Dexmedetomidine enhances ropivacaine-induced sciatic nerve injury in diabetic rats
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Published version
Author(s)
Type
Journal Article
Abstract
Background
Previous studies suggest that dexmedetomidine has a protective effect against local anaesthetic-induced nerve injury in regional nerve blocks. Whether this potentially protective effect exists in the context of diabetes mellitus is unknown.
Methods
A diabetic state was established in adult male Sprague–Dawley rats with intraperitoneal injection of streptozotocin. Injections of ropivacaine 0.5%, dexmedetomidine 20 μg kg−1 (alone and in combination), or normal saline (all in 0.2 ml) were made around the sciatic nerve in control and diabetic rats (n=8 per group). The duration of sensory and motor nerve block and the motor nerve conduction velocity (MNCV) were determined. Sciatic nerves were harvested at post-injection day 7 and assessed with light and electron microscopy or used for pro-inflammatory cytokine measurements.
Results
Ropivacaine and dexmedetomidine alone or in combination did not produce nerve fibre damage in control non-diabetic rats. In diabetic rats, ropivacaine induced significant nerve fibre damage, which was enhanced by dexmedetomidine. This manifested with slowed MNCV, decreased axon density, and decreased ratio of inner to outer diameter of the myelin sheath (G ratio). Demyelination, axon disappearance, and empty vacuoles were also found using electron microscopy. An associated increase in nerve interleukin-1β and tumour necrosis factor-α was also seen.
Conclusions
Ropivacaine 0.5% causes significant sciatic nerve injury in diabetic rats that is greatly potentiated by high-dose dexmedetomidine. Although the dose of dexmedetomidine used in this study is considerably higher than that used in clinical practice, our data suggest that further studies to assess ropivacaine (alone and in combination with dexmedetomidine) use for peripheral nerve blockade in diabetic patients are warranted.
Previous studies suggest that dexmedetomidine has a protective effect against local anaesthetic-induced nerve injury in regional nerve blocks. Whether this potentially protective effect exists in the context of diabetes mellitus is unknown.
Methods
A diabetic state was established in adult male Sprague–Dawley rats with intraperitoneal injection of streptozotocin. Injections of ropivacaine 0.5%, dexmedetomidine 20 μg kg−1 (alone and in combination), or normal saline (all in 0.2 ml) were made around the sciatic nerve in control and diabetic rats (n=8 per group). The duration of sensory and motor nerve block and the motor nerve conduction velocity (MNCV) were determined. Sciatic nerves were harvested at post-injection day 7 and assessed with light and electron microscopy or used for pro-inflammatory cytokine measurements.
Results
Ropivacaine and dexmedetomidine alone or in combination did not produce nerve fibre damage in control non-diabetic rats. In diabetic rats, ropivacaine induced significant nerve fibre damage, which was enhanced by dexmedetomidine. This manifested with slowed MNCV, decreased axon density, and decreased ratio of inner to outer diameter of the myelin sheath (G ratio). Demyelination, axon disappearance, and empty vacuoles were also found using electron microscopy. An associated increase in nerve interleukin-1β and tumour necrosis factor-α was also seen.
Conclusions
Ropivacaine 0.5% causes significant sciatic nerve injury in diabetic rats that is greatly potentiated by high-dose dexmedetomidine. Although the dose of dexmedetomidine used in this study is considerably higher than that used in clinical practice, our data suggest that further studies to assess ropivacaine (alone and in combination with dexmedetomidine) use for peripheral nerve blockade in diabetic patients are warranted.
Date Issued
2019-01-01
Date Acceptance
2018-08-12
Citation
British Journal of Anaesthesia, 2019, 122 (1), pp.141-149
ISSN
1471-6771
Publisher
Elsevier
Start Page
141
End Page
149
Journal / Book Title
British Journal of Anaesthesia
Volume
122
Issue
1
Copyright Statement
© 2018 The Author(s). Published by Elsevier Ltd on behalf of British Journal of Anaesthesia. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Subjects
Science & Technology
Life Sciences & Biomedicine
Anesthesiology
diabetes mellitus
local anaesthetics
peripheral nerve injuries
neurotoxicity
PERINEURAL DEXMEDETOMIDINE
REGIONAL ANESTHESIA
BLOCK
DURATION
BUPIVACAINE
NEUROPATHY
NEUROTOXICITY
INFLAMMATION
LIDOCAINE
ANALGESIA
1103 Clinical Sciences
Publication Status
Published
Date Publish Online
2018-10-04