title: Inhaled carbon dioxide causes dose-dependent paradoxical bradypnea in animals anesthetized with pentobarbital, but not with isoflurane or ketamine.
abstract: BACKGROUND
  In spontaneously breathing mice anesthetized with pentobarbital, we observed unexpected paradoxical bradypnea following 5% inhaled CO2.
  
  
  METHODS
  Observational study 7-8 week CB6F1/OlaHsd mice (n = 99), anesthetized with 30 mg/kg intraperitoneal pentobarbital. Interventional study: Adult male Wistar rats (n = 18), anesthetized either with 30 mg/kg intraperitoneal pentobarbital, 100 mg/kg intraperitoneal ketamine or 1.5% isoflurane. Rats had femoral artery cannulas inserted for hemodynamic monitoring and serial arterial blood gas measurements.
  
  
  RESULTS
  Observational study: There was a marked reduction in respiratory rate following 4 min of normoxic hypercapnia; average reduction of 9 breaths/min (p < 0.001) (17% reduction from baseline). Interventional study: increasing CO2 caused dose-dependent increase in respiratory rate for ketamine-xylazine (p = 0.007) and isoflurane (p = 0.016) but dose-dependent decrease in respiratory rate for pentobarbital (p = 0.046). Increasing inspired CO2 caused dose-dependent acidosis following pentobarbital and isoflurane (p = 0.013 and p = 0.017, respectively); but not following ketamine-xylazine (p = 0.58).
  
  
  CONCLUSIONS
  Inhaled CO2 caused paradoxical dose-dependent bradypnea in animals anesthetized with pentobarbital, an observation not hitherto reported as a part of anesthesia-related respiratory depression.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Jerusalem, Israel. Electronic address: yginosar@netvision.net.il.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Ginosar
authors.affiliation: The Goldyne Savad Institute of Gene Therapy, Jerusalem, Israel; MRI Laboratory, Human Biology Research Center, Hadassah Hebrew University Medical Center, Ein Karem, Jerusalem, Israel.
authors.forename: Nathalie Corchia
authors.initials: NC
authors.lastname: Nachmanson
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Jerusalem, Israel.
authors.forename: Joel
authors.initials: J
authors.lastname: Shapiro
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Jerusalem, Israel.
authors.forename: Charles
authors.initials: C
authors.lastname: Weissman
authors.affiliation: The Goldyne Savad Institute of Gene Therapy, Jerusalem, Israel; MRI Laboratory, Human Biology Research Center, Hadassah Hebrew University Medical Center, Ein Karem, Jerusalem, Israel.
authors.forename: Rinat
authors.initials: R
authors.lastname: Abramovitch
mesh_terms: D000142:Acidosis, Respiratory / Q000097:blood / Q000139:chemically induced; D000280:Administration, Inhalation; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D002245:Carbon Dioxide / Q000008:administration & dosage*; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D007530:Isoflurane / Q000494:pharmacology*; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010424:Pentobarbital / Q000494:pharmacology*; D017208:Rats, Wistar; D012119:Respiration / Q000187:drug effects; D056152:Respiratory Rate / Q000187:drug effects*
chemical_list: D000777:Anesthetics; D002317:Cardiovascular Agents; D002245:Carbon Dioxide; D007649:Ketamine; D007530:Isoflurane; D010424:Pentobarbital
keywords: Anesthesia; Animals; Carbon dioxide ventilatory response; Control of respiration; Respiratory rate