Propofol Target-Controlled Infusion with the Eleveld Model in Opioid-Sparing and Opioid-Free Anaesthesia: A Narrative Review
- 1Department of Anaesthesiology, General Hospital of Athens “G. Gennimatas”, 11527 Athens, Greece
- 2Department of Anaesthesiology and Intensive Care, Aristotle University of Thessaloniki, School of Medicine, AHEPA University Hospital, 54636 Thessaloniki, Greece
- 3First Department of Anaesthesiology, School of Medicine, National and Kapodistrian University of Athens, Aretaieion University Hospital, 11528 Athens, Greece
Abstract
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.
Related
- Age-related differences in extubation time following propofol-based target-controlled infusion in pediatric medium-duration surgery: A prospective cohort study
- Perioperative Cerebral Metabolism in Patients Under General Anaesthesia With Sevoflurane or Propofol: Evaluation of the Arterial and Jugular Bulb Metabolome.
- Severe Propofol Infusion Syndrome Managed With Multimodal Critical Care: A Case Report.
- Comparison of sevoflurane and propofol on the novel oxygenation index and respiratory mechanics in gynecological laparoscopic surgery: a randomized controlled trial
- Shoulder‐Tip Pain After Laparoscopic Surgery: A Narrative Review of Intraperitoneal Anaesthesia
BibTeX
@article{chatzistavridis2026propofol,
title = {{Propofol Target-Controlled Infusion with the Eleveld Model in Opioid-Sparing and Opioid-Free Anaesthesia: A Narrative Review}},
author = {Panagiotis Chatzistavridis and Anna Gkiouliava and Amalia Douma and Kassiani Theodoraki},
journal = {Journal of Clinical Medicine},
year = {2026},
month = oct,
doi = {10.3390/jcm15218300},
url = {https://www.mdpi.com/2077-0383/15/21/8300},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Propofol Target-Controlled Infusion with the Eleveld Model in Opioid-Sparing and Opioid-Free Anaesthesia: A Narrative Review
AU - Panagiotis Chatzistavridis
AU - Anna Gkiouliava
AU - Amalia Douma
AU - Kassiani Theodoraki
PY - 2026
DA - 2026/10/25
JO - Journal of Clinical Medicine
DO - 10.3390/jcm15218300
UR - https://www.mdpi.com/2077-0383/15/21/8300
AB - 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.
SN - 2077-0383
ER -