Dose-response relationship of clonidine in tetracaine spinal anesthesia

The study was undertaken to define a dose-response relationship for clonidine in prolonging canine tetracaine spinal anesthesia. Using a randomized blind cross-over design, six mongrel dogs were given subarachnoid injections (1 ml) of the following solutions over an 8-week period: tetracaine 4 mg (control), or tetracaine 4 mg with clonidine in doses of 10, 25, 50, 100, 150, 200, and 300 micrograms. With clonidine doses equal to or exceeding 50 micrograms/ml, motor and sensory blockade were significantly (P less than 0.01) prolonged, when compared to the control times. Analysis of data by second order polynomial regression analysis produced a relationship defined by Y = 23.241 + 1.104(x) - 0.0023(x2) with r2 = 0.92 and P less than 0.001 for sensory blockade and Y = 38.7072 + 1.64425(x) - 0.004125(x2) with r2 = 0.90 and P less than 0.005 for motor blockade. From these curves, a plateau in clonidine dose-response for both sensory blockade and motor blockade occurred at 150 micrograms. The increase in duration of spinal anesthesia with clonidine may be related to a direct post-synaptic alpha 2 adrenoceptor arteriolar effect, a spinal cord pre- or post-synaptic alpha 2 antinociceptive action or supraspinal alpha 2 modulation of nociception. No animals showed evidence of neurologic dysfunction during the study. The authors conclude that a well-defined dose-response relationship exists for clonidine in canine tetracaine spinal anesthesia.