An absorbable local anesthetic matrix provides several days of functional sciatic nerve blockade

Chi-Fei Wang, Alimorad G. Djalali, Ankur Gandhi, David Knaack, Umberto De Girolami, Gary Strichartz, Peter Gerner

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

BACKGROUND: Functional blockade of peripheral nerves is the primary objective of local anesthesia, and it is often desirable to have a persistent blockade, sustained throughout and beyond a surgical procedure. Current local anesthetics give effective analgesia for <8-12 h after a single bolus injection. We report on an implantable, controlled-release drug delivery system intended for use in bone and consisting of a Food and Drug Administration- approved matrix containing lidocaine that is capable of local delivery for several days. METHODS: XybrexTM, an absorbable, controlled-release delivery system containing 16% (w/w) lidocaine, was implanted next to the sciatic nerve of male rats (300-350 gm), at lidocaine doses of 5.3, 10.6, 16, and 32 mg lidocaine per rat. For comparison, a lidocaine HCl solution (0.2 mL, 2% = 4 mg) was injected in close proximity to the sciatic nerve. Rats were assessed behaviorally for analgesia by a forceps pinch of the lateral digits, and for motor block by quantifying the extensor postural thrust. Potential neurotoxicity of sciatic nerves was evaluated histologically at 24 h, 4 days, and 4 wk after implantation. The kinetics of lidocaine's release from the matrix was measured in vitro by ultraviolet detection of lidocaine in samples collected at 2.5, 6.5, 20, and 24.25 h. RESULTS: Xybrex at the highest doses (300 and 600 mg/kg, containing 16 and 32 mg of lidocaine free base, respectively) provided complete analgesia to an intense pinch for 7.0 ± 2.0 h, 6.9 ± 1.7 h and partial analgesia for 60.0 ± 5.4 h, 58.8 ± 4.2 h, respectively, compared to 0.61 ± 0.03 h of complete analgesia and 0.96 ± 0.03 h of partial analgesia by sciatic block from the 2% lidocaine solution (containing 4 mg lidocaine). These same high doses of Xybrex produced complete motor block for 17.0 ± 3.3 h, 17.6 ± 3.3 h with full recovery in 352.0 ± 55.7 h (14.7 ± 2.3 days), 579.0 ± 36.1 h (24.1 ± 1.5 days) respectively. Data are reported as mean ± se. P ± 0.001 for all Xybrex groups compared to the 2% lidocaine group. Minor local tissue inflammation/pathology, primarily in the connective tissue and muscle 0.1 mm adjacent to the nerve, was observed equally in animals treated with Xybrex and 2% lidocaine solution. There were no behavioral signs of systemic toxicity. The in vitro release followed exponential kinetics and its comparison to the time-course of functional nociceptive deficit implied that the duration of nociception represented the local, immediate interaction of lidocaine between the nerve and the matrix and not a cumulative effect of previously released drug. CONCLUSIONS: Xybrex is an absorbable, controlled-release drug delivery system that provides several days of analgesia for rat peripheral nerves without apparent significant local neurotoxicity or systemic toxicity.

Original languageEnglish
Pages (from-to)1027-1033
Number of pages7
JournalAnesthesia and analgesia
Volume108
Issue number3
DOIs
Publication statusPublished - 2009 Jan 1

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Nerve Block
Sciatic Nerve
Lidocaine
Local Anesthetics
Analgesia
Drug Delivery Systems
Peripheral Nerves
Nociception
Local Anesthesia
United States Food and Drug Administration
Surgical Instruments
Connective Tissue

All Science Journal Classification (ASJC) codes

  • Anesthesiology and Pain Medicine

Cite this

Wang, C-F., Djalali, A. G., Gandhi, A., Knaack, D., De Girolami, U., Strichartz, G., & Gerner, P. (2009). An absorbable local anesthetic matrix provides several days of functional sciatic nerve blockade. Anesthesia and analgesia, 108(3), 1027-1033. https://doi.org/10.1213/ane.0b013e318193596a
Wang, Chi-Fei ; Djalali, Alimorad G. ; Gandhi, Ankur ; Knaack, David ; De Girolami, Umberto ; Strichartz, Gary ; Gerner, Peter. / An absorbable local anesthetic matrix provides several days of functional sciatic nerve blockade. In: Anesthesia and analgesia. 2009 ; Vol. 108, No. 3. pp. 1027-1033.
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abstract = "BACKGROUND: Functional blockade of peripheral nerves is the primary objective of local anesthesia, and it is often desirable to have a persistent blockade, sustained throughout and beyond a surgical procedure. Current local anesthetics give effective analgesia for <8-12 h after a single bolus injection. We report on an implantable, controlled-release drug delivery system intended for use in bone and consisting of a Food and Drug Administration- approved matrix containing lidocaine that is capable of local delivery for several days. METHODS: XybrexTM, an absorbable, controlled-release delivery system containing 16{\%} (w/w) lidocaine, was implanted next to the sciatic nerve of male rats (300-350 gm), at lidocaine doses of 5.3, 10.6, 16, and 32 mg lidocaine per rat. For comparison, a lidocaine HCl solution (0.2 mL, 2{\%} = 4 mg) was injected in close proximity to the sciatic nerve. Rats were assessed behaviorally for analgesia by a forceps pinch of the lateral digits, and for motor block by quantifying the extensor postural thrust. Potential neurotoxicity of sciatic nerves was evaluated histologically at 24 h, 4 days, and 4 wk after implantation. The kinetics of lidocaine's release from the matrix was measured in vitro by ultraviolet detection of lidocaine in samples collected at 2.5, 6.5, 20, and 24.25 h. RESULTS: Xybrex at the highest doses (300 and 600 mg/kg, containing 16 and 32 mg of lidocaine free base, respectively) provided complete analgesia to an intense pinch for 7.0 ± 2.0 h, 6.9 ± 1.7 h and partial analgesia for 60.0 ± 5.4 h, 58.8 ± 4.2 h, respectively, compared to 0.61 ± 0.03 h of complete analgesia and 0.96 ± 0.03 h of partial analgesia by sciatic block from the 2{\%} lidocaine solution (containing 4 mg lidocaine). These same high doses of Xybrex produced complete motor block for 17.0 ± 3.3 h, 17.6 ± 3.3 h with full recovery in 352.0 ± 55.7 h (14.7 ± 2.3 days), 579.0 ± 36.1 h (24.1 ± 1.5 days) respectively. Data are reported as mean ± se. P ± 0.001 for all Xybrex groups compared to the 2{\%} lidocaine group. Minor local tissue inflammation/pathology, primarily in the connective tissue and muscle 0.1 mm adjacent to the nerve, was observed equally in animals treated with Xybrex and 2{\%} lidocaine solution. There were no behavioral signs of systemic toxicity. The in vitro release followed exponential kinetics and its comparison to the time-course of functional nociceptive deficit implied that the duration of nociception represented the local, immediate interaction of lidocaine between the nerve and the matrix and not a cumulative effect of previously released drug. CONCLUSIONS: Xybrex is an absorbable, controlled-release drug delivery system that provides several days of analgesia for rat peripheral nerves without apparent significant local neurotoxicity or systemic toxicity.",
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Wang, C-F, Djalali, AG, Gandhi, A, Knaack, D, De Girolami, U, Strichartz, G & Gerner, P 2009, 'An absorbable local anesthetic matrix provides several days of functional sciatic nerve blockade', Anesthesia and analgesia, vol. 108, no. 3, pp. 1027-1033. https://doi.org/10.1213/ane.0b013e318193596a

An absorbable local anesthetic matrix provides several days of functional sciatic nerve blockade. / Wang, Chi-Fei; Djalali, Alimorad G.; Gandhi, Ankur; Knaack, David; De Girolami, Umberto; Strichartz, Gary; Gerner, Peter.

In: Anesthesia and analgesia, Vol. 108, No. 3, 01.01.2009, p. 1027-1033.

Research output: Contribution to journalArticle

TY - JOUR

T1 - An absorbable local anesthetic matrix provides several days of functional sciatic nerve blockade

AU - Wang, Chi-Fei

AU - Djalali, Alimorad G.

AU - Gandhi, Ankur

AU - Knaack, David

AU - De Girolami, Umberto

AU - Strichartz, Gary

AU - Gerner, Peter

PY - 2009/1/1

Y1 - 2009/1/1

N2 - BACKGROUND: Functional blockade of peripheral nerves is the primary objective of local anesthesia, and it is often desirable to have a persistent blockade, sustained throughout and beyond a surgical procedure. Current local anesthetics give effective analgesia for <8-12 h after a single bolus injection. We report on an implantable, controlled-release drug delivery system intended for use in bone and consisting of a Food and Drug Administration- approved matrix containing lidocaine that is capable of local delivery for several days. METHODS: XybrexTM, an absorbable, controlled-release delivery system containing 16% (w/w) lidocaine, was implanted next to the sciatic nerve of male rats (300-350 gm), at lidocaine doses of 5.3, 10.6, 16, and 32 mg lidocaine per rat. For comparison, a lidocaine HCl solution (0.2 mL, 2% = 4 mg) was injected in close proximity to the sciatic nerve. Rats were assessed behaviorally for analgesia by a forceps pinch of the lateral digits, and for motor block by quantifying the extensor postural thrust. Potential neurotoxicity of sciatic nerves was evaluated histologically at 24 h, 4 days, and 4 wk after implantation. The kinetics of lidocaine's release from the matrix was measured in vitro by ultraviolet detection of lidocaine in samples collected at 2.5, 6.5, 20, and 24.25 h. RESULTS: Xybrex at the highest doses (300 and 600 mg/kg, containing 16 and 32 mg of lidocaine free base, respectively) provided complete analgesia to an intense pinch for 7.0 ± 2.0 h, 6.9 ± 1.7 h and partial analgesia for 60.0 ± 5.4 h, 58.8 ± 4.2 h, respectively, compared to 0.61 ± 0.03 h of complete analgesia and 0.96 ± 0.03 h of partial analgesia by sciatic block from the 2% lidocaine solution (containing 4 mg lidocaine). These same high doses of Xybrex produced complete motor block for 17.0 ± 3.3 h, 17.6 ± 3.3 h with full recovery in 352.0 ± 55.7 h (14.7 ± 2.3 days), 579.0 ± 36.1 h (24.1 ± 1.5 days) respectively. Data are reported as mean ± se. P ± 0.001 for all Xybrex groups compared to the 2% lidocaine group. Minor local tissue inflammation/pathology, primarily in the connective tissue and muscle 0.1 mm adjacent to the nerve, was observed equally in animals treated with Xybrex and 2% lidocaine solution. There were no behavioral signs of systemic toxicity. The in vitro release followed exponential kinetics and its comparison to the time-course of functional nociceptive deficit implied that the duration of nociception represented the local, immediate interaction of lidocaine between the nerve and the matrix and not a cumulative effect of previously released drug. CONCLUSIONS: Xybrex is an absorbable, controlled-release drug delivery system that provides several days of analgesia for rat peripheral nerves without apparent significant local neurotoxicity or systemic toxicity.

AB - BACKGROUND: Functional blockade of peripheral nerves is the primary objective of local anesthesia, and it is often desirable to have a persistent blockade, sustained throughout and beyond a surgical procedure. Current local anesthetics give effective analgesia for <8-12 h after a single bolus injection. We report on an implantable, controlled-release drug delivery system intended for use in bone and consisting of a Food and Drug Administration- approved matrix containing lidocaine that is capable of local delivery for several days. METHODS: XybrexTM, an absorbable, controlled-release delivery system containing 16% (w/w) lidocaine, was implanted next to the sciatic nerve of male rats (300-350 gm), at lidocaine doses of 5.3, 10.6, 16, and 32 mg lidocaine per rat. For comparison, a lidocaine HCl solution (0.2 mL, 2% = 4 mg) was injected in close proximity to the sciatic nerve. Rats were assessed behaviorally for analgesia by a forceps pinch of the lateral digits, and for motor block by quantifying the extensor postural thrust. Potential neurotoxicity of sciatic nerves was evaluated histologically at 24 h, 4 days, and 4 wk after implantation. The kinetics of lidocaine's release from the matrix was measured in vitro by ultraviolet detection of lidocaine in samples collected at 2.5, 6.5, 20, and 24.25 h. RESULTS: Xybrex at the highest doses (300 and 600 mg/kg, containing 16 and 32 mg of lidocaine free base, respectively) provided complete analgesia to an intense pinch for 7.0 ± 2.0 h, 6.9 ± 1.7 h and partial analgesia for 60.0 ± 5.4 h, 58.8 ± 4.2 h, respectively, compared to 0.61 ± 0.03 h of complete analgesia and 0.96 ± 0.03 h of partial analgesia by sciatic block from the 2% lidocaine solution (containing 4 mg lidocaine). These same high doses of Xybrex produced complete motor block for 17.0 ± 3.3 h, 17.6 ± 3.3 h with full recovery in 352.0 ± 55.7 h (14.7 ± 2.3 days), 579.0 ± 36.1 h (24.1 ± 1.5 days) respectively. Data are reported as mean ± se. P ± 0.001 for all Xybrex groups compared to the 2% lidocaine group. Minor local tissue inflammation/pathology, primarily in the connective tissue and muscle 0.1 mm adjacent to the nerve, was observed equally in animals treated with Xybrex and 2% lidocaine solution. There were no behavioral signs of systemic toxicity. The in vitro release followed exponential kinetics and its comparison to the time-course of functional nociceptive deficit implied that the duration of nociception represented the local, immediate interaction of lidocaine between the nerve and the matrix and not a cumulative effect of previously released drug. CONCLUSIONS: Xybrex is an absorbable, controlled-release drug delivery system that provides several days of analgesia for rat peripheral nerves without apparent significant local neurotoxicity or systemic toxicity.

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