Effects of Adjuvants to Local Anaesthetics on Their Duration

Abstract

The effects of addition of hyaluronic acid (sodium hyaluronate, Healon) to different local anaesthetics of the amide type on the duration of sensory or motor blocks following various regional anaesthetic procedures were studied in animal experiments. In the rat infra-orbital nerve block model, the addition of 0.1-0.5% hyaluronic acid (HA) to 2% prilocaine increased the duration of sensory block of varying degrees in a dose-dependent way by up to 500% of values obtained with plain prilocaine. The duration of degree 5 blocks produced by 0.5% etidocaine and 0.5% bupivacaine was also significantly prolonged when 0.4% HA was included to 206% and 282% of control, respectively, while blocks induced by 2% lidocaine were prolonged to 123% of control. The duration of motor block following spinal anaesthesia in the mouse was prolonged in a dose-dependent way when HA was added to prilocaine, bupivacaine and etidocaine. For solutions containing 0.4% HA, prolongations to 254%, 166% and 134% of control, respectively, were obtained. A concomitant increase of latency to onset of block and failure rate occurred with increasing concentrations of HA. The duration of corneal anaesthesia in the rabbit increased by 57% and 44% when 0.3% HA was added to prilocaine and bupivacaine, respectively. The duration of infiltration anaesthesia was not affected by the addition of HA to the local anaesthetic solutions. Addition of HA had no effect on the onset, depth and duration of prilocaine-induced block of the nervous transmission in vitro. The duration of infra-orbital nerve block and spinal anaesthesia shows a significant relation to the relative viscosity of the local anaesthetic solution.

Hyaluronan Does Not Affect Bupivacaine’s Inhibitory Action on Voltage-Gated Potassium Channel Activities in Bovine Articular Chondrocytes

“…These findings suggest that hyaluronan, if mixed with bupivacaine, may not affect bupivacaine's anesthetic function. It has been reported in animal [17] and human studies [18] that the duration of sensory nerve blockade from bupivacaine is prolonged by addition of hyaluronan. Hassan et al described this extended action of the local anesthetic, but they did not determine the exact mechanism.…”

“…Hassan et al described this extended action of the local anesthetic, but they did not determine the exact mechanism. They speculated that hyaluronan may bind to the local anesthetic drug, thereby delaying the drug's access to the channel proteins [17]. We have previously shown that hyaluronan can prevent bupivacaine-induced chondrotoxicity [11].…”

Rheological blends for drug delivery. II. Prolongation of nerve blockade, biocompatibility, and in vitro–in vivo correlations

“…Thus, the benefits typically achieved by increasing the polymer concentration (and thus the viscosity) of the delivery vehicle are minimized because of the rapid rate of HA hydration. Indeed, this hydration phenomenon may contribute to the inconsistencies in the literature regarding the effectiveness of viscous HA solutions as a delivery vehicle for local anesthetics 15, 20, 21. Blending a lower humectancy polymer such as HPMC reduces the rate of bulk polymer hydration, thereby maintaining a coherent, high‐viscosity gel delivery vehicle for a longer period of time in vivo and facilitating more prolonged bupivacaine release.…”

“…The successful use of polymer solutions (or blends) in drug delivery therefore depends directly on the biophysical properties of the chosen polymers. Hyaluronic acid (HA), a linear polysaccharide composed of alternating units of β‐1,4‐ D ‐glucuronic acid and β‐1,3‐ N ‐acetyl‐ D ‐glucosamine, is of particular interest because of its good biocompatibility, excellent humectancy, and high aqueous solubility; its anionic charge may also be useful to improve the retention of cationic local anesthetics within the matrix 15–22. However, viscoelastic solutions have been inconsistent in prolonging the duration of nerve blockade in vivo .…”

Aptamer-incorporated hydrogels for visual detection, controlled drug release, and targeted cancer therapy

“…Therefore, to slow the drug-release process and prolong drug action, different strategies have been adopted, either by modulating the interaction between the drug and hydrogel matrix or by modifying the gel network. Taking advantage of interactions between ionic polymers and charged loading agents, drugs such as naphazoline [31], NSAIDs [32], anesthetics [33], and amphotericin B [34] have been successfully conjugated to different kinds of hydrogel system for sustained drug release. Drugs can also be covalently linked to polymers, but the release process is initiated by chemical or enzymatic cleavage of the polymer–drug linkage.…”