Minto and Eleveld Remifentanil Target Controlled Infusion (TCI) Models: a Clinical Comparison

Overview

Remifentanil is commonly used as an opioid during general anesthesia. In recent years, several pharmacokinetic/pharmacodynamic (PK/PD) models for target-controlled infusion (TCI) have been developed, with the Eleveld model being one of the most recent and designed for broad applicability. The aim of this study is to compare the Eleveld TCI model with the routinely used Minto model, in order to evaluate potential differences in the predicted effect-site concentrations (CeR) required to achieve equivalent analgesia levels, as measured by qNOX (CONOX monitor) and the Analgesia Nociception Index (ANI). Post-Tetanic Count (PTC) was also assessed during the maintenance phase to investigate possible differences in nociceptive index responses between the two TCI models.

Remifentanil is a short-acting synthetic opioid frequently used as part of balanced general anesthesia due to its favorable pharmacokinetic profile, which includes rapid onset, short context-sensitive half-time, and predictable elimination. These properties make it ideal for administration via target-controlled infusion (TCI), allowing anesthesiologists to maintain a desired effect-site concentration (Ce) with high precision. Over the past two decades, several pharmacokinetic/pharmacodynamic (PK/PD) models have been developed to guide TCI of remifentanil. Among these, the Minto model has been widely adopted in routine clinical practice. It was originally derived from data collected in healthy volunteers and incorporates covariates such as age, weight, height, and sex. However, its applicability across broader patient populations has been questioned, particularly in individuals outside the demographic or physiological range of the original dataset. More recently, the Eleveld model has been introduced as a general-purpose model for remifentanil TCI. It was developed using a large pooled dataset covering a wide range of patient types, including pediatric, adult, and elderly individuals. This model aims to offer more accurate and consistent predictions of drug concentrations and effects across diverse clinical scenarios. The primary aim of this study is to compare the Eleveld and Minto models with respect to the effect-site concentration (CeR) of remifentanil required to achieve comparable levels of intraoperative analgesia. Analgesia was assessed using two objective nociception monitors: the qNOX index (derived from the CONOX monitor) and the Analgesia Nociception Index (ANI). These indices provide continuous, real-time information on the balance between nociceptive stimulation and the analgesic effect, allowing for a quantitative comparison between the two models. To further explore the analgesic efficacy and responsiveness under each model, investigators introduced controlled nociceptive stimuli during the maintenance phase of anesthesia. Specifically, the Post-Tetanic Count (PTC) stimulation was applied during anesthesia maintenance to serve as a standardized noxious input. The response of the analgesia monitoring indices (qNOX and ANI) to this stimulus was analyzed, enabling the assessment of how each TCI model modulates analgesic depth in the face of a defined nociceptive challenge. By comparing the CeR values, the baseline and post-stimulus nociception indices, and their temporal patterns under the two models, this study aims to determine whether the Eleveld model offers any clinical or pharmacodynamic advantages over the traditional Minto model in guiding remifentanil administration during general anesthesia.