When the STEMI disappears before you get to the ED!

So what do you do when your STEMI disappears? 

Spontaneous reperfusion (SR) is well-described in the cardiology literature. One moment you have a classic STEMI on the ECG, and the next you have nada. I wrote about just such a patient in a prior post. In that case, EMS had acquired this ECG in a patient with chest pain:

However, when her symptoms improved they ran a second ECG, and found:

This dramatic improvement suggests 2 questions. First, is this a good sign? Second, did the medics do anything (like oxygen, nitro, or aspirin) that could have caused the improvement?

Is this a good sign?
Yes.
 
In a 2008 study (Spontaneous reperfusion in ST-elevation myocardial infarction: comparison of angiographic and electrocardiographic assessments.), finding ≥ 70% resolution of ST elevation on the ECG was a very good sign, and predicted a far lower rate of bad things - mortality and re-infarct rates were 0% as illustrated in this graph:

SR = Spontaneous reperfusion

Other studies have also shown that  resolution of the ST elevation before PCI is associated with patent vessels before PCI, after PCI, and better outcomes overall. The table below gives you the numbers. (TIMI 3 flow = normal blood flow in the coronary artery, 0 = complete occlusion)

Source

Even if PCI was significantly delayed, the patients with SR in a 2008 study did very well. Only 8% of those patients had primary PCI (as opposed to 100% of the patients with persistent ST elevation. Again, check the graph:

A = PCI or lysis;  B = Primary PCI only

Onto the second question...

 

Do oxygen, aspirin, nitroglycerin, or morphine cause spontaneous reperfusion?

Hard to say. 

Although SR may occur in up to 15% of STEMIs, this isn't well-studied. One of the studies mentioned above (Relation of clinically defined spontaneous reperfusion to outcome in ST-elevation myocardial infarction) checked whether SR occured more often in patients who received aspirin or heparin from EMS or in the ED, and didn't find an association:

Dr Smith describes a STEMI case in which he felt that nitroglycerin had caused SR, and thus contributed to a delay in PCI. In his discussion he cites an abstract (copied below) from an EMS study, possibly the world's only clinical study on this topic. The brief version is that 6% of STEMI patients had partial or total SR in the period after NTG administration. Of course, it was retrospective, uncontrolled, etc. 

On top of that, it's hard to say if 6% is a high rate or not. Some researchers think the overall rate of SR in STEMI is about 15%, so 6% may actually be lower than expected.

Source

As for oxygen, there's no evidence of any sort, good or bad.

The Bottom Line
Although a good number of patients have serial ECGs that show resolution of ST elevations, we don't exactly know why. Although these patients appear to be at lower risk of complication, it is hardly zero risk. When in doubt, get ECGs early and often.



*************************************************
Mahoney BD, Hildebrandt DA, Allegra P. 
Normalization of Diagnostic For STEMI Prehospital ECG with Nitroglycerin Therapy. 
Prehospital Emergency Care 2008;15:105, Abstract 24.
Hypothesis. The decision to take a patient for emergent reperfusion therapy is largely determined by an ECG diagnostic for ST Elevation Myocardial Infarction (STEMI). Hildebrandt et al have proven that  prehospital 12 Lead ECGs followed by an immediate call for reperfusion team mobilization reduce door to balloon times.We hypothesize that prehospital ECGs will normalize in some STEMI patients after  nitroglycerin (NTG)therapy or due to spontaneous reperfusion.  NTG therapy before an ECG, or the absence of a prehospital ECG capacity in some services may lead to missing the early diagnosis of STEMI thus delaying reperfusion therapy. 

Methods. A prospective analysis of consecutive adult patients  presenting to an urban/suburban two paramedic ambulance service fromJuly 15, 2006, to August 15, 2007, who have diagnostic ECGs for STEMI.  Paramedics managing a possible myocardial infarction patient were instructed to obtain rapidly an ECG prior to treatment with NTG. If the initial ECG was diagnostic for STEMI the paramedic called to mobilize the reperfusion team. A second ECG was done prior to arrival at the ED. The ECGs were later reviewed by emergency physicians and cardiologists who confirmed the presence of a diagnostic prehospital ECG and STEMI.  

Results. During the 13 month interval, 87 patients had an initial ECG that was diagnostic for STEMI. These patients received no NTG from the paramedics prior to obtaining the first ECG. An average of 16 minutes 42 seconds later, 3 patients had an ECG that was no longer diagnostic for STEMI and 3 had a partial normalization in their ECG that made diagnosis of STEMI more difficult. 

Conclusions. Prehospital ECGs diagnostic for STEMI can normalize or become nondiagnostic after NTG administration or due to spontaneous reperfusion or evolution. In the absence of a prehospital ECG, it is possible that 6 of 87 (7%) of STEMI patients in this study would have had reperfusion delayed due to a rapid change in their ECG. Limitations include no control group receiving NTG prior to the first ECG.

Hyperoxia during CPR associated with improved survival

There has been some great discussion on the web recently about the potential danger of hyperoxia. Mike McEvoy was interviewed on EMS 12-lead about the emergency and ICU evidence, and a vigorous discussion took place on EMTLIFE about the same topic. Rogue Medic weighed in as well, asking the question "How many hundreds of thousands of patient have we killed with oxygen and our refusal to require evidence of improved outcomes?" 

In the midst of this heated dialogue about reactive oxygen species, a recent study was published that may be an important addition to this discussion. 

The new paper
The study, "Increasing arterial oxygen partial pressure during cardiopulmonary resuscitation is associated with improved rates of hospital admission," was conducted in an Austrian EMS system. The ambulances are staffed with physicians, and are equipped with portable ABG analyzers as well. They retrospectively analyzed all non-trauma cardiac arrest calls over a 7-year span, and found 145 patients that had received ABG analysis of the PaO2 during the code. The ABGs were obtained after compressions, intubation, and 100% oxygen had been started. 

After dividing the patients into low, intermediate, and high levels of PaO2, they examined which patients had survived to hospital admission (HA), as well as the "cerebral performance category"(CPC) of the longer-term survivors. About half of the 145 cardiac arrest patients with an ABG had ROSC.

It turned out that patients with intermediate (61-300 mm Hg) or high (> 300 mm Hg) levels of PaO2 were incrementally more likely to survive to hospital admission. This positive association did not extend to showing a significant improvement in cerebral performance in survivors, however, despite a suggestive trend.

How does this fit with prior studies?
One retrospective study conducted in the ICU demonstrated an association between post-ROSC hyperoxia and increased mortality, while a similar trial showed no consistent association. No other trials have looked at pre-ROSC PaO2, however.

The accompanying editorial attempts to explain this seeming paradox - that hyperoxia pre-ROSC increases survial, but worsens survival post-ROSC - but I wonder if it is premature to try and reconcile these studies. Given all the known limitations of retrospectively-obtained data, and of this trial in particular, perhaps we should await controlled trials that more clearly define the role of oxygen levels and survival. As the authors note, "Reasons for the benefit of higher oxygen tensions during CPR can more easily be hypothesized than explained." Given the conflicting data, it might behoove us to proceed cautiously in modifying the targets for oxygen delivery in cardiac arrest.

Can capnography help the intubated trauma patient?

I had a conversation with a paramedic student recently, regarding a dyspneic patient who had either CHF or COPD. While I was explaining the utility of checking for JVD and other old-fashioned tests, she replied with "How about we just check the end-tidal CO2?" The dialogue about capnography continued something like this:

Paramedic: "The waveform might show some shark-fining, which would point to COPD, but if the nebs weren't working, and the patient looked shocky, you might worry that poor perfusion from CHF is producing a falsely low PetCO2, and you could start nitro."

Me: "After we intubate them, yellow means yes!"

I realized I wasn't contributing much to that discussion. 

Around the same time, I found a new study that looked at the use of end-tidal capnography to adjust ventilations for trauma patients, and the results were intriguing. So, in the interest of sounding smarter to the paramedic students, I plunged into the world of EMS capnography.

(Very) Brief review of capnography for EMS
People breath in oxygen, and breath out carbon dioxide. The level of carbon dioxide in the arterial blood is a very important number, and it's written as PaCO2, or the Partial pressure, in the artery, of CO2. Typically it runs around 35 - 45 mm Hg.

Google images - who knew?

This number is the one that counts when we're adjusting the rate or volume on a ventilator. Only problem is that we need to use a needle to draw an arterial blood gas (ABG), and then use a sizable machine to analyze the blood. It hurts too!

Of course, we breath out carbon dioxide, so we can also check the Partial pressure of CO2 as we breath out, especially the very last bit, at the end of the tide of airflow; the PetCO2. The point labeled "D" in the figure below marks the point at which PetCO2 is measured.

source

Usually the PaCO2 and the PetCO2 are pretty close to one another, and the arterial level is typically only 3-5 points higher than the end-tidal level. Another way to put it:

                   PaCO2 - PetCO2 ≤ 5 mm Hg

Well, usually that is ...

EMS and end-tidal capnography
EMS has been able to use capnography to do some important things. Rather than copy an extensive list, I'll turn this over to Peter Canning, over at Street Watch. He has compiled a list of the 10 Things Every Paramedic Should Know About Capnography, and it's a great focused summary. (Meaning, 90% of what I know comes from this article!). 

Of course, capnography can used to confirm intubation. It can also be used in cardiac arrest to check for ROSC, or assist in deciding on termination of efforts. Some evidence suggests that it has a role in diagnosing obstructive lung disease (asthma, COPD), as well as various other problems. 

First on his list, however, is its utility in monitoring ventilations, avoiding hypo- and hyperventilation. In the hospital, this is simple: If the PaCO2 from the ABG  is less than 35, the patient is being hyperventilated, and either the rate or the tidal volume needs to be decreased. With capnography, the numbers and waveform would look like this:

source

If the PaCO2 over 45, one of those parameters needs to be increased, because the patient is being hypoventilated. 

source

Because capnography is so much simpler and faster than using ABGs, it has been hoped that EMS could be able to modify ventilations just as well as in-hospital people can. So what does this recent study tell us about that potential?

"Utility of Prehospital Quantitative End Tidal CO2?"

Missouri EMS researchers wanted to test how well patients could be ventilated by EMS after intubation. They choose to focus on patients who had suffered either severe trauma or burns, and ended up with 160 patients (87% trauma, 13% burn-relate) who were transported to a level 1 trauma center. Overall, these were serious trauma cases - 75% had a GCS < 8 prior to intubation, and 1 out of 5 died in the hospital.

Paramedics had been trained in the use of end-tidal capnography to avoid hyper- or hypo-ventilation. During transport EMS recorded the PetCO2 levels, and adjusted the ventilations accordingly. Upon arrival to the ED, ventilations were maintained at the same rate and volume that EMS had used, and an ABG was obtained. The PaCO2 from this ABG was then analyzed against the end-tidal reading obtained during transport.

On average, the prehospital PetCO2 (34 mm Hg) was significantly lower than the ED PaCO2 (44 mm Hg); i.e. PaCO2 - PetCO2 = 10 mm Hg.  

This overall  difference between the PaCO2 and the PetCO2 only got larger when the sicker subsets of patients were examined. 

• Patients who died during hospitalization: PaCO2 - PetCO2 = 17 mm Hg.
• Patients with a pH < 7.2: PaCO2 - PetCO2 = 20 mm Hg.

So, were these results expected? What has the rest of the prehospital capnography literature showed? And how should we use capnography in the future?

FIrst, I'll review the studies that suggested that end-tidal capnography was potentially very accurate, and then I'll go over the studies that highlighted problems in applying it to the EMS patient population.


Studies that showed benefit of capnography
A 2003 helicopter study had suggested that capnography could help prevent hypoventilation in severely injured patients. Randomly assigned helicopter medics were able to use PetCO2 monitoring to adjust ventilation of intubated trauma patients, and ABGs were checked upon arrival to the trauma center. The patients were a mix of general poly-trauma, with high injury severity scores. The study suggested a big benefit - medics who had access to the ETCO2 monitor were far more likely to avoid hypoventilation and achieve normoventilation (although there was no change in hyperventilation).

Next, end-tidal CO2 was used to manage ventilations in a 2004 ground EMS study conducted in San Diego. The researchers enrolled 291 patients with severe head injury who had been intubated. Most of the patients had ventilation managed through standardized setting, but for about 1/2 of the patients the paramedics had ventilator management protocols that targeted a PetCO2 of 30-35 mm Hg, and avoided a PetCO2 < 25 mm Hg. As in the present study, the PaCO2 was confirmed by ABG after arrival at the ED. The use of the end-tidal capnography resulted in about 8% less hyperventilation.
 
Studies that suggested problems with it.
A 2005 study was conducted by a French EMS agency that uses specialist physicians, and uses ambulances equipped with ventilators, end-tidal capnography, and portable ABG analyzers as well. They looked at 100 patients that had been intubated over the course of 16 months, and examined how the PetCO2 levels corresponded to the PaCO2. An important note: only the PaCO2 values were used to adjust the vent. The patients were a mix of medical and trauma. They found that, even though, on average, the PaCO2 was the same as the PetCO2, there was significant variability in individual patients.

•  For 27% of the patients: PaCO2 - PetCO2 > 10 mm Hg
•  For 2% of the patients: PaCO2 - PetCO2 < -10 mm Hg

In other words, over a third of the patients would have been ventilated using false setting, had PetCO2 been used. In graph form:

An ED-based study from 2009, by Korean researchers, looked at 66 patients with severe head injury who had been intubated in the ED, and were mechanically ventilated. ABGs were obtained simultaneously with PetCO2 readings, and the paired values were compared. In general there was a good correlation between the two methods, and the PaCO2 exceeded the PetCO2 by less than 4 mm Hg, on average. However, this relationship broke down in the sicker patients; e.g. those with acidosis, greater injury scores, hypotension, or chest trauma.

A second 2009 trial conducted on 180 trauma patients who were intubated in the ED showed an extremely poor relationship between PaCO2 and PetCO2 obtained simultaneously. In the subset of patients with an isolated mild head injury the correlation was somewhat better. Noentheless, the authors concluded that: 

If the recommendations for ventilation to an PetCO2 of 35 mm Hg to 40 mm Hg were implemented in this population, 80% of patients would have a PaCO2 > 40 mm Hg and 30% would have a PaCO2 > 50 mm Hg.

Not good!

How to use the results of this new study.
Although these studies employed a variety of protocols (for example, different definitions of hyperventilation), 2 common threads  emerge. 

The first is that if the trauma is either mild, or limited to the head, then PetCO2 is probably an accurate surrogate for PaCO2, and can be used to modify ventilations. On the other hand, if a person has sustained trauma to multiple organ systems, or is showing any signs of shock, then the PetCO2 may (or may not) significantly underestimate the PaCO2 - there's no way to know. You're flying blind, vent-wise.

It turns out that this is sort of a common theme in using end-tidal capnography - it works best in patients with a single problem, but loses utility when the patient gets complex. Specifically, PetCO2 is no longer accurate when the patient has problems both with ventilation and perfusion.

Take asthma and CHF as another example. Both can present with hypoxia, true, but asthma usually only involves the lung, a ventilation problem. A number of studies have shown that certain qualitative aspects of the waveform - the "shark's fin" - may serve as a way to demonstrate improvement or worsening. 

Source

On the other hand, CHF can involve both the pulmonary and the cardiac systems, at the least. There can be a complex relationship between things that drive the PetCO2 down (like poor perfusion from systolic failure) and those that drive it up (such as impaired ventilation from coexistent COPD). 

With these complexities, it isn't at all clear how to use end-tidal capnography in CHF, despite the advice offered in some EMS magazines. The best research that described using capnography to diagnose CHF versus COPD/asthma comes from a single article in the Croatian Medical Journal. Not something to hang your hat on.

By way of contrast, you can use PetCO2 to predict the degree of metabolic acidosis in pediatric DKA (studies here and here), or in pediatric gastroenteritis. These are strictly problems of metabolic acidosis (which would be reflected in the PetCO2), while only in the rare extreme cases would perfusion be affected.

The Bottom Line
The current study is consistent with prior studies, and it appears that end-tidal capnography is not yet reliable enough to use in severely traumatized or burned patients. Using capnography in this population runs the risk of underestimating the PaCO2, leading to hypoventilation.

Nitroglycerin - Old and New: Pt 3

I really wasn't planning on doing a part 3, since I had thought there was only so much you could say! A recent discussion on Facebook, however, revealed a surprising amount of enthusiasm for a seemingly boring question:

"SL Nitro tabs or spray?"
It probably matters somewhat whether the NTG is being used to treat ACS or CHF, but that didn't come up in the discussion. Other concerns and opinions, as well as some questions, came up, and I thought it would interesting to see what research was out there to back up some statements or answer questions. 

First off, some straight-forward information of UpToDate about the kinetics of the various forms of nitroglycerin. This shouldn't be viewed as the final answer, but it probably isn't far from it.
 

I'll be using quotations out of the comments from the FB post, since this probably represents the thinking of a good number of people (or at least the thinking of people who like to talk about tab versus spray on a Friday night!

Or a Friday night! (Source)

 Onto the questions!
 
"I heard it works faster? Not sure if its true."
...
 "I have always wondered with the sprays just how much nitro they are getting. I know its supposed to be the same as a tab but I guess I just wonder."
 
Does the spray work faster, or the tablet? Which formulation gives a higher dose? Three studies, all from the 90s, suggest that if there is a difference, it's a small one!

Danish researchers compared 2 sprays of 0.4 mg each versus one 0.5 mg tablet, and checked the blood levels. Not surprisingly, the higher-dose sprays reached a higher dose than the tablets, and faster as well. However, after they corrected for the higher dose, they calculated the time-to-onset and blood levels to be equivalent.

Researchers from Montreal took a different tack. Instead of looking at blood levels, they looked at how quickly nitro spray or tablets could cause arterial vasodilation. Both the tablet and the spray were 0.4 mg. The graph shows the response: note that both the spray and the tablet had each reached their max effect at the 3 minute mark. However, the spray both acted more quickly, and had a more prolonged effect, and also had a higher maximum response.
 

A third group took yet another approach. Instead of looking at brachial artery dilation, or plasma levels, they gave nitro during cardiac catheterizations to directly evaluate cardiac effects. After giving 0.4 mg of the spray or tablet, they found a mixed picture. For example, the spray reduced the LV end-diastolic pressure 30 seconds faster than the tablet, but was 30 seconds slower at lowering the LV end-systolic picture. Basically a wash.

"The tabs have the added problem of the non-english speaking patients not understanding the directions and just swallowing them."  
I would add that it is often difficult to get a English-speaking patient to lift up their tongue. In their defense, how often in your life are you asked to do that? It can seem like an odd, "Simon-says" request. 

Therefore, it's an advantage, I think, that you can just shoot the spray at the tongue, under or over. According to the manufacturer of one brand of nitro spray, it can be sprayed on either area, which ought to make conversations simpler in the back of the rig at 2 AM!

Source

 
"Our pt have dry mouth from being anxious. Tabs don't dissolve in a dry area."
Perhaps the best place to store NTG isn't in a little brown bottle - perhaps it should be kept under the tongues of CHF patients who are struggling to breath. It certainly seems to be the best place to keep a pile of NTG tabs from dissolving!

For example, back in 1986, one doctor found that:

"The addition of 1 ml of saline under the tongue of a patient with visibly dry sublingual tissue will moisten the tissue in preparation for dissolving the nitroglycerin. This simple action has frequently resulted in prompt relief of pain when previous doses of nitroglycerin administered by the patient, and later by hospital staff, had failed."

There also appears to be some science to back up this impression. A group from Japan took an innovative route; instead of looking at critical patients, they had subjects with stable angina ride an exercise bicycle until they felt critical! Well, not critical, but until they felt chest pain. The researchers then did two things. First, they checked how wet or dry the subjects' mouths were. Second, they gave them either nitro tabs SL, or a nitro spray.

It turns out that, for those subjects who had wet mouths, it didn't matter which med they got. But the subjects with dry mouths had their chest pain relieved much more quickly with the spray!

Taking it a step further, another team of researchers looked at giving a teaspoon of water at the same time as giving the SL NTG or the spray NTG. The patients were getting a cardiac cath at the same time (but did not have their mouths checked for wetness!). They found that the patients who got the teaspoon of water with the SL tab had a much greater drop in BP than those who got the SL tab without water. With the spray, however,they got the same drop in BP either with or without the water.

So if you don't have the spray, probably the best idea would be to squirt in some saline or H20 right before you pop in the tabs!

Ask FD to help! (source)

 
"Is paste an option?" ... "Having the paste which allows for slower absorption and removal value where after a spray, there is no taking it back."
Many paramedics have a high regard for the topical ointment preparation of NTG. I'm not sure why, since topical drugs are not very useful in EMS - they absorb slowly, wear off slowly, and have uncertain absorbation, especially when patients are cold, vasoconstricted, or poorly perfusing. The table at the start of the post really illustrates this - it can take 30 minutes to start working, and 7 hours to wear off!

I only found one study that compared intravenous, pill, and paste NTG delivery. They took patients with unstable angina, and split them into 2 groups - IV NTG, or a combination of pills & paste. They adjusted the doses in both groups so that everyone dropped their BP by about the same amount. They found two things.

First, both seemed to relieve the symptoms of angina at the same rate. That's good, because that's the only time I use the paste - when I have a hemodynamically stable patient complaining of mild-moderate chest pain.

Second, they found, unsurprisingly, that IV NTG can achieve a higher blood level than the paste. On the IV stuff, levels of NTG were, on average, around 18 ng/ml, whereas the levels 2 hours after paste application only got up to 1.3 ng/ml.

This issue about the "slow & low" blood levels doesn't matter so much for angina, or even a STEMI. NTG likely doesn't save lives in ACS, and we have other agents that can treat pain. But when EMS is treating a hypertensive CHF patient, they need therapy that works fast, works hard, and that can be "turned off" fast as well. The paste doesn't seem to do any of that.

The Bottom Line
IV nitroglycerin is the ideal EMS drug. 

It works almost instantly, it gets to peak effect almost instantly, it's very good at treating severe hypertensive CHF, and it can be titrated very precisely. Also, we don't need to take the CPAP mask off every 5 minutes to give tablets and water. (You know, they call it continuous positive airway pressure for a reason!)

But until your service can work out the training and supply issues for the IV pumps, and until the cost of the spray comes down a smidge, we may be stuck with the tablets for a while longer. Just understand the differences!

Nitroglycerin - Old and New: Pt 2

A paramedic from AMR in Bridgeport told me about an interesting patient he treated recently. And by "interesting," I mean "briefly terrifying." He was bringing in a 75 y.o. male with chest pain, and had given the patient aspirin, and acquired an ECG. 

I scribbled on it. It's not a clue.

A few things on the ECG bothered him, and the patient's symptoms suggested ischemic symptoms. Since the vital signs were fine, he then gave 1 tab of nitroglycerin (NTG) under the tongue. 

Within 90 seconds, the patient became pale, sweaty, and described feeling pretty awful. The blood pressure bottomed out in the 70s, and the medic noted a drop in the heart rate. He acquired ECG #2:

Small change.

Fortunately, a dram of atropine and a jigger of normal saline rapidly fixed the bradycardia and hypotension. 

Concerned that he had "unmasked" a right-ventricular MI, he then obtained a third ECG, this time with V4R, to interrogate the right side:

TV4 is V4R - rest of precordial leads are the usual.

The rest of the transport was uninteresting, as well as his time in the ED. Although he was admitted, his ECG didn't show any changes from prior, and his troponins were negative. No MI.  
So what happened here? Does the second ECG suggest a cause of the bradycardia? For that matter, what about the first and third ECGs? In what way was the NTG involved?

I'll discuss a few basic questions about NTG-related hypotension, and also discuss an interesting new study out of Montreal, before finishing up with an infrequent adverse effect of nitro.

Why are we concerned about giving NTG during an AMI?
As most paramedic students would be able to tell you, we're worried mostly about MIs that involve the inferior wall, since about half of these involve the RV. Since infarctions of the RV tend to make the patient very sensitive to preload-reducing drugs, it is commonly taught to avoid NTG if there are signs of an inferior infarct. A small study from 1989, for example, looked at a group of patients with diagnosed inferior-wall MI, and found that evidence of RV involvement was strongly associated with NTG-related hypotension.

Many people recommend that you grab an ECG before giving NTG to a patient with suspected cardiac ischemia. While there are different reasons offered for this, the typical reason is to look for an inferior MI, and thus avoid hypotension caused by an RV infarct. 

(On the other hand, Dr Smith is concerned that NTG could "mask" a STEMI - read "Wait until after the ECG to give Nitroglycerin." Pretty dramatic example!)

So, given the apparent importance of this advice, is NTG-related hypotension common?

How often do patients drop their BP after NTG?
Not often!

For instance, a study from 1994 looked at 300 EMS patients that got NTG for CHF or chest pain, and only 4 developed a SBP < 90 mmHg. That's only 1.3%, and even those 4 patients did fine after the NTG wore off.

Another study looked at over 1,500 patients who received NTG from EMS, and only 12 patients had significant adverse hemodynamic effects - only 0.7% of the total.Some folks had some big drops in their BP, but nobody died. Similarly, only 1 patient out of 288 in a third study had hypotension. That patient improved with a 300ml NS bolus.

Okay, so reactions are rare. When these do happen, though, do they predict anything about a presence or location of an MI?

Does a hypotensive reaction to NTG predict an inferior-wall MI? (Breaking news!)
This comes from an abstract presented at the 2013 NAEMSP Scientific Assembly, and so should be considered preliminary. Nonetheless, it appears to be an interesting addition to the nitro literature. (The whole abstract is copied at the bottom of the post)

Researchers in Montreal searched their EMS database for patients who had been transported for suspected ACS. They then picked out the patients who ended up being diagnosed with a STEMI, and who had also received NTG from EMS. Although these patients got prehospital ECGs, the EMTs weren't trained to read them - just to acquire and and transmit. They likely were not able to identify a "likely RV infarct," and were not instructed to withold NTG from anybody based on the ECG. This amounted to about 800 patients over a 2 year period. 

The researchers divide the ECGs into inferior-wall STEMIs and non-inferior-wall STEMIs, and looked at what giving NTG did to either group. They found two things:

• First, patients with an inferior-wall STEMI were more likely to have hypotension initially.  
• Second, after they got NTG, patients with an inferior MI were not more likely to have hypotension, or even a significant drop in BP.

Although you should be cautious if you have a hypotensive patient with huge ST elevations in V4R, it's not clear that the evidence suggests that we routinely need ECGs before giving NTG. 

So what happened to our patient with the bradycardia and hypotension? 

The Bezold-Jarish reflex
He fainted. You can also call it a vasovagal reaction, or a triggering of the Bezold-Jarish reaction, but it's all basically your standard faint

Well, maybe not just like that, but pretty darn close. He never actually "passed out," but given his vitals and symptoms, he wouldn't have stayed upright for long. Fortunately, he was already laying down on a stretcher, so he never lost consciousness. Staying supine when you brady down is a pretty good policy. 

But there's other evidence besides the vital signs that suggest  a vasovagal mechanism, and not a preload-sensitive cardiac ischemia. Take a closer look at the second ECG:

Sinus activity has been totally suppressed, and the rate has dropped down to a typical junctional speed. This is an AV dissociation, rather than 3rd degree block, since the ventricular rate (39) is higher than the atrial rate (0). The QRS hasn't widened at all, suggesting the block is at or above the level of the AV junction. As I noted in a previous post, these are the classic features of a vasovagal bradycardia & syncope.  

The Bezold-Jarish reflex is the likely mechanism, where initial tachycardia triggers a strong burst of activity from the vagal nerve, dropping the blood pressure and suppressing the SA and AV nodes.

From the Cardiology & CCU FB page

The (relative) hypovolemia that you might see when someone gets too much NTG, especially with an RV infarct, would be more likely to produce a compensatory tachycardia, and wouldn't usually produce such dramatic AV blocks.  

Is this something new and rare that I've stumbled across? Sadly, no. There are numerous case reports describing hypotension and bradycardia after giving NTG to patients, many of whom were shown not to be having any MI at all, let alone an RV infarct.

For example, in a 1990 case report, a 36 y.o. male received 2 NTG tabs in the course of a work-up of chest pain. Despite an intially normal ECG, he dropped his BP down to 77/40, and developed a brief brady-asystole. 

His vitals improved without drugs or IV fluids, and his labs and stress test ruled-out MI.

Another case report from 2007 (free access!) describes a similar sudden-onset junctional bradycardia and hypotension in a 60-y.o. male after NTG administration. Further back in ancient history (1981), a case series of 4 patients with this same pattern of bradycardia with hypotension and a narrow-complex bradycardia without sinus activity were described.

In yet another case, a 54 y.o. woman with chest pain (who ultimately ruled-out for MI) was given NTG for chest pain, and developed bradycardia. She described "lightheadedness and malaise," but never dropped her blood pressure.

Atropine (despite the blood pressure) helped the heart rate normalize.

The Bottom Line 
So now that I've described all these nasty bradycardias, should you withhold that next dose? Probably not. Even with EMS giving NTG to thousands of patients in the studies above, the rate of serious adverse effects is ≤ 1%. Those reactions also tend to be transient as well.

I should also point out that the SHCGB Guidelines do not require an ECG before NTG. After all, patients take this medication on their own all the time. On the other hand, they are not calling 911 every day, so the prudent paramedic should be getting ECGs early and often!


________________________________________________________  
103. DOES PREHOSPITAL ADMINISTRATION OF NITROGLYCERIN FOR CHEST PAIN CAUSE HYPOTENSION IN ACUTE INFERIOR WALL STEMI? A RETROSPECTIVE COHORT STUDY
Dave Ross, et al. Urgences-sante; Hopital du Sacre-Coeur de Montreal Montreal
Background. Patients with inferior ST-segment elevation myocardial infarction (STEMI), associated with right ventricular infarction, are potentially at higher risk of developing hypotension when administered nitroglycerin (NTG). However, current basic life support primary care paramedic (PCP) protocols do not differentiate location of STEMI prior to NTG administration.  
Objective. We sought to determine whether NTG administration is more likely to cause hypotension (systolic blood pressure <90 mmHg) in inferior STEMI compared with non-inferior STEMI.  
Methods. We conducted a retrospective chart review of prehospital patients with chest pain of suspected cardiac origin and computer-interpreted prehospital electrocardiograms (ECGs) indicating “acute MI.” Computerized interpretation was performed by the GE Marquette 12SLR-Zoll E Series. Patients were treated by PCPs. We included all local STEMI cases identified as part of a provincial STEMI registry project. Charts were reviewed by trained data extractors using a predefined instruction list. Univariate analysis was used to compare differences in proportions of hypotension after NTG administration, drop in systolic blood pressure greater than or equal to 30 mmHg, and hypotension on initial prehospital blood pressure between patients with inferior wall STEMI and those with STEMI in another region (non-inferior).  
Results. Over a 29-month period, we identified 1,466 STEMI patients. Of those, 798 (54.4%) had complete data and received NTG. Hypotension occurred after NTG in 36 of 461 inferior STEMIs and 29 of 337 non-inferior STEMIs, 7.8% vs. 8.6%, p = 0.69. A drop in systolic blood pressure greater than or equal to 30 mmHg occurred in 23.5% of inferior STEMIs and 23.8% of non-inferior STEMIs, p = 0.91. Initial hypotension was noted in significantly more inferior STEMIs compared with non-inferior STEMIs, 9.9% vs. 4.9%, p = 0.005. Interrater agreement for chart review of the primary outcome was excellent (kappa = 0.94). 
Conclusion. Patients with chest pain and inferior wall STEMI on their computer-interpreted prehospital ECG who receive nitroglycerin do not seem to develop hypotension more frequently than patients with STEMI in other territories, although they are more commonly hypotensive on presentation. Current PCP protocols for NTG administration in computer-interpreted prehospital ECG STEMI appear to be safe.