Background and Goal of Study: The addition of clonidine to ropivacaine has been shown to prolong the duration of peripheral nerve blocks. The mechanism of action remains unclear. We hypothesized, that clonidine used as an adjunct to ropivacaine extends the duration of an adductor canal block by a peripheral mechanism, compared to ropivacaine alone.
Materials and method: We conducted a paired, blinded, randomized trial in healthy male volunteers. Each participant received bilateral adductor canal block containing 20ml ropivacaine 0.5% + 1 ml clonidine 150µg/ml in one leg and 20ml ropivacaine 0.5% + 1 ml saline in the other leg in a randomized, blinded fashion. The primary outcome measure was duration of sensory block assessed with ability to discriminate temperature (alcohol swab). Secondary outcome measures were duration of sensory block assessed by: pinprick, maximum pain during tonic heat stimulation, warmth detection threshold and heat pain detection threshold. The latter three sensory modalities were measured using the Modular Sensory Analyzer Thermal Stimulator (2.5 cm², Thermotest, Somedic A/B, Hörby, Sweden). We performed an intention to treat analysis using a paired T-test.
Results and discussion: We enrolled 21 volunteers and all completed the trial. There was no significant difference in duration of sensory block assessed with an alcohol swab: Mean duration in the leg receiving ropivacaine + clonidine was 19.4h (95% CI: 18.2-20.6) compared to 19.3h (95% CI: 18.2-20.4) in the leg receiving ropivacaine + placebo with a mean difference of 0.1h (95% CI: -1.0 to 1.3), P= 0.83. Nor were there statistical significant differences in block duration when assessed by: pinprick, maximum pain during tonic heat stimulation, warmth detection threshold or heat pain detection threshold. 
The prolonging effect of adding clonidine to ropivacaine found in other studies may be caused by absorption of the perineural administered clonidine and consequently a systemic effect. The main strength of our study is that we were able to control for any systemic contribution of clonidine, which would have equally affected both blocks in this bilateral model. The main limitation of our trial is that we are unable to determine whether there is a systemic effect, and if so the magnitude of this effect. 
Conclusion(s): Clonidine used as an adjunct to ropivacaine does not prolong the duration of an adductor canal block by a peripheral mechanism.

Does clonidine have a perineural mechanism of action, when used as an adjuvant to ropivacaine - a paired, blinded, randomized trial in healthy volunteers