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Propofol Clearance in Morbidly Obese Children and Adolescents

Influence of Age and Body Size

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Abstract

Background and Objective

Given the alarming increase in obesity among children undergoing surgery, the main aim of this study was to characterize propofol clearance in a cohort of morbidly obese children and adolescents in relation to their age and body weight characteristics.

Methods

A prospective pharmacokinetic study in morbidly obese children and adolescents undergoing elective surgery was conducted. Serial blood samples were collected and nonlinear mixed-effects modelling using NONMEM® was performed to characterize propofol pharmacokinetics with subsequent evaluation of age and body size descriptors.

Results

Twenty obese and morbidly obese children and adolescents with a mean age of 16 years (range 9–18 years), a mean total body weight (TBW) of 125 kg (range 70–184 kg) and a mean body mass index of 46kg/m2 (range 31–63 kg/m2) were available for pharmacokinetic modelling using a two-compartment pharmacokinetic model (n = 294 propofol concentration measurements). Compared with lean body weight and ideal body weight, TBW proved to be the most predictive covariate for clearance [CL (L/min)= 1.70 × (TBW/70)0.8]. Central volume of distribution, peripheral volume and intercompartmental clearance were 45.2 L, 128 L and 1.75 L/min, respectively, with no predictive covariates identifiable.

Conclusion

In the population pharmacokinetic model for propofol in morbidly obese children and adolescents, TBW proved to be the most significant determinant for clearance. As a result, it is anticipated that dosage of propofol for maintenance of anaesthesia in morbidly obese children and adolescents should be based on TBW using an allometric function.

Trial registration number (clinicaltrials.gov)

NCT00948597

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Acknowledgements

We would like to acknowledge the Teen Longitudinal Assessment of Bariatric Surgery team at Cincinnati Children’s Hospital Medical Center (www.Teen-LABS.org) for their support during this study. This study was funded by the Translational Research Initiative grant from Cincinnati Children’s Research Foundation, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA. We would like to acknowledge financial support from NIH grant 1K24HD050387 (AAV). We also acknowledge the work of Elke H.J. Krekels, MSc during manuscript preparation.

The authors have indicated they have no financial relationships relevant to this article to disclose. The authors have no conflicts of interest that are directly relevant to the content of this study.

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Authors and Affiliations

  1. Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein, the Netherlands

    Jeroen Diepstraten & Catherijne A. J. Knibbe

  2. Division of Pediatric Anesthesia, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA

    Vidya Chidambaran, Senthilkumar Sadhasivam & Hope R. Esslinger

  3. Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA

    Vidya Chidambaran, Senthilkumar Sadhasivam, Thomas H. Inge &  Alexander A. Vinks

  4. Division of Clinical Pharmacology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA

    Shareen L. Cox &  Alexander A. Vinks

  5. Division of Pediatric General and Thoracic Surgery, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA

    Thomas H. Inge

  6. Division of Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden, the Netherlands

    Catherijne A. J. Knibbe

Authors
  1. Jeroen Diepstraten
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  2. Vidya Chidambaran
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  3. Senthilkumar Sadhasivam
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  4. Hope R. Esslinger
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  5. Shareen L. Cox
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  6. Thomas H. Inge
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  7. Catherijne A. J. Knibbe
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  8. Alexander A. Vinks
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Corresponding author

Correspondence to Alexander A. Vinks.

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Diepstraten, J., Chidambaran, V., Sadhasivam, S. et al. Propofol Clearance in Morbidly Obese Children and Adolescents. Clin Pharmacokinet 51, 543–551 (2012). https://doi.org/10.1007/BF03261930

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