Myotoxicity of Dexamethasone as an off-label adjuvant to Bupivacaine in a rat model
Franz Josef Nierscher*, Daniel Lahner*#, Claudia Kaibl#, Soheyl Bahrami#, Peter Marhofer§, Gerhard Fritsch*
* Anesthesia and General Intensive Care, AUVA-Trauma Center, Vienna, Austria
# Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria
§ Anaesthesia, General Intensive Care, and Pain Medicine, Medical University of Vienna, Vienna, Austria
Correspondence to: [email protected]
After local intramuscular injection of Bupivacaine inflammation, edema, and necrosis can occur . Up to date mechanisms of toxicity have not been completely discovered. Some pathways including the imbalance of the intracellular Ca++ homeostasis and stimulated autophagosome activity with impaired clearance have been claimed responsible . In clinical practice Dexamethasone has evolved as an off-label local anesthetic adjuvant in peripheral nerve blocks . However, little information is available on its myotoxic effects. This study was designed to investigate the short-term myotoxic potential of Dexamethasone as an off-label adjuvant to Bupivacaine in a rat model.
Materials and Methods
After approval by the animal use committee of the city of Vienna (MA58/870834/2016/13, Vienna, Austria) 20 male Sprague Dawley rats were studied in four groups. Under general anesthesia 200 µl of the study medication was slowly injected into the right quadriceps muscle. Group B received 0.5% Bupivacaine alone, group BD received 0.5% Bupivacaine + 80µg Dexamethasone (equals 8mg Dexamethasone/20ml Bupivacaine 0.5%), group D received 200µl 0.9% normal saline + 80µg Dexamethasone, and group N received 0.9% normal saline. Plasma Creatine Kinase (CK) levels were obtained 3 (T1) and 24 (T2) hours after injection. Animals were sacrificed 48 hours after injection and muscle samples obtained. After fixation and hematoxylin and eosin staining, a blinded pathologist examined the samples by light microscopy. Muscle damage was graded using the Benoit-Yagiela-Ferrell Damage Scoring System (Table 1) . We used the Kruskal-Wallis test and performed post-hoc testing using the Dunn’s multiple comparison test with adjusted P values for comparison among groups.
The plasma CK levels three and 24 hours after the injection are shown in figure 1. A significant difference was observed between the groups in T1 (Figure 1). Within groups B and BD plasma levels of CK decreased significantly from T1 to T2 (Figure 1). The Benoit-Yagiela-Ferrell damage score differed significantly between the BD and D group, between the BD and N group, and not between the other groups (Figure 2).
According to our results, the use of Dexamethasone as an off-label adjuvant to Bupivacaine does not appear more myotoxic than Bupivacaine alone. CK was described to start leaking from damaged muscle cells shortly after intramuscular Bupivacaine injection. In addition, the increase of plasma CK levels was reported to reflect the amount of muscle damage in a linear manner in both humans and rats . We also observed an almost threefold plasma CK increase in the B and BD group at T1, whereas the D and N group remained within the normal range. Its return to normal range at T2 in the B and BD group indicates myofibrillar lysis . This is in agreement with our histology samples obtained 48 hours after injection that showed extensive muscle necrosis in almost all animals of group BD and in some of group B. We conclude that the use of off-label Dexamethasone as Bupivacaine adjuvant does not alter short-term myotoxicity induced by Bupivacaine alone. The long-term effect remains to be studied.
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