No ideal method of pain relief during labor and in the post cesarean patient has been found. A variety of undesirable and dangerous side effects, such as maternal sedation, respiratory depression, hypotension, motor blockade, and fetal sedation and respiratory depression occur with intravenous, intramuscular, and epidural narcotics and epidural local anesthetics.

A new class of agents, alpha2-adrenergic agonists, may provide analgesia without accompanying sedation, hypotension, motor blockade, and respiratory depression. Clonidine, the prototype alpha2-agonist, provides segmental analgesia in animals and humans when given intrathecally, potentiates intrathecal morphine-induced analgesia, and provides effective analgesia to terminally ill cancer patients tolerant to intrathecal morphine. However, clonidine has not been thoroughly evaluated for toxicity as an epidural agent, nor has it been evaluated as an epidural agent during pregnancy.

The aim of the proposed series of investigations is to determine the side effects and toxicity of epidural clonidine and clonidine-morphine combinations in nonpregnant and pregnant ewes. Effects on maternal behavior, hemodynamic parameters, arterial blood gases, spinal cord blood flow and histology, uterine blood flow and tone, and fetal hemodynamic parameters and arterial blood gases will be determined after epidural, intrathecal, and intravenous injections. This work is intended to provide the basis of safety and efficacy upon which initial clinical trials of epidural clonidine in the pregnant and post cesarean patient can be made.

R29GM035523

1985-09-01

1990-08-31