# Bradycardia after nitro administration



## KellyBracket (Mar 17, 2013)

I caused this once in an elderly female - gave her nitro, and watched her brady down to the 30s for a few minutes. Of course, being in the ED, it's hard to get a "STAT" ECG. Irony.

One of the AMR medics coming to our ED, fortunately, was a little quicker on the draw, and managed to get a great series of 12-leads on someone who, it turns out, didn't tolerate nitro too well.

The first ECG (screenshot61) is a 70 y.o female with mild chest pain _before_ NTG.

The second (screenshot62) is how she responded _after_ NTG. Her BP was not so hot either!

This ever happen to anyone else? Any thoughts on _why_ it happened?

I have information on the outcome, as well as my thoughts on the etiology.


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## STXmedic (Mar 17, 2013)

Never seen it myself. 

I'll give a stab at the etiology. 

Depending on the site of the occlusion (obviously has some pretty significant Q's inferiorly, especially lead III), the Nitro may have initially caused a drop in blood pressure significant enough to further limit blood flow through the occlusion. Assuming the occlusion was in the RCA (again basing off of the Q in III and avF), blood flow to the SA Node became insufficient, leading to a junctional escape when the SA stopped firing.

It's hard to tell from my phone if there is significant elevation anteriorly.

Very interesting. Thanks for sharing!


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## KellyBracket (Mar 17, 2013)

Ah, I should have mentioned one thing, and it's important. The patient ended up ruling-out for ACS. Actually, in both my case and the medic's case.

So, no ischemia or thrombus, no RV ischemia!


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## STXmedic (Mar 17, 2013)

KellyBracket said:


> Ah, I should have mentioned one thing, and it's important. The patient ended up ruling-out for ACS. Actually, in both my case and the medic's case.
> 
> So, no ischemia or thrombus, no RV ischemia!



Well shoot, there goes that theory... :lol:

I'll try again tomorrow after some sleep. My critical thinking is diminishing quickly


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## Nova1300 (Mar 17, 2013)

What you saw is something called the BJ reflex.  No, I'm not being funny.  It's pretty complicated physiology, but its not uncommon after a dose of nitrates.  We see it a lot in the OR after grandma gets a spinal for her total hip.  Wikipedia has a little blurb on it if you are interested.  Search Bezold-Jarisch reflex.


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## KellyBracket (Mar 17, 2013)

That was faster than I thought it would be. I do think I have to be careful calling it the "BJ" reflex in mixed company. It just seems like, I don't know, there's a certain possibility of misunderstanding...

As a technical explanation, though, I think it's right on the money! 

I wrote the case up, with a little bit more explanation, at *Nitroglycerin - Old and New: Pt 2 *. I also present a longer discussion about NTG-related hypotension in the presence of MI, and if it predicts inferior-wall/RV ischemia. 

*Nova1300*, the literature suggests that the "BJ reflex" is uncommon with NTG, but I wanted to see if medics had seen this. I suspect it's more common than the handful of case reports suggests!


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## Nova1300 (Mar 17, 2013)

I have never fully understood the stupid thing.  But, it's something about that quick drop in preload that sets it off.  I see it mostly in dry (NPO) older patients, and for some reason in really fit younger patients. I have seen it on induction in marathon runners and like I said, after spinals on old folks.  I'm gonna agree, it is likely more common with nitrates than is reported, because it drops the preload just like general and neuraxial.


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## Dwindlin (Mar 17, 2013)

See it with spinal anesthesia occasionally.


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## Aprz (Mar 17, 2013)

Interesting. I read about it prior to this thread because the Facebook group Prehospital 12-lead ECG (ems12lead) posted up a diagram of it and mentioned it. Too bad I didn't recall that when I read this thread. :[


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## Dwindlin (Mar 17, 2013)

Nova1300 said:


> I have never fully understood the stupid thing.  But, it's something about that quick drop in preload that sets it off.  I see it mostly in dry (NPO) older patients, and for some reason in really fit younger patients. I have seen it on induction in marathon runners and like I said, after spinals on old folks.  I'm gonna agree, it is likely more common with nitrates than is reported, because it drops the preload just like general and neuraxial.



Leading thought right now is it is an over-riding of the normal response to dropped pre-load.  Pressure receptors in the volume depleted ventricle sense a false high pressure and thus activate a response opposite of what is helpful (vasodialation and bradycardia).


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## Clare (Mar 17, 2013)

I was going to say ischaemic sinoatrial node as well .... but now I just confuze :unsure:


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## KellyBracket (Mar 20, 2013)

That's a good point to make, since we could be talking about two mechanisms of hypotension in inferior MI post-NTG. Transient reduction of preload in the poorly-contracting RV myocardium, or direct effect of ischemia on the conduction system. I haven't seen any discussion that suggests that these could be inter-related, but no one has said they _can't_...

If there had been characteristic ST changes in the inferior leads, or even equivocal changes, but with a (+) troponin, then ischemia of the SA or AV nodes might indeed be a cause. As in our patient, the QRS would be expected to be narrow. 

Clinically, however, the patients with RCA occlusion-related bradycardia look fairly well, while severe pre-syncopal symptoms, including hypotension, are *not* typical.

Speaking of ischemic signs on the ECG: the medic was concerned about slight STE in leads V2, V3. I chalked these up to repolarization changes of LVH, although the S waves in those leads aren't that impressive. OTOH, neither is the STE!


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## Melclin (Mar 21, 2013)

I've seen this several times and others at work have agreed. Anecdotally? reasonably common. 

Whether or not there is a causal link between it and the nitro is another matter.


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## TomB (Mar 23, 2013)

The blood supply to the SA node is very high up in the RCA so it would require a proximal occlusion to cause direct ischemia of the SA node. 

I first read about the Bezold-Jarisch reflex and it's association with acute inferior STEMI in Braunwald's Heart Disease, Fifth Edition (1997)

"Sinus bradycardia is a common arrhythmia occurring during the early phases of AMI, and it is particularly frequent in patients with inferior and posterior infarction. Observations in mobile CCUs indicate that 25 to 40% of patients with AMI have EKG evidence of sinus bradycardia within the first hour of the onset of symptoms; however, 4 hours after infarction commences, the incidence of sinus bradycardia has declined to 15 to 20%. Stimulation of cardiac vagal afferent receptors (which are more common in inferoposterior than the anterior or lateral portions of the left ventricle), with resulting efferent cholinergic stimulation of the heart, produces vagotonia with resultant bradycardia and hypotension. This is a manifestation of the Bezold-Jarisch reflex that is mediated by the vagus nerves and occurs during reperfusion, particularly of the RCA. Often sinus bradycardia is a component of vasovagal or vasodepressor response, which may be intensified by severe pain as well as by Morphine, and may be related to vasovagal syncope.

"On the basis of data obtained in experimental infarction and from some clinical observations, it appears that the increased vagal tone that produces sinus bradycardia during the early phase of AMI may actually be protective, perhaps because it decreases myocardial oxygen demands..."

"Isolated sinus bradycardia, unaccompanied by hypotension or ventricular ectopy, should be observed rather than treated initially...Atropine often contributes to restoration of aterial pressure and hence coronary perfusion and should be employed if hypotension accompanying any degree of sinus bradycardia is present. The favorable aspects of Atropine may be accompanied by regression of ST segment elevation. Elevation of the lower extremities also often elevates arterial pressure by redistributing blood from the systemic venous bed to the thorax, thereby augmenting ventricular preload, cardiac output, and arterial pressure."

p.1249 

"The AV conduction system has a dual blood supply, the AV branch of the RCA and the septal perforating branch from the LAD. Therefore, complete heart block can occur in patients with either anterior or inferior infarction. Complete heart block develops in 5 to 15% of all patients with AMI; the incidence may be even higher in patients with RV infarction. As with other forms of AV block, the prognosis depends on the anatomical location of the block in the conduction system and the size of the infarction.

"Complete heart block in inferior infarction usually results from an intranodal or supranodal lesion and develops gradually, often progressing from first degree or type I second degree block. The escape rhythm is usually stable without asystole and often junctional, with a rate exceeding 40 beats/min and a narrow QRS complex in 70% of cases and a slower rate and wide QRS in the others...The mortality may approach 15% unless RV infarction is present, in which case the mortality associated with complete AV block may be more than doubled.

"In patients with anterior infarction, third degree AV block often occurs suddenly, 12 to 24 hours after the onset of infarction, although it is usually preceded by intraventricular block and often Mobitz type II AV block. Such patients have unstable escape rhythms with wide QRS complexes and rates less than 40 beats/min; ventricular asystole may occur quite suddenly. The mortality in this group of patients is extremely high, approximately 70 to 80%.

"...patients with inferior MI and AV block have larger infarcts and more depressed right ventricular and left ventricular function than do inferior infarcts with no AV block. As already noted, junctional escape rhythms with narrow QRS complexes occur commonly in this setting. In patients with anterior infarction, AV block usually develops as a result of extensive septal necrosis that involves the bundle branches. The high mortality in this group of patients with slow idioventricular rhythm and wide QRS complexes is the consequence of extensive myocardial necrosis resulting in severe left ventricular failure and often shock.

"...Some investigators contend that ventricular pacing is useless when employed to correct complete AV block in patients with anterior infarction in view of the poor prognosis in this group regardless of therapy. We agree with others, however, that ventricular or AV sequential pacing is indicated in essentially all patients with AMI with complete AV block..."

"...although it is generally agreed that pacing is indicated in patients with inferior wall infarction and complete AV block, it is of particular importance when the ventricular rate is very slow (< 40 to 50 beats/min), if ventricular irritability or hypotension is present, or if pump failure develops; Atropine is only rarely of value in these patients. Only when complete heart block develops in less than 6 hours after the onset of symptoms is Atropine likely to abolish the AV block or cause acceleration of the escape rhythm. In such cases the AV block is likely to be transient and related to increases in vagal tone rather than the more persistent block seen later in the course of MI, which generally requires cardiac pacing."

p.1250,1251


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## KellyBracket (Mar 23, 2013)

TomB -

I love this topic! It can get overwhelming though, so let me see if I can summarize what has been described so far. Hypotension and bradycardia after NTG administration could be seen in a few distinct contexts:

1) In a patient with *no ongoing ACS*, the NTG can trigger a BJ reflex (i.e. vasovagal reaction). This occurs abruptly, can cause sinus slowing and AV block, is transient, and the hypotension may or may not be reversed with atropine.

2) In a patient with an *inferior + RV MI*, a dose of NTG can trigger hypovolemia due to a poorly contractile RV, and reduced ability to deal with decreased preload. These patients may be hypotensive to start with, and IV fluids are helpful. Bradycardia is *not* typically seen with the hypotension induced by NTG administration.

3) A patient with a *large inferior or anterior MI* may have bradycardia and hypotension _before_ they get NTG, with subsequent worsening of the vitals after NTG. The bradycardia may be mediated through 3 different pathways:
     a. A moderate vagal tone can be caused by the infarct, and "may actually be protective." Atropine _may_ help.
     b. Direct ischemia of various parts of the conduction system, depending on the infarct location. PCI, fibrinolysis _should_ help.
     c. Release of metabolites causes bradycardia; e.g. adenosine, potassium. Aminophylline/theophylline _may_ help.

Whew, that's enough. In my blog post I tried to stay away from this last category, the bradycardias and blocks directly related to ischemia of the conduction system, since the topic gets big fast! OTOH, it gets interesting fast. 

Tom, anything I leave out, or any good examples from your files?


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## TomB (Mar 24, 2013)

KellyBracket said:


> TomB -
> 
> I love this topic! It can get overwhelming though, so let me see if I can summarize what has been described so far. Hypotension and bradycardia after NTG administration could be seen in a few distinct contexts:
> 
> ...



It sounds right to me. I would just mention that increased vagal tone is very common with acute inferior/posterior STEMI and atropine is likely to help in this circumstance. By "help" I mean reversing the rate and vascular tone changes associated with increased vagal tone (the exact term used is hypervagotonia so I think it's at least "moderate"). Whether or not it's desirable to treat sinus bradycardia and marginal blood pressure in the setting of acute inferior/posterior STEMI is situational and always controversial when discussed although Braunwald talks about the desirability of using atropine when the patient is showing signs of shock and states that ST-elevation even resolves somewhat after 0.5 mg atropine. I think the take away message is to realize that vascular tone is already likely to be compromised and that's one more reason to hold off on the nitroglycerin or at least start an IV and give plenty of fluid first.


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## Nova1300 (Mar 24, 2013)

Im not sure how comfortable i would be giving a patient with myocardial ischemia atropine.  A little electricity, yes.  But atropine?? 

But, hey-- I didn't write any cardiology textbooks.


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## Clare (Mar 24, 2013)

Nova1300 said:


> Im not sure how comfortable i would be giving a patient with myocardial ischemia atropine.  A little electricity, yes.  But atropine??
> 
> But, hey-- I didn't write any cardiology textbooks.



I'm not ICP ... but, balance of risk between somebody who is severely bradycardic because of an ischaemic SA node so is shocked vs. increasing oxygen demand in an ischaemic myocardium.  

Pacing and atropine, in my mind, do exactly the same thing, but with different means; i.e. one is chemical chronotrope one is electrical.


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## Handsome Robb (Mar 25, 2013)

Clare said:


> I'm not ICP ... but, balance of risk between somebody who is severely bradycardic because of an ischaemic SA node so is shocked vs. increasing oxygen demand in an ischaemic myocardium.
> 
> Pacing and atropine, in my mind, do exactly the same thing, but with different means; i.e. one is chemical chronotrope one is electrical.



Pacing is also controllable as far as rate goes. Atropine not so much. 

I've heard lots of different opinions, mostly against atropine and that's what I was taught too. I'm interested to see what these guys have to say about it. 

This is a cool thread, definitely learned something new!


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## KellyBracket (Mar 25, 2013)

If Braunwald is in my ED for a consult, I'd ask him if he wanted to give the atropine (or norepi, or pacing) to treat the STE, but I think otherwise we'll be getting the cath lab warmed up regardless!


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## Nova1300 (Mar 25, 2013)

I find atropine to be rather sneaky.  In some patients it brings about a modest increase in HR at low doses.  In others, they skyrocket. Also, if I were to use it in this patient it would be worked in very slowly -- but therein lies another problem, the so called " paradoxic effect" of low dose atropine.  

If I was going to raise this patients HR with drugs, it would likely be with robinul, to keep the anticholinergic out of the brain and because I'm more comfortable with its effects.  

But I still like electricity. And I'm stubborn.


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## Veneficus (Mar 25, 2013)

TomB said:


> Whether or not it's desirable to treat sinus bradycardia and marginal blood pressure in the setting of acute inferior/posterior STEMI is situational and always controversial when discussed although Braunwald talks about the desirability of using atropine *when the patient is showing signs of shock* and states that ST-elevation even resolves somewhat after 0.5 mg atropine.



I first disclaim I do not like cardiology.

But looking at this statement, it makes perfect sense. If a patient has clinical evidence of shock, there is a failure of delivery of O2. Assuming, no anemia, good heme saturation, and no hemorrhage, with a catecholamine response to stress, it would likely minimize the effects of loss of vascular capilary tone, with any dilation from NTG (GTN) in the venous system. 

Increasing cardiac output, theorhetically should increase venous return right?

So from the logical point Q=SV x HR, 

increasing HR is more easily achieved than stroke volume in injured cardiac tissue. 

I see the argument of increasing demand, but also in a bit of logic, the tissue most likely injured because of increased demand is behind the block. Not receiving direct blood supply (with atropine) but maybe some from collateral circulation. 

The Actual tissue with metabolic increase still should have intact blood supply. Which I would expect to be able to meet its increased demands by the increased output.

One of the most devastating parts of shock is when the heart cannot meet its own circulatory demands. More output will intervene in that.

But I highlighted what I think to be the key phrase to the whole argument.

It doesn't stipulate showing bradycardia, or low BP, it directly talks about inadequete tissue perfusion of such extent to produce clinical signs.


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