Endotracheal and IV epinephrine go head to head
For some time the Neonatal Resuscitation Program has recommended IV epinephrine preferentially over the endotracheal route. I have written about epinephrine twice before with the last one being Is epinephrine via the ETT really so bad? Previous studies looking at epinephrine has really asked the question “How likely am I to get return of spontaneous circulation (ROSC) if I give endotracheal epinephrine and follow this with IV epinephrine?” This really doesn’t address the question on which the recommendation for IV epinephrine has been made which is if you actually give the first dose of epinephrine IV to you get a a faster ROSC.
Why might one better than the other?
It probably makes sense to start here. In a patient with poor cardiac output or asystole, injecting epinephrine into the heart via the intravascular route (at birth through a UVC most likely) leads to deposition of the drug within the heart. With cardiac compressions blood passes through the right ventricle to the lung and then back to the left side with eventual passage of blood containing epinephrine to the coronary arteries. Epinephrine then can stimulate the heart to begin pumping or with more vigour leading to increased carotid blood flow which is the all important need for perfusing the brain. In the case of endotracheal epinephrine one is relying on the absorption of the drug from the alveolar capillary interface and for this to be effective, ideally the whole dose of the drug provided would need to be distributed to the terminal airways. If you don’t have great blood flow in the case of asystole and compressions are not effective it stands to reason that there are multiple reasons why the drug might not get to the coronaries in the same way as if given directly into the venous return to the heart.
Let’s go head to head
It should come as no surprise that given the push to give the first dose IV there would over time be a shift to having a large enough sample to look at a direct comparison vs looking at IV AFTER ETT. There will of course still be those that give the fist dose via ETT as it really is just much easier. As you move through the steps of NRP you reach placement of the ETT faster than placement of a UVC and having been there it really is tempting since you have the option to give the first dose via the ETT. Remember the speed with which you can give the first dose as that will come up again later in this piece.
Halling et al published Use of Initial Endotracheal Versus Intravenous Epinephrine During Neonatal Cardiopulmonary Resuscitation in the Delivery Room: Review of a National Database. The article is as described wherein the authors examined in a retrospective fashion the responses to a first dose via IV vs ETT to see how they differ. Their sample size was fairly decent for a neonatal study. Their group under study were taken from a larger pool of 1288 patients who had received chest compressions. Of those 538 had both chest compressions and epinephrine and after excluding 130 for various reasons this left 408 patients for study. The newly born infants were on average about 31-32 weeks gestational age and about 55% in both groups were under 34 weeks at birth. There were 281 patients with an initial dose via the ETT and 127 with dosing first via the IV route. Looking at Table II from the study reveals some surprising findings.
Those who received their first dose via the endotracheal route had a statistically higher chance of having ROSC at 70.11% vs 58.27%. Additional doses to achieve ROSC could have been again via the ETT or IV and in the Initial ETT group, of the 281 patients, 169 received only ETT epinephrine of whom 132 had ROSC while 113 received IV epinephrine after ETT of which 65 achieved ROSC. If you look at secondary outcomes the chance of ROSC after only the first dose was also equal in both groups at 34.16 and 36.22% with a trend towards greater survival with an initial dose of ETT epinephrine. This would seem to fly in the face of prior studies would it not? Are the drugs equally efficacious or is something else going on here?
I believe the difference in outcomes relates to the final line in the above table. Patients who were given ETT epinephrine as the first dose had a median time to first dose of 2 minutes shorter. As I mentioned above the placement of the ETT comes before UVC placement in the stepwise progression of NRP so you just have an opportunity to get the epinephrine in faster. As shown in the next figure, the relationship between timing of dosing and ROSC can be seen.
Final Thoughts
There isn’t anything wrong with giving IV epinephrine but the question is can you really give it at the same time as you would through the ETT? If a myocardium is stunned from hypoxia and is either beating very slowly or asystolic it may be that the extra two minutes of inadequate perfusion matters in terms of getting the heart muscle to respond. I suspect this is the reason why if you compare ETT vs IV dosing and look at the response to a first dose to achieve ROSC there is no difference. I could argue that the IV dose is actually superior as it can achieve the same chance of ROSC after one dose even if given two minutes later. If you look at the overall effect though of starting with an earlier dose via ETT your chances of successful resuscitation and survival may be better if you start with the ETT. The purists out there will no doubt point out that the trial here is retrospective so it is possible that there are factors that have not been taken into account that are unbalanced between groups. My counter to that however is that this may be the near best evidence we will get. I am not sure if a true RCT will ever be done as it would be very difficult I suspect for practitioners to follow NRP and delay giving epinephrine via the ETT when it is right there and a patient is doing quite poorly. There would be some of course who would but I could see many breaches in protocol from nervous team members.
I think what the study really says is that if you choose to start with ETT epinephrine it doesn’t preclude you from trying to place a UVC quickly following the first dose and following up with an IV dose. This sort of research is quite reassuring to those who still give the first dose via the ETT but doesn’t negate efforts that should be made to establish IV access in those most severely compromised.