Calcium Chloride Prolongs the Effects of Lidocaine and Bupivacaine in Rat Sciatic Nerve

• Published in: Regional anesthesia and pain medicine Vol. 34; no. 4; pp. 333 - 339
• Main Authors: Hung, Yu-Chun, Suzuki, Suzuko, Chen, Chien-Chuan, Pan, Yu-Yen, Wang, Tao-Yeuan, Cheng, Jen-Kun, Wang, Ging Kuo, Gerner, Peter
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01-07-2009; BMJ Publishing Group LTD
• Subjects: Anesthetics, Local; Animals; Bupivacaine; Calcium Chloride - pharmacology; Drug Interactions; Electrophysiology; Lidocaine; Male; Motor Activity - drug effects; Motor Activity - physiology; Nerve Block; Proprioception - physiology; Rats; Rats, Sprague-Dawley; Regional anesthesia; Sciatic Nerve - drug effects; Sciatic Nerve - pathology; Sciatic Nerve - physiology; Sodium Channels - drug effects; Time Factors
• ISSN: 1098-7339; 1532-8651
• DOI: 10.1097/AAP.0b013e3181ac7f49

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 (CaCl
2) 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 GH
3 cells expressing Na
+ channels. Furthermore, we tested for histologic changes due to CaCl
2.
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% CaCl
2 (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 GH
3 cells. Sciatic nerves were harvested at day 7 and stained with hemotoxylin/eosin.
The addition of CaCl
2 overall prolonged the duration of blockade by lidocaine or bupivacaine. Adding 10 mM CaCl
2 to 300 μM lidocaine caused a right shift of the steady-state Na
+-channel inactivation curve, indicating that the CaCl
2 reduced the potency of lidocaine. Rat sciatic nerves treated with 1% lidocaine coadministered with 5% CaCl
2 showed microscopic signs of neurotoxicity.
The mechanism of prolonged nerve block of CaCl
2 coadministered with LAs seems to be a raised threshold for nerve excitation. Major histopathologic changes at higher concentrations of CaCl
2 are evident, and therefore, clinical application as an adjuvant to LAs seems unlikely.