Concerns Regarding “Single-Syringe Total Intravenous Anesthesia With Propofol and Remifentanil: A Prospective Cohort Study”
Year: 2025
Type: article
Abstract: To the Editor I read the article published by Bennion et al in Anesthesia & Analgesia regarding intravenous anesthesia using a single-syringe containing both propofol and remifentanil.1 This concept periodically resurfaces in the literature and on social media, often attracting interest from proponents of intravenous anesthesia. While the goal of simplification is understandable, I remain concerned about the safety and adherence to established guidelines associated with this method. The history of total intravenous anesthesia (TIVA) and target controlled infusion (TCI) is marked by pioneering ideas and remarkable innovation—often fueled by a “garage computing” spirit—that, between the 1980s and early 2000s, drove significant advances in pharmacokinetic understanding and clinical application. This innovative momentum, coupled with a regulatory environment far more permissive than today’s, enabled rapid technological development but also gave rise to applications that, in retrospect, may be considered questionable. For example, previous studies have highlighted multiple instances of inconsistent pharmacokinetic model implementation, inappropriate extrapolation of anthropometric data beyond validated limits, and regulatory gaps that have enabled an unstandardized use of pharmacokinetic/pharmacodynamic (PK-PD) models implemented in TCI pumps.2 Such issues, among others, have contributed to the long-standing reluctance of regulatory bodies—most notably the US FDA—which continues to restrict the clinical adoption of TCI systems in the United States to this day. In this context, the recent development of generalized PK-PD models represents a significant paradigm shift. The Eleveld models for propofol and remifentanil, designed as unified frameworks applicable across diverse patient populations—including adults, children, the elderly, and individuals with obesity—enhance the external validity of TCI and offer a more sophisticated, systematic, and prospectively validated approach to drug delivery.3 Most importantly, the Eleveld models have improved standardization, consistency, and patient safety in TCI, helping to restore confidence in the technology and support its broader adoption in contemporary anesthesia practice. The Association of Anaesthetists and the Society for Intravenous Anaesthesia have issued comprehensive guidelines emphasizing the safe practice of TIVA. These guidelines explicitly discourage mixing drugs in the same syringe due to concerns about compatibility, chemical stability, and the risk of dosing errors. In particular, combining propofol—a lipid-based emulsion—with agents like remifentanil can result in physical or chemical instability, potentially compromising both efficacy and safety.4 Moreover, this practice may undermine the advantages offered by advanced PK-PD models. Mixing agents can alter their pharmacokinetic profiles, leading to unpredictable drug behavior and increasing the risk of adverse outcomes.5 Modern effective anesthesia management requires the distinct monitoring and titration of hypnotic and analgesic components. Combining propofol and remifentanil in a single syringe eliminates the ability to independently adjust dosages based on patient response, potentially leading to inadequate anesthesia or increased risk of adverse effects. Maintaining separate infusions enables independent titration of hypnotic and analgesic agents, which is essential for patient safety, particularly when managing drugs with distinct onset and duration of action. From a methodological perspective, it is concerning that the study does not explicitly report the total doses of propofol and remifentanil administered, nor does it provide detailed infusion profiles across the various phases of anesthesia.In conclusion, while the authors’ effort to explore simplified TIVA techniques is acknowledged, the use of a single syringe for propofol and remifentanil raises substantial concerns regarding safety, guideline adherence, and methodological transparency. More importantly, this approach runs counter to the progress made in recent years by the scientific community to promote standardization, safety, and model validation in TCI practice. Reintroducing techniques that compromise the ability to independently titrate hypnotic and analgesic agents risks undermining these collective efforts and may jeopardize patient safety.
Source: Anesthesia & Analgesia
Author: Michele Introna
Language: English
Subfield: Anesthesiology and Pain Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funder: Ministero della Salute
OpenAlex ID: W4416424304