title: The effects of ketamine on dexmedetomidine-induced electrophysiologic changes in children.
abstract: BACKGROUND
  Dexmedetomidine is an alpha2-adrenergic agonist used for sedation and analgesia in children. We previously showed that dexmedetomidine depresses sinus and AV nodal function resulting in adverse hemodynamic effects such as bradycardia and increased blood pressure. We hypothesized that these effects of dexmedetomidine might be antagonized by co-administration of ketamine, which has sympathomimetic properties.
  
  
  METHODS
  Twenty-two children (ages 5-17 years) undergoing electrophysiologic (EP) study and ablation for supraventricular tachycardia were enrolled. Patients were kept sedated with continuous infusion of propofol at a fixed rate. Hemodynamic and EP parameters were measured before and after a loading dose of dexmedetomidine (1 μg·kg(-1)). A continuous infusion of dexmedetomidine (0.7 μg·kg(-1) ·h(-1)) was initiated and a ketamine loading dose (1 mg·kg(-1)), followed by continuous infusion (1 mg·kg(-1) ·h(-1)), was given. A repeat set of hemodynamic and EP parameters were then measured at the time of projected peak tissue concentration for both drugs.
  
  
  RESULTS
  A significant increase in mean arterial pressure (MAP) was seen compared with baseline after loading of dexmedetomidine. This returned to baseline after co-administration of ketamine (mean difference between baseline and after ketamine 1.8 mmHg; 95%CI, -7.8 to 4.3; P = <0.001). A decrease in heart rate was seen after dexmedetomidine followed by a return to baseline after co-administration of ketamine (mean difference between baseline and after ketamine -6.5 bpm; 95%CI, -11.2 to -1.8; P = 0.005). Sinus node recovery time was lengthened after dexmedetomidine but returned to baseline after ketamine (mean difference between baseline and after ketamine -16.2 ms; 95%CI, -63 to 30; P = 0.014). QT was prolonged after dexmedetomidine and returned to baseline after ketamine (mean difference between baseline and after ketamine -34.2 ms; 95%CI, -48.4 to -20.2; P = 0.004). AV nodal effective refractory period was also impaired after dexmedetomidine and showed weak evidence for return to baseline function after ketamine (mean difference between baseline and after ketamine -22.8 ms; 95%CI, -40.2 to -5.2; P = 0.069).
  
  
  CONCLUSIONS
  The concurrent use of ketamine may mitigate the negative chronotropic effects of dexmedetomidine.
authors.affiliation: Department of Anesthesiology, Stanford University School of Medicine, Stanford, CA, USA. dchar@stanford.edu
authors.forename: Danton
authors.initials: D
authors.lastname: Char
authors.forename: David R
authors.initials: DR
authors.lastname: Drover
authors.forename: Kara S
authors.initials: KS
authors.lastname: Motonaga
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Gupta
authors.forename: Christina Y
authors.initials: CY
authors.lastname: Miyake
authors.forename: Anne M
authors.initials: AM
authors.lastname: Dubin
authors.forename: Gregory B
authors.initials: GB
authors.lastname: Hammer
mesh_terms: D000293:Adolescent; D000758:Anesthesia; D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D054537:Atrioventricular Block / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D020927:Dexmedetomidine / Q000494:pharmacology*; D004562:Electrocardiography / Q000187:drug effects; D055724:Electrophysiological Phenomena / Q000187:drug effects*; D005260:Female; D006321:Heart / Q000187:drug effects; D006329:Heart Conduction System / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D013617:Tachycardia, Supraventricular / Q000139:chemically induced / Q000503:physiopathology
chemical_list: D000778:Anesthetics, Dissociative; D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine; D007649:Ketamine
keywords: congenital cardiac anesthesia; dexmedetomidine; ketamine