Janelle D Vaughns1, Victoria C Ziesenitz2,3,4, Elaine F Williams5, Alvina Mushtaq5, Ricarda Bachmann6, Gisela Skopp6, Johanna Weiss7, Gerd Mikus7, Johannes N van den Anker5,8,9. 1. Division of Anesthesiology, Sedation and Perioperative Medicine, Children's National Health System, Washington, DC, USA. 2. Division of Pediatric Clinical Pharmacology, Children's National Health System, Washington, DC, USA. Ziesenitz.md@gmail.com. 3. Department of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Heidelberg, Germany. Ziesenitz.md@gmail.com. 4. Division of Paediatric Pharmacology and Pharmacometrics, University of Basel Children's Hospital, 4056, Basel, Switzerland. Ziesenitz.md@gmail.com. 5. Division of Pediatric Clinical Pharmacology, Children's National Health System, Washington, DC, USA. 6. Institute of Legal and Traffic Medicine, University of Heidelberg, Heidelberg, Germany. 7. Department of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Heidelberg, Germany. 8. Intensive Care and Department of Pediatric Surgery, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands. 9. Division of Paediatric Pharmacology and Pharmacometrics, University of Basel Children's Hospital, 4056, Basel, Switzerland.
Abstract
BACKGROUND: The number of obese pediatric patients requiring anesthesia is rapidly increasing. Although fentanyl is a commonly used narcotic during surgery, there are no pharmacokinetic (PK) data available for optimal dosing of fentanyl in adolescents with clinically severe obesity. MATERIALS AND METHODS: An institutional review board-approved exploratory pilot study was conducted in six adolescents aged 14-19 years undergoing bariatric surgery. Mean total body weight (TBW) and mean BMI were 137.4 ± 14.3 kg and 49.6 ± 6.4 kg/m2 (99.5th BMI percentile), respectively. Fentanyl was administered intravenously for intraoperative analgesia based on ideal body weight per standard of care. PK blood samples were drawn over a 24-h post-dose period. Fentanyl PK parameters were calculated by non-compartmental analysis. RESULTS: Mean fentanyl AUC0-∞ was 1.5 ± 0.5 h·ng/mL. Systemic clearance of fentanyl was 1522 ± 310 mL/min and 11.2 ± 2.6 mL/min·kg TBW. Volume of distribution was 635 ± 282 L and 4.7 ± 2.1 L/kg TBW. While absolute clearance was increased, absolute volume of distribution was comparable to previously established adult values. CONCLUSIONS: These results suggest that fentanyl clearance is enhanced in adolescents with clinically severe obesity while volume of distribution is comparable to previously published studies. STUDY REGISTRATION: NCT01955993 (clinicaltrials.gov).
BACKGROUND: The number of obese pediatricpatients requiring anesthesia is rapidly increasing. Although fentanyl is a commonly used narcotic during surgery, there are no pharmacokinetic (PK) data available for optimal dosing of fentanyl in adolescents with clinically severe obesity. MATERIALS AND METHODS: An institutional review board-approved exploratory pilot study was conducted in six adolescents aged 14-19 years undergoing bariatric surgery. Mean total body weight (TBW) and mean BMI were 137.4 ± 14.3 kg and 49.6 ± 6.4 kg/m2 (99.5th BMI percentile), respectively. Fentanyl was administered intravenously for intraoperative analgesia based on ideal body weight per standard of care. PK blood samples were drawn over a 24-h post-dose period. Fentanyl PK parameters were calculated by non-compartmental analysis. RESULTS: Mean fentanyl AUC0-∞ was 1.5 ± 0.5 h·ng/mL. Systemic clearance of fentanyl was 1522 ± 310 mL/min and 11.2 ± 2.6 mL/min·kg TBW. Volume of distribution was 635 ± 282 L and 4.7 ± 2.1 L/kg TBW. While absolute clearance was increased, absolute volume of distribution was comparable to previously established adult values. CONCLUSIONS: These results suggest that fentanyl clearance is enhanced in adolescents with clinically severe obesity while volume of distribution is comparable to previously published studies. STUDY REGISTRATION: NCT01955993 (clinicaltrials.gov).
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