Propofol monotherapy versus propofol combined with midazolam for deep sedation during complex electrophysiological procedures

Background Complex electrophysiological procedures (CEP) require deep sedation to ensure patient immobility, precision, and optimal working conditions. While sedation has traditionally involved midazolam combined with propofol, propofol monotherapy is increasingly favored owing to its favorable pharmacokinetics. This study compared sedation characteristics, hemodynamic effects, and safety outcomes between propofol alone and a propofol–midazolam regimen in CEP. Methods This prospective observational study was conducted between September 2019 and May 2025. Patients undergoing CEP (3D mapping, cryoballoon ablation, or pulsed-field ablation [PFA]) requiring deep sedation were included. Participants received either propofol alone (Group P) or propofol with an induction bolus of midazolam (Group PM). Propofol was administered via target-controlled infusion; midazolam was given only during induction. Continuous monitoring comprised arterial blood pressure (ABP), heart rate (HR), and oxygen saturation (SpO2), and serial arterial blood gases. Total propofol dose, procedure duration, and sedation-related adverse events were recorded at 30-minute intervals. Results A total of 449 patients were included (median age 69 [61–76] years; 57.2% male). Procedural distribution comprised 3D electroanatomical mapping (52.8%), cryoballoon ablation (33.6%), and PFA (13.6%). Reduced left ventricular ejection fraction was present in 44.7% of patients. Baseline demographic and clinical characteristics were comparable between groups. Total propofol consumption was significantly higher in the monotherapy group (630 [480–780] mg) compared with the combination group (550 [350–800] mg; p = 0.014). At 30 minutes, Group PM demonstrated a more pronounced reduction in HR (72 vs. 77 bpm; p = 0.026), accompanied by a transient decrease in arterial pH (7.31 vs. 7.34; p < 0.001) and an elevated arterial CO2 partial pressure (46.7 vs. 44.1 mmHg; p = 0.03). No significant differences in arterial blood pressure were observed at this time point. After one and two hours, systolic and mean ABP were significantly lower in Group P (1 h p < 0.001; 2 h p < 0.05). Oxygen saturation was also reduced in the monotherapy group at one hour (p = 0.029) and showed a similar trend at two hours (p = 0.070). Beyond the early procedural phase, HR and arterial blood gas parameters did not differ meaningfully between groups. Conclusion The early phase of sedation with a propofol–midazolam combination was associated with transient respiratory suppression and a short-lived decline in HR. In contrast, during prolonged procedural phases, propofol monotherapy led to lower ABP and SpO2, likely reflecting cumulative propofol exposure. These observations emphasize the need for individualized sedation strategies tailored to procedural duration and patient-specific factors. Additional research is warranted to further substantiate these findings.