Dexamethasone Does not Compensate for Local Anesthetic Cytotoxic Effects on Tenocytes : Morphine or Morphine Plus Dexamethasone May Be a Safe Alternative

Purpose: The purposes of this in vitro study were to investigate whether the addition of dexamethasone can compensate for any cytotoxic effects of the amide-type local anesthetics (LA) bupivacaine and ropivacaine and whether morphine and morphine-6-glucuronide (M6G) may be a safe alternative for peritendinous application.

Methods: Biopsies of human biceps tendons (n = 6) were dissected and cultivated. Cells were characterized by the expression for tenocyte markers, collagen I, biglycan, tenascin C, scleraxis, and RUNX via reverse transcriptase-polymerase chain reaction and immunohistochemistry. Tenocytes were incubated with bupivacaine, ropivacaine, morphine, M6G, or a saline control with and without addition of dexamethasone for 15, 60, or 240 min. Cell viability was determined by quantifying the presence of adenosine-triphosphate.

Results: Significant time-dependent cytotoxic effects were observed for LA after all exposure times. After 15, 60, and 240 minutes, cell viability decreased to 81.1%, 49.4% and 0% (P < .001) for bupivacaine and to 81.4%, 69.6%, and 9.3% (P < .001) for ropivacaine compared to saline control. Dexamethasone did not compensate for these cytotoxic effects. Cell viability was not affected after 15, 60-min exposures to morphine and M6G but decreased significantly (P < .001) after 240 minutes compared to saline control. However, in combination with dexamethasone, tenocyte viability was significantly increased at all times for morphine (P < .01) and at 15 and 60 minutes for M6G (P < .01).

Conclusions: The results showed that amide-type LA have a time-dependent cytotoxic effect on human tenocytes in vitro, which could not be compensated for by dexamethasone, whereas morphine and M6G had no cytotoxic effects on tenocytes after 15 and 60 minutes. The addition of dexamethasone to morphine and M6G had a positive effect on viability, which increased significantly compared to the opioids.

Clinical relevance: It is known that amide-type local anesthetics used for local joint analgesia have chondrotoxic side-effects. The combined application of morphine and dexamethasone may be a safe alternative.


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