The role of analgesics in respiratory depression: a rabbit model

Abstract

The study of the effect of analgesics in the newborn is difficult in the clinical situation and resort must be made to animals. Pethidine given within 1 hour of delivery is believed to cause less depression than when the time interval is longer. This study investigates whether it is pethidine or its metabolites which cause respiratory depression by comparing the respiratory effects of pethidine and its metabolites in the newborn rabbit. Fentanyl and buphrenorphine were also investigated as alternative analgesics. The response in the newborn rabbit to anoxia, is periods of dyspnoea, primary apnoea, and gasping. The metabolites of pethidine increased the primary apnoea signifying depression almost as much as pethidine. Depression was also produced when anoxia was induced 5 minutes after pethidine. Fentanyl caused less depression than pethidine or its metabolites excepting normeperidinic acid. Buphrenorphine administration resulted in the least depression with little difference between the low and high doses. Thus both pethidine and its metabolites are factors in the persisting depression, while buphrenorphine compared well with pethidine and fentanyl.