Yonsei Med J.  2017 Nov;58(6):1216-1221. 10.3349/ymj.2017.58.6.1216.

A Simulation Study of Propofol Effect-Site Concentration for Appropriate Sedation in Pediatric Patients Undergoing Brain MRI: Pharmacodynamic Analysis

• Na SH
• Song Y
• Kim SY
• Byon HJ
• Jung HH
• Han DW

• KMID: 2418905
• DOI: http://doi.org/10.3349/ymj.2017.58.6.1216

Abstract

PURPOSE
We aimed to establish the propofol effect-site concentration (Ce) for appropriate sedation by pharmacodynamic analysis and to determine the propofol Ce during occurrence of sedation-related side effects in pediatric patients undergoing brain magnetic resonance imaging (MRI).
MATERIALS AND METHODS
In 50 pediatric patients scheduled for brain MRI, sedation was induced with 2.0 mg/kg propofol; additional propofol doses were 0.5-1 mg/kg. Propofol Ce was simulated by inputting the propofol administration profiles of patients into a pediatric compartmental model (Choi model). The relationship between propofol Ce and probabilities of sedation and recovery were analyzed using a sigmoidal Emax model. The simulated propofol Ce for sedation-related side effects was investigated. Population model parameters were estimated using the Nonlinear Mixed-Effects Modelling software.
RESULTS
The mean values of propofol Ceâ‚…â‚€ for sedation during the preparation, scanning, and recovery phases were 1.23, 0.43, and 0.39 µg/mL. The simulated propofol Ce values during oxygen desaturation (SpOâ‚‚<90%) (3 patients; 6%), hypotension (16 patients; 32%), and bradycardia (12 patients; 24%) were 3.01±0.04, 2.05±0.63, and 2.41±0.89 µg/mL, respectively.
CONCLUSION
The required propofol Ceâ‚…â‚€ for applying monitors during the preparation phase before the start of MRI was higher than the propofol Ceâ‚…â‚€ required during the scanning phase. During low-intensity stimulation phases, such as scanning, propofol bolus dose should be strictly titrated not to exceed the propofol Ce that can lead to oxygen desaturation because of the relatively low propofol Ce (Ce₉₅, 1.43 µg/mL) required for sedation in most patients.

Keyword

Effect-site concentration; magnetic resonance imaging; population pharmacodynamics modelling; propofol; sedation; simulation

MeSH Terms

Adolescent
Anesthesia
Anesthetics, Intravenous/administration & dosage/pharmacology
Bradycardia/complications
Brain/*diagnostic imaging
Child
Dose-Response Relationship, Drug
Female
Humans
Hypnotics and Sedatives/administration & dosage/*pharmacology
Hypotension/chemically induced
Magnetic Resonance Imaging
Male
*Models, Biological
Probability
Propofol/administration & dosage/*pharmacology
Anesthetics, Intravenous
Hypnotics and Sedatives
Propofol

Figure

• 

  Fig. 1 Probability curves for propofol Ce versus sedation (preparation and scanning phase) and recovery (recovery phase). The simulated Ce95 values for sedation in preparation and scanning phase and recovery in recovery phase are 2.77, 1.43, and 0.31 µg/mL, respectively. Preparation phase, period starting from application of monitors for recoding electrocardiography readings, non-invasive blood pressure, and arterial oxygen saturation prior to the start of MRI; scanning phase, period of MR image acquisition; recovery phase, period from the end of MRI to the recovery of the patient. Ce, effect-site concentration; MRI, magnetic resonance imaging.

• 

  Fig. 2 Propofol Ce required for 95% probability of sedation during the preparation (2.77 µg/mL) and scanning phase (1.43 µg/mL), respectively. Blue line represents target propofol Ce for sedation and red line represents actual propofol Ce achieving target propofol Ce. A: preparation phase, period starting from application of monitors for recording electrocardiography readings, non-invasive blood pressure, and arterial oxygen saturation prior to the start of MRI. B: scanning phase, period of MR image acquisition. C: recovery phase, period from the end of MRI to the recovery of the patient. Ce, effect-site concentration; MRI, magnetic resonance imaging.

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