Pharmacovigilance and toxicological studies on safety signals associated with the combined use of propofol and midazolam.

BACKGROUND

Propofol and midazolam are widely used in sedation and general anesthesia, but there has been a lack of systematic research on safety signals caused by the combination medication.

METHODS

We collected data on drug safety signals related to propofol and midazolam from the FAERS database (2004Q1-2025Q1). Disproportionality analysis, Time-to-event, and Weibull distribution are performed for signal monitoring and risk assessment. We further analyze the potential mechanism of allergic reactions caused by the combination medication.

RESULTS

A strong signal for Propofol Infusion Syndrome (PRIS) was detected with propofol alone (ROR: 4514.44, 95% CI: 3851.09–5292.06), whereas no risk reduction was observed with combination medication (ROR: 2219.2, 95% CI: 1753.85–2808.03). Anaphylactic Shock (ROR: 39.45, 95% CI: 30.49–51.04) had high signal values. Time-to-event onset analysis in the combination therapy group showed that the most common onset time for safety signals was 3–7 days (46.3%). The Scale Parameter α was the smallest in the combination medication group (6.37, 95% CI: 5.48–7.26). Further research is needed to determine whether the PI3K-Akt signaling pathway represents a potential mechanism underlying anaphylactic reactions induced by the combination medication.

CONCLUSIONS

Early monitoring should be performed when propofol and midazolam are used in combination. At the same time, the occurrence of anaphylactic reactions should be taken seriously when combining medications.