Safety of clonidine and dexmedetomidine in peripheral nerve blocks: a systematic review of preclinical evidence
Authors' conclusion
Preclinical evidence suggests that perineural α2-adrenergic receptor agonists are safe at clinically relevant doses on healthy nerves. While they probably do not offer a clinically significant neuroprotective effect at therapeutic doses (≤2 μg kg-1), they can increase neurotoxicity in compromised nerves.
Study context
- Population
- Preclinical in vivo and in vitro models of perineural clonidine or dexmedetomidine25 studies (19 in vivo, 6 in vitro)
- Comparison
- Perineural clonidine or dexmedetomidine
- Outcome
- Indicators of neurotoxicity (e.g. apoptosis, demyelination, axonal degeneration) and neuroprotection (e.g. anti-inflammatory effects, neuronal preservation)
Methodological detailsin vivo and in vitro studies, SYRCLE risk-of-bias tool, Search of PubMed, CENTRAL, Embase and Scopus up to July 13, 2025, plus reference screening and large language model queries
- In vivo and in vitro studies
- SYRCLE risk-of-bias tool
- Search of PubMed, CENTRAL, Embase and Scopus up to July 13, 2025, plus reference screening and large language model queries
Pooled result
As reported in the abstract
- High-dose α2-agonists can induce direct toxicity in vitro
- No evidence of neurotoxicity in vivo, even at doses exceeding clinical use
- Reduced apoptosis, axonal degeneration and inflammation vs untreated groups; protective effects at clinically relevant concentrations only after intraneural injection
- In models with pre-existing nerve injury, associated with exacerbated demyelination and inflammation
Original publication
Safety of clonidine and dexmedetomidine in peripheral nerve blocks: a systematic review of preclinical evidence. Br J Anaesth. Published 31 October 2025. doi:10.
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