Episode 75- Does caffeine reduce the efficacy of adenosine?

Hello and welcome to Episode 75 of ER-Rx- a podcast tailored to your clinical needs. I’m your host, Adis Keric, and in this Pharmacy Consult episode I’m gonna give you one possible reason that adenosine you gave your patient in SVT didn’t work- and a big shout-out goes to listener Nick G who recommended this topic.

Paroxysmal supraventricular tachycardia or SVT leads to over 50,000 ER visits every year in the US. It happens because of abnormal electrical impulse conduction- typically a reentry circuit– within the AV node or outside of it in the surrounding cardiac tissue. In stable patients, we can try vagal maneuvers (like the Valsalva or the modified Valsalva) and if that fails, adenosine is technically considered the first-line med of choice -although calcium channel blockers like diltiazem have also been shown to work very well and are starting to become more and more used- but that’s a topic for a whole ‘nother episode.

Adenosine has a few mechanisms of action but the ones we care about in this setting is that it slows AV nodal conduction and breaks that re-entry circuit. Guidelines call for a 6 mg IV dose given by ultra-rapid injection and increasing doses to 12 and even 18 mg if needed. These doses are successful in reverting patients back to normal sinus rhythm about 60-90% of the time, with the higher doses being more effective. But it looks like it just really sucks getting adenosine. Have you ever seen this? More than 80% of patients get side effects like flushing, dizziness, chest pain, anxiety, and some describe it as “I felt like I was dying,” – which I guess in a sense they are given the med literally stops their heart for a second or two.

There’s some older conflicting evidence that methylxanthines, like theophylline and caffeine, can reduce the efficacy of adenosine. This is because caffeine also binds to and competes with adenosine for adenosine 1 receptors (mostly found on cardiac tissue) as well as adenosine 2 receptors.

One group of authors wanted to address this mostly theoretic concern with a study they published back in 2009. This is one of the most cited studies on the topic that’ll you’ll come across if you Google this issue. In this multicenter, case-controlled observational study, 68 patients received a 6 mg dose of adenosine for SVT. Fifty-two (77%) of the patients reverted to sinus rhythm after the 6 mg dose, and there was no difference in baseline characteristics, including overall daily caffeine intake, between patients who did and did not revert. But, the patients that did not revert had ingested significantly more caffeine in the last 2, 4, 6, and 8 hours prior to getting adenosine—remember that the half-life of caffeine is 4-8 hours, and that’s why they looked at these specific time points. Also, for each of these time points, more caffeine-negative patients than caffeine-positive patients reverted (and they didn’t quantify what “caffeine positive” meant; they could have had just one small cup of tea, or 10 Red Bulls- you either had caffeine or you didn’t is what was on the patient questionnaire). The most noticeable effect was within the 2 and 4-hour marks, but that effect was lost at the 6- or 8-hour marks—again making our pharmacokinetics happy as we can expect that a lot of the caffeine they drank would be metabolized by then.

In a nutshell, drinking any caffeine within 4 hours of a 6-mg adenosine dose significantly reduced the rate of reverting out of SVT. If the patient had any caffeine at any time period at 6 or 8 hours before adenosine, there was no difference in efficacy, but the study may have been underpowered to detect a difference at the 6- and 8-hour time points. The results also hint that a higher, 12 mg dose may still work and could overcome caffeine’s inhibitory effects. In this study, 8 patients who didn’t revert with a 6 mg dose reverted after a 12 mg dose, and 7 of those patients had ingested caffeine within the last 4 hours. So, if a 6 mg dose fails, it’s reasonable to expect that going up to 12 mg would work in patients that recently drank caffeine.

In conclusion, if adenosine didn’t revert your patient out of SVT, it could be that Grande mocha they just drank. But there still remains a lack of data to definitively prove this, and this was by no means a perfect study. It had only 68 patients, results could have been affected by “recall bias”- since patients were asked about their caffeine intake after conversion to sinus rhythm, and the main outcome only stratified patients as “caffeine positive” or “caffeine negative”—there could have been huge variations in how much caffeine patients drank prior to getting adenosine. But still, next time you’re reaching for adenosine, ask your patient about recent caffeine intake and adjust your dose, or your choice of medication, accordingly.

As always, thank you so much for your time, and thank you for wanting to learn more about pharmacotherapy. If you have any comments or anything you’d like to add to this episode, please reach out to me on the @errxpodcast Instagram page or on my website, errxpodcast.com- I’d love to respond to all comments and criticisms.

I also want to take one second to shout out a listener for their review on Apple Podcasts. They said:

“Love this podcast for anyone working in an ER or ICU. If you aren’t a pharmacist you will still get tons of useful information to improve your practice. Adis has a knack for finding a happy balance between explaining the pharmacokinetics and practical use for patients at the bedside. Highly recommend!”

Thank you so much for that awesome review.

Lastly, I want to thank everyone who subscribed to the newsletter on the website to enter into a drawing for a prize package, and as promised, I wanted to let you all know that a winner has been chosen- I actually reached out to them today by email. They’ll be getting some ER-Rx podcast swag from me, some Pharm-So-Hard Podcast swag that was donated by the amazing Jimmy Pruitt, and they’ll also be receiving 2 free downloads for the awesome PediSTAT app—and I want to say a huge thank you to the actual creator of the app, Dr. James Kempema, for this donation.