Respiratory effects of epidural and subcutaneous morphine, meperidine, fentanyl and sufentanil in the rat.

This study compared the respiratory effects of subcutaneous and epidural morphine, meperidine, fentanyl, and sufentanil in rats breathing air or 8% CO2 in air. A whole body plethysmographic technique was used to measure minute volumes of breathing. The ED50s of subcutaneously injected morphine, meperidine, fentanyl, and sufentanil in depressing the minute volume response to 8% CO2 in air were 2300 micrograms/kg, 8800 micrograms/kg, 20 micrograms/kg, and 2.3 micrograms/kg, respectively. These doses were nearly the same as the subcutaneous ED50s of these compounds in producing analgesia, found in an earlier study. Roughly equianalgesic doses of the four opiates after epidural injection, however, failed to cause any detectable respiratory effect. Fourfold greater doses increased significantly the incidence of low minute volumes with fentanyl and sufentanil, but soon after epidural injection, i.e., at the time that analgesia was produced. None of the epidurally injected opiates had a significant delayed effect on respiration. However, one of the seven rats treated epidurally with the higher dose of morphine developed depression of the minute volume response to 8% CO2 in air as late as 7 hours after the injection. We conclude that epidural injection, in contrast to subcutaneous injection, of analgesic doses of morphine, meperidine, fentanyl, and sufentanil produces no significant respiratory effects.