Determination of the EC90 of remifentanil for blocking the adrenergic responses to intubation when administered with propofol: an up-down sequential allocation study protocol using the k-in-a-row design versus biased-coin design

Background Endotracheal intubation(EI), as a noxious stimulus, can cause significant adrenergic responses. Remifentanil and propofol have excellent controllable pharmacokinetic characteristics and are commonly used in anesthesia induction. It is vital to assess how drug effects change with increasing doses using dose-response characterisation in anesthesia induction. It has a great clinical significance for optimizing medication strategies to reduce cardiovascular response during EI that determine effect-site concentration (Ce) of remifentanil to block adrenergic responses (BAR) to EI in 90% participants (EC ₉₀ BAR _EI ) and establish a dose-response curve. However, the EC ₉₀ BAR _EI of remifentanil using the k-in-a-row design (KRD) versus biased-coin design (BCD) up-and-down methods (UDM) when administered with propofol has not been established. The present study was designed to determine and evaluate the EC ₉₀ BAR _EI of remifentanil using BCD versus KRD undergoing propofol anesthesia induction. Methods This is a prospective, randomized sequential allocation dose-finding trial to determine and evaluate the EC ₉₀ of remifentanil required to BAR to EI using the KRD versus BCD UDMs when administered with propofol. We will recruit patients who are Implemented elective surgery for EI under general anesthesia, and randomly allocate them in a 1:1 ratio to the KRD versus BCD groups in advance. The Ce for the follow-up participants increased, decreased or remain same according to the 'negative' or 'positive' response of the previous participant, based on the dose-transition rules of the KRD versus BCD sequential UDMs. Positive response was defined as success. The primary outcomes are the rate of success and Ce of remifentanil blocking adrenergic responses to EI when administered with propofol using KRD versus BCD UDMs in 90% participants. Secondary outcomes include changes of hemodynamic indicators, sedation levels, and safety during anesthesia induction and EI. We plan to enroll 120 participants undergoing elective surgery for EI under general anesthesia and receive one of the KRD versus BCD UDMs. The EC90 and 90% confidence intervals(90%CIs) were estimated using R-Foundation centered isotonic regression (CIR) and the pooled adjacent violators algorithm(PAVA) with bootstrapp. Discussion This is the first prospective, randomized adaptive dose-finding trial to quantify and assess the EC ₉₀ BAR _EI of remifentanil using KRD versus BCD UDMs undergoing propofol anesthesia induction. The results of this study contribute to optimizing the target controlled infusion(TCI) strategy of remifentanil during EI, and analyzing the efficacy of two rule-based designs for high percentile dose-finding in anesthesiology research as the basis for rational drug administration schemes. Trial registration: Chinese Clinical Trial Registry, ChiCTR2300078275.Registered on 3rd December 2023.