Inhaled carbon dioxide causes dose-dependent paradoxical bradypnea in animals anesthetized with pentobarbital, but not with isoflurane or ketamine

Introduction: 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.