Propofol Target-Controlled Infusion with the Eleveld Model in Opioid-Sparing and Opioid-Free Anaesthesia: A Narrative Review

Background/Objectives: The Eleveld pharmacokinetic–pharmacodynamic (PK-PD) model is among the most extensively validated general-purpose models for propofol target-controlled infusion (TCI). It includes a binary covariate for concomitant drug administration, commonly labelled as opioid use, which reduces elimination clearance (CL) and the volume of the second peripheral compartment (V3) in an age-dependent manner. This works well for conventional opioid-based anaesthesia but is less clear for multimodal, opioid-sparing regimens built around ketamine, magnesium sulfate, dexmedetomidine and intravenous lidocaine. This review discusses how these four non-opioid adjuvants may interact with Eleveld-based propofol TCI dosing. Methods: We conducted a structured, non-systematic literature search of PubMed/MEDLINE, the Cochrane Library and the MDPI full-text index between May and early August 2026, combining terms for the Eleveld model and propofol TCI with terms for each adjuvant and for pharmacodynamic endpoints (EC50, Ce50, bispectral index, propofol requirement). Studies without a propofol-specific endpoint were excluded from the adjuvant-effect analysis. Results: Dexmedetomidine reduced the propofol concentration required for defined clinical and electroencephalographic endpoints. Magnesium sulfate reduced propofol dose requirements to a lesser extent, although concentration–response data are lacking. Ketamine’s interaction with propofol was additive rather than synergistic, and its effect on the bispectral index was dose-dependent. Lidocaine reduced propofol requirements mainly during surgical stimulation, a context-dependent effect distinct from a fixed hypnotic potency. Conclusions: The Eleveld model remains the best-validated general-purpose tool for propofol TCI, and its concomitant-drug covariate is a pragmatic, data-driven solution to a real gap in its source data. Clinicians should anticipate reduced propofol requirements with dexmedetomidine and, to a lesser extent, magnesium, interpret the processed-EEG response to ketamine cautiously, and expect lidocaine’s sparing effect mainly under stimulation, while titrating to clinical and electroencephalographic endpoints. Dedicated covariates for these agents, informed by prospective validation in opioid-free regimens, represent a logical next step in the model’s development.