“Go or No-Go” for Nitro? – Reevaluating Nitrates in the Right-Ventricular STEMI

Research

Much of the research surrounding the use of nitroglycerin in myocardial infarction occurred in the 1980s and 1990s, including the ISIS-4 and GISSI-3 studies, which were examined in a 2009 Cochrane Review that showed only modest mortality benefit for nitrates when used within 24 hours at day 2 (RR 0.81, 95% CI [0.74,0.89], p<0.0001). No further benefit was observed with nitrate therapy beyond this point. (5) Yusuf, et al. also commented on mortality benefit for nitroglycerin (and nitroprusside) in a 1988 Lancet review. (6)

Kinch and Ryan (1994): In a review of the literature, the authors point out that animal studies of induced right ventricular infarction resulted in acute RV dilatation, an increase in right-sided filling pressures, and a decrease in RV systolic and end-diastolic pressure. This subsequent loss in atrial pressure and reduced RV contractility was theorized to be the primary cause of reduced cardiac output and aortic pressure in patients with RVMI. Because of NTG venodilation at doses typically used by emergency healthcare personnel (0.4 mg sublingually or up to 40 mg/min IV), it was suggested that a reduction in this preload would cause further decreased cardiac output and worsening cardiogenic shock, coronary perfusion, and increased cardiac oxygen demand. (7)

Robichaud, et al. (2016): In 1,466 prehospital STEMI cases, 821 (56.0%) received NTG. Hypotension occurred post NTG in 38/466 inferior STEMIs and 30/339 non-inferior STEMIs, 8.2% vs. 8.9%, p = 0.73. A drop in systolic blood pressure ≥ 30 mmHg post NTG occurred in 23.4% of inferior STEMIs and 23.9% of non-inferior STEMIs, p = 0.87. The authors concluded that NTG administration to patients with chest pain and inferior STEMI on their computer-interpreted electrocardiogram is not associated with a higher rate of hypotension compared to patients with STEMI in other territories. (8)

Observations

While commonly used for symptom control, data surrounding mortality benefit in early studies may show a modest benefit, at best, and are not clearly convincing. However, there are benefits to symptom control in the management of these patients, such as reduction in the stimulation of the sympathetic nervous system, thereby decreasing myocardial oxygen demand with reduced chronotropy and inotropy. 

While the physiology of a right-ventricular infarct suggests that the use of nitrates could significantly affect preload and, therefore, introduce hemodynamic instability, more recent (but limited) research has suggested this may not necessarily be as prominent as once thought. The studies investigating this are limited and this is an area that certainly warrants further investigation. As Jaton (2017) points out in his review, “even if these rare adverse events such as hypotension or arrhythmia occur, NTG has a short half-life (in vivo 3 minutes) which will resolve transient hypotension and bradycardia with minimal detriment. Adverse events related to NTG such as hypotension also are commonly responsive to fluid bolus and rarely require advanced intervention with chronotropes or inotropes.” (3).

However, nitroglycerin, regardless of the area of infarct, does have the potential to further destabilize a patient who is already hypotensive or who has labile pressures. In this population it is still necessary to assess volume status (and fluid resuscitate or use vasoactive agents as indicated) and consider the use of pain medications that can alleviate symptoms without causing the same degree of hypotension, such as fentanyl.

At the end of the day, the current accepted guidance and recommendations regarding use of nitrates in right-ventricular myocardial infarction remain to avoid their use. However, the risk may not be as serious as once thought and warrants further analysis and research.