Intra-articular bupivacaine : a literature review including a pilot study investigating the safety of intra-articular bupivacaine to chondrocytes

Van Der Merwe, Willem Jacobus (2015-12)

Thesis (MMed)--Stellenbosch University, 2015.

Thesis

ENGLISH ABSTRACT: Background: Today, intra-articular bupivacaine injections are common practice, with very good analgesic effects. This method of analgesia is utilized by general practitioners, orthopedic surgeons and anesthesiologists. Unfortunately, since 2004, more than 200 cases of chondrolysis were noted following intra-articular bupivacaine infusion. Numerous studies have investigated the safety of intra-articular bupivacaine. The aim of this thesis was to quantify the risk of chondrolysis with intra-articular bupivacaine and to guide medical practitioners in safe practice. Methods: A literature review was done of the most recently published original research, meta-analysis and review articles. Adverse outcomes were mostly associated with bupivacaine infusions, rather than with single intra-articular doses of bupivacaine. Limited data on the safety of a single dose of intra-articular bupivacaine was found. We conducted a pilot study to investigate the safety of a single dose of intra-articular bupivacaine. A paired, case-controlled, experiment was done using four merino sheep. The nul hypothesis was that a single dose of intra-articular bupivacaine did not cause chondrolysis when compared with a dose of intra-articular normal saline. Our results were added to the thesis to further quantify the risk. Results: Numerous in vitro and in vivo studies confirmed that bupivacaine is chondrotoxic. The chondrotoxic effect is time, dose and concentration dependent. Our pilot study revealed that single dose intra-articular bupivacaine may also be unsafe for chondrocytes. Conclusion: The administration of intra-articular bupivacaine is toxic to chondrocytes. The chondrotoxic effect of intra-articular bupivacaine is time, dose and concentration dependent. Infusions of intra-articular bupivacaine should be contra-indicated. From the limited data available on single dose intra-articular bupivacaine, it appears that it is also chondrotoxic. Magnesium, morphine and clonidine may be safer for intra-articular use, but this needs further investigation.

AFRIKAANSE OPSOMMING: Agtergrond: Vandag word bupivacaine gebruik as intra-artikulêre inspuiting met baie goeie analgetiese effek. Hierdie metode word ontgin deur, onder andere, algemene praktisyns, ortopediese chirurge en anestesioloë. Sedert 2004 is meer as 200 gevalle van chondrolise aangeteken na die toediening van intra-artikulêre bupivacaine infusies. Talle studies het gevolg om die veiligheid van intra-artikulêre bupivacaine te ondersoek. Die doel van hierdie skripsie is om die risiko verbonde aan intra-artikulêre bupivacaine te kwantifiseer en aan mediese praktisyns veilige riglyne te stel. Metode: ‘n Literatuur oorsig is gedoen, insluitende die mees onlangs gepubliseerde oorspronklike navorsing, meta-analises asook oorsig artikels. Ongunstigde uitkomstes is meestal geassosieer met intra-artikulêre bupivacaine infusies, eerder as met enkel dosering intra-artikulêre bupivacaine. Beperkte data met betrekking tot die gebruik van bupivacaine as enkel dosering intra-artikulêr is beskikbaar. Om die veiligheid van enkel dosering intra-artikulêre bupivacaine te ondersoek is ‘n loodsstudie gedoen. Dit is ‘n gevalle-kontrole in-vivo eksperiment, met vier merino skape. Die nul hipotese is dat ‘n enkel dosering intra-artikulêre bupivacaine nie meer chondrolise veroorsaak, as ‘n enkel dosering intra-artikulêre normale saline nie. Die resultate is ingesluit as deel van die stawende data om die risiko te kwantifiseer. Resultate: Talle in-vitro asook in-vivo studies het bevestig dat bupivacaine chondrotoksies is. Die toksiese effek is tyd, dosis en konsentrasie afhanklik. Ons loodsstudie het ook getoon dat enkel dosering intra-artikulêre bupivacaine moontlik skadelik vir kraakbeen kan wees. Gevolgtrekking: Die toediening van intra-artikulêre bupivacaine is toksies vir chondrosiete. Die chondrotoksiese effek is tyd, dosis en konsentrasie afhanklik. Infusies van intra-artikulêre bupivacaine is dus gekontraïndikeer. Die beperkte data oor enkel dosering intra-artikulêre bupivacaine dui ook moontlik chondrotoksisiteit aan. Magnesium, morfien en clonidine kan moontlik as veiliger alternatief oorweeg word, maar benodig verdere navorsing.

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