We read with great interest the study by Zhou et al. evaluating ciprofol versus propofol for sedation during gastrointestinal endoscopy in overweight patients 1. The large multicenter design and standardized monitoring framework provide valuable comparative data for contemporary endoscopic anesthesia. Nevertheless, several interpretive aspects merit closer consideration. The primary endpoint combined hypoxia and severe hypoxia despite their differing clinical consequences. Although the reduction in severe hypoxia reached statistical significance, we described it as modest because the absolute risk difference was 3.27%, corresponding to an approximate number needed to treat of 31. This magnitude remains clinically relevant, but it is more appropriately interpreted as a moderate absolute gain rather than a large effect. Composite outcomes can complicate clinical interpretation when component events differ in severity, frequency, and practical relevance to periendoscopic risk 2. In this trial, the between-group difference was more clearly driven by severe hypoxia than by hypoxia overall, suggesting that component-specific reporting may be more informative than the composite alone. Interpretation of respiratory safety is also shaped by exposure patterns. Sedation dosing was based on total body weight, yet the propofol group required more frequent supplemental boluses and greater cumulative top-up dosing, indicating materially different intraprocedural drug exposure. This raises the possibility that part of the observed hypoxia gradient reflects differential dose escalation rather than pharmacologic superiority alone. Exposure-adjusted analyses would therefore strengthen causal attribution 3. The uniform pre-induction administration of sufentanil introduces an additional pharmacodynamic layer. Opioid coadministration may potentiate respiratory depression and interact differently across sedative regimens 4. Taken together, these findings support ciprofol as a promising sedation strategy, but the mechanistic basis of its apparent respiratory advantage remains incompletely resolved. Separating composite endpoint components and accounting for differential cumulative exposure would help determine how much of the observed benefit is drug-specific and how much is protocol-dependent. Neeraj Singh: conceptualization, methodology, validation, supervision, project administration, writing – original draft, writing – review and editing. Monika Srivastav: writing – original draft, writing – review and editing. The authors have nothing to report. The authors declare no conflicts of interest. The authors have nothing to report.
Singh et al. (2026) studied this question.