Effects of Intermittent Femoral Nerve Injections of Bupivacaine, Levobupivacaine, and Ropivacaine on Mitochondrial Energy Metabolism and Intracellular Calcium Homeostasis in Rat Psoas Muscle

Abstract

Bupivacaine, levobupivacaine, and ropivacaine injected via femoral nerve block catheters induce a deleterious effect in mitochondrial energy, whereas only levobupivacaine disturbs calcium homeostasis.

Time course of mitochondrial metabolism alterations to repeated injections of bupivacaine in rat muscle

“…After anesthesia with intraperitoneal pentobarbital sodium 40 mgÁkg -1 and a subcutaneous injection of lidocaine 10 mg, a 20G plexus catheter with a 0.9 mm outer diameter (Pajunk, Geisingen, Germany) was inserted under the inguinal ligament near the left femoral nerve sheath, as previously described. 6 In the first phase of the experiment, 12 rats were used for measurement of bupivacaine accumulation in muscle. Then, 41 rats were divided into seven different groups: 1) the first group (n = 5) was the control group (rats without catheter); 2) three groups (n = 6 per group) received normal saline injections (1 mLÁkg -1 , with a delay of eight hours between injections) via the femoral nerve catheter, for total durations of 40, 56, and 112 hr, i.e., five, seven, or 14 injections, respectively; and 3) three groups (n = 6 per group) received 0.25% bupivacaine injections (1 mLÁkg -1 , with a delay of eight hours between injections) via the femoral nerve catheter, for total durations of 40, 56, and 112 hr, i.e., five, seven, or 14 injections, respectively.…”

“…The rats were killed by cervical dislocation eight hours after the last perineural injection when bupivacaine concentration in psoas muscles was below the threshold of detection, i.e., \0.3 lgÁg -1 of tissue. 6 Measurement of bupivacaine accumulation in rat muscle…”

“…6 However, in the case of this experiment, the rats were sacrificed one hour (n = 6) or eight hours (n = 6) after the seventh injection, and a large piece of gracilis muscle was removed to measure bupivacaine concentrations. These concentrations were determined using a high performance chromatographic (HPLC) method, as described previously.…”

“…These concentrations were determined using a high performance chromatographic (HPLC) method, as described previously. 6 Briefly, standard tissue samples containing known amounts of bupivacaine were prepared by spiking homogenized tissues from 1 mgÁmL -1 methanol stock solutions of bupivacaine to yield concentrations from 100-1,000 ngÁmL -1 . The tissue samples were washed in cold isotonic buffer and were then blotted, weighed, and quickly frozen at -80°C.…”

“…3 However, peripheral nerve blocks with durations [ 48 hr increase the odds of local inflammation or infection (odds ratio [OR] 4.61, 95% confidence interval [CI] 1.6-15.9) 2 and can be associated with rare but well-documented bupivacaineinduced myotoxicity. 4 Bupivacaine-induced myotoxicity is associated with alterations in mitochondrial metabolism, 5,6 as previously described in different experimental models ranging from isolated rat mitochondria to human myocytes in culture. Different effects can coexist, including 1) specific inhibition of mitochondrial respiratory chain complex I as observed in isolated mitochondria; 2) oxidative phosphorylation (OXPHOS) uncoupling; and 3) specific inhibition of the enzymatic mitochondrial activity, e.g., citrate synthase.…”