Local anaesthesia efficacy: discrepancies between in vitro and in vivo studies

Abstract

Electrophysiological studies on isolated nerves have been used extensively in the past to assess the comparative efficiency of local anaesthetics as agents of peripheral nerve blockade. It is shown here that three closely related amide local anaesthetics behave differently in vitro and in vivo. In terms of onset of action and of maximum suppression of the evoked action potential, mepivacaine proved a less efficient anaesthetic than lidocaine or prilocaine on isolated nerves, but in parallel studies on the sciatic nerve of live animals and in the absence of vasoconstrictors: (a) mepivacaine's potency was superior to that of the other two agents, (b) its speed of onset of anaesthetic action was at least as good and (c) its duration of action was found to be considerably longer. These results, in combination with the physical properties of the anaesthetics examined, favour differential ionization as the cause of the reduced performance of mepivacaine in the nerve bath. Thus, studies on isolated nerves, which are often quoted in the pharmacological literature, can be poor guides to the in vivo comparative efficacy of local anaesthetics.

Intratesticular mepivacaine versus lidocaine in anaesthetised horses undergoing Henderson castration

“…Given that the nerve membranes are made of lipoproteins, this allows the anaesthetics to have faster membrane penetration for a quicker onset. The pKa values of mepivacaine and lidocaine are 7.6 and 7.9 respectively . The closer to physiologic pH (7.4) a drug is, the quicker the onset of action.…”

Articaine is More Effective than Lidocaine or Mepivacaine in Rat Sensory Nerve Conduction Block in vitro

“…In animal studies, 3% mepivacaine depressed the compound action potential (CAP) of the rat sciatic nerve better than did 2% lidocaine (Pateromichelakis and Prokopiou, 1988). Articaine (4%) was more effective than 2% lidocaine in blocking conduction in the frog (Muschaweck and Rippel, 1974) or rat peripheral nerve (Stankovic v ova and Štolc, 1993).…”

Estudo comparativo entre soluções a 0,5% de levobupivacaína, bupivacaína em excesso enantiomérico de 50% e bupivacaína racêmica em anestesia peridural para cirurgia de abdômen inferior

“…Comparing isomers to racemic bupivacaine, an in vitro study 13 has shown that the dextrogyrous one is more potent (1.36), the levogyrous is less potent (0.45) and the 50% enantiomeric excess bupivacaine has similar potency (0.88). However, the clinical use of local anesthetics is more complex than what has been shown in animals, and in vivo potencies do not correlate to in vitro results 14 . Local factors affecting anesthetic spread and block extension are of major impact on clinical effects.…”

“…As falhas foram parciais, havendo complementação com dose adicional e sedação em todas as pacientes.DISCUSSÃONeste estudo foi observada a homogeneidade demográfica entre os grupos com exceção da idade sendo esta maior no grupo I. Embora este dado seja provavelmente casual em razão do tamanho da amostra, a idade, como fator isolado, apresenta pouca influência no bloqueio peridural em adultos, mas ganha importância, quando se considera a população de crianças e idosos 5 . Avaliação do Bloqueio Sensitivo acima de T 4 mais complexo do que o demonstrado em animais, sendo que as potências in vivo não se correlacionam às encontradas in vitro14 . Os fatores locais que afetam a difusão e a extensão do anestésico local representam fator de grande impacto sobre os efeitos clínicos.…”