What is the treatment for chest pain unrelieved by nitroglycerin (glyceryl trinitrate) and morphine, with a normal electrocardiogram (EKG)?

Management of Refractory Chest Pain with Normal ECG

When chest pain persists despite nitroglycerin and morphine but the ECG remains normal, you must obtain serial ECGs, measure cardiac troponins immediately, and maintain high clinical suspicion for acute coronary syndrome (ACS) because a normal initial ECG does not exclude ongoing myocardial ischemia or infarction. 1

Immediate Actions Required

Serial ECG Monitoring

• Repeat ECGs must be performed when symptoms persist or clinical condition deteriorates, even if the initial ECG is normal 1
• Up to 6% of patients with evolving ACS are discharged from the ED with a normal ECG 1
• A normal ECG does not exclude ACS and decision-making should never be based solely on a single normal or nondiagnostic ECG 1
• Obtain repeat ECGs every 15-30 minutes or with any change in symptoms, as electrocardiographic changes may evolve over time 1

Cardiac Biomarker Assessment

• Cardiac troponin (cTn) is the most sensitive test for diagnosing acute myocardial injury and must be measured immediately 1
• Troponin measurement is necessary in conjunction with clinical data (history, examination, ECG) to implement appropriate therapy 1
• Serial troponin measurements should be obtained if initial values are normal but clinical suspicion remains high 1

Consider Posterior and Right Ventricular Involvement

• Obtain supplemental ECG leads V7-V9 to rule out posterior MI, which commonly presents with a normal standard 12-lead ECG 1
• In patients with inferior wall changes or suspicion, record right precordial leads (V3R and V4R) to identify right ventricular infarction 1
• Left circumflex or right coronary artery occlusions may be associated with a normal ECG 1

Reassess Pain Management Strategy

Optimize Nitrate Therapy

• Continue intravenous nitroglycerin for persistent ischemia if not already administered 1
• Ensure nitrates are not contraindicated: systolic BP must be ≥90 mmHg, no recent phosphodiesterase-5 inhibitor use (24 hours for sildenafil/vardenafil, 48 hours for tadalafil) 1
• Important caveat: Relief of chest pain with nitroglycerin does NOT distinguish cardiac from non-cardiac chest pain - research demonstrates that 41% of patients without active coronary disease experience pain relief with nitroglycerin 2, 3

Morphine Considerations

• Intravenous morphine should be titrated carefully for persistent pain, but use with caution 1
• Morphine is associated with increased mortality in unstable angina/NSTEMI in registry data 1
• Consider that morphine may be reasonable for STEMI but evidence is weaker for undifferentiated chest pain 1

Add Beta-Blocker Therapy

• Initiate oral beta-blockers within the first 24 hours if not contraindicated 1
• Beta-blockers are particularly effective for ongoing ischemia with tachycardia and hypertension 1
• Contraindications include heart failure, low-output state, risk for cardiogenic shock, or hemodynamic instability 1
• Avoid intravenous beta-blockers when risk factors for shock are present 1

Rule Out Life-Threatening Alternatives

Critical Differential Diagnoses to Exclude

When chest pain is refractory to standard ACS treatment with a normal ECG, immediately consider:

• Aortic dissection - obtain CT angiography if clinical suspicion exists (tearing/ripping pain, pulse differential, widened mediastinum) 4
• Pulmonary embolism - assess Wells criteria and consider D-dimer or CT pulmonary angiography 4
• Coronary vasospasm - if ST-segment elevation completely normalizes after nitroglycerin with complete symptom relief, early coronary angiography within 24 hours is recommended 1
• Pericarditis - look for positional pain, friction rub, diffuse ST elevation 4

Disposition and Monitoring Strategy

Continuous Cardiac Monitoring

• Initiate continuous ECG monitoring immediately to detect life-threatening arrhythmias 1
• This allows prompt defibrillation if ventricular tachycardia or fibrillation develops 1

Urgent Cardiology Consultation

• Do not delay consultation or transfer for definitive care - consultation delays are associated with increased mortality 4
• If symptoms persist despite maximal medical therapy, consider urgent coronary angiography 1
• Recurrent episodes of chest pain or ST-segment changes require immediate angiography 1

Admission Criteria

• All patients with refractory chest pain despite treatment require hospital admission for observation and serial testing 1
• Even with normal initial ECG and troponins, persistent symptoms mandate continued evaluation 1
• Establish intravenous access for medication administration 1

Common Pitfalls to Avoid

• Never assume pain relief with nitroglycerin confirms cardiac etiology - this is a common misconception not supported by evidence 2, 3
• Never discharge a patient based solely on a single normal ECG when clinical suspicion for ACS remains high 1
• Do not use NSAIDs for pain relief - they should be discontinued immediately as they increase risk of major adverse cardiac events 1
• Recognize atypical presentations - women and elderly patients frequently present with dyspnea, fatigue, or nausea rather than classic chest pain 4
• Avoid immediate-release nifedipine without a beta-blocker - this is contraindicated 1

Additional Pharmacotherapy

Antiplatelet Therapy

• Ensure aspirin 160-325 mg has been administered (chewed, non-enteric) unless contraindicated 1
• Consider adding P2Y12 inhibitor if ACS is confirmed 1

Calcium Channel Blockers

• Non-dihydropyridine calcium channel blockers (diltiazem, verapamil) are reasonable for recurrent ischemia with contraindications to beta-blockers 1
• Ensure no left ventricular dysfunction, cardiogenic shock risk, or high-degree AV block 1