.
Ten years in the making, randomized trial results on a half-century-old resuscitation mainstay should spur a sober look at societal beliefs and values. “People have referred to adrenaline as being a double-edged sword and in fact that's what this trial has shown, that adrenaline can restart the heart but in doing so it's not good for the brain,” lead investigator Gavin Perkins.
Epinephrine (also known as adrenaline) is a neurotransmitter in the sense that, within the brain, it help neurons to communicate with one another. However, because epinephrine is mainly produced by the adrenal glands and has functions peripherally (i.e., outside the brain), it can also be considered a hormone.