The ED95 of Ciprofol for Laryngeal Mask Airway Insertion With Fentanyl in Children: A Biased-Coin Dose-Finding Trial

This is a prospective, single-blind (participant and outcomes assessor-blinded), biased-coin design up-and-down sequential allocation trial. A total of 180 pediatric patients (ASA I-II) scheduled for elective surgery requiring LMA insertion will be enrolled and divided into three age groups: toddlers (1-3 years), preschoolers (4-6 years), and school-age children (7-12 years), with 60 patients per group.

All patients will receive a fixed dose of fentanyl (1 μg/kg) and a predetermined bolus dose of ciprofol, administered intravenously over 1 minute. The initial ciprofol dose is set at 0.35 mg/kg, with a dose step size of 0.1 mg/kg. The dose for each subsequent patient is determined by the biased-coin design: if the previous patient achieves successful LMA insertion (no movement), the next patient receives the same dose with a probability of 0.947 or a 0.1 mg/kg lower dose with a probability of 0.053. If the previous patient fails (movement occurs), the next patient receives a 0.1 mg/kg higher dose.

The study employs a single-blind design: the anesthesiologist who administers the study drug is aware of the ciprofol dose, whereas the anesthesiologist who performs the LMA insertion and the observer who evaluates the patient's response are both blinded to the dose assignment. LMA insertion will be attempted 90 seconds after drug administration. Successful insertion is defined as the absence of jaw tightness, gross purposeful movement, coughing, gagging, or laryngospasm during LMA insertion and cuff inflation. The primary outcome is the ED95 of ciprofol for successful LMA insertion in each age group, estimated using isotonic regression with bootstrap resampling.

• Ciprofol (Drug): All patients will receive a fixed dose of fentanyl (1 μg/kg) and a predetermined bolus dose of ciprofol, administered intravenously over 1 minute. The initial ciprofol dose is set at 0.35 mg/kg, with a dose step size of 0.1 mg/kg. The dose for each subsequent patient is determined by the biased-coin design: if the previous patient achieves successful LMA insertion (no movement), the next patient receives the same dose with a probability of 0.947 or a 0.1 mg/kg lower dose with a probability of 0.053. If the previous patient fails (movement occurs), the next patient receives a 0.1 mg/kg higher dose.
• Fentanyl (Drug): All patients will receive a fixed dose of fentanyl (1 μg/kg) and a predetermined bolus dose of ciprofol

Primary outcomes

• ED95 of ciprofol for LMA insertion in children [At LMA insertion, 90 seconds after drug injection]: The ED95 of ciprofol (combined with fentanyl 1 μg/kg) for successful LMA insertion, defined as absence of movement, coughing, gagging, or laryngospasm during insertion and cuff inflation.

Secondary outcomes

• Incidence of adverse events within 5 minutes [Within 5 minutes after drug injection]
• mean arterial pressure (MAP) [from before induction to 1 minute afte LMA insertion]: blood pressure were documented at the following time points: T1 (before induction), T2 (at LMA insertion), and T3 (1 minute after LMA insertion)
• heart rate [from before induction to 1 minute afte LMA insertion]: T1 (before induction), T2 (at LMA insertion), and T3 (1 minute after LMA insertion)
• Bispectral Index (BIS) [From before induction to 1 minute afte LMA insertion]: BIS values were documented at the following time points: T1 (before induction), T2 (at LMA insertion), and T3 (1 minute after LMA insertion)
• Pediatric Anesthesia Emergence Delirium (PAED) scale score [Within 15-30 minutes in PACU]

Sex: All, ages: 1 Year to 12 Years

Inclusion Criteria:

* American Society of Anesthesiologists (ASA) physical status I or II
* Aged 1 to 12 years
* Scheduled for elective surgery requiring general anesthesia with laryngeal mask airway (LMA) insertion (e.g., ophthalmic surgery, skin lesion excision, minor abdominal or urological procedures, with expected surgical duration ≤ 2 hours)
* Written informed consent obtained from parents or legal guardians

Exclusion Criteria:

* Known allergy or hypersensitivity to ciprofol, fentanyl, or any study-related drugs
* Intellectual disability, cognitive-affective disorders, psychiatric or neurological diseases
* Inability to cooperate with peripheral intravenous cannulation
* History of reactive airway disease or suspected difficult airway
* Body mass index (BMI) ≥ 30 kg/m² or ≤ 15 kg/m²
* History of sedative medication use
* Inability to understand the study protocol or participation in another clinical trial within the past 30 days