The future of target-controlled infusion and new pharmacokinetic models

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Purpose of reviewTo summarize recent developments in the understanding of the pharmacology of the hypnotic and opioid drugs, with relevance to target-controlled infusions and newer pharmacokinetic models.Recent findingsGeneral-purpose models have been developed for propofol, remifentanil, and dexmedetomidine, suitable for use in a wide variety of patients, but still not universally applicable. A validation study of the predictive performance of the Eleveld propofol model showed reasonable performance in children, healthy adults, and obese adults but poorer performance in elderly patients. Observational studies show that complications during total intravenous anesthesia often arise from omission of basic safety checks and inadequate knowledge, rather than model misspecification. Specifically, there is a lack of understanding of the influence of the clinical situation on the pharmacodynamics of hypnotic drugs. Artificial intelligence is likely to produce useful drug infusion rate advisory systems, or even closed-loop control systems that could potentially provide better patient-individualized titration of anesthetic drugs.SummaryFurther efforts to develop new models are unlikely to be clinically beneficial. Efforts should rather be made to ensure better education and a better appreciation of variability in pharmacodynamics and the need for better ways of tailoring drug doses to individual patient needs.