Ciprofol versus Propofol for General Anesthesia Induction in Major Orthopedic Surgery: Efficacy and Safety Analyses Pertaining to Anesthetic Parameters

Background: Propofol is the standard agent for anesthesia induction but is frequently associated with injection-site pain and hemodynamic instability. Ciprofol (HSK3486), a novel GABAA receptor agonist, has emerged as a potential alternative. This study aimed to evaluate the efficacy and safety of ciprofol compared to propofol when induction of general anesthesia in patients undergoing major orthopedic surgery. Methods: In this study, 245 patients (ASA I–II) were allocated into ciprofol (CL, n=107) or propofol (PL, n=138) cohorts for major orthopedic surgery. All participants received midazolam (0.03 mg/kg), sufentanil (0.3 μg/kg), and preoxygenation. Induction was initiated with ciprofol (0.4 mg/kg over 30s) or propofol (2 mg/kg). Successful induction required a modified Observer's Assessment of Alertness/Sedation (OAA/S) score ≤1 within one minute. Persistent sedation failure necessitated a secondary dose (0.2 mg/kg of in ciprofol in CL cohort; PL: 1 mg/kg propofol in PL cohort). If failure continued, 0.5 mg/kg propofol served as rescue sedation for both groups. Post-intubation, anesthesia was maintained via sevoflurane in 50% oxygen. Results: Both cohorts achieved high induction success rates. One-minute post-administration, the median OAA/S score was 1 for both groups, though the PL cohort exhibited a higher frequency of deep sedation (OAA/S=0) compared to the CL cohort (p<0.001). The median time to successful induction was comparable between CL (49 seconds) and PL (48 seconds) (p=0.136). However, the CL cohort demonstrated significantly greater hemodynamic stability, with a lower incidence of hypotension (9% vs. 28% in PL, p<0.001). Furthermore, ciprofol significantly reduced injection-site pain, with a median VAS of 4 compared to 5 in the propofol group (p<0.001), and a lower proportion of patients experiencing moderate-to-severe pain (p=0.018). BIS changes also favored the CL cohort (49.89 ± 3.15 vs. 40 ± 3.35, p<0.001). Regarding intubation-related adverse events, the PL cohort experienced significantly higher rates of hypotension (28%) compared to the CL cohort (9%; p<0.001). Conclusions: Ciprofol is a highly effective alternative to propofol for anesthesia induction in major orthopedic surgery. It provides rapid onset and successful sedation while offering superior clinical advantages, specifically reduced injection-site pain and enhanced hemodynamic stability during the critical induction and intubation phases.