Wintermeeting 2024: Hernan Boveri

Lost in LOC. Titrating to effect. What does it reveal?

Dr. Hernán Boveri, Italian Hospital of Buenos Aires, Argentina.

Saturday 20 January 9:00-9:30

Currently, propofol is the most widely used intravenous anesthetic drug capable of providing safe general anesthesia. Propofol can be administered using different techniques including target-controlled infusion (TCI).One of the greatest strengths of TCI technology lies in its ability to maintain the pharmacological condition once the predefined clinical effect has been achieved. TCI models were developed based on data from healthy volunteers and may not apply to all clinical situations, potentially resulting in under-dosing or overdosing both of which are adverse situations for patients. Individual variability in the pharmacokinetic parameters of anesthetics is a clinical challenge, as is pharmacodynamic variability.

The large variation between patients in the concentration at the effect site that produces unconsciousness makes it difficult to establish the minimum concentration that provides effective sedation in a given patient. This would be of little importance if large doses were well tolerated and had no consequences. This inaccuracy resulting from concentrations based on population models requires the anesthesiologist to manually titrate (or calibrate the drug requirements of each individual) the target concentration for each patient based on observations of the desired therapeutic effect. Using depth of anesthesia monitors such as BIS or SedLine, this can be done in a rational way.  Evidence suggests that combining the concentration at the effect site provided by TCI systems with the hypnotic effect information provided by depth of anesthesia monitors offers a higher level of care. However, in many situations, it is not possible to place a depth of anesthesia monitor due to the anatomical location of the surgical procedure (head and neck surgeries or neurosurgery), or this technological resource is not available for various reasons.

It has been observed that for anesthetic induction with Propofol, Ke0 extracted by bolus or rapid infusion models overestimate the value of the calculated effect-site concentration (Ce). If this calculated Ce is used during induction as a reference to maintain anesthesia, the hypnotic effect is likely to be overdosed. Conversely, performing infusions at low speeds allows for more homogeneous drug mixing in the blood and less dissociation between Cp and Ce. In that case, the value of Cp could even be usable as an equivalent to Ce for titration purposes.

Today's common practice involves performing anesthetic inductions with propofol in TCI modelled at the effect site, using referential pharmacodynamic values (population statistics). This includes a significant loading bolus at speeds of 1200 ml/h and frequently presents hemodynamic problems such as apnea and hypotension, overestimates Ce; therefore, they are not really accurate in representing the effect and most importantly, do not allow titrating the individual requirement in each case.

In 2018, Eleveld et al. published a general-purpose PK/PD model for propofol. Not only is it an attractive model because it can be applied to a broad population, but it also has implemented a Ce50 for BIS, which could serve as a guideline to titrate patients from the induction of anesthesia. When comparing this recommended Ce50 against a careful titration-to-effect technique using the same pharmacokinetic model, do we achieve the same results?

This lecture will highlight the importance of considering the pharmacokinetic and pharmacodynamic variability and different titration strategies using TCI will be discussed.

In the workshops, clinical examples of how to titrate at induction of anesthesia with several pharmacokinetic models for propofol will be demonstrated using TIVAtrainer simulation software.

After the session, attendees should be able to titrate adult patients at induction of anesthesia, with Marsh and Eleveld models, especially when an EEG monitor is not available, aiming to overcome PK and PD variability.