Propofol mono vs. Propofol + Midazolam – a prospective evaluation of safety and subjective well-being in 24.441 patients

Aims of the study: In this prospective multicenter trial of 24.441 patients we evaluated the occurrence of adverse events and patients subjective condition regarding the sedation regimen of Propofol mono (P) or a combination of Propofol and Midazolam (P+M).

Methods: In this prospective multicenter trial, 24.441 patients received endoscopic sedation with either P or P+M. 15.690 patients stated their subjective condition in a questionnaire 24 hours after the endoscopic procedure.

Results: We observed 4 major adverse events (3 mask ventilations and 1 laryngospasm) in this study that occurred during 2 P and 2 P+M sedations. 117 minor adverse events were recorded during the study. Minor adverse events occurred significantly more often in patients sedated with P (n = 74) compared to P+M (n = 38; p < 0.0001). Minor adverse events occurred more often (p < 0.008) in patients receiving colonoscopy and sedation with P (44.6%) compared to P+M (17.0%), while the effect of the sedative was less pronounced for patients during EGD (P: 8.0%, P+M: 6.3%) and for patients during double examination (P: 13.4%, P+M: 10.7%). The most prevalent minor adverse event was hypoxemia. Logistic regression analysis showed that receiving P as a sedative was associated with a higher probability of hypoxemia (68.8%) compared to receiving P+M (31.2%, p < 0.0001). Correlation analyses further showed a significant association for the occurrence of hypoxemia and the total dosage of propofol administered (r = 0.043, p < 0.001).

24 hrs after the endoscopic procedure, patients sedated with P felt significantly better than patients having received P+M (p < 0.02). Yet, when comparing dizziness, nausea and vomiting 24 hours after the endoscopic procedure to the day of the examination (worse, same, better) patients with P sedation reported a smaller improve in symptoms than patients with P+M (p < 0.001). Additionally, patients sedated with P reported higher levels of pain sensation than patients with P+M (p < 0.01) 24 hrs after the examination.

Discussion: We observed more adverse events when patients were sedated with P compared to P+M. Adverse events increased in a dose-dependent manner for P but not M.