Calcium chloride prolongs the effects of lidocaine and bupivacaine in rat sciatic nerve.
OBJECTIVE
Elevated extracellular calcium ion has been shown to shift the voltage dependence of Na+- and K+-ion channels rightward, making the nerve less excitable. We hypothesized that calcium chloride (CaCl2) when used as an adjuvant prolongs and intensifies the block by local anesthetics (LAs). We investigated the effects of LAs combined with calcium in rat sciatic nerve blockade and in cultured rat GH3 cells expressing Na+ channels. Furthermore, we tested for histologic changes due to CaCl2.


METHODS
We anesthetized rats with sevoflurane, exposed the sciatic nerves, and injected 0.2 mL of 1% lidocaine or 0.1% bupivacaine, alone or coadministered with 0.625%, 1.25%, 2.5%, or 5% CaCl2 (n = 8-10 per group). We assessed the complete-block time and complete-recovery time of proprioception, motor function, and nocifensive reaction. To elucidate the mechanism of nerve block, we performed electrophysiology experiments in cultured rat GH3 cells. Sciatic nerves were harvested at day 7 and stained with hemotoxylin/eosin.


RESULTS
The addition of CaCl2 overall prolonged the duration of blockade by lidocaine or bupivacaine. Adding 10 mM CaCl2 to 300 microM lidocaine caused a right shift of the steady-state Na+-channel inactivation curve, indicating that the CaCl2 reduced the potency of lidocaine. Rat sciatic nerves treated with 1% lidocaine coadministered with 5% CaCl2 showed microscopic signs of neurotoxicity.


CONCLUSIONS
The mechanism of prolonged nerve block of CaCl2 coadministered with LAs seems to be a raised threshold for nerve excitation. Major histopathologic changes at higher concentrations of CaCl2 are evident, and therefore, clinical application as an adjuvant to LAs seems unlikely.
Hung
Yu-Chun
YC
Department of Anesthesiology, Mackay Memorial Hospital, Mackay Medicine, Nursing and Management College, Taipei, Taiwan.
Suzuki
Suzuko
S
Chen
Chien-Chuan
CC
Pan
Yu-Yen
YY
Wang
Tao-Yeuan
TY
Cheng
Jen-Kun
JK
Wang
Ging Kuo
GK
Gerner
Peter
P
D000779:Anesthetics, Local; D000818:Animals; D002045:Bupivacaine; D002122:Calcium Chloride / Q000494:pharmacology*; D004347:Drug Interactions; D004594:Electrophysiology; D008012:Lidocaine; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009407:Nerve Block; D011434:Proprioception / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D015222:Sodium Channels / Q000187:drug effects; D013997:Time Factors
D000779:Anesthetics, Local; D015222:Sodium Channels; D008012:Lidocaine; D002122:Calcium Chloride; D002045:Bupivacaine