Analgesic and sympatholytic effects of low-dose intrathecal clonidine compared with bupivacaine: a dose–response study in female volunteers

• Published in: British journal of anaesthesia : BJA Vol. 111; no. 2; pp. 256 - 263
• Main Authors: Ginosar, Y, Riley, E.T., Angst, M.S.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-08-2013
• Subjects: Adult; anaesthesia, spinal; Analgesia - methods; Analgesics - pharmacology; Anesthesia, Spinal - methods; Anesthetics, Local - pharmacology; bupivacaine; Bupivacaine - pharmacology; clonidine; Clonidine - pharmacology; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; human volunteers; Humans; injection, intrathecal; Injections, Spinal - methods; Pain - drug therapy; Pain Measurement - methods; pain threshold; sympatholytics; Sympatholytics - pharmacology; Young Adult; human volunteers; bupivacaine; sympatholytics; clonidine; injection, intrathecal; anaesthesia, spinal; female; pain threshold
• ISSN: 0007-0912; 1471-6771
• DOI: 10.1093/bja/aet027

A wide range of doses has been suggested for intrathecal clonidine, but no dose-ranging study has examined analgesic effects below 100 µg. The primary aim of this volunteer study was to assess the dose vs analgesic effect relationship for doses of intrathecal clonidine below 100 µg.
After IRB approval and signed informed consent, 11 healthy female volunteers participated in this randomized, double-blinded, cross-over study using a dose-ranging sparse-sampling technique. Participants received intrathecal clonidine (doses 0–100 µg; n=10) and intrathecal bupivacaine (doses 0–8.8 mg; n=9) on separate study days. At baseline, 30, and 60 min from drug administration, experimental heat pain tolerance was assessed at both a lumbar and a cranial dermatome. Heat and cold perception thresholds were assessed at the same time intervals. Heart rate (HR), arterial pressure, and forearm–finger and toe-leg cutaneous temperature gradients (Tfinger–arm and Ttoe–leg) were used as measures of sympatholysis.
Both intrathecal clonidine and bupivacaine caused significant, dose-dependent analgesic effects at the leg but not the head. Significant analgesia to experimental heat pain was detected above 25 µg clonidine and 3 mg bupivacaine. Administration of bupivacaine but not clonidine resulted in a significant dose-related decrease in HR and Ttoe–leg; neither drug caused dose-related sympatholytic effects in the doses used.
After 50 µg clonidine or 5 mg bupivacaine, the heat pain tolerance increased by ∼1°C, similar to the analgesic effect of 5 mg epidural morphine or 30 µg epidural fentanyl in previous studies using this experimental heat pain model. Our results provide additional data for rational dose selection of intrathecal clonidine.