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Assessment of Ketamine Adult Anesthetic Doses in Pediatrics Using Pharmacokinetic Modeling and Simulations
Author(s) -
Elkomy Mohammed H.,
Alruwaili Nabil,
Elmowafy Mohammed,
Shalaby Khaled,
Drover David R.,
Ramamoorthy Chandra
Publication year - 2019
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/phar.2243
Subject(s) - ketamine , pharmacokinetics , volume of distribution , medicine , dosing , anesthesia , bolus (digestion) , anesthetic , plasma clearance , population , intravenous bolus , loading dose , pharmacology , surgery , environmental health
Background Although few studies have used ketamine for induction and maintenance of pediatric anesthesia, official dosage recommendations are lacking. This study evaluates the outcomes of adult anesthetic doses in a pediatric population through pharmacokinetic modeling and computer simulations in an attempt to recommend an adequate ketamine dosing regimen. Methods Ketamine plasma concentration‐time data in 19 children (age 8 months to 16 years; weight 5.5 to 67 kg) were analyzed according to a non‐compartmental pharmacokinetic approach. The relationship between pharmacokinetic parameters and demographic covariates was mathematically characterized. A one‐compartment open model was implemented to simulate the plasma profile following administration of 1–4.5 mg/kg IV bolus dose and 0.1–0.5 mg/kg/min continuous infusion of ketamine and to predict anesthesia onset and offset. Key Results Pharmacokinetic parameters determined were clearance 0.025 ± 0.008 L/kg/min; distribution volume 3.3 ± 1.3 L/kg; half‐life 2.6 ± 1 h; and mean residence time 2.3 ± 0.64 h. Body weight was the best predictor of clearance and distribution volume according to a 0.75‐power model. Using weight to scale doses was associated with limited variability in simulated concentrations. Ketamine administered as 2.25 mg/kg IV bolus dose, followed by 0.1 mg/kg/min continuous IV infusion enables anesthesia initiation within 3 minutes and maintains it for 3 hours. Conclusions & Inferences Weight‐based dosing minimizes age‐dependent variation in the plasma concentration of ketamine. Low‐to‐intermediate adult doses are suitable for induction and maintenance of safe anesthesia in children undergoing short‐term surgical operations. However, this finding requires validation in controlled clinical trials before it is adopted into surgical standard practices.