Lack of concentration-dependent local toxicity of highly concentrated (5%) versus conventional 0.5% bupivacaine following musculoskeletal surgery in a rat model.
Bupivacaine
Continuous wound infusion
Femoral surgery
Histopathology
Local anesthetics
Spinal surgery
Journal
Journal of experimental orthopaedics
ISSN: 2197-1153
Titre abrégé: J Exp Orthop
Pays: Germany
ID NLM: 101653750
Informations de publication
Date de publication:
08 Mar 2023
08 Mar 2023
Historique:
received:
30
11
2022
accepted:
01
03
2023
entrez:
8
3
2023
pubmed:
9
3
2023
medline:
9
3
2023
Statut:
epublish
Résumé
Various sustained-release formulations incorporate high bupivacaine concentrations but data on local toxicity is lacking. This study explores local toxic effects of highly concentrated (5%) bupivacaine compared to clinically used concentrations in vivo following skeletal surgery, to assess the safety of sustained-release formulations with high bupivacaine concentrations. Sixteen rats underwent surgery, in which screws with catheters affixed were implanted in the spine or femur in a factorial experimental design, allowing single-shot or continuous 72 h local administration of 0.5%, 2.5% or 5.0% bupivacaine hydrochloride. During the 30-day follow-up, animal weight was recorded and blood samples were obtained. Implantation sites underwent histopathological scoring for muscle damage, inflammation, necrosis, periosteal reaction/thickening and osteoblast activity. Effects of bupivacaine concentration, administration mode and implantation site on local toxicity scores were analyzed. Chi-squared tests for score frequencies revealed a concentration-dependent decrease in osteoblast count. Moreover, spinal screw implantation led to significantly more muscle fibrosis but less bone damage than femoral screw implantation, reflecting the more invasive muscle dissection and shorter drilling times related to the spinal procedure. No differences between bupivacaine administration modes regarding histological scoring or body weight changes were observed. Weight increased, while CK levels and leukocyte counts decreased significantly during follow-up, reflecting postoperative recovery. No significant differences in weight, leukocyte count and CK were found between interventional groups. This pilot study found limited concentration-dependent local tissue effects of bupivacaine solutions concentrated up to 5.0% following musculoskeletal surgery in the rat study population.
Identifiants
pubmed: 36884187
doi: 10.1186/s40634-023-00591-2
pii: 10.1186/s40634-023-00591-2
pmc: PMC9995632
doi:
Types de publication
Journal Article
Langues
eng
Pagination
21Informations de copyright
© 2023. The Author(s).
Références
J Toxicol Pathol. 2016;29(3 Suppl):49S-103S
pubmed: 27621538
Pharmacotherapy. 2013 Apr;33(4):383-91
pubmed: 23553809
Tissue Eng Part A. 2010 Sep;16(9):2861-70
pubmed: 20528102
Comp Med. 2019 Dec 1;69(6):451-467
pubmed: 31896391
Can J Anaesth. 1994 Aug;41(8):733-7
pubmed: 7923523
J Pain. 2021 Nov;22(11):1385-1395
pubmed: 33964414
J Vis Exp. 2014 Oct 09;(92):e51558
pubmed: 25350129
Acta Anaesthesiol Scand. 1968;12(4):153-69
pubmed: 4896937
Anesthesiol Clin North Am. 2005 Mar;23(1):21-36
pubmed: 15763409
J Pharmacokinet Biopharm. 1974 Aug;2(4):313-35
pubmed: 4449008
Anesthesiology. 2013 Apr;118(4):934-44
pubmed: 23392233
J Pain Res. 2017 Dec 13;10:2807-2813
pubmed: 29263696
Altern Lab Anim. 2004 Sep;32 Suppl 2:49-51
pubmed: 15601226
Anesth Analg. 1993 Nov;77(5):1048-56
pubmed: 8105724
Reg Anesth Pain Med. 2004 Jul-Aug;29(4):333-40
pubmed: 15305253
Clin Pharmacol Ther. 2018 Jun;103(6):943-945
pubmed: 29570781
Exp Toxicol Pathol. 2004 Jul;55(6):433-49
pubmed: 15384249
Clin Drug Investig. 2013 Feb;33(2):109-15
pubmed: 23229686
Mater Today (Kidlington). 2017 Jan-Feb;20(1):22-31
pubmed: 28970739
Front Pain Res (Lausanne). 2021 Aug 20;2:723883
pubmed: 35295435
Acta Orthop Scand. 1994 Oct;65(5):559-63
pubmed: 7801763
Can Med Assoc J. 1959 Jun 1;80(11):872-3
pubmed: 13662938
J Neurosurg Spine. 2016 Jul;25(1):88-93
pubmed: 26943250
Br J Anaesth. 1997 May;78(5):507-14
pubmed: 9175963
Anesthesiology. 2012 Apr;116(4):841-56
pubmed: 22343474
Orthopedics. 2002 Nov;25(11):1259-62
pubmed: 12452343
Acta Biomater. 2022 Jul 1;146:145-158
pubmed: 35562007
Anesth Analg. 2003 Aug;97(2):512-519
pubmed: 12873946