Exploring Evidence-Based Medicine in Emergency Care

Reference: Wilkinson-Stokes M, Betson J, Sawyer S. Adverse events from nitrate administration during right ventricular myocardial infarction: a systematic review and meta-analysis. Emerg Med J. February 2023 Date: January 24, 2024 Guest Skeptic: Dr. Rupinder Sahsi is a fellow EBM enthusiast with academic appointments at McMaster University and Wright State University who works as an emergency physician in Kitchener-Waterloo, Ontario, Canada. He is also an assistant medical director for EMS at the Centre for Paramedic Education and Research in Hamilton, Ontario, Canada. Case: You are an advanced care paramedic dispatched to the scene of a 53-year-old female with chest pain. She developed retrosternal chest discomfort shortly after she came in from using her snowblower. You provide her with two tablets of ASA to chew while your partner acquires an ECG, which ultimately shows clear ST elevation in the inferior leads and some ST changes in V1-V2 that make you wonder if your patient is having an acute myocardial infarction (MI) with right-sided ventricular involvement (RVI). Your patient rates their pain as an 8/10 and looks visibly uncomfortable. Do you give nitroglycerin? Background: You have likely heard the caution to avoid nitrates in acute myocardial infarctions that have right ventricular involvement. What is that based upon? As is often the case, when you go back to the primary literature, you discover we are standing on pillars of salt and sand. The evidence for this recommendation is a single observational study of 40 patients published in 1989 [1]. Yet, the findings in those 40 patients went on to be the evidence commonly cited by the American Heart Association (AHA) [2] and the European Society of Cardiology (ESC) [3] in their recommendation against the use of nitrates in acute MIs if there is right ventricular involvement. The pathophysiologic rationale was that nitrates would cause vasodilation and thus reduce RV preload, decreasing left end diastolic volume, and ultimately resulting in clinically important hypotension. Many times, pathophysiology has been used to explain something in medicine only to be discovered later that the body is much more complicated than we thought. That 40-patient study by Ferguson et al did show a statistically significant increased likelihood of hypotension in RVMI patients who received nitrates, but to me, the study design was just plain weird. This was a retrospective trial that looked at 40 patients with inferior MIs. Twenty of them had hypotension after nitrates and 20 of them were not hypotensive. They looked back and saw that a higher proportion of patients with inferior MI and hypotension had ECG evidence of RV involvement. Sounds okay, but by having equal numbers of hypotensive and non-hypotensive patients, they’ve exaggerated the incidence of hypotension. It’s not 50-50. In all comers with MI, the rate is probably closer to <3%. On top of that, there was no standardization of the nitrate dose or route of administration, so it’s hard to know how to extrapolate the findings to our standard nitrate admin protocols. I was not surprised by this information. Fanaroff et al looked at the ACC/AHA guidelines from 2008-2018 [4]. They found 26 guidelines with 2,930 recommendations. Only 9% were Level A while 50% were Level B and 41% were Level C. Compare that previously mentioned 40-patient study to the 2016 Canadian study by Robichaud et al which was 22 times larger (n=1,004) than the Ferguson study [5]. It looked at the administration of a standardized amount of nitroglycerin in MI patients with various vascular territories involved. It shows no statistical difference in adverse events between patients with and without RVMI – a relative risk of 1.02 (95% CI: 0.49 to 2.15) p-value = 0.95. Clinical Question: Is nitrate administration to patients with right ventricular myocardial infarction (RVMI) associated with increased adverse events compared with nitrat...