The critical role of concentration for lidocaine block of peripheral nerve in vivo: studies of function and drug uptake in the rat.
BACKGROUND
The adjustment of local anesthetic dosage for peripheral nerve block must meet two basic requirements: a drug concentration sufficient to inhibit Na+ channels to the point of impulse failure and a volume of drug sufficient to expose a length of nerve longer than the "critical length" for propagation failure. This study examines the lidocaine dosage requirement, in milligrams, for functionally assayed sciatic nerve block in the rat using a fourfold range of volume corresponding to concentrations from 2 to 7 mg/ml and compares these blocks with the intraneural lidocaine content after injection of equipotent doses.


METHODS
Lidocaine was injected percutaneously at the sciatic nerve in volumes of 0.05 ml, 0.1 ml, and 0.2 ml (all at pH 6.8), and quantitative neurobehavioral assays were conducted on male Sprague-Dawley rats weighing from 200 to 250 g. The dose requirements for 50% maximum possible effect (ED50) and for just achieving complete block (i.e., minimal blocking dose for 90% effect), the fraction of completely blocked animals, and the duration of complete block at all doses were assessed for the inhibition of three different functions: proprioception, motor, and nocifensive activities. Radiolabeled (14C) lidocaine was injected in separate experiments, and the total drug content and its longitudinal distribution were determined in nerves dissected from animals (sevoflurane anesthetized) at 10 min, the time of peak block, after injection of the E50 and minimal blocking dose for 100% effect for the three different volumes.


RESULTS
For all functions, the smaller the volume, the lower was the E50, resulting in a nearly constant concentration to achieve an equivalent degree of block. Durations of block were longer, and the dose to full block was lower for the smaller injected volumes. Intraneural lidocaine, at the equipotent doses for analgesia, was not related to concentration but rather increased with increasing volume, being almost proportional to the given dose. The longitudinal spread of lidocaine was also greater with increasing volume of lidocaine solution.


CONCLUSIONS
Blocks of greater depth and longer duration result from injection of smaller volumes and, correspondingly, higher lidocaine concentrations containing the same dose. The corollary is that lower lidocaine doses are required to achieve the same effect when smaller volumes are injected. Curiously, when the equivalent E50 is injected, total drug taken into the nerve is less from the smaller volumes than from the larger volumes, even though the peak functional effects are equal. Total intraneural local anesthetic may not represent the effective drug in the compartment that contains nerve axons, the actual location of neural blockade.
Nakamura
Tadashi
T
Pain Research Center, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Popitz-Bergez
Frederique
F
Birknes
John
J
Strichartz
Gary R
GR
D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006614:Hindlimb / Q000502:physiology; D008012:Lidocaine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology; D009407:Nerve Block; D010146:Pain / Q000523:psychology; D010525:Peripheral Nerves / Q000187:drug effects* / Q000378:metabolism; D011434:Proprioception / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane
D018685:Anesthetics, Inhalation; D000779:Anesthetics, Local; D008738:Methyl Ethers; D000077149:Sevoflurane; D008012:Lidocaine