Sirens to Scrubs: Acute Coronary Syndromes, Part Two – To the Lab!

In Sirens to Scrubs, Working in EM by Richard ArmourLeave a Comment

Disclaimer: The procedures and therapies discussed in this post are extrapolated from a number of ambulance services globally. This does not replace the direction of readers’ ambulance service clinical guidelines or protocols and should not be used in place of local guidelines or protocols. If you believe something in this post would benefit your ambulance service, contact your local medical director(s) before altering your own practice. 

In Part One of this series our dashing paramedics have reviewed the pathophysiology of Acute Coronary Syndromes (ACS), historical findings and risk factors associated with ACS and have subsequently identified that their patient is suffering from a large ST-Segment Myocardial Infarction (STEMI). What happens in the prehospital environment for patients with ACS? Read on to find out…

About Sirens to Scrubs

Sirens to Scrubs was created with the goal of helping to bridge the disconnect between pre-hospital and in-hospital care of emergency patients. The series offers in-hospital providers a glimpse into the challenges and scope of practice of out-of-hospital care while providing pre-hospital providers with an opportunity to learn about the diagnostic pathways and ED management of common (or not-so-common) clinical presentations. By opening this dialogue, we hope that these new perspectives will be translated into practice to create a smoother, more efficient, and overall positive transition for patients as they pass through the ED doors.

Objectives

  1. Review the fundamental components of ACS care as it applies to the prehospital environment
  2. Develop a deeper understanding of ACS treatments to appreciate more advanced management initiatives

Fundamentals of Prehospital Care of Acute Coronary Syndromes

Aspirin is a cornerstone of the therapy provided by paramedics in ACS, remaining a Class 1 recommended intervention in both the American Heart Association (AHA) and European Society of Cardiology (ESC) guidelines.1–3 Aspirin exerts its effects in ACS by preventing the further accumulation of platelets around the coronary plaque described in Part One of this series. For every 42 patients suffering from ACS, Aspirin has the potential to save one life. Quite incredible for an unassuming pill! The optimal dosing of Aspirin in ACS remains somewhat contested, with some studies potentially suggesting an association with a higher dose (324mg) of Aspirin and significant in-hospital bleeding when compared with a lower dose (162mg), despite an apparent equal clinical effect.4 The dose employed by ambulance services in Canada and internationally is variable, with doses ranging from 150mg to 325mg as recommended by the AHA and ESC.

Sublingual nitroglycerin, or glyceryl trinitrate, is the primary vasodilating agent used in prehospital care for patients with ACS. Nitroglycerin administration results in decreased myocardial oxygen consumption through several mechanisms. As a smooth muscle relaxant, it causes:

  • Venodilation, which reduces the amount of blood returning to the heart (preload)
    • Reduces stress on the ventricular wall
    • Reduces the amount of volume in the ventricles during diastole (after the blood has been pumped out), which is the time in which the heart is perfused. High volumes in the ventricles during diastole act to compress the small arterioles that feed the myocardium. By decreasing this volume, we allow more blood to reach deep into the inner layers of the heart.
  • Arterial dilation, which reduces the pressure against which the ventricles have to pump blood (afterload)
    • Coronary arteries also dilate, in particular, the arteries involved in collateral circulation (blood vessels which have developed to bypass an atherosclerotic section). This improves blood flow to the myocardium, bringing with it oxygen and taking away waste products.
  • Inhibition of coronary artery vasospasm, which often contributes to ACS

Sublingual nitroglycerin is generally dosed at 0.4mg every 5 minutes whilst ischemic symptoms persist, with cautions as the cumulative dose increases in case of excessive vasodilation and a secondary paradoxical tachycardia.

Myocardial ischemia is undoubtedly a painful, or at the very least uncomfortable, experience. A fundamental aspect of prehospital care is the alleviation of suffering in the form of analgesia, which is particularly relevant in the setting of ACS. Historically, this has been achieved through the use of intravenous (IV) morphine titrated incrementally to effect. Although this remains current practice in many ambulance services worldwide, some have seen a shift to fentanyl as the analgesic of choice in ACS.

Although the administration of high flow oxygen to patients has long been associated with prehospital care, most ambulance services have now moved away from routine administration of oxygen to patients with ACS without evidence of clinical hypoxaemia (Sp02 < 94%). The shift in prehospital care away from routine oxygen therapy was largely driven by the results of the AVOID and DETO2X trials, which found that the routine administration of oxygen to patients with myocardial infarction appeared to increased infarction size and early myocardial injury, without improving 1-year mortality.5,6 The ESC also updated their guidance to recommend against oxygen therapy (Class III recommendation), although the AHA guidelines still possess a degree of ambiguity in suggesting oxygen may be beneficial in some groups of patients.1–3 In ambulance services still applying oxygen routinely in myocardial infarction, it is entirely possible this may be a practice change on the horizon for your service. However, it is essential that any change made in individual practice is supported by local guidelines and protocols, and so paramedics should continue to practice as advised by their medical directorate.

A Deeper Dive into Physiology, Evidence and Potential Upcoming Changes

Aspirin entered into the spotlight in the care of patients with ACS following the landmark ISIS-2 trial in 1988.7 The mechanism of action of Aspirin in ACS is predominantly related to its irreversible inhibition of cyclooxygenase (COX) enzymes, specifically COX-1 enzymes. In platelets, the COX-1 enzyme is responsible for producing Thromboxane A2, a substance that binds to receptors on activated platelets and causes activation of additional platelet and aggregation, forming platelet plugs. Thus, Aspirin prevents further clot formation, preventing the growth of the troublesome thrombus.

Nitroglycerin mimics the actions of endogenous nitric oxide, increasing the levels of intracellular cGMP. Raised levels of intracellular cGMP inhibit the entry of calcium into cells, which is the causative mechanism in the induction of vascular smooth muscle relaxation. Although generally described as a ‘symptom-relief medication’, a 2009 Cochrane Review found that in patients suffering from ACS administration of intravenous nitroglycerin provided a reduction in mortality at 2 days, if administered within 24 hours of symptom onset.8 Unfortunately, given that the review included only intravenous nitrates it cannot be extrapolated to sublingual nitrates (we are unaware of any ambulance services currently using IV nitrates).

Owing to an observed superior safety profile, many ambulance services, emergency departments, and cardiology wards have shifted to fentanyl as the analgesic of choice in ACS. This change has occurred in conjunction with recent studies that have demonstrated delayed uptake of P2Y12 receptor inhibitors – clopidogrel (Plavix) ticagrelor (Brillinta) and prasugrel (Effient) – when IV morphine is administered.9,10 Platelets have several receptor types; in addition to the TXA2 receptor discussed above, P2Y12 receptors, when bound, lead to platelet aggregation. Thus, these agents are given in addition to ASA to inhibit platelet aggregation in ACS. Data extrapolated from the pharmacology of transdermal fentanyl appears to suggest that fentanyl would have a lesser impact on gastric motility, although the confirmation of this theory will likely not be known until the publication of the upcoming PERSEUS randomized controlled trial, designed to look at this exact issue.11

Coronary Systems of Care  

The ability of paramedics to acquire and interpret 12-Lead electrocardiograms (ECGs) undoubtedly represents one of the most important developments in the prehospital profession. In general, the acquisition of a 12-Lead ECG is a skill performed by paramedics in Canada at the level of Primary Care Paramedic (PCP) and higher, although in some regions Advanced Care Paramedics (ACP) and higher are required to initiate STEMI Bypass procedures (where available). Recognition of STEMI by paramedics in the prehospital field has continually been demonstrated to reduce the time taken for the patient to arrive at definitive care. In general, there are two primary systems in place for STEMI notifications where Percutaneous Coronary Intervention (PCI) is the definitive therapy of choice. The first involves the transmission of the ECG to the emergency department (ED) of the receiving hospital, with the ultimate decision as to whether to activate (or not activate) the coronary catheterization lab (commonly known as the ‘cath lab’) resting in the hands of the emergency physician. The second involves the paramedic activating the cath lab without emergency physician oversight, either with a transmission to the receiving cardiologists or autonomously without transmission. Both systems have strong merits, with emergency physician oversight potentially assisting in avoiding false-positive activations of the cath lab, although paramedic-led bypass has been shown to potentially further reduce the time from first medical contact to balloon.

What about the Non-ST-Segment Elevation Myocardial Infarctions we discussed last week?

Paramedic identification of a Non-ST-Segment Elevation Acute Coronary Syndrome (NSTE-ACS) generally leads to a discussion with local emergency physicians and cardiologists at specialty resource centres in order to coordinate the optimal care for the patient. Although many NSTE-ACS patients will be managed with aggressive medical therapy, there is a select subgroup who may benefit from early PCI. In some services, such as the London Ambulance Service NHS Trust, this has led to the development of ‘High-Risk ACS Pathways’. Patients in these pathways will present with historical findings concerning for NSTE-ACS and ECG findings consistent with myocardial ischemia, such as non-localised ST-depression or localized flipped T waves, and will be transported to specialty resource centres capable of 24 hour PCI, without pre-activating the entire cath lab team.

Advanced Coronary Care in the Prehospital Environment

Although PCI is considered the optimal therapy for patients suffering from STEMI, it is (unfortunately) both impractical and fiscally not possible to have PCI centres in every community. In general, guidelines will advocate for a PCI approach to STEMI care in cases where the time from point of initial medical contact to the commencement of PCI is less than 120 minutes (in some areas, less than 90 minutes). In communities where this is not possible, patients will be managed with thrombolysis and either emergency transfer for rescue PCI (in cases where fibrinolysis does not resolve the STEMI) or routine angiogram within 1-2 days. However, what if you are a paramedic working in a region where the nearest hospital is over two hours away?! Pioneered in Australia and the United Kingdom, prehospital, paramedic-initiated thrombolysis has been shown to be safe and effective in the management of STEMI patients not eligible for PCI as first-line therapy.12–15

The initiation of prehospital thrombolysis will involve the use of advanced cardiac medications such as Clopidogrel (Plavix), ticagrelor (Brillinta), Heparin, Enoxaparin, and tenecteplase. Although the following discussion of the mechanism of action of these medications may appear intimidating, compare them against the previous post and your own understanding of ACS to better understand how they all fit in the management of ACS!

Both clopidogrel and ticagrelor function by binding to P2Y12 receptors and blocking them, inhibiting the activation of the GPIIb/IIIa complex found in platelets. As a reminder, activated GPIIb/IIIa promotes platelet aggregation (see, we told you that GPIIb/IIIa was important and would make sense!)

The pharmacology of both Heparin and Enoxaparin are heavily dependent on an in-depth understanding of the coagulation cascade, so we will only briefly touch over the key elements. Heparin works in the setting of ACS by accelerating the action of circulating antithrombin III, which in turn inactivates a number of factors in the coagulation cascade. Although this does not reverse the coagulation in the already-developed thrombus, this is critical in preventing the continued growth and occlusion of the coronary artery. Enoxaparin has a similar mechanism of action, as it also accelerates the action of circulating antithrombin III. However, Enoxaparin has a greater affinity for different elements in the coagulation cascade when compared with heparin.

Finally, tenecteplase binds to the fibrin-rich thrombus we were left with at the end of Part One. As it binds with the fibrin-rich thrombus, tenecteplase causes the release of plasmin. Plasmin in turn degrades the fibrin mesh surrounding the clot, releasing the trapped contents, reducing the size of the thrombus and allowing sweet, sweet oxygen-rich blood to return to the myocardium. Yay!

If any Canadian services are employing prehospital thrombolysis, we would love to hear from you! British Columbia Emergency Health Services will shortly be commencing a trial of prehospital ticagrelor and heparin in regions where the time to PCI exceeds 120 minutes and it would be excellent to hear of other services experiences with similar interventions (collaboration is king)!

Review and Wrap-Up

Exhausted? We certainly are! Managing a STEMI in the prehospital environment is complicated!

Some key take-home points:

  • Aspirin, Nitroglycerin, Analgesia (Morphine or Fentanyl) and occasionally Oxygen make up the fundamentals of prehospital care of ACS patients
  • Most ambulance services (if not all) now have the ability to record and interpret 12-Lead ECGs, with any that appear to be a STEMI normally streamlined into a STEMI Bypass Protocol which may or may not involve the oversight of a physician
  • In austere environments, some ambulance services have begun employing prehospital thrombolysis to manage STEMI patients who will not arrive at a PCI centre within 120 minutes. This involves the use of advanced pharmacology such as Clopidogrel or ticagrelor, heparin or enoxaparin and tenecteplase. Look for this to potentially arrive in some of our regional communities in Canada in the future!

Stay tuned for the next segment of “Sirens to Scrubs: Acute Coronary Syndromes” – in the meantime, find more Sirens to Scrubs articles here!

A special thanks to @Phoebe_Bibi for her graphic representation of coronary systems of care!

As always, if you have any questions, thoughts, alternative perspectives, or requests for future topics, feel free to comments below or send me an email at [email protected]. Please keep in mind that, although I will do my best to publish information that is accurate across Canada, there will inevitably be some regional differences in both pre-hospital and in-hospital management of emergency patients. As a paramedic and Emergency Medicine resident in Ontario, some posts may wind-up being somewhat Ontario-centric, hence, I encourage anyone whose experiences differ from mine to contribute to the conversation by commenting below.

References

1.
Ibanez B, James S, Agewall S, et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018;39(2):119-177. [PubMed]
2.
O’Gara P, Kushner F, Ascheim D, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127(4):e362-425. [PubMed]
3.
Roffi M, Patrono C, Collet J, et al. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016;37(3):267-315. [PubMed]
4.
Berger J, Stebbins A, Granger C, et al. Initial aspirin dose and outcome among ST-elevation myocardial infarction patients treated with fibrinolytic therapy. Circulation. 2008;117(2):192-199. [PubMed]
5.
Hofmann R, Svensson L, James S. Oxygen Therapy in Suspected Acute Myocardial Infarction. N Engl J Med. 2018;378(2):201-202. [PubMed]
6.
Stub D, Smith K, Bernard S, et al. Air Versus Oxygen in ST-Segment-Elevation Myocardial Infarction. Circulation. 2015;131(24):2143-2150. [PubMed]
7.
Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Lancet. 1988;2(8607):349-360. [PubMed]
8.
Perez M, Musini V, Wright J. Effect of early treatment with anti-hypertensive drugs on short and long-term mortality in patients with an acute cardiovascular event. Cochrane Database Syst Rev. 2009;(4):CD006743. [PubMed]
9.
Giannopoulos G, Deftereos S, Kolokathis F, Xanthopoulou I, Lekakis J, Alexopoulos D. P2Y12 Receptor Antagonists and Morphine: A Dangerous Liaison? Circ Cardiovasc Interv. 2016;9(9). [PubMed]
10.
Kubica J, Kubica A, Jilma B, et al. Impact of morphine on antiplatelet effects of oral P2Y12 receptor inhibitors. Int J Cardiol. 2016;215:201-208. [PubMed]
11.
Degrauwe S, Roffi M, Lauriers N, et al. Influence of Intravenous Fentanyl Compared with Morphine on Ticagrelor Absorption and Platelet Inhibition in Patients with St-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: Rationale and Design of the Perseus Randomized Trial. Eur Heart J Cardiovasc Pharmacother. August 2018. [PubMed]
12.
Ranchord A, Prasad S, Matsis P, Harding S. Paramedic-administered prehospital thrombolysis is safe and reduces time to treatment. N Z Med J. 2009;122(1302):47-53. [PubMed]
13.
Björklund E, Stenestrand U, Lindbäck J, Svensson L, Wallentin L, Lindahl B. Pre-hospital thrombolysis delivered by paramedics is associated with reduced time delay and mortality in ambulance-transported real-life patients with ST-elevation myocardial infarction. Eur Heart J. 2006;27(10):1146-1152. [PubMed]
14.
Khan S, Murray P, McCormick L, et al. Paramedic-led prehospital thrombolysis is safe and effective: the East Anglian experience. Emerg Med J. 2009;26(6):452-455. [PubMed]
15.
Sherrid M, Greenberg H, Marsella R, Mathisen D, Lynn S, Dwyer E. A pilot study of paramedic-administered, prehospital thrombolysis for acute myocardial infarction. Clin Cardiol. 1990;13(6):421-424. [PubMed]
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Richard Armour

Richard Armour

Richard Armour is an Advanced Care Paramedic with the British Columbia Ambulance Service and Associate Faculty with the Justice Institute of British Columbia. Having completed a Bachelor of Paramedic Practice in Australia, he moved to the United Kingdom where he worked as a Paramedic for the London Ambulance Service NHS Trust prior to moving to Canada. Now pursuing an MSc in Advanced Emergency Care and a Masters of Paramedicine, Richard has a keen interest in prehospital patient safety, clinical audit and research.
Richard Armour
- 1 day ago
Paula Sneath

Paula Sneath

Paula is a PGY1 in Emergency Medicine at McMaster University and an Advanced Care Paramedic in Ontario. She has a strong interest in improving access to education and resources for paramedics in Canada and fostering relationships between EM providers.
Paula Sneath
- 3 weeks ago