# Real-world use of theophylline in critically ill patients with sinus pauses: a case series

## TL;DR

This case series explores the use of theophylline as a non-invasive treatment for sinus pauses in two critically ill patients who could not receive a pacemaker due to active infections.

## Contribution

The paper presents theophylline as a potential alternative to pacemaker implantation in patients with contraindications.

## Key findings

- Theophylline resolved sinus pauses in two patients within 24 hours.
- Theophylline was safely used in patients with active infections who were poor candidates for device placement.
- Theophylline's mechanisms include enhancing sinus node automaticity and reducing pause duration.

## Abstract

A sinus pause is is defined as a delay in sinus node depolarization exceeding 3 s following atrial depolarization. In patients with pauses greater than 5 s accompanied by hemodynamic compromise, the primary treatment is permanent pacemaker (PPM) implantation. However, in the presence of an active infection, alternative strategies such as temporary transvenous pacing or pharmacologic agents may be more appropriate. This report highlights the use of theophylline as a non-invasive therapeutic option in two patients with asymptomatic sinus pauses who had contraindications to PPM placement.

Patient A was a 74-year-old woman with a history of pulmonary arterial hypertension treated with subcutaneous treprostinil and a recent episode of catheter-associated Staphylococcus aureus bacteremia, for which she was receiving chronic suppressive doxycycline. She was admitted for acute decompensated heart failure. Patient B was a 24-year-old man with a history of cerebral palsy and chronic respiratory failure who was admitted for bacterial pneumonia. While in the intensive care unit, both patients experienced recurrent, asymptomatic sinus pauses lasting up to 8.6 s.

Given their active infections, both patients were deemed poor candidates for device placement and were therefore initiated on theophylline. Within 24 h of initiation, the sinus pauses resolved in both patients. Theophylline doses were adjusted to maintain a therapeutic concentration between 10 and 20 µg/mL. Later during hospitalization, Patient A developed atrial fibrillation with rapid ventricular response, prompting discontinuation of theophylline. Patient B was discharged on theophylline 50 mg twice daily, along with a 30-day event monitor and cardiology follow-up. Theophylline exerts its positive chronotropic effects primarily through non-selective phosphodiesterase inhibition and adenosine-1 receptor antagonism. These mechanisms enhance automaticity and reduce atrioventricular node refractoriness, augmenting sinus node automaticity and reducing the frequency and duration of sinus pauses.

While these cases highlight the potential role of theophylline as a temporizing pacing strategy, additional research is needed to determine whether and how theophylline can be safely incorporated into treatment protocols for patients who are not suitable for device-based pacing.