In a normotensive adult with chest pain, how should an intravenous nitroglycerin infusion be initiated, titrated, monitored, and what are the contraindications?

Intravenous Nitroglycerin for Normotensive Adults with Chest Pain

Start IV nitroglycerin at 10 µg/min and titrate upward by 5–10 µg/min every 3–5 minutes until chest pain resolves or blood pressure limits are reached, maintaining systolic blood pressure ≥90 mmHg at all times. 1

Initiation Protocol

Starting Dose and Equipment

• Begin the infusion at 10 µg/min using non-polyvinyl chloride (polyethylene) tubing to prevent drug absorption into standard PVC tubing 1, 2
• For normotensive patients with acute coronary syndrome, this starting dose provides reliable hemodynamic effects while minimizing hypotension risk 2, 3

Indications for IV Nitroglycerin

• Persistent anginal chest pain after sublingual nitroglycerin therapy (up to 3 doses of 0.3–0.4 mg every 5 minutes) 1
• Acute coronary syndrome accompanied by hypertension or pulmonary edema 1
• Refractory ischemic chest pain despite maximally tolerated anti-ischemic medications 1

Titration Strategy

Standard Titration Steps

• Increase by 5–10 µg/min every 3–5 minutes based on pain relief and blood pressure response 1, 2
• If no response at 20 µg/min, escalate to 10 µg/min increments every 3–5 minutes 2, 3
• At doses >50 µg/min without adequate response, consider 20 µg/min increments 4, 3
• The usual maximum dose for acute coronary syndrome is 200 µg/min; beyond this, alternative vasodilators should be considered due to increased hypotension risk 2, 3

Titration Endpoints

• Complete resolution of chest pain or anginal symptoms 2, 4, 3
• Reduction in mean arterial pressure by 10% in normotensive patients (do not lower systolic BP below 110 mmHg) 2, 3
• Achievement of hemodynamic stability without excessive tachycardia (avoid heart rate increases >10 beats/min above baseline) 4

Absolute Contraindications

Blood Pressure Thresholds

• Systolic blood pressure <90 mmHg or a drop of ≥30 mmHg below baseline 1, 2, 3
• These thresholds are absolute contraindications and must be verified before every dose escalation 2, 3

Drug Interactions

• Recent phosphodiesterase-5 inhibitor use:
  • Within 24 hours of sildenafil or vardenafil 1
  • Within 48 hours of tadalafil 1
  • Within 12 hours of avanafil 1
• This combination can cause profound, potentially fatal hypotension 2, 3

Clinical Conditions

• Suspected right ventricular infarction (patients are critically dependent on adequate RV preload and can experience profound hypotension) 1, 3
• Volume depletion or hypovolemia (must be corrected before initiating nitroglycerin) 2, 3
• Severe aortic stenosis (marked hypotension may occur following initiation) 3

Monitoring Requirements

Blood Pressure Monitoring

• Measure blood pressure every 3–5 minutes during active titration 2, 4, 3
• For doses >50–100 µg/min or borderline systolic BP (90–110 mmHg), place an arterial line for precise continuous monitoring 2, 4, 3
• Non-invasive blood pressure monitoring is usually adequate at lower doses (<50 µg/min) 3

Cardiac Monitoring

• Continuous cardiac monitoring is mandatory to detect arrhythmias and monitor heart rate response 4
• Watch for reflex tachycardia, which may necessitate beta-blocker addition (if not contraindicated by heart failure or bradycardia) 3

Clinical Assessment

• Continuously assess for symptom relief: resolution of chest pain, dyspnea, or pulmonary congestion 2, 4, 3
• Monitor for adverse effects including headache (common but rarely requires discontinuation) 4

Tolerance and Duration

Tachyphylaxis Development

• Tolerance typically begins after 7–8 hours of continuous infusion 2
• Becomes clinically significant after 24 hours, necessitating dose escalations to maintain efficacy 1, 2, 3
• For infusions extending beyond 24 hours, periodic dose increases may be required 2, 4

Weaning Strategy

• When the patient remains symptom-free for 12–24 hours, begin gradual weaning 2, 4, 3
• Transition to oral or topical nitrate therapy during the wean 2, 4
• Intermittent dosing strategies can help minimize tolerance development 2, 4

Critical Pitfalls to Avoid

Common Errors

• Do not delay IV nitroglycerin while waiting for sublingual doses to act if blood pressure is adequate; transition promptly to IV for reliable dosing 4
• Never use standard PVC tubing—drug absorption can reduce delivered dose by up to 85% at slow infusion rates 2, 5, 6
• Avoid excessive blood pressure reduction (>25% within the first hour), especially in elderly or renally impaired patients, to prevent organ hypoperfusion 2, 4
• Do not use nitroglycerin as monotherapy—it should be part of comprehensive ACS management including antiplatelet therapy, anticoagulation, and consideration for revascularization 1

Special Population Considerations

• Patients with renal dysfunction are at higher risk for hypotension; use slower titration and more frequent monitoring 3
• Elderly patients may not tolerate aggressive blood pressure lowering; maintain systolic BP ≥110 mmHg in previously normotensive individuals 2, 3
• Right ventricular infarction is a critical contraindication—these patients require adequate preload and can experience cardiovascular collapse with nitrates 1, 3

Adjunctive Therapy Considerations

• Morphine (2–4 mg IV) may be used for pain resistant to maximally tolerated anti-ischemic medications, but it may delay oral P2Y12 inhibitor absorption 1
• Fentanyl (25–50 µg IV) is an alternative opioid with similar considerations regarding P2Y12 inhibitor effects 1