This study presents a systematic review conducted according to the PRISMA 2020 guidelines, evaluating pharmacokinetic-pharmacodynamic (PK-PD) models for target-controlled infusion (TCI) of propofol. A structured search was performed across PubMed, Summon, Google Scholar, Web of Science, and Scopus, identifying 427 sources, of which 17 met the inclusion criteria. The analysis revealed that nine studies compared existing models, six focused on the development of new PK-PD models, and two explored broader implications of TCI in anesthesia. Comparative studies indicate that while the Eleveld model generally offers superior predictive accuracy, it does not consistently outperform the Marsh and Schnider models across all populations. The Schnider model demonstrated better bias control in elderly patients, while the Eleveld model improved drug clearance estimation in obese patients. However, inconsistencies remain in predicting brain concentrations of propofol. Newly proposed models introduce adaptive dosing strategies, incorporating allometric scaling, lean body weight, and machine learning techniques, yet require further external validation. The results highlight ongoing challenges in achieving universal applicability of TCI models, underscoring the need for future research in refining precision dosing and personalized anesthesia management.

Department of Anesthesiology and Intensive Care General University Hospital U Nemocnice 499 2 Prague CZ 128 08 Czech Republic

Department of Biomedical Technology Faculty of Biomedical Engineering Czech Technical University Prague nám Sítná 3105 Kladno CZ 272 01 Czech Republic

Zobrazit více v PubMed

Barrowman J, Wilson M. Total intravenous anaesthesia. Anaesth Intensive Care Med 2022;23:54–9. 10.1016/j.mpaic.2021.09.003.

Vandemoortele O, Hannivoort LN, Vanhoorebeeck F, Struys MMRF, Vereecke HEM. General Purpose Pharmacokinetic-Pharmacodynamic Models for Target-Controlled Infusion of Anaesthetic Drugs: A Narrative Review. J Clin Med 2022;11:2487. 10.3390/jcm11092487. PubMed PMC

Bidkar PU, Dey A, Chatterjee P, Ramadurai R, Joy JJ. Target-controlled infusion – Past, present, and future. J Anaesthesiol Clin Pharmacol n.d.:10.4103/joacp.joacp_64_23. https://doi.org/10.4103/joacp.joacp_64_23. PubMed PMC

Nimmo AF, Absalom AR, Bagshaw O, Biswas A, Cook TM, Costello A, et al. Guidelines for the safe practice of total intravenous anaesthesia (TIVA): Joint Guidelines from the Association of Anaesthetists and the Society for Intravenous Anaesthesia. Anaesthesia 2019;74:211–24. 10.1111/anae.14428. PubMed

Samuda, Waterson. TCI Anesthesia: New and More Universal Models. Hosp Mag 2022. https://hospitalsmagazine.com/tci-anesthesia-new-and-more-universal-models/ (accessed May 2, 2024).

Braathen MR, Rigby-Jones AE, Ræder J, Spigset O, Heier T. Pharmacokinetics of propofol in severely obese surgical patients. Acta Anaesthesiol Scand 2024;68:726–36. 10.1111/aas.14407. PubMed

Linassi F, Zanatta P, Spano L, Burelli P, Farnia A, Carron M. Schnider and Eleveld Models for Propofol Target-Controlled Infusion Anesthesia: A Clinical Comparison. Life 2023;13:2065. 10.3390/life13102065. PubMed PMC

PRISMA 2020 flow diagram. PRISMA Statement n.d. https://www.prisma-statement.org/prisma-2020-flow-diagram (accessed April 17, 2025).

Hüppe T, Maurer F, Sessler DI, Volk T, Kreuer S. Retrospective comparison of Eleveld, Marsh, and Schnider propofol pharmacokinetic models in 50 patients. Br J Anaesth 2020;124:e22–4. 10.1016/j.bja.2019.10.019. PubMed

Hosseinirad S, van Heusden K, Dumont GA. Evaluating inter-individual variability captured by the Eleveld pharmacokinetics model. J Clin Monit Comput 2024;38:505–18. 10.1007/s10877-023-01083-5. PubMed

Vellinga R, Hannivoort LN, Introna M, Touw DJ, Absalom AR, Eleveld DJ, et al. Prospective clinical validation of the Eleveld propofol pharmacokinetic-pharmacodynamic model in general anaesthesia. Br J Anaesth 2021;126:386–94. 10.1016/j.bja.2020.10.027. PubMed

Kim TK. Obesity and anesthetic pharmacology: simulation of target-controlled infusion models of propofol and remifentanil. Korean J Anesthesiol 2021;74:478–87. 10.4097/kja.21345. PubMed PMC

Schnider TW, Minto CF, Egan TD, Filipovic M. Relationship Between Propofol Target Concentrations, Bispectral Index, and Patient Covariates During Anesthesia. Anesth Analg 2021;132:735. 10.1213/ANE.0000000000005125. PubMed

Van Hese L, Theys T, Absalom AR, Rex S, Cuypers E. Comparison of predicted and real propofol and remifentanil concentrations in plasma and brain tissue during target-controlled infusion: a prospective observational study. Anaesthesia 2020;75:1626–34. 10.1111/anae.15125. PubMed

Wu Z, Gong J, He X, Wu Z, Shen J, Shang J. Body mass index and pharmacodynamics of target-controlled infusion of propofol: A prospective non-randomized controlled study. J Clin Pharm Ther 2022;47:662–7. 10.1111/jcpt.13594. PubMed

Coetzee JF, Links A, Levin AI. Assessment of the clinical validity of an adjusted Marsh pharmacokinetic model using an effect-site rate constant (ke0) of 1.21 min-1. South Afr J Anaesth Analg 2021;27:83–91. 10.36303/SAJAA.2021.27.2.2583.

Araújo AM, Machado H, De Pinho PG, Soares-da‐Silva P, Falcão A. Population Pharmacokinetic‐Pharmacodynamic Modeling for Propofol Anesthesia Guided by the Bispectral Index (BIS). J Clin Pharmacol 2020;60:617–28. 10.1002/jcph.1560. PubMed

Zhong G, Xu X. General purpose propofol target-controlled infusion using the marsh model with adjusted weight input. J Anesth 2024;38:275–8. 10.1007/s00540-024-03312-w. PubMed

Kawata M, Yonezawa A, Mineharu Y, Itohara K, Mizota T, Matsui Y, et al. Development of extended pharmacokinetic models for propofol based on measured blood and brain concentrations. Sci Rep 2024;14:6326. 10.1038/s41598-024-56863-z. PubMed PMC

Kim KM, Choi B-M, Noh G-J. Population pharmacokinetic and pharmacodynamic model of propofol externally validated in Korean elderly subjects. J Pharmacokinet Pharmacodyn 2023;50:97–109. 10.1007/s10928-022-09836-6. PubMed

Paolino N, Schiavo M, Latronico N, Paltenghi M, Visioli A. PK/PD model based design of PID control for closed-loop anesthesia. IFAC J Syst Control 2024;27:100247. 10.1016/j.ifacsc.2024.100247.

Vellinga R, Eleveld DJ, Struys MMRF, van den Berg JP. General purpose models for intravenous anesthetics, the next generation for target-controlled infusion and total intravenous anesthesia? Curr Opin Anaesthesiol 2023;36:602–7. 10.1097/ACO.0000000000001300. PubMed

Schnider TW, Nieuwenhuijs-Moeke GJ, Beck-Schimmer B, Hemmerling TM. Pro-Con Debate: Should All General Anesthesia Be Done Using Target-Controlled Propofol Infusion Guided by Objective Monitoring of Depth of Anesthesia? Anesth Analg 2023;137:565–75. 10.1213/ANE.0000000000006293. PubMed

Gepts E, Camu F, Cockshott ID, Douglas EJ. Disposition of propofol administered as constant rate intravenous infusions in humans. Anesth Analg 1987;66:1256–63. PubMed

Marsh B, White M, Morton N, Kenny GNC. PharmacokineticC Model Driven Infusion Of Propofol In Children. Br J Anaesth 1991;67:41–8. 10.1093/bja/67.1.41. PubMed

Eleveld DJ, Colin P, Absalom AR, Struys MMRF. Pharmacokinetic–pharmacodynamic model for propofol for broad application in anaesthesia and sedation. Br J Anaesth 2018;120:942–59. 10.1016/j.bja.2018.01.018. PubMed

Short TG, Campbell D, Egan TD. Increasing the utility of target-controlled infusions: one model to rule them all. Br J Anaesth 2018;120:887–90. 10.1016/j.bja.2018.02.012. PubMed

Absalom AR, Mani V, De Smet T, Struys MMRF. Pharmacokinetic models for propofol—defining and illuminating the devil in the detail. Br J Anaesth 2009;103:26–37. 10.1093/bja/aep143. PubMed

Engbers FHM, Dahan A. Anomalies in target-controlled infusion: an analysis after 20 years of clinical use. Anaesthesia 2018;73:619–30. 10.1111/anae.14212. PubMed