title: Methylphenidate actively induces emergence from general anesthesia.
abstract: BACKGROUND
  Although accumulating evidence suggests that arousal pathways in the brain play important roles in emergence from general anesthesia, the roles of monoaminergic arousal circuits are unclear. In this study, the authors tested the hypothesis that methylphenidate (an inhibitor of dopamine and norepinephrine transporters) induces emergence from isoflurane general anesthesia.
  
  
  METHODS
  Using adult rats, the authors tested the effect of intravenous methylphenidate on time to emergence from isoflurane general anesthesia. They then performed experiments to test separately for methylphenidate-induced changes in arousal and changes in minute ventilation. A dose-response study was performed to test for methylphenidate-induced restoration of righting during continuous isoflurane general anesthesia. Surface electroencephalogram recordings were performed to observe neurophysiological changes. Plethysmography recordings and arterial blood gas analysis were performed to assess methylphenidate-induced changes in respiratory function. Intravenous droperidol was administered to test for inhibition of methylphenidate's actions.
  
  
  RESULTS
  Methylphenidate decreased median time to emergence from 280 to 91 s. The median difference in time to emergence without methylphenidate compared with administration of methylphenidate was 200 [155-331] s (median, [95% CI]). During continuous inhalation of isoflurane, methylphenidate induced return of righting in a dose-dependent manner, induced a shift in electroencephalogram power from delta (less than 4 Hz) to theta (4-8 Hz), and induced an increase in minute ventilation. Administration of intravenous droperidol (0.5 mg/kg) before intravenous methylphenidate (5 mg/kg) largely inhibited methylphenidate-induced emergence behavior, electroencephalogram changes, and changes in minute ventilation.
  
  
  CONCLUSIONS
  Methylphenidate actively induces emergence from isoflurane general anesthesia by increasing arousal and respiratory drive, possibly through activation of dopaminergic and adrenergic arousal circuits. The authors' findings suggest that methylphenidate may be useful clinically as an agent to reverse general anesthetic-induced unconsciousness and respiratory depression at the end of surgery.
authors.affiliation: Department of Anaesthesia, Harvard Medical School, Boston, Massachusetts, USA. ksolt@partners.org
authors.forename: Ken
authors.initials: K
authors.lastname: Solt
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Cotten
authors.forename: Aylin
authors.initials: A
authors.lastname: Cimenser
authors.forename: Kin F K
authors.initials: KF
authors.lastname: Wong
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Chemali
authors.forename: Emery N
authors.initials: EN
authors.lastname: Brown
mesh_terms: D000759:Adjuvants, Anesthesia / Q000494:pharmacology; D000465:Algorithms; D000472:Alkalosis, Respiratory / Q000097:blood / Q000139:chemically induced; D000762:Anesthesia Recovery Period; D000768:Anesthesia, General; D018685:Anesthetics, Inhalation; D000818:Animals; D001143:Arousal / Q000187:drug effects; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004329:Droperidol / Q000494:pharmacology; D004569:Electroencephalography / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007530:Isoflurane; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D010991:Plethysmography; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015656:Respiratory Mechanics / Q000187:drug effects
chemical_list: D000759:Adjuvants, Anesthesia; D018685:Anesthetics, Inhalation; D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D007530:Isoflurane; D004329:Droperidol