S‐ketamine and s‐norketamine plasma concentrations after nasal and i.v. administration in anesthetized children

Summary Background : It has been suggested that nasal administration of s‐ketamine may be used to improve sedation or premedication in combination with nasal midazolam in pediatric patients. In this study we measured and compared plasma concentrations of s‐ketamine and its main metabolite s‐norketamine after nasal and i.v. administration in preschool children. Methods : During sevoflurane anaesthesia, 20 children, aged 1–7 years, weight 11–25 kg, received s‐ketamine 2 mg·kg −1 either intranasally (Group IN, n  = 10), or i.v. (Group IV, n  = 10). Six venous blood samples were obtained up to 60 min after drug administration for measurement of s‐ketamine and s‐norketamine plasma concentrations. Results : Plasma concentrations [mean ± sd] of s‐ketamine in group IN peaked at 355 ± 172 ng·ml −1 within 18 ± 13 min. vs. 1860 ± 883 ng·ml −1 within 3 ± 1 min. in group IV ( P  < 0.01). Plasma concentrations of s‐norketamine in group IN peaked at 90 ± 128 ng·ml −1 within 50 ± 11 min. vs. 429 ± 277 ng·ml −1 within 40 ± 16 min. in group IV ( P  < 0.01). One child in group IN experienced rapid and high level s‐ketamine absorption with a peak plasma concentration of 732 ng·ml −1 after 2 min., which decreased to 274 ng·ml −1 after 60 min. Systolic blood pressure and heart rate remained unaltered in both study groups after s‐ketamine administration. Conclusions : Nasal administration of s‐ketamine 2 mg·kg −1 results in a wide spread of plasma concentrations and absorption times. Rapid and high level drug absorption after nasal drug administration is possible. The use of a pulse oximeter and continuous observation after nasal administration of s‐ketamine for pediatric premedication is recommended.