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

Y. Ginosar, E. T. Riley, M. S. Angst

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11 Scopus citations


BackgroundA 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.MethodsAfter 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 (T finger-arm and Ttoe-leg) were used as measures of sympatholysis.ResultsBoth 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.ConclusionsAfter 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.

Original languageEnglish
Pages (from-to)256-263
Number of pages8
JournalBritish journal of anaesthesia
Issue number2
StatePublished - Aug 2013


  • anaesthesia, spinal
  • bupivacaine
  • clonidine
  • female
  • human volunteers
  • injection, intrathecal
  • pain threshold
  • sympatholytics


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