title: Calcium chloride prolongs the effects of lidocaine and bupivacaine in rat sciatic nerve.
abstract: 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.
authors: Department of Anesthesiology, Mackay Memorial Hospital, Mackay Medicine, Nursing and Management College, Taipei, Taiwan.
authors: Yu-Chun
authors: YC
authors: Hung
authors: Suzuko
authors: S
authors: Suzuki
authors: Chien-Chuan
authors: CC
authors: Chen
authors: Yu-Yen
authors: YY
authors: Pan
authors: Tao-Yeuan
authors: TY
authors: Wang
authors: Jen-Kun
authors: JK
authors: Cheng
authors: Ging Kuo
authors: GK
authors: Wang
authors: Peter
authors: P
authors: Gerner
mesh_terms: 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
chemical_list: D000779:Anesthetics, Local; D015222:Sodium Channels; D008012:Lidocaine; D002122:Calcium Chloride; D002045:Bupivacaine