QX-OH/Levobupivacaine: Fixed-dose combination to provide a long-acting postoperative pain of knee surgery in rodents

Although total knee arthroplasty (TKA) is a commonly performed procedure, anesthetic efficacy in post-surgical pain remains an issue. Exparel (45mM liposome bupivacaine), a relatively long-acting local anesthetic, has shown efficacy in blocking peripheral nerve or periarticular infiltration to achie...

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Bibliographic Details
Published in:European journal of pharmaceutical sciences Vol. 111; pp. 418 - 424
Main Authors: Zhao, WenLing, Yang, Jun, Zhang, YuJun, Liu, Jin, Zhang, WenSheng
Format: Journal Article
Language:English
Published: Netherlands Elsevier B.V 01.01.2018
Subjects:
Anesthetics, Local - administration & dosage
Anesthetics, Local - pharmacology
Animals
Arthroplasty, Replacement, Knee - adverse effects
Bupivacaine - administration & dosage
Bupivacaine - analogs & derivatives
Bupivacaine - pharmacology
Drug Therapy, Combination
Levobupivacaine
Lidocaine - administration & dosage
Lidocaine - analogs & derivatives
Lidocaine - pharmacology
Liposome bupivacaine
Local anesthetic toxicity
Nerve Block - methods
Pain Management
Pain, Postoperative - drug therapy
Postoperative analgesia
QX-OH
Rats
Total knee arthroplasty
QX-OH
Total knee arthroplasty
Local anesthetic toxicity
Liposome bupivacaine
Postoperative analgesia
Levobupivacaine
ISSN:0928-0987, 1879-0720, 1879-0720
Online Access:Get full text
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Summary:Although total knee arthroplasty (TKA) is a commonly performed procedure, anesthetic efficacy in post-surgical pain remains an issue. Exparel (45mM liposome bupivacaine), a relatively long-acting local anesthetic, has shown efficacy in blocking peripheral nerve or periarticular infiltration to achieve better post-TKA analgesia. In the present work, we tested whether a fixed-dose combination of QX-OH (35mM) and levobupivacaine (10mM) (QX-OH/LB) could confer longer-lasting pain relief and reduce periarticular tissue toxicity compared to liposome bupivacaine (45mM) after TKA operation. In the sciatic nerve block, the duration of sensory block by QX-OH/LB was 2-fold higher than by liposome bupivacaine (median [25th, 75th percentiles], 9.83 [9.33, 10.83] hours versus 4.83 [4.83, 5] hours; P=0.001). Liposome bupivacaine failed to improve post-surgical travel distance and speed (P=0.373) in rats 6h after TKA surgery (versus saline). Similar results were observed in operated mice treated with liposome bupivacaine. However, QX-OH/LB increased locomotor activities markedly both in rats and mice at 6h post-TKA (P<0.001). In addition, there was no difference in the inflammatory recruitment and articular structural damage among murine models-treated with QX-OH/LB, liposome bupivacaine and saline. In conclusion, we show that QX-OH/LB is a safe and long-lasting anesthetic than liposome bupivacaine in the post-TKA pain management in murine models. [Display omitted]
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ISSN:0928-0987
1879-0720
1879-0720
DOI:10.1016/j.ejps.2017.10.025