Exploration of the Optimal Dose Combination of Ciprofol and Oxycodone in Painless Oocyte Retrieval: A Randomized Controlled Trial Research

Technical Summary: Optimal Dose Combination of Ciprofol and Oxycodone in Painless Oocyte Retrieval

Problem Statement
Painless oocyte retrieval is a critical component of in vitro fertilization and embryo transfer (IVF-ET). While the current clinical standard often involves propofol combined with remifentanil, this regimen presents significant drawbacks, including injection pain, respiratory depression, bucking, and postoperative nausea and vomiting (PONV). Although ciprofol (a novel GABAA receptor agonist) offers a safer profile regarding respiratory depression and injection pain compared to propofol, and oxycodone provides stable analgesia with fewer adverse reactions than remifentanil, the optimal dosage combination of these two agents for painless oocyte retrieval remains undefined. There is an urgent need to optimize the dosage of ciprofol combined with oxycodone to balance sedation, analgesia, and safety.

Methodology
This study was a single-center, prospective, randomized controlled trial conducted at the First Affiliated Hospital of Hebei North University.

• Participants: 300 ASA physical status I/II women (aged 20–45, BMI 18.5–28.0 kg/m²) scheduled for elective painless oocyte retrieval.
• Study Design: A two-factor randomized design created 15 subgroups based on varying doses of oxycodone and ciprofol:
  • Oxycodone Doses: O₁ (0.05 mg/kg), O₂ (0.075 mg/kg), O₃ (0.10 mg/kg).
  • Ciprofol Induction Doses: C₁ (0.3 mg/kg) through C₅ (0.5 mg/kg).
• Protocol: Oxycodone was administered intravenously 5 minutes prior to induction to align peak plasma concentration with the start of the procedure. Ciprofol was induced over 30–50 seconds. Anesthesia was maintained with ciprofol at 1.0 mg/kg/h.
• Data Collection: Hemodynamic parameters (HR, MAP), recovery metrics (additional drug dosage, recovery time to Aldrete score ≥9), and adverse reactions (body movement, hypoxemia, PONV) were recorded at specific time points (T0–T5). Postoperative pain was assessed using Visual Analogue Scale (VAS) scores.
• Analysis: Statistical analysis was performed using SPSS 23.0, with P < 0.05 considered significant.

Key Results

• Hemodynamic Stability: Groups O₂C₂, O₂C₃, O₂C₄, and O₃C₁ demonstrated significantly smaller fluctuations in heart rate and mean arterial pressure compared to the O₃C₄ and O₃C₅ groups (P < 0.05). The O₃C₄ and O₃C₅ groups (higher doses of both drugs) showed greater instability, likely due to excessive central sympathetic inhibition.
• Recovery and Drug Consumption: The O₂C₂, O₂C₃, O₂C₄, O₂C₅, and O₃C₁ groups required significantly less additional ciprofol and had shorter recovery times compared to reference groups with higher drug consumption (P < 0.05).
• Adverse Reactions: The O₂C₃ group exhibited the lowest total incidence of adverse reactions (15%). However, statistical analysis indicated no significant difference in safety between the O₂C₂, O₂C₄, and O₁C₄ groups compared to the O₂C₃ reference group (P > 0.05).
• Analgesia: All groups achieved satisfactory analgesic effects with low postoperative VAS scores, showing no significant inter-group differences (P > 0.05).
• Optimal Combination: The study identified that the combination of oxycodone 0.075 mg/kg and ciprofol 0.35 mg/kg (Group O₂C₂) achieved the best balance. While O₂C₃ had the lowest raw adverse event rate, O₂C₂ utilized a lower dose of ciprofol (0.35 mg/kg vs. 0.4 mg/kg in O₂C₃) while maintaining equivalent efficacy and safety.

Key Contributions

1. Dose Optimization: The study provides specific evidence-based dosing recommendations for the novel combination of ciprofol and oxycodone in the context of painless oocyte retrieval.
2. Safety Profile: It demonstrates that this combination can minimize common adverse events associated with traditional propofol-remifentanil regimens, particularly respiratory depression and PONV.
3. Hemodynamic Management: The research highlights that moderate doses of oxycodone (0.075 mg/kg) combined with moderate ciprofol doses (0.35–0.45 mg/kg) provide superior hemodynamic stability by balancing visceral pain blockade against excessive sedation-induced vasodilation.
4. Recovery Efficiency: The findings support the "rapid recovery" goal of outpatient surgery, showing that adequate analgesia with oxycodone reduces the need for additional ciprofol, thereby shortening recovery time.

Significance and Claims
The authors conclude that the combination of oxycodone 0.075 mg/kg and ciprofol 0.35 mg/kg represents the optimal clinical anesthesia scheme for painless oocyte retrieval. This regimen is claimed to offer:

• Good anesthetic and analgesic effects.
• Stable intraoperative hemodynamics.
• Low incidence of body movement and hypoxemia.
• Rapid recovery and the lowest incidence of total adverse reactions.
• A superior balance between sedation, analgesia, and safety compared to other tested combinations.

The paper positions these findings as a data-driven reference for optimizing clinical anesthesia programs. However, the authors modestly acknowledge limitations, including the single-center nature of the study, the lack of individualized dosing based on factors like age or follicle count, and the absence of long-term follow-up regarding embryonic development or pregnancy outcomes. They state that large-scale, multi-center studies are necessary to further verify long-term safety and applicability.