Target Controlled Infusion (TCI) of Propofol: Computation Method
Target Controlled Infusion (TCI) of propofol is computed using a computer-programmed pharmacokinetic model that calculates the infusion rate necessary to achieve and maintain a predetermined drug concentration in the blood or at the effect site.
Basic Principles of TCI Propofol
- TCI systems use an infusion pump connected to a computer programmed with drug-specific, population-based pharmacokinetic models to deliver propofol 1.
- The computer calculates the necessary infusion rate to achieve the target drug concentration and signals the pump to deliver the appropriate amount 1.
- Unlike constant-rate infusions which may lead to drug accumulation, TCI uses mathematical models to calculate the initial dose needed and then makes appropriate adjustments to maintain the desired level 1.
Types of TCI Systems
Open-Loop Systems
- In open-loop systems, the physician selects a target concentration, and the system delivers propofol to achieve that concentration 1.
- The pharmacokinetic model adjusts for patient characteristics including age, sex, body weight, and comorbid disease 1.
- Continuous monitoring is required as individual responses to a given drug concentration will differ due to pharmacodynamic variability 1.
Closed-Loop Systems
- Closed-loop systems use real-time feedback from measures of drug effect (e.g., BIS monitoring) to regulate the delivered drug concentration 1.
- The operator selects the desired level of drug effect, and the computer regulates the infusion to maintain that set-point 1.
- These systems provide more individualized sedation, potentially reducing undersedation and oversedation 1.
Pharmacokinetic Models for TCI
- Currently, two main pharmacokinetic models are pre-programmed in TCI systems 2:
Target Modes
Plasma Targeting
- Aims to achieve a specific plasma concentration of propofol 2.
- When using the Schnider model in plasma targeting mode, the small fixed V1 results in very small initial doses compared to the Marsh model 2.
Effect-Site Targeting
- Aims to achieve a user-defined target effect-site concentration as rapidly as possible 2.
- The Schnider model should preferably be used in effect-site targeting mode, which administers larger initial doses (though still smaller than the Marsh model) 2.
- Effect compartment-controlled TCI can shorten the time to loss of consciousness without causing hypotension 3.
Clinical Application of TCI Propofol
Initial Dosing
- For sedation during procedures like endoscopy, initial plasma concentrations typically range from 0.8-4 μg/mL depending on the desired level of sedation 1.
- For moderate sedation during neuraxial anesthesia, a mean target plasma concentration of 1.13 ± 0.17 μg/mL has been found effective using BIS monitoring 4.
Maintenance Dosing
- Maintenance dosing requires adjustment based on patient response and clinical effect 5.
- For general anesthesia maintenance, infusion rates of 50-100 μg/kg/min in adults are generally recommended 5.
- For MAC sedation, rates of 25-75 μg/kg/min are typically used 5.
Monitoring and Adjustments
- Continuous monitoring of the patient is essential as individual responses to a given drug concentration will differ 1.
- Adjustments to the target concentration should be made based on clinical response and physiological parameters 1.
- BIS monitoring can be used to guide propofol TCI, with a BIS value between 60-80 typically indicating adequate sedation 4.
Potential Pitfalls and Caveats
- Precision limitations: While TCI systems show little systematic bias, they demonstrate poor precision. A target of 1.0 μg/ml may result in actual plasma concentrations ranging from 0.44-1.38 μg/ml (95% confidence interval) 6.
- Model selection impact: Different pharmacokinetic models can yield different clinical effects at the same target concentration 7.
- Morbid obesity concerns: In morbidly obese patients, the lean body mass equation in the Schnider model can generate paradoxical values resulting in excessive maintenance infusion rates 2.
- System variations: Different TCI systems may implement effect-site targeting differently, potentially resulting in significantly different induction doses in some patients 2.
Safety Considerations
- Respiratory depression, hypoxia, and apnea can occur with TCI propofol, requiring continuous monitoring 1.
- In elderly, debilitated, or ASA-PS III or IV patients, rapid bolus administration should be avoided, and doses should be reduced by approximately 80% 5.
- Computer-assisted personalized sedation systems can enhance safety by automatically reducing or stopping infusions in response to clinical or physiological indications of oversedation 1.
By understanding these principles and considerations, clinicians can effectively compute and administer TCI propofol to achieve optimal sedation or anesthesia while minimizing adverse effects.