A 58 year old male walks into your emergency department clutching his chest, sweating profusely and complaining of 10/10 crushing chest Pain. Your first thought is, of course, that he is experiencing some sort of myocardia infarction (MI), so you have one of the techs start an EKG while you get vital signs and a history. He says the pain started 30 minutes ago, that it came out of nowhere, and that he doesn't take any medications or have any medical history because he hasn't been to a doctor since his early 40's. His heartrate is 105, blood pressure is 156/92, Oxygen saturation is 95% and his respiratory rate is 20. The EKG shows a lateral STEMI.

Lets say you now assume care of this Patient. What do you expect to do? Well, if you were trained more than 2 or 3 years ago, there's a good chance you learned the acronym MONA. In fact, I hear this is still being taught to new nurses today in some schools. MONA stands for Morphine, Oxygen, Nitroglycerin and Aspirin. For a long time, this was considered the gold standard of initial MI treatment. Every patient should receive morphine, aspirin, anticipate nitro administration and be placed on oxygen, or so we have been taught. Spoiler alert: MONA is getting kicked out.

The argument for routine morphine use was essentially that it would decrease myocardial oxygen demand. A reduction in pain, heartrate and anxiety were thought to be the main source of this effect. It was also said that oxygen should be administered in all cases as a way of ensuring adequate O2 was present in the blood that did get past the clot to oxygenate the poorly perfused tissue. Nitro would dilate the vessels, increasing perfusion and decreasing cardiac work load. Finally, of course, aspirin is an antiplatelet meant to prevent the clot from enlarging. Lets look at each of these individually.

MONA

Morphine

As a powerful analgesic, morphine seems like a common sense choice to treat chest pain in MI. While it does relieve pain, it's also been shown to have some important drawbacks in this setting. A systematic review published in 2019 [1] examined mortality, adverse cardiac events and antiplatelet interactions with morphine use in heart attacks and found the following:

• In-hospital mortality rates were increased with morphine use. The studies were mostly of poor quality, though, so more studies are needed.
• Adverse cardiac events were more common in cases of morphine use, but, again, the studies were generally judged to be of low quality.
• Morphine was demonstrated to impair the effects of P2Y12 inhibitors, a class of antiplatelet drugs, ticagrelor for example, that have become a mainstay of MI treatment (these will be discussed briefly later). This effect has been well demonstrated and is the most important finding of this review.

Meanwhile, there have been a variety of studies looking at infarct size and morphine use, demonstrating both larger infarctions [2] and smaller infarctions [3,4]. Oh, the joys of research.

Because of these finding, morphine is no longer considered standard treatment for all MI patients. As the effects have been far from definitively proven in either direction, its routine use seems unwise.

Fentanyl has been proposed as an alternative to morphine, in the hopes that it might not have the same draw backs in the setting on STEMIs and NSTEMIs. My experience, in a busy STEMI receiving center ED, is that MDs now prefer fentanyl over morphine in the setting of AMIs. At least one study has shown, however, that fentanyl has a similar effect on antiplatelet medications that morphine does [5].

Alternate methods of pain control are warranted given the conflicting findings regarding opioid use. One thing to keep in mind is that most of the pain from an AMI is the result of impaired perfusion of the cardiac muscle. So, restoring some degree of perfusion and/or reducing cardiac oxygen demand are liable to help with pain. Nitroglycerin and beta-blockers are both candidates for this, both of which will be discussed later. Then we can reserve narcotic medications for refractory pain.

The M is out of the standard AMI response plan.

Oxygen

Blocked coronary arteries are a problem not because blood isn't getting through, but because of the things the blood carries. In this case, we're talking primarily about oxygen. An AMI doesn't necessarily mean than absolutely no blood is getting past, so it stands to reason that if only a small amount of blood is getting through, we should pack as much oxygen as possible into it, right? Unfortunately, the answer isn't that easy.

Hyperoxia has a number of negative physiologic effects. Of primary relevance to our topic here, an elevated blood oxygen level causes vasoconstriction, decreases cardiac output and leads to more damage to cardiac muscle [6]. One study of patients receiving cardiac catheterization showed that administering 100% oxygen caused about 40% increase in coronary vascular resistance and caused coronary blood flow to decrease by almost a third [7]. Think about those numbers for a minute.

At least this is one topic with a straight forward action to take, or in this case avoid. Do not routinely administer oxygen to cardiac patients. There will be cases in which it is warranted, say in the case of pulmonary edema from left sided failure. As a rule, though, there ought to be a good reason to be giving supplemental oxygen.

Nitroglycerin

Everyone knows nitroglycerin is used for chest pain. Give it sublingual up to three times every 15 minutes for chest pain, right? People walk around with a bottle of nitro in their pocket to take for angina. What could possibly be the problem with giving this in the ED for chest pain?

Nitro use in the setting of STEMI and NSTEMI is still supported, but is another one that should not be given routinely to all AMI patients. The biggest concern comes from giving nitro to STEMI patients and the substantial effect it has on blood pressure. There's typically been a fear that any patient with an inferior STEMI/right ventricular infarct will suffer complete cardiovascular collapse should they receive nitroglycerin. While studies are questioning this particular fear [8], it's important to remember that all STEMI patients really are to be considered unstable. If we are going to be using medications that don't have an effect on mortality, as in this case [9], we need to be extra careful and only do so when there is a good reason.

What's a good reason? Pain control is the answer. Cardiac oxygen demand without adequate perfusion is the source of most AMI pain. If we cannot yet increase the perfusion, we can use nitro to reduce the oxygen demand. Nitroglycerin reduces the preload and afterload, thereby reducing the hearts workload (it has to push less volume and against less resistance). Nitro has been around for so long because it is effective at relieving pain in AMI patients.

Three down, one to go...

Aspirin

Aspirin is an anti inflammatory and antiplatelet medication. Its active chemical, salicylic acid, has been in use for thousands of years, refined from willow bark and other sources. It's uses have been numerous throughout history, but is now fairly restricted to MI prevention and treatment, due to the significant side effects it possesses. This medication has been so promoted that many patients will know it's use for heart attack and take it before even arriving to the hospital.

The antiplatelet property of aspirin helps to prevent the expansion of any clot in the coronary arteries. It's also been suggested that the anti-inflammatory may help preserve or promote blood flow. Studies of this medication have been performed for decades on this use, and have consistently shown it's effectiveness. One relatively recent study demonstrated specifically that giving aspirin within an hour of arrival to the ED for an AMI resulted in decreased mortality 30 days later [10]. This shows not only that it is important, but urgent, that it should be administered sooner rather than later.

Finally, we have a component of MONA that should be given to everyone as quickly as reasonably possible. The only real exception to this is a history of severe allergic reaction. Even patients that cannot swallow can be given an aspirin suppository [11] in hopes of obtaining the benefits. So, lets hold onto the A.

What About THROMBINS2?

If you haven't heard of this one, it's been suggested as a replacement for MONA to identify the components of AMI treatment. THROMBINS2 stands for Thienopyridines, Heparin, RAS blockers, O2, Morphine, Beta-blockers, Interventions, Nitro, Statins and Salicylate. Talk about a mouth full.

We've already discussed oxygen, morphine, nitroglycerin and salicylate (aspirin), but below is a very brief description of the other components of THROMBIN2

• Thienopyridines refers to P2Y12 inhibitors, a form of antiplatelet that works differently than aspirin. Some examples include clopidogrel and ticagrelor. These medications have proven, consistent benefits for AMI in terms of adverse cardiac events. The term "dual antiplatelet therapy" refers to giving these alongside aspirin and is well supported.
• Heparin is an anticoagulant that blocks the effects of thrombin. It is particularly valuable due to its rapid onset and cessation of effects, so it doesn't delay PCI. It's use may reduce mortality by more than 50% while awaiting definitive treatment [9].
• Renin Angiotensin System blockers like ACE inhibitors have benefits to mortality, particularly in the setting of heart failure and reduced ejection fraction [9], though the goal time frame for initiation is usually within 24 hours of hospital arrival and is overall a longer term intervention.
• Beta Blockers reduce blood pressure and heartrate, thereby reducing myocardial oxygen demand. It's long term effects in the setting of AMI are questionable, and should only be used in the absence of shock or heart failure. This is another medication doesn't require very early administration according to recommendations [9].
• Intervention refers primarily to Percutaneous Coronary Intervention (PCI); the use of a catheter to directly treat coronary artery dysfunctions like placing stents. PCI is now considered the definitive treatment in STEMI patients. Intervention could also refer to fibrinolytic administration which, while not as ideal as PCI, can be performed in facilities without interventional cardiology.
• The statins are perhaps the most interesting of these recommendations. Cholesterol control is known to be important to acute coronary syndrome prevention. Apparently, though, some studies are suggesting that statins should be started as early as possible in the acute phase of an MI not only for cholesterol control, but also for it's anti-inflammatory, anti-platelet, and positive endothelial effects [12]. Maybe one day we'll be giving atorvastatin as urgently as we do aspirin.

The good thing about MONA, was that is was simple and to the point, exactly how ER nurses function. Coming from the point of view of an emergency department nurse, I hate THROMBINS2. We don't need a list of everything you should plan on giving, or consider giving, these patients at some point. From our point of view, what are the things that have to be ready for in the first hour or two? I would advocate for PATH.

What is PATH?

Once it's been determined that you are dealing with some form of AMI, there are four main things to consider immediately:

Prepare - in the case of a STEMI, put your patient on the defibrillator. They can go into a lethal arrhythmia at the drop of a hat. Get adequate IV access early. You also need to consider if PCI or some other form of immediate intervention will be required and "prepare" for that (get consents, gain additional IV access, strip them for the cath lab, etc).

Anti-platelet - At least aspirin, if not a P2Y12 inhibitor as well.

Treat pain - I like stating it this way (instead of separating the options) because different situations call for different medications. Nitro is an excellent option, and beta-blockers could be considered, especially if trying to avoid the concerns related to morphine mentioned earlier. But is the patient bradycardic and barely maintaining their blood pressure? Then perhaps you should consider fentanyl instead. Plus, morphine isn't completely off the table, just to be used with caution.

Heparin - This anticoagulant has significant short term benefits and can be given without concern over the timing of PCI.

Note that there is no mention of RAS blockers, Beta-blockers or statins. For our purposes, there isn't a need to have these less immediate medications top of mind. They may be needed, just not emergently. Oxygen is also left off for a reason. We don't need a reminder to administer oxygen, since O2 will cause more harm than good unless actual hypoxia is present.

Conclusion

It's time to return to our patient from the beginning. Remember that he was complaining about severe pain, he has a lateral STEMI and the following vital signs: heartrate 105, blood pressure 156/92, oxygen saturation 95% on room air and a respiratory rate of 20.

Lets prepare by getting him on the crash cart, get two big IVs and call the cardiac cath lab. Since it's after hours, the cath lab team is on call, so we have a little time before they arrive. Our patient has the blood pressure to spare, so lets start with nitro for his pain and consider beta blockers if needed. We are going to give aspirin, which the patient chews and swallows. A heparin bolus is given and, since the cath lab still hasn't arrived we will start a heparin drip. By the time the team arrives, his is in a gown with all of his clothes removed, belongings bagged and the ER physician has even gotten consent for the procedure. PCI is performed and he has an excellent prognosis.

Did you learn MONA in school? How recently? Let me hear your comments.