ST elevation myocardial infarction nitrate therapy

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Overview of Nitroglycerin
Nitrates are widely used in the management of patients with myocardial infarction. Historically, there were concerns in the distant past that nitrates would precipitate "coronary steal": as a result of vasodilating epicardial arteries and resistance vessels, it was hypothesized that nitrates would cause the shunting of blood flow to healthy tissue and away from infarcting tissue. This concern does not appear to be well founded. While nitrates can be of benefit in STEMI, caution should be exercised in their administration to patients with right ventricular infarct physiology (hypotension, ST elevation in right sided leads).

Mechanism(s) of Benefit
In determining whether nitrates should be administered and in determining the dose, the following mechanisms of benefit (as well as potential for harm) associated with nitrate administration should be kept in mind:


 * Reduction in preload via venodilation. While this may be of benefit in many STEMI patients, this may lead to hypotension and hypoperfusion in those patients with right ventricular infarction with ST segment elevation in lead V4R.


 * Reduction in afterload via arterial dilation. This may be of particular relevance in the patient with pulmonary edema or papillary muscle rupture or other mechanical complications.


 * Vasodilation of epicardial coronary arteries. While a modest component of vasoconstriction may be present in the majority of STEMI patients, relief of vasospasm may be particularly important in those rare patients with coronary spasm as the precipitating event.


 * Dilation of collateral vessels. This vasodilatory benefit must, however, be balanced against the load dependence of collateral filling and optimization of the subendocardial to epicardial flow ratio

Clinical Trial Data Supporting Nitrate Administration
A large randomized trial (ISIS 4) of nitrate administration (1 month of oral controlled-release mononitrate (30 mg initial dose titrated up to 60 mg once daily) versus matching placebo) demonstrated no significant mortality benefit of nitrate administration in the setting of STEMI. Similarly, when data were pooled from 22 trials enrolling more than 80,000 patients treated with nitrates either intravenously or orally, mortality rates were 7.7% in the control group and 7.4% in the nitrate group. Taken together, randomized and pooled data are consistent with a possible, but very modest treatment effect of nitrates such that only 3 to 4 deaths might be prevented for every 1,000 patients treated. Despite this lack of mortality benefit, nitrates may imporve a patient's quality of life by relieving pain and easing breathing by reducing the pulmonary capillary wedge pressure.

Contraindications to Nitrate Administration

 * Right ventricular infarction in which the patient is critically dependent upon preload for RV filling and cardiac output
 * Viagra and other phosphodiesterase inhibitors within 24 hours (48 hours for tadalafil). Nitrates and these agents share a common mechanism of action in facilitating the release of nitric oxide. Both clases of agent also increase cyclic guanosine monophosphate (cGMP).
 * Systolic blood pressure 30 mm Hg less than usual
 * Systolic blood pressures less than 90 mm Hg
 * Severe bradycardia

Initial sublingual Dosing
Before administering nitrates, contraindications to nitrate administration should be assessed first (see above: presence of hypotension, RV infarct, ingestion of phosphodiesterase inhibitors, profound bradycardia). The standard initial dose of nitroglycerin at the time of presentation of STEMI is 0.4 mg administered sublingually.

Maintenance Dosing
Intravenous nitroglycerin offers an advantage over sublingual administration in so far as it allows careful titration of the dosing in response to the patient’s blood pressure. The standard approach to dosing intravenous nitroglycerin is to begin the infusion rate at 5 to 10 mcg per minute. The infusion rates is increased by 5 to 20 mcg per minute until either: In dosing nitrates, the following should be avoided:
 * Symptoms are relieved
 * The mean arterial blood pressure (MAP) is reduced by 10% of its baseline level in normotensive patients
 * The mean arterial blood pressure (MAP) is reduced by up to 30% for hypertensive patients
 * The systolic blood pressure is lowered below 90 mm Hg
 * The systolic blood pressure drops greater than 30 mm Hg below baseline.

Nitrates versus Beta-Blocker Administration
In so far as the mortality benefits of nitrates are limited, their dosing should be titrated to a blood pressure that does not limit the co-administration of beta-blockers, which have, in contrast, been associated with advantages in mortality and infarct size reduction.

==ACC / AHA Guidelines (DO NOT EDIT) ==

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Class I
1. Patients with ongoing ischemic discomfort should receive sublingual nitroglycerin (0.4 mg) every 5 minutes for a total of 3 doses, after which an assessment should be made about the need for intravenous nitroglycerin. (Level of Evidence: C)

2. Intravenous nitroglycerin is indicated for relief of ongoing ischemic discomfort, control of hypertension, or management of pulmonary congestion. (Level of Evidence: C)

Class III
1. Nitrates should not be administered to patients with systolic blood pressure less than 90 mm Hg or greater than or equal to 30 mm Hg below baseline, severe bradycardia (less than 50 beats per minute [bpm]), tachycardia (more than 100 bpm), or suspected RV infarction. (Level of Evidence: C)

2. Nitrates should not be administered to patients who have received a phosphodiesterase inhibitor for erectile dysfunction within the last 24 hours (48 hours for tadalafil). (Level of Evidence: B)}}