scholarly journals Ultralong Peripheral Nerve Block by Lidocaine:Prilocaine 1:1 Mixture in a Lipid Depot Formulation

2006 ◽  
Vol 104 (1) ◽  
pp. 110-121 ◽  
Author(s):  
Lars Söderberg ◽  
Henrik Dyhre ◽  
Bodil Roth ◽  
Sven Björkman
Keyword(s):  
Sciatic Nerve ◽  
Nerve Block ◽  
Local Anesthetic ◽  
In Vitro Release ◽  
Sciatic Nerve Block ◽  
Depot Formulation ◽  
Duration Of Action ◽  
Depot Preparations

Background The aim of this study was to develop stable and easily injectable lipid depot preparations of local anesthetics in which the drug concentration can be varied according to desired duration of action. Methods The formulations contained a 2.0, 5.0, 10, 20, 40, 60, 80, or 100% eutectic mixture of lidocaine and prilocaine base in medium-chain triglyceride. Duration of sciatic nerve block and local neurotoxicity was investigated in rats with 2.0% lidocaine:prilocaine HCl solution and 99.5% ethanol as controls. The rate of release of local anesthetic from the site of administration and the possibility to predict in vivo depot characteristics from in vitro release data were investigated for the 20 and 60% formulations. Results The duration of sensory sciatic block was prolonged 3 times with the 20% formulation and approximately 180 times with the 60% formulation, in comparison with the 2% aqueous solution. With the 80 and 100% formulations, all animals still showed nerve block after 2 weeks. The in vivo release of local anesthetic could be approximately predicted from in vitro data for the 20% but not for the 60% formulation. The formulations of 60% or greater and ethanol showed neurotoxic effects. Conclusions The pharmaceutical properties of these formulations compare favorably with those of other depot preparations. The high-percentage ones showed the longest duration of action yet reported for sciatic nerve block in rats. The possibility of using a high-concentration local anesthetic depot formulation as an alternative to ethanol or phenol for long-term nerve blocks in chronic pain merits further investigation.

N-Butyl Tetracaine as a Neurolytic Agent for Ultralong Sciatic Nerve Block

1996 ◽  
Vol 85 (6) ◽  
pp. 1386-1394. ◽  
Author(s):  
G. K. Wang ◽  
M. Vladimirov ◽  
C. Quan ◽  
W. M. Mok ◽  
J. G. Thalhammer ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Nerve Block ◽  
Local Anesthetic ◽  
Single Injection ◽  
Nerve Fibers ◽  
Sciatic Nerve Block ◽  
Na Currents ◽  
Dependent Inhibition ◽  
Withdrawal Response

Background Neurolytic agents such as phenol (5% to 10%) and absolute alcohol have long been used clinically to destroy the pathogenic nerve regions that manifest pain. Both phenol and alcohol are highly destructive to nerve fibers. However, these agents exert only weak local anesthetic effects and therefore are difficult to administer to alert patients without pain. This report describes a tetracaine derivative that displays both local anesthetic and neurolytic properties. Studies with such a compound may lead to the design of neurolytic agents that are more effective and more easily administered than phenol and alcohol. Methods A tetracaine derivative, N-butyl tetracaine quaternary ammonium bromide, was synthesized, and its ability to elicit sciatic nerve block of sensory and motor functions in vivo was tested in rats. A single dose of 0.1 ml N-butyl tetracaine at 37 mM was injected into the sciatic notch. Transverse sections of treated sciatic nerves were subsequently examined to determine the neurolytic effect of this drug. Finally, the local anesthetic properties of N-butyl tetracaine were studied in vitro; both tonic inhibition and use-dependent inhibition of Na+ currents in neuronal GH3 cells were characterized under whole-cell voltage-clamp conditions. Results N-butyl tetracaine at 37 mM (equivalent to 1.11% tetracaine-hydrochloric acid concentration) elicited prolonged sciatic nerve block of the withdrawal response to noxious pinch in rats for more than 2 weeks. The withdrawal response was fully restored after 9 weeks. Parallel to sensory block, motor functions of the hind legs were similarly blocked by this drug. Morphologic examinations 3 and 5 weeks after a single injection of drug revealed degeneration of many sciatic nerve fibers, consistent with the results of functional tests. Finally, N-butyl tetracaine was found to be a potent Na+ channel blocker in vitro. It produced strong tonic and use-dependent inhibition of Na+ currents with a potency comparable to that of tetracaine. Conclusions A single injection of N-butyl tetracaine produces ultralong sciatic nerve block in rats. This compound possesses both local anesthetic and neurolytic properties and may prove useful as a neurolytic agent in pain management.

Pharmacodynamics and Pharmacokinetics of Lidocaine in a Rodent Model of Diabetic Neuropathy

2018 ◽  
Vol 128 (3) ◽  
pp. 609-619 ◽  
Author(s):  
Werner ten Hoope ◽  
Markus W. Hollmann ◽  
Kora de Bruin ◽  
Hein J. Verberne ◽  
Arie O. Verkerk ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Diabetic Neuropathy ◽  
Nerve Block ◽  
Local Anesthetic ◽  
Local Anesthetics ◽  
Nerve Fibers ◽  
Rodent Model ◽  
Sciatic Nerve Block ◽  
Zucker Diabetic Fatty Rats

Abstract Background Clinical and experimental data show that peripheral nerve blocks last longer in the presence of diabetic neuropathy. This may occur because diabetic nerve fibers are more sensitive to local anesthetics or because the local anesthetic concentration decreases more slowly in the diabetic nerve. The aim of this study was to investigate both hypotheses in a rodent model of neuropathy secondary to type 2 diabetes. Methods We performed a series of sciatic nerve block experiments in 25 Zucker Diabetic Fatty rats aged 20 weeks with a neuropathy component confirmed by neurophysiology and control rats. We determined in vivo the minimum local anesthetic dose of lidocaine for sciatic nerve block. To investigate the pharmacokinetic hypothesis, we determined concentrations of radiolabeled (14C) lidocaine up to 90 min after administration. Last, dorsal root ganglia were excised for patch clamp measurements of sodium channel activity. Results First, in vivo minimum local anesthetic dose of lidocaine for sciatic nerve motor block was significantly lower in diabetic (0.9%) as compared to control rats (1.4%). Second, at 60 min after nerve block, intraneural lidocaine was higher in the diabetic animals. Third, single cell measurements showed a lower inhibitory concentration of lidocaine for blocking sodium currents in neuropathic as compared to control neurons. Conclusions We demonstrate increased sensitivity of the diabetic neuropathic nerve toward local anesthetics, and prolonged residence time of local anesthetics in the diabetic neuropathic nerve. In this rodent model of neuropathy, both pharmacodynamic and pharmacokinetic mechanisms contribute to prolonged nerve block duration.

Relation between Functional Deficit and Intraneural Local Anesthetic during Peripheral Nerve Block

1995 ◽  
Vol 83 (3) ◽  
pp. 583-592. ◽  
Author(s):  
F. A. Popitz-Bergez ◽  
S. Leeson ◽  
G. R. Strichartz ◽  
J. G. Thalhammer
Keyword(s):  
Steady State ◽  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Block ◽  
Local Anesthetic ◽  
Peripheral Nerve Block ◽  
Longitudinal Distribution ◽  
Functional Block

Background During peripheral nerve block, local anesthetic (LA) penetrates within and along the nerve to produce the observed functional deficits. Although much is known about the kinetics and steady-state relation for LA inhibition of impulse activity in vitro in isolated nerve, little is known about the relation between functional loss and intraneural LA content in vivo. This study was undertaken to investigate the relation of functional change to intraneural LA. Methods A sciatic nerve block was performed in rats with 0.1 ml 1% lidocaine radiolabeled with 14C. The total intraneural uptake of LA was determined at different times after injection, and the distribution of lidocaine along the nerve was assayed at different stages of functional block. Drug content was also compared with equilibrium lidocaine uptake in the isolated rat sciatic nerve. Results Total intraneural lidocaine in vivo increased to near steady-state in about 3 min, stabilizing at approximately 14.3 nmol/mg wet tissue for about 12 min before decreasing to zero at 70 min after injection. Although intraneural lidocaine was 1.6% of the injected dose during full block, only 0.3% was left when deep pain sensation returned and 0.065% was still detected when functions fully recovered. Despite these large differences in total lidocaine content, the longitudinal distribution remained constant. Intraneural lidocaine concentrations obtained at full block and partial recovery could be achieved in vitro by equilibration in 0.7-0.9 and 0.2-0.3 mM lidocaine, respectively. Conclusions During peripheral nerve block only a small amount of injected LA penetrates into the nerve. The intraneural content of LA correlates with the depth of functional block.

The Local Anesthetic Properties and Toxicity of Saxitonin Homologues for Rat Sciatic Nerve Block In Vivo

2000 ◽  
Vol 25 (1) ◽  
pp. 52-59 ◽  
Author(s):  
Daniel S. Kohane ◽  
Nu T. Lu ◽  
Arman C. Gökgöl-Kline ◽  
Maria Shubina ◽  
Yu Kuang ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Nerve Block ◽  
Local Anesthetic ◽  
Sciatic Nerve Block ◽  
Rat Sciatic Nerve

The local anesthetic properties and toxicity of saxitonin homologues for rat sciatic nerve block in vivo

2000 ◽  
Vol 25 (1) ◽  
pp. 52-59 ◽  
Author(s):  
D KOHANE ◽  
N LU ◽  
A GOKGOLKLINE ◽  
M SHUBINA ◽  
Y KUANG ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Nerve Block ◽  
Local Anesthetic ◽  
Sciatic Nerve Block ◽  
Rat Sciatic Nerve

Structure-Activity Relation of N-alkyl Tetracaine Derivatives as Neurolytic Agents for Sciatic Nerve Lesions 

1998 ◽  
Vol 88 (2) ◽  
pp. 417-428 ◽  
Author(s):  
Ging Kuo Wang ◽  
Marina Vladimirov ◽  
Hao Shi ◽  
Wai Man Mok ◽  
Johann G. Thalhammer ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Nerve Block ◽  
Local Anesthetic ◽  
Drug Application ◽  
Rapid Onset ◽  
Na Channel ◽  
Channel Blockers ◽  
Sciatic Notch ◽  
Structure Activity

Background N-butyl tetracaine has local anesthetic and neurolytic properties. An injection of this drug at the rat sciatic notch produces rapid onset and nerve impairment lasting > 1 week. This study aimed to elucidate the structure-activity relation of various tetracaine derivatives to design better neurolytic agents. Methods N-alkyl tetracaine salts (n = 2-6) were synthesized, and their ability to elicit sciatic nerve impairment of sensory and motor functions in vivo was tested in rats. A single dose (0.1 ml at 37 mM) was administered close to the sciatic nerve at the sciatic notch. Regeneration was assessed morphologically in transverse sections of treated nerves. Finally, the drug potency in blocking Na+ currents was studied under voltage-clamp conditions. Results N-ethyl and N-propyl tetracaine derivatives were non-neurolytic and elicited complete sciatic nerve block lasting 3-7 h. In contrast, N-butyl, N-pentyl, and N-hexyl tetracaine derivatives were strong neurolytic agents and elicited functional impairment of sciatic nerve for > 1 week. All derivatives were strong Na+ channel blockers, more potent than tetracaine if applied intracellularly. External drug application showed marked differences in their wash-in rate: tetracaine > N-hexyl > N-butyl > N-ethyl tetracaine. All derivatives were trapped within the cytoplasm and showed little washout within 7 min. Conclusions When n-alkylation is 4-6, n-alkyl tetracaine appeared as a strong neurolytic agent. Neurolytic derivatives retained their local anesthetic activity and elicited rapid onset of nerve block after injection. Such derivatives are potential local anesthetic-neurolytic dual agents for chemical lesions of the sciatic nerve.

scholarly journals Intraneural Ultrasound-guided Sciatic Nerve Block

2018 ◽  
Vol 129 (2) ◽  
pp. 241-248 ◽  
Author(s):  
Gianluca Cappelleri ◽  
Andrea Luigi Ambrosoli ◽  
Marco Gemma ◽  
Valeria Libera Eva Cedrati ◽  
Federico Bizzarri ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Nerve Block ◽  
Local Anesthetic ◽  
Sciatic Nerve Block ◽  
Effective Volume ◽  
Ultrasound Guided ◽  
Biased Coin Design ◽  
Patient Reported ◽  
Sensory Motor

Abstract What We Already Know about This Topic What This Article Tells Us That Is New Background Both extra- and intraneural sciatic injection resulted in significant axonal nerve damage. This study aimed to establish the minimum effective volume of intraneural ropivacaine 1% for complete sensory-motor sciatic nerve block in 90% of patients, and related electrophysiologic variations. Methods Forty-seven consecutive American Society of Anesthesiologists physical status I-II patients received an ultrasound-guided popliteal intraneural nerve block following the up-and-down biased coin design. The starting volume was 15 ml. Baseline, 5-week, and 6-month electrophysiologic tests were performed. Amplitude, latency, and velocity were evaluated. A follow-up telephone call at 6 months was also performed. Results The minimum effective volume of ropivacaine 1% in 90% of patients for complete sensory-motor sciatic nerve block resulted in 6.6 ml (95% CI, 6.4 to 6.7) with an onset time of 19 ± 12 min. Success rate was 98%. Baseline amplitude of action potential (mV) at ankle, fibula, malleolus, and popliteus were 8.4 ± 2.3, 7.1 ± 2.0, 15.4 ± 6.5, and 11.7 ± 5.1 respectively. They were significantly reduced at the fifth week (4.3 ± 2.1, 3.5 ± 1.8, 6.9 ± 3.7, and 5.2 ± 3.0) and at the sixth month (5.9 ± 2.3, 5.1 ± 2.1, 10.3 ± 4.0, and 7.5 ± 2.7) (P < 0.001 in all cases). Latency and velocity did not change from the baseline. No patient reported neurologic symptoms at 6-month follow-up. Conclusions The intraneural ultrasound-guided popliteal local anesthetic injection significantly reduces the local anesthetic dose to achieve an effective sensory-motor block, decreasing the risk of systemic toxicity. Persistent electrophysiologic changes suggest possible axonal damage that will require further investigation.

Effect of Local Anesthetic Dilution on the Onset Time and Duration of Double-Injection Sciatic Nerve Block

2015 ◽  
Vol 59 (6) ◽  
pp. 287-288
Author(s):  
Gianluca Cappelleri ◽  
Andrea Luigi Ambrosoli ◽  
Stefania Turconi ◽  
Marco Gemma ◽  
Erika Basso Ricci ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Nerve Block ◽  
Local Anesthetic ◽  
Onset Time ◽  
Sciatic Nerve Block ◽  
Double Injection

Mitigation of Direct Neurotoxic Effects of Lidocaine and Amitriptyline by Inhibition of p38 Mitogen-activated Protein Kinase In Vitro  and In Vivo 

2006 ◽  
Vol 104 (6) ◽  
pp. 1266-1273 ◽  
Author(s):  
Philipp Lirk ◽  
Ingrid Haller ◽  
Robert R. Myers ◽  
Lars Klimaschewski ◽  
Yi-Chuan Kau ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
P38 Mapk ◽  
Local Anesthetic ◽  
Apoptotic Cell ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
P38 Mapk Inhibitor ◽  
Mapk Inhibitor

Background Local anesthetic-induced direct neurotoxicity (paresthesia, failure to regain normal sensory and motor function) is a potentially devastating complication of regional anesthesia. Local anesthetics activate the p38 mitogen-activated protein kinase (MAPK) system, which is involved in apoptotic cell death. The authors therefore investigated in vitro (cultured primary sensory neurons) and in vivo (sciatic nerve block model) the potential neuroprotective effect of the p38 MAPK inhibitor SB203580 administered together with a clinical (lidocaine) or investigational (amitriptyline) local anesthetic. Methods Cell survival and mitochondrial depolarization as marker of apoptotic cell death was assessed in rat dorsal root ganglia incubated with lidocaine or amitriptyline either with or without the addition of SB203580. Similarly, in a sciatic nerve block model, the authors assessed wallerian degeneration by light microscopy to detect a potential mitigating effect of MAPK inhibition. Results Lidocaine at 40 mm/approximately 1% and amitriptyline at 100 microm reduce neuron count, but coincubation with the p38 MAPK inhibitor SB203580 at 10 mum significantly reduces cytotoxicity and the number of neurons exhibiting mitochondrial depolarization. Also, wallerian degeneration and demyelination induced by lidocaine (600 mm/approximately 15%) and amitriptyline (10 mm/approximately 0.3%) seem to be mitigated by SB203580. Conclusions The cytotoxic effect of lidocaine and amitriptyline in cultured dorsal root ganglia cells and the nerve degeneration in the rat sciatic nerve model seem, at least in part, to be mediated by apoptosis but seem efficiently blocked by an inhibitor of p38 MAPK, making it conceivable that coinjection might be useful in preventing local anesthetic-induced neurotoxicity.

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