What workup is indicated for a 32‑year‑old woman experiencing palpitations while taking acetaminophen‑codeine (Tylenol with codeine), an unspecified dual medication, and intranasal fluticasone (Flonase)?

Workup for Palpitations in a 32-Year-Old Woman on Tylenol with Codeine and Flonase

Begin with a 12-lead ECG and 48-hour ambulatory (Holter) monitoring to identify the underlying rhythm disturbance, as these are the essential first-line diagnostic tests for any patient presenting with palpitations. 1, 2

Initial Diagnostic Testing

Mandatory First-Line Tests

• 12-lead ECG is required immediately to assess for baseline conduction abnormalities, QT interval prolongation, pre-excitation patterns, or structural heart disease markers 1, 2
• 48-hour ambulatory ECG monitoring is recommended for patients with frequent or sustained palpitations to capture the arrhythmia and correlate symptoms with rhythm 1, 2
• Resting echocardiography should be performed to exclude structural heart disease, particularly in patients with concerning history or physical examination findings 1

Key Historical Elements to Elicit

• Timing and triggers: Determine if palpitations occur at rest, during exertion, or at work, as work-related palpitations increase the likelihood of cardiac etiology 2
• Sleep disturbance: Ask specifically if palpitations affect sleep, which suggests higher risk of cardiac cause 2
• Medication timing: Establish temporal relationship between medication use (particularly codeine) and symptom onset 3
• Family history: Screen for sudden cardiac death, cardiomyopathy, or inherited arrhythmia syndromes 2

Medication-Specific Considerations

Codeine as Potential Culprit

• Codeine can cause palpitations through multiple mechanisms, including histamine release and sympathetic activation 3
• Consider discontinuing the acetaminophen-codeine combination temporarily to assess if symptoms resolve 3
• Acetaminophen alone does not cause arrhythmias and can be continued at appropriate doses (maximum 4000 mg/day) if pain control is needed 4

Flonase (Fluticasone) Assessment

• Intranasal fluticasone does not cause cardiac arrhythmias at recommended doses and has negligible systemic bioavailability 5, 6
• Flonase can be safely continued during the workup 5, 6

Risk Stratification for Further Testing

High-Risk Features Requiring Expanded Workup

If any of the following are present, proceed with additional testing:

• Exercise stress testing is indicated if the patient reports exertional palpitations or has risk factors for coronary artery disease 1, 2
• Echocardiography with Doppler should assess for structural abnormalities, valvular disease, or cardiomyopathy if physical examination reveals murmurs, elevated jugular venous pressure, or edema 1, 2
• Electrophysiology study may be considered if non-invasive testing suggests accessory pathway, pre-excitation, or recurrent supraventricular tachycardia 1

Low-Risk Features Allowing Conservative Approach

• If 48-hour monitoring captures benign ectopy (isolated PVCs or PACs) without sustained arrhythmia, and structural heart disease is excluded, reassurance and medication review may be sufficient 2
• Implantable loop recorder should be considered only if symptoms are recurrent and unexplained after initial workup, and the patient is at low risk for sudden cardiac death 1

Common Pitfalls to Avoid

• Do not assume all palpitations are benign in young women; cardiac causes must be systematically excluded 2
• Do not overlook drug-drug interactions: While codeine itself can cause palpitations, verify the patient is not taking other QT-prolonging medications or substances 3
• Do not order an implantable loop recorder as first-line testing; 48-hour Holter monitoring is more appropriate initially and often diagnostic 1
• Do not attribute symptoms to anxiety without completing objective cardiac evaluation, as psychiatric causes are diagnoses of exclusion 2

Immediate Management Steps

1. Obtain 12-lead ECG today to measure QT interval and assess for structural abnormalities 1, 2
2. Order 48-hour ambulatory monitoring to capture symptomatic episodes 1
3. Discontinue codeine and switch to acetaminophen alone (up to 1000 mg every 6 hours, maximum 4000 mg/day) 4, 3
4. Continue Flonase as it does not contribute to arrhythmia risk 5, 6
5. Reassess in 1-2 weeks after monitoring results return and codeine has been discontinued 2, 3