THE DOSE-RESPONSE AND TIME-EFFECT RELATIONSHIPS OF INTRATHECAL BUPIVACAINE IN RATS - THE INFLUENCE OF EPINEPHRINE AND PH

The present study defined the dose-response relationship of intrathecally injected bupivacaine in rats. The effect was a quantified drug-induced and graded reduction in the magnitude of the withdrawal reflexes elicited by transcutaneous electrical stimulation. Intrathecal epinephrine reduced the magnitude of the withdrawal reflexes. The combination of epinephrine and bupivacaine resulted in a dose-response relationship different from that of bupivacaine alone, and the combination was more effective than bupivacaine alone. The intrathecal combinations of bupivacaine and 25-mu-g of the alpha-adrenergic antagonist idazoxan had an effect not different from that of bupivacaine alone, but the duration of effect was shorter. The dose-response relationship of bupivacaine was not different whether the pH of the solution was 4.4 or 6.1. The results concerning the effect as a function of time confirm those of earlier studies: 1) the duration of effect depends on the dose of bupivacaine: 2) epinephrine protracts the duration of effect: 3) the pH is of no relevance. Thermal tests for nociception showed that antinociception outlasted motor symptoms. Epinephrine enhanced this effect of bupivacaine, but did not change the duration of motor impairment.