What to do if symptoms persist after 3 doses of nitroglycerin (sublingual nitroglycerin) for acute angina?

Call 9-1-1 Immediately and Transport to Emergency Department

If chest pain persists after 3 doses of sublingual nitroglycerin (one tablet every 5 minutes for 15 minutes total), the patient must call 9-1-1 immediately and be transported to the hospital by ambulance. 1, 2

Immediate Patient Actions

• Stop taking additional nitroglycerin beyond the 3 doses, as further self-medication delays proper medical care and worsens outcomes 3, 2
• Call 9-1-1 immediately rather than having friends or relatives drive the patient to the hospital 1
• Chew aspirin 162-325 mg (non-enteric coated) while awaiting ambulance arrival, unless contraindicated or already taken 1, 3
• Remain seated or lying down to prevent falls from hypotension 2

Rationale for Emergency Transport

The 2013 ACC/AHA guidelines modified the traditional "3 doses before calling" recommendation specifically to encourage earlier EMS activation in patients with suspected acute coronary syndrome (ACS). 1 The updated approach recognizes that:

• Persistent pain after 3 nitroglycerin doses represents a medical emergency requiring immediate professional evaluation 3, 2
• Patients with chest pain lasting >20 minutes require immediate emergency department evaluation regardless of nitroglycerin response 1, 3
• Self-medication with additional nitroglycerin has been documented as a frequent cause of dangerous delay in patients with ACS 1

Emergency Department Management

Once the patient arrives at the ED, the following interventions should occur:

• Obtain 12-lead ECG within 10 minutes to evaluate for STEMI or other ischemic changes 3
• Initiate IV nitroglycerin therapy starting at 10 μg/min and increasing by 10 μg/min every 3-5 minutes until symptom relief, as sublingual nitroglycerin-refractory chest pain often responds to IV administration 3, 4
• Obtain serial cardiac biomarkers to evaluate for myocardial infarction 3
• Continuous cardiac monitoring during nitroglycerin administration 3
• Immediate cardiology consultation as the patient is considered high-risk 3

Critical Contraindications to Additional Nitroglycerin

Before any additional nitroglycerin (IV or otherwise) is administered in the hospital:

• Do not give if systolic blood pressure <90 mmHg or ≥30 mmHg below baseline 3, 2
• Do not give if phosphodiesterase inhibitors (sildenafil, tadalafil, vardenafil) were used within 24-48 hours 3, 5, 2
• **Use caution with bradycardia <50 bpm** or tachycardia >100 bpm in absence of heart failure 3
• Perform right-sided ECG in inferior wall MI to rule out right ventricular infarction before giving nitroglycerin 3

Special Considerations for Chronic Stable Angina

The guidelines make one important distinction: In patients with known chronic stable angina whose symptoms significantly improve after the first nitroglycerin dose, it may be appropriate to complete all 3 doses (one every 5 minutes) before calling 9-1-1 if symptoms resolve completely. 1 However, if symptoms are unimproved or worsening after the first dose, or if the pain is different than typically experienced, call 9-1-1 immediately without waiting for additional doses. 1

Common Pitfalls to Avoid

• Do not delay calling 9-1-1 to take additional nitroglycerin beyond 3 doses 3, 2
• Do not assume the pain is "just angina" if it differs from the patient's typical pattern 1, 2
• Do not have the patient driven by family/friends instead of calling EMS, as ambulance transport allows for earlier treatment and ECG evaluation 1
• Do not administer aspirin if the patient is already on anticoagulation (especially elderly patients ≥65 years), as this substantially increases bleeding risk 6