Nitro paste is NOT an emergency medicine drug – The Evidence

Many paramedics argue strongly for including nitroglycerin paste as an arrow in their pharmacologic quiver when treating acute congestive heart failure.

As opposed to using arrows with nitroglycerin.  You Duke boys!

As opposed to using arrows with nitroglycerin.
You Duke boys!

Baffles me.

True, you don’t need to break the seal of the CPAP to give it, and you don’t need to use an IV. But this medication hardly belongs in the emergency department, let alone a 21st-century EMS rig.

Before I get to the most recent evidence, I first want to highlight this perspective about why prehospital use of paste doesn’t make sense.

Rant!

First off, let me ask: In what other medical emergency, where a patient is diaphoretic, ghost-white, and tachy-crazy, do we apply an ointment – stat!

Stat!

Stat!

And why not? Because we already know that pharmacokinetics proves that this is not a “stat!” kind of drug:

  1. Nitro paste takes a looong while to reach a peak level (about 60 minutes), and
  2. You end up with pretty weak blood levels with paste. Like, 18 times lower blood levels, compared with IV.

So maybe a poultice of nitroglycerin and tail-of-toad was all the rage back in 1780, but we’ve made a few other medical advances since then…

Well, this was genius. But the rest of the medicine was garbage back then.

Well, this was genius. But the rest of the medicine was garbage back then.

But even more importantly, dosage is measured in inches?!? No other medication is measured this way! Even in the 19th century, the commonly prescribed (and completely toxic) mercury pills were prescribed in precise weights (e.g. 1 grain). Even if we don’t dose nitro paste in milligrams, you would at least expect that a liquid drug would be dispensed in 3-dimensional units (i.e. volume), or maybe even  2-dimensional units(i.e. area).

Instead, we administer it in 1-dimensional quantities, squeezed out of a fancy ketchup packet. Depending on how you rip the packet, and how thick (and how wide) your “1-inch” glob is, the patient could receive widely different doses.

Unfair comparison. Ketchup now has better packaging than NTG paste

Unfair comparison. Ketchup now has better packaging than NTG paste

Utterly nonsensical – It’s like we don’t even care about getting the dose right.

Well there’s a reason we don’t care: It doesn’t work.

The study: “Hemodynamic effects of NTG ointment in ED patients.”

This wasn’t randomized or controlled (but then again, the early studies that are usually cited in support of NTG paste weren’t exactly high-quality either). However, the data was collected prospectively.

Methods:

Physicians in an emergency department enrolled patients who appeared to be in acute CHF, and who had NTG paste ordered for treatment.

Before the paste was slathered on, impedance cardiography (a noninvasive hemodynamic test) was performed. This test is supposed to provide data similar to that which could only be obtained with the use of complicated heart catheters (“Swans”) in the past. They measured not only the mean arterial pressure (MAP), but also systemic vascular resistance (SVR), cardiac output (CO), and thoracic fluid content (TFC), a rough measure of edema in the chest. This testing was repeated at intervals after the paste was applied.

MAP and SVR were the primary outcomes.

Results:

Most patients got “1 inch” of paste. Interestingly, while 20% of the patients received morphine, none got CPAP. Old school, brah!

Treat CHF with morphine? Then you likely know what this is.  Just sayin'.

Treat CHF with morphine? Then you likely know what this is.
Just sayin’.

A modest decrease in the MAP was seen after 120 minutes (106 mm Hg –> 99 mm Hg), but it’s unclear if this was because of the NTG paste.  Since this study was uncontrolled, this mild improvement could have been the natural course of the episode; i.e. regression to the mean, or “tincture of time.”

The SVR did not show any improvement; also known as afterload, SVR is the main target when treating acute hypertensive CHF, so this is pretty disappointing.

screenshot1248

One of the secondary outcomes, TFC, showed a statistically significant decrease, but the clinical significance of a drop of 0.5 kOhm(-1) is dubious (see here and here).

So, basically a negative study. The nitro paste didn’t change the hemodynamics.

So what do you expect us to do now?
Either maximize your use of sublingual tabs or oral spray, or work to get IV NTG included in your protocols.  If you are going to break the seal on the CPAP to give NTG tabs or spray, give a good amount, and maximize absorption.

  • Hypertensive acute CHF patients require a stout dose of NTG to address the afterload – 2, 3, or even 4 tabs of SL NTG may be needed, and are quite safe.
  • These same patients may have (paradoxically) dry mouths, and squirting a bit of saline can enhance absorption of the tabs.
  • If you are using the spray, be aware that you don’t have to get under the tongue, you can also paint the top of the tongue as well.

And if you really want to avoid messing with your nice mask seal, and your service can’t afford fancy IV pumps, advocate for “push-dose vasodepressors.” Bolus doses of IV NTG as high as 2 mg, or even 3 mg, have been shown to be both effective and safe.

18 Comments

  • Kenneth Churning says:

    Nitro paste depends highly on peripheral circulation. Should a Pt. be in or aquire, Right heart MI with NTG paste on, your fighting a battle and the paste won’t quit working at the time you wipe it off. Nitro paste should never be an emergency drug. I’ve given up to 18 sprays of NTG to a CHF Pt. inroute to an ER and cured their distress by arrival. Nitro paste wouldn’t have touched that until my run form was finished and I was restocking my bag.

  • Thomas says:

    I agree with alot of what is in this article. I do not feel that NitroPaste has any place in the treatment of acute chest pain/MI. HOWEVER, there is another acute use for this drug in the paste form. The vessel dilation that it causes is eventually systemic, but initially it is localized. So it’s a great medication when you need to reproduce localized vessel dilation. When would this be needed in an acute care setting?
    Consider a patient in acute anaphylaxis who decides to self administer an IM dose of epi. Only he accidently injects it into his hand (held the auto pen backwards, it happens). Epi is a vasoconstrictor. Before long his hand would be cyanotic and he would be at risk for losing the distal extremity. However, with the acute administration of topical nitro,the vessels can be dilated, perfusion can return, and you can save his hand! Food for thought.

    • Many people do this, although the evidence is surprisingly weak that 1) most digital epi injections require specific treatment, and 2) that NTG paste actually improves the (usually good) outcomes!

    • Thomas says:

      Sufficient evidence or not, the processes make sense. If it was my own hand which was hypoperfusing, I would try to vasodilate. I’d wager to say you’d do the same.

  • Mike Bouser says:

    First, I’m a little butt-hurt about your opinion of medics that used interventions you find archaic and ineffective. We were told by doctors, nurses, and others in positions of power that these were the best things that could be done for patients. I guess nobody in the last twenty years was as smart as you, who can’t do anything without the permission of a physician willing to sign your protocols. Like us. So you used a study to refute another study that was as old and flawed as the first. Basically, even though you cited a study, your whole article is an opinion. I would love to have IV nitro to use with CHF patients, as well as AMI patients, but that’s not my reality. Thank you.

    • “Your whole article is an opinion.”

      I’ve heard sort of response a few times now, and I’m not sure how to take this. I presented links to a number of older studies, and then reviewed the methods and results of the new study to a fair degree. I think I backed up my argument pretty well, and I’m welcome to hear any sort of response to my interpretation of the data.

      One way of characterizing my post would be to call it a review of a recent study, in the context of prior literature, by someone who is not only an MD, but also a (former) paramedic, with a special interest in emergency cardiology. Hey. I’m no Steve Smith or Amal Mattu, but I have some modest credentials in the area. So “opinion” could also be seen as “informed perspective.”

      Plenty of you readers also have an informed perspective – we’d like to hear more of it!

  • Mike Bouser says:

    My apologies. I just saw that the author is an MD. You don’t worry about protocols. No disrespect was meant. Everything else in my previous post stands. You should maybe mention the ER doctors that ordered nitro paste in your article. That’s probably where paramedics got the idea.

    • Yeah, totes our bad!

      Indeed, paramedics (hopefully) are learning from MD/DOs in the emergency department, and taking these practices out into the field.

      The problem? A lot of physicians still think that NTG paste is useful for this indication. (Or that SL NTG maxes out after 3 doses, or that all NTG infusions have to start at 10 µg/minute, etc….

      • Dave says:

        As someone already stated, we practiced as we were taught and how medical control advised us at times. And while we’d all love to instantly have the newest trends on our trucks, it’s not that simple. I don’t know about other states, but in MA, by the time a drug or treatment got through all the commitees and everything else needed for approval, something else may have come along. This is the same state that took high dose epi off the trucks after it ws given IV a few times. So they just dumbed it down to epi pens across the board.

  • John says:

    Interesting, but I would like to see an article about whether or not nitro should be administered in the first place; in whatever form. The only outcome based evidence produced for effective treatment of MI is aspirin. So, why do we still cling to nitro?

    • Huh. On re-reading my post, I never made it clear at the onset that I was only discussing the use of NTG past for acute CHF. I’m going to correct that now – Thanks!

      For acute hypertensive CHF, nitro is the bees’ knees. Prevents intubation, very effective.

      For STEMI, yeah, not so hot. For mild angina, great!

  • Brent says:

    We have NTG Tabs with addition of NTG patches in a controlled delivery system.

    Immediate effect of the tabs with background transdermal administration.

    I don’t agree with widespread IV NTG.

  • Jamie says:

    first of all the purpose of using ntg is to reduce the preload in a chf pt. yes the standard 0.4 mg metered dose spray works pretty fast because it’s absorbed rapid by the mucosa. Nitro paste 2 percent is a thick paste that is applied to the left upper chest. It must be absorbed into the skin. Not rubbed into the skin. Sues the rate of absorbs on is slower but it’s not meant to be a first line emergency medicine. Common science will tell you that you need to use sublingual ntg prior to applying the Cpap mask but please use caution and acquire a 12 lead and even a right side 15 lead to be sure that nothing is hidding on the right side of the heart. The nitro paste is meant to be used after sublingual ntg has relieved the patients distress. It should be used in the same manor for cardiac chest pain.

  • Matt says:

    it seems the best treatment has been overlooked; lasix. Nitro paste will help potentiate the effects of lasix. Works very well if you have a patient with a drastically reduced EF and SL nitro may cause too much vasodilation rapidly. I agree that IV nitro is the best method but that is not always an option. Saying that topical nitro has no place in emergency medicine in chf is too bold a statement. When the patient is admitted it becomes more useful but it cannot be overlooked in the acute phase of a chf exacerbation.

  • EMS Artifact says:

    Interesting post.
    As you point out, nitropaste is ineffective in treating acute CHF. Of all the treatments I used over the years for this, CPAP is by far the best.
    That is followed by NTG spray, which my system started using in the late 1980s when it was first available. Our protocol then (and now) was 0.8mg sprays if the systolic BP was greater than 150.
    We used it, uh, liberally in the days before CPAP and it worked well.
    My practice was to give NTG until the CPAP was ready. After that, we didn’t like to break the seal, so we weren’t able to give any more. My research lead me to one of the studies you cited on IV NTG.
    Sadly my suggestion to our medical director that we apply for a pilot project to give IV NTG was met with silence. She just didn’t think it would work.
    Too bad, because I think the combination of CPAP and a bolus of NTG would be quite beneficial for patients.

  • Lance Lynch says:

    Interesting post, Doc. I’ve been interested (but admittedly too busy and under-motivated) in finding literature regarding paste’s effectiveness, etc. In response to folks ‘butt-hurt’ – aren’t changes, improvements and advances in medicine what keeps this field interesting? I tend to think of folks resistant to ‘change’ in the light of those who do things ‘because that’s the way we’ve always done them’… You know the types. It’s fantastic that the same stuff we were doing to provide ‘quality’ care 15, 10 or even 5 years ago isn’t the same stuff that we’re doing today (barring the rants that each of the topics deserve – consider MAST pants, Mega-dose epi, Ca+ in ‘EMD’ [remember that?!]… ‘backboards’). Granted, dogmalysis is painful and uncomfortable at times, the effective use of current evidence is necessary for growth of the field and providing the best patient outcomes we can at any given time.

  • Matt says:

    I really like this article and agree completely on the futility of nitro paste. I was a little surprised you didn’t mention the use of SL or IV ACE Inhibitors for the treatment of APE/CHF. You mention after load reduction as a goal. How do you feel ACE Inhibitors play a role in EMS treatment of APE/CHF?

  • Ray says:

    The limitations we medics may have is our protocols and medications that are carried by our service. Although I personally view protocols as a guide mostly, we can still get into problems if we do anything outside the protocol scope.

    I would love to take the push-dose vasodepressor out in the field. Need some links for those articles.

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