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 46 kg/m(2) (range 31-63 kg/m(2)) 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.
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 obesechildren and adolescents in relation to their age and body weight characteristics. METHODS: A prospective pharmacokinetic study in morbidly obesechildren 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 obesechildren 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 46 kg/m(2) (range 31-63 kg/m(2)) 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 obesechildren 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 obesechildren and adolescents should be based on TBW using an allometric function.
Authors: Kathryn E Kyler; Jonathan Wagner; Chelsea Hosey-Cojocari; Kevin Watt; Valentina Shakhnovich Journal: Paediatr Drugs Date: 2019-10 Impact factor: 3.022
Authors: Peter N Johnson; Katy Stephens; Philip Barker; Erica Bergeron; Sin Yin Lim; Tracy M Hagemann; Teresa V Lewis; Stephen Neely; Jamie L Miller Journal: J Pediatr Intensive Care Date: 2019-06-21
Authors: Margreet W Harskamp-van Ginkel; Kevin D Hill; Kristian C Becker; Kristian Becker; Daniela Testoni; Michael Cohen-Wolkowiez; Daniel Gonzalez; Jeffrey S Barrett; Daniel K Benjamin; David A Siegel; Patricia Banks; Kevin M Watt Journal: JAMA Pediatr Date: 2015-07 Impact factor: 26.796
Authors: J Diepstraten; V Chidambaran; S Sadhasivam; H J Blussé van Oud-Alblas; T Inge; B van Ramshorst; E P A van Dongen; A A Vinks; C A J Knibbe Journal: CPT Pharmacometrics Syst Pharmacol Date: 2013-09-11