Small-Dose Intrathecal Clonidine and Isobaric Bupivacaine for Orthopedic Surgery: A Dose-Response Study

In Brief We examined the dose-response relationship of intrathecal clonidine at small doses (≤150 μg) with respect to prolonging bupivacaine spinal anesthesia. We aimed for establishing doses of intrathecal clonidine that would produce clinically relevant prolongation of spinal anesthesia and pain relief without significant side effects. Eighty orthopedic patients were randomly assigned to intrathecally receive isobaric 0.5% bupivacaine, 18 mg, plus saline (Group 1), clonidine 37.5 μg (Group 2), clonidine 75 μg (Group 3), and clonidine 150 μg (Group 4). Duration of the sensory block (regression below level L1) was increased in patients receiving intrathecal clonidine: 288 ± 62 min (Group 1, control), 311 ± 101 min in Group 2 (+8%), 325 ± 69 min in Group 3 (+13%), and 337 ± 78 min in Group 4 (+17%) (estimated parameter for dose 0.23 [95% confidence interval −0.05–0.50]). Duration of pain relief from intrathecal clonidine administration until the first request for supplemental analgesia was significantly prolonged: 295 ± 80 min (Group 1, control), 343 ± 75 min in Group 2 (+16%), 381 ± 117 min in Group 3 (+29%), and 445 ± 136 min in Group 4 (+51%) (estimated parameter for dose 1.02 [95% confidence interval 0.59–1.45]). Relative hemodynamic stability was maintained and there were no between-group differences in the sedation score. We conclude that small doses of intrathecal clonidine (≤150 μg) significantly prolong the anesthetic and analgesic effects of bupivacaine in a dose-dependent manner and that 150 μg of clonidine seems to be the preferred dose, in terms of effect versus unwarranted side effects, when prolongation of spinal anesthesia is desired. IMPLICATIONS: Small doses of intrathecal clonidine (≤150 μg) coadministered to isobaric bupivacaine provide dose-dependent and clinically significant prolongation of spinal anesthesia and pain relief while preserving hemodynamic stability and causing no sedation. In contrast to other approaches to prolong spinal anesthesia (combined spinal-epidural technique) or to relieve postoperative pain (intrathecal opioids), intrathecal clonidine ≤150 μg does not cause an additional technical challenge or unpredictable pharmacological risk.