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

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.