Ketamine Infusions for Pediatric Sedation and Analgesia

Marcia L. Buck, PharmD, FCCP, FPPAG


Pediatr Pharm. 2016;22(6) 

In This Article

Pharmacokinetics and Pharmacodynamics

Ketamine is available as an injection for IV or IM use, but may also be administered intraosseously, intranasally, or orally. It is widely distributed into body tissues, with higher levels in the brain, lung, liver, and body fat. It is not bound to serum proteins. Ketamine undergoes a biphasic clearance. The initial (alpha) phase includes distribution into the central nervous system (CNS) and results in the drug's anesthetic effects. The average peak concentrations of ketamine after a single dose in adults are 0.75 mcg/mL in plasma and 0.2 mcg/mL in cerebrospinal fluid (CSF). The duration of the alpha phase is approximately 45 minutes, with a half-life of 10 to 20 minutes. The anesthetic action of ketamine ends during the beta phase, as it is redistributed out of the CNS and more extensively into the peripheral tissues.[2,3]

During redistribution, ketamine undergoes N-dealkylation to form norketamine, an active metabolite with one-third the potency of the parent compound. The usual half-life of the beta phase is 2 to 2.5 hours in adults. In addition to N-dealkylation, ketamine is metabolized via hydroxylation of the cyclohexone ring, conjugation with glucuronic acid, and dehydration. The resulting active and inactive metabolites are excreted in the urine.[2,3] The pharmacokinetic profile of ketamine in children has been evaluated in several studies. Hartvig and colleagues evaluated 10 children receiving ketamine infusions of 1–2 mg/kg/hr for sedation and analgesia during mechanical ventilation after cardiac surgery.[6] The authors found clearance of 0.96 L/hr/kg, similar to studies in adults, with a beta elimination half-life of 3.1 ± 1.6 hours and a norketamine half-life of 6.0 ± 1.8 hours.