Dataset Information

The relationship between the effect-site concentration of propofol and sedation scale in children: a pharmacodynamic modeling study.

ABSTRACT:

Background

Continuous infusion of propofol has been used to achieve sedation in children. However, the relationship between the effect-site concentration (C_e) of propofol and sedation scale has not been previously examined. The objective of this study was to investigate the relationship between the C_e of propofol and the University of Michigan Sedation Scale (UMSS) score in children with population pharmacodynamic modeling.

Methods

A total of 30 patients (aged 3 to 6 years) who underwent surgery under general anesthesia with propofol and remifentanil lasting more than 1 h were enrolled in this study. Sedation levels were evaluated using the UMSS score every 20 s by a 1 μg/mL stepwise increase in the C_e of propofol during the induction of anesthesia. The pharmacodynamic relationship between the C_e of propofol and UMSS score was analyzed by logistic regression with nonlinear mixed-effect modeling.

Results

The estimated C_e50 (95% confidence interval) of propofol to yield UMSS scores equal to or greater than n were 1.84 (1.54-2.14), 2.64 (2.20-3.08), 3.98 (3.66-4.30), and 4.78 (4.53-5.03) μg/mL for n = 1, 2, 3, and 4, respectively. The slope steepness for the relationship of the C_e versus sedative response to propofol (95% confidence interval) was 5.76 (4.00-7.52).

Conclusions

We quantified the pharmacodynamic relationship between the C_e of propofol and UMSS score, and this finding may be helpful to predict the sedation score at the target C_e of propofol in children.

Trial registration

http://www.clinicaltrials.gov (No.: NCT03195686 , Date of registration: 22/06/2017).

SUBMITTER: Jang YE

PROVIDER: S-EPMC8427954 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Publications

The relationship between the effect-site concentration of propofol and sedation scale in children: a pharmacodynamic modeling study.

Jang Young-Eun YE Ji Sang-Hwan SH Lee Ji-Hyun JH Kim Eun-Hee EH Kim Jin-Tae JT Kim Hee-Soo HS

BMC anesthesiology 20210909 1

<h4>Background</h4>Continuous infusion of propofol has been used to achieve sedation in children. However, the relationship between the effect-site concentration (C<sub>e</sub>) of propofol and sedation scale has not been previously examined. The objective of this study was to investigate the relationship between the C<sub>e</sub> of propofol and the University of Michigan Sedation Scale (UMSS) score in children with population pharmacodynamic modeling.<h4>Methods</h4>A total of 30 patients (age ...[more]

PMID: 34503455

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Project description:ImportanceLittle is known about the impact of different anesthetic agents used for routine magnetic resonance imaging (MRI) sedation on pulmonary function in children.ObjectiveTo compare the incidence of pulmonary atelectasis after MRI sedation with propofol vs propofol-ketamine.Design, setting, and participantsThis double-masked randomized clinical trial screened 117 consecutive pediatric patients aged 3 to 12 years with American Society of Anesthesiologists physical status I to II undergoing elective MRI under deep sedation from November 2, 2022, to April 28, 2023, at a tertiary referral center. Four patients met the exclusion criteria, and 5 patients refused to participate. The participants and outcome assessors were masked to the group allocation.InterventionsDuring the MRI, the propofol group received 0.2 mL/kg of 1% propofol and 2 mL of 0.9% saline followed by a continuous infusion of propofol (200 μg/kg/min) and 0.9% saline (0.04 mL/kg/min). The propofol-ketamine group received 0.2 mL/kg of 0.5% propofol and 1 mg/kg of ketamine followed by a continuous infusion of propofol (100 μg/kg/min) and ketamine (20 μg/kg/min).Main outcome and measureThe incidence of atelectasis assessed by lung ultrasonography examination.ResultsA total of 107 children (median [IQR] age, 5 [4-6] years; 62 male [57.9%]), with 54 in the propofol group and 53 in the propofol-ketamine group, were analyzed in this study. Notably, 48 (88.9%) and 31 (58.5%) patients had atelectasis in the propofol and propofol-ketamine groups, respectively (relative risk, 0.7; 95% CI, 0.5-0.8; P < .001). The incidence of desaturation and interruption of the MRI due to airway intervention or spontaneous movement did not significantly differ between the groups. The propofol-ketamine group showed a faster emergence time than the propofol group (15 [9-23] vs 25 [22-27] minutes in the propofol-ketamine vs propofol group; median difference in time, 9.0 minutes; 95% CI, 6.0-12.0 minutes; P < .001). No patient was withdrawn from the trial due to adverse effects.Conclusions and relevanceIn this randomized clinical trial, the propofol-ketamine combination reduced sedation-induced atelectasis while allowing for faster emergence compared with propofol alone.Trial registrationcris.nih.go.kr Identifier: KCT0007699.

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

The relationship between the effect-site concentration of propofol and sedation scale in children: a pharmacodynamic modeling study.

Background

Methods

Results

Conclusions

Trial registration

Publications

The relationship between the effect-site concentration of propofol and sedation scale in children: a pharmacodynamic modeling study.

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