Tuesday, December 18, 2012

Trick of the Trade: Combine Adenosine with the Flush


The success of adenosine depends as much on the administration technique as it does the mechanism of action. The 2010 Advanced Cardiac Life Support (ACLS) Guidelines recommend the following when administering adenosine:
"6 mg IV as a rapid IV push followed by a 20 mL saline flush; repeat if required as 12 mg IV push"
While most drugs are metabolized in the liver, adenosine doesn't even make it that far, being metabolized in the erythrocytes and vascular endothelial cells. With this extremely short half-life (10 seconds), it is important to help it reach the heart before it's metabolized and excreted without being effective.

There are a variety of methods to administer adenosine. Some will push it through a running IV line, followed by two 10-mL saline flushes.


Others will utilize a stopcock, where the adenosine is hooked up to one port and a 10-mL saline flush is hooked up to the other. After the adenosine is pushed, the swivel is switched and the 10-mL saline flush quickly follows.

Others, still, will use a hybrid of these two methods. The problem with all of these approaches is that it takes time to switch syringes. Even if utilizing the stopcock, nurse unfamiliarity with how to maneuver the port from OFF to ON may lead to some fumbling. With almost any other drug, a few seconds lost here or there wouldn't matter. But it can with adenosine.

Trick of the Trade: Combine the adenosine and flush solution in one syringe.
  • Grab a 20-mL (or 30-mL) syringe.
  • Draw up the adenosine AND the normal saline in the same 20-mL syringe.
  • Administer via fast IV push (can be through a running IV line).
The major advantage to this approach is that it obviates the need for any syringe switching or stopcock swiveling. There's no need for additional flushes since your diluted adenosine syringe doubles as the flush. If you don't have 20-mL syringes, you can still add the adenosine to one of the two 10-mL saline flushes to get the same effect. Flush volumes as low as 5 mL have been effective [4].

Adenosine is stable in, and compatible with, normal saline [2, 3]. Even if you're giving a 12 mg dose, the adenosine will only take up 4 mL of volume, leaving 16 mL for the normal saline. A small study from Korea demonstrated the feasibility and effectiveness of this approach compared to the standard techniques [7]. The efficacy of diluted adenosine was also demonstrated in a study by Lopez-Palop et al., albeit by the intracoronary route [6].

Read more about when to consider alternative doses of adenosine from my previous post.

Original: December 18, 2012
Last updated: January 18, 2013

References
  1. Neumar RW, Otto CW, Link MS, et al. Part 8: adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122(18 Suppl 3):S729-67. [PMID 20956224]
  2. Ketkar VA, Kolling WM, Nardviriyakul N, et al. Stability of undiluted and diluted adenosine at three temperatures in syringes and bags. Am J Health Syst Pharm 1998;55(5):466-70. [PMID 9522931]
  3. Kaltenbach M, Hutchinson DJ, Bollinger JE, et al. Stability of diluted adenosine in polyvinyl chloride infusion bags. Am J Health Syst Pharm 2011;68(16):1533-6. [PMID 21817085]
  4. Gausche M, Persse DE, Sugarman T, Shea SR, Palmer GL, Lewis RJ, Brueske PJ, Mahadevan S, Melio FR, Kuwate JH, et al. Adenosine for the prehospital treatment of paroxysmal supraventricular tachycardia. Ann Emerg Med 1994;24(2):183-9. [PMID 8037382]
  5. Ng GA, Martin W, Rankin AC. Imaging of adenosine bolus transit following intravenous administration: insights into antiarrhythmic efficacy. Heart 1999;82(2):163-9. PubMed [PMID: 10409529] PDF
  6. Lopez-Palop R, Saura D, Pinar E, et al. Adequate intracoronary adenosine doses to achieve maximum hyperaemia in coronary functional studies by pressure derived fractional flow reserve: a dose response study. Heart 2004;90(1):95-6. [PMID 14676256]
  7. Choi SC, Yoon SK, Kim GW, et al. A convenient method of adenosine administration for paroxysmal supraventricular tachycardia. J Korean Soc Emerg Med 2003;14(3):224-7.
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17 comments:

  1. Will this not further reduce the half-life?

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  2. As long as it works just as well I don't see an issue with trying it that way. I can see a time savings.

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  3. I would think this will dilute the Adenosine reducing the effectivness. Isn't this why we give 6mg followed by 12 mg and 12 mg? The problem seems to be in the way you are giving it. use IV tubing with 2 ports. Push the drug followed by the flush from the second port farther up the tubing, and have someone squeeze the bag. Use 2 people. It seems you're making this harder than it should be by using the stopcock. We do this in the field and in the emergency center where I work as a Paramedic.

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  4. Your flush volume is too low

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  5. This was easier in the days prior to needle-less IV systems. Two needles side by side in one port and flush the 6mg immediately followed by the 20cc NS flush. I will try not to use the words "standard of care" or "golden-rule" but every time I gave Adenosine this way it worked the first time (except for those pesky a-fibs hiding out). 20cc is plenty enough to get the drug there in my (and my cardiologist friends) opinion. Another trick which is not mentioned in this article is begin your IV high in the arm, antecubital fossa at the minimum. Good luck!

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  6. Thanks for all of the comments. To address a few, diluting adenosine in normal saline does not affect its half-life or effectiveness. Ketkar and colleagues demonstrated this in their 1998 study (see reference 2 above).

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  7. I'm not so sure reference 2 proved efficacy of adenosine mixed into a flush. I don't have access to the article in full I see nothing in their results which would indicate they measured its clinical efficacy.

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    1. Thanks Christopher. You're correct, that study did not address efficacy, just stability (nor did reference 3). The point is that since adenosine is stable in normal saline, there should be no decrease in efficacy compared to pushing it followed by normal saline. This concept is further supported by studies such as Gausche, et al (http://www.ncbi.nlm.nih.gov/pubmed/8037382) who demonstrated good efficacy with only 5 mL of saline flush following the adenosine admistration. As long as the technique gets the drug to the heart before it is metabolized, efficacy should be good.

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    2. My assumption (because it is not based on knowledge of true causal factors) has been that the size of the flush simply helped ensure the bolus made it to central circulation. Within reason the bolus will stay at a reasonable concentration (my physics education is telling me to quit making assumptions) upon reaching central circulation.

      In the case of dilution, it seems intuitive that the arrival will be of a bolus of lesser concentration and it will take more cardiac cycles (related to SV and EF) to get it all there.

      Of course this is all based on assumption of fluid flow and a model where boluses of medication remain in a "slug"...

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  8. Great comments. What I learned:

    1. Looking at Gausche et al's study in the prehospital setting that Bryan references (I added as reference #4) showing that adenosine 12 mg IVP is effective with only a 5 mL saline flush. Not based on any evidence, I've always used 10-20 mL of flush, which I'm now thinking is overkill.

    2. Diluting adenosine into a single syringe before injection does NOT degrade the half-life of adenosine.

    3. I think there are trade offs between single-large volume IV bolus of adenosine vs a two-step, more concentrated bolus of adenosine. Although more dilute (former), it has no "moving parts" (latter). This trick of the trade may make up for the time lost while switching syringes or coordinating a saline flush.

    Interesting trick. Would love to hear people's experiences with this. Great tip, Bryan!

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    1. I think the point I made regarding the longer transit time (more SV + EF dependent cycles) with a more dilute injection is valid, although I'll freely admit it was based initially upon assumptions :)

      However, looking at Ng's adenosine+Tc99m imaging study in Heart (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1729130/) there is a clear advantage to the small bolus followed by the large flush. With estimated an estimated half life of 1.5s once mixed into the bloodstream, I think any advantage you can get in efficient distribution must be taken into account.

      That being said, perhaps the tradeoff is you use 12mg in a 20cc flush, minimizing the potential for longer transit of the desired dose.

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    2. Interesting study. Adding the Ng reference above as #5!

      I'm not sure if the study shows that a small bolus followed by large flush has an advantage. For the 10 patients, they all got an adenosine bolus and 10 mL saline flush. They tested at a proximal site (antecubital) vs distal site (hand) checked for time-to-heart block. Of course, proximal was faster.

      I'm my conceptual vision of this 1-step trick, the adenosine actually gets to the heart faster (albeit more dilute) than the 2-step method. However, the remain last drops of adenosine arrives later than the 2-step method. So, I think we end up with the same conclusion: 12 mg adenosine diluted in 20 mL saline syringe as a single push. This allows for overall longer transit time range.

      Interestingly in the Gausche et al study, the prehospital providers only gave 12 mg adenosine as a starting dose.

      Great discussion.

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    3. The other side of this is what they've learned using adenosine infusions for FFR measurements. When boluses of adenosine are used (effectively a higher conc) they're more likely to see AVN block than when they use infusions (effectively a lower conc).

      Either way, if you're armed with the knowledge that adenosine's effects are dependent upon a therapeutic central circ concentration, it follows that we should be aware of the limitations of:

      1) our selected IV/IO or central line site and its transit time
      2) our dose
      3) our rate of administration

      Certainly glad I participated in the discussion! We'll see how my next SVT goes :)

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    4. I think the crux of the matter is this: Does diluting the adenosine in a 20 mL flush really 'dilute' it any more than is already happening by the blood and flush that follows using the traditional technique? Although this trick of the trade hasn't been formally studied, it is quite effective and suggests the force with which you can push the 20 mL dilute solution makes up for the time delay from switching syringes.

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    5. Found a small study that supports this technique: http://koreamed.org/SearchBasic.php?RID=0082JKSEM%2F2003.14.3.224&DT=1&QY=%22J+Korean+Soc+Emerg+Med%22+%5BJTI%5D++AND+2003+%5BDPY%5D+AND+Aug+%5BDPM%5D+AND+3+%5BISSU%5D

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  9. Ultimately, anything is better than accidentally squirting yourself in the face with part of the adenosine while trying to use a stop-cock and fumbling with adenosine and saline flushes!

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