Dataset Information

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

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 Ce?? for sedation during the preparation, scanning, and recovery phases were 1.23, 0.43, and 0.39 ?g/mL. The simulated propofol Ce values during oxygen desaturation (SpO? <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 ?g/mL, respectively.

Conclusion

The required propofol Ce?? for applying monitors during the preparation phase before the start of MRI was higher than the propofol Ce?? 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 (Ce??, 1.43 ?g/mL) required for sedation in most patients.

SUBMITTER: Na SH

PROVIDER: S-EPMC5653488 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Publications

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

Na Se Hee SH Song Young Y Kim So Yeon SY Byon Hyo Jin HJ Jung Hwan Ho HH Han Dong Woo DW

Yonsei medical journal 20171101 6

<h4>Purpose</h4>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).<h4>Materials and methods</h4>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 ...[more]

PMID: 29047247

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Project description:OBJECTIVES:Outcomes associated with a sedative regimen comprised ketamine + propofol for pediatric procedural sedation outside of both the pediatric emergency department and operating room are underreported. We used the Pediatric Sedation Research Consortium database to describe a multicenter experience with ketamine + propofol by pediatric sedation providers. DESIGN:Prospective observational study of children receiving IV ketamine + propofol for procedural sedation outside of the operating room and emergency department using data abstracted from the Pediatric Sedation Research Consortium during 2007-2015. SETTING:Procedural sedation services from academic, community, free-standing children's hospitals, and pediatric wards within general hospitals. PATIENTS:Children from birth to less than or equal to 21 years old. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:A total of 7,313 pediatric procedural sedations were performed using IV ketamine + propofol as the primary sedative regimen. Median age was 84 months (range, < 1 mo to ? 21 yr; interquartile range, 36-144); 80.6% were American Society of Anesthesiologists-Physical Status less than III. The majority of sedation was performed in dedicated sedation or radiology units (76.1%). Procedures were successfully completed in 99.8% of patients. Anticholinergics (glycopyrrolate and atropine) or benzodiazepines (midazolam and lorazepam) were used in 14.2% and 41.3%, respectively. The overall adverse event and serious adverse event rates were 9.79% (95% CI, 9.12-10.49%) and 3.47% (95% CI, 3.07-3.92%), respectively. No deaths occurred. Risk factors associated with an increase in odds of adverse event included ASA status greater than or equal to III, dental suite, cardiac catheterization laboratory or radiology/sedation suite location, a primary diagnosis of having a gastrointestinal illness, and the coadministration of an anticholinergic. CONCLUSIONS:Using Pediatric Sedation Research Consortium data, we describe the diverse use of IV ketamine + propofol for procedural sedation in the largest reported cohort of children to date. Data from this study may be used to design sufficiently powered prospective randomized, double-blind studies comparing outcomes of sedation between commonly administered sedative and analgesic medication regimens.

Project description:BackgroundOptimal dosing of propofol to maintain appropriate anesthetic depth is challenging in severely obese (SO) adolescents. We previously reported that total body weight (TBW) is predictive of propofol clearance. This study was aimed at characterizing pharmacokinetics (PK) and pharmacodynamics (PD) of propofol in SO adolescents, using bispectral index (BIS), and toward developing PK/PD model-based dosing guidelines.MethodsA prospective PK/PD study was conducted in 26 SO children and adolescents aged 9-18 years (body mass index 31-69 kg·m(-2)), undergoing surgery with intravenous propofol anesthesia clinically titrated by providers blinded to BIS. BIS data and propofol infusion schemes were recorded. Venous blood samples collected during and after propofol infusion were assayed for propofol concentrations. A propofol PK/PD model was developed using NONMEM and model-based simulations were performed to determine propofol dosing regimens targeting BIS of 50 ± 10.ResultsA three-compartment PK model linked to a sigmoidal inhibitory Emax PD model by a first-order rate constant, adequately described the propofol concentration (n = 375) and BIS (n = 3334) data. TBW was the most predictive covariate for propofol clearance [CL (l·min(-1) ) = 1.65 × (TBW/70)(0.75)]. An effect-site propofol concentration of 3.19 μg·ml(-1) was estimated for half-maximal effect, with no identifiable predictive covariates. The proposed maintenance dosing regimen targeted to a BIS of 50 ± 10, based on our PK/PD model, was able to predict desired propofol concentrations and BIS in a representative obese teen when used in conjunction with accepted PK/PD models for children/obese adults (PK:Eleveld/PD: Cortinez), further supporting evidence for the dosing based on TBW.ConclusionThis is the first study to describe the PK/PD of propofol in SO adolescents. The proposed maintenance dosing regimen for propofol uses TBW in an allometric function as a dosing scalar, with an exponent of 0.75. Our results suggest no relevant effect of obesity on the propofol concentration-BIS relationship.

Dataset Information

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

Purpose

Materials and methods

Results

Conclusion

Publications

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

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