Bupivacaine is widely used as a local anesthetic. Central nervous system (CNS) and cardiovascular toxicity are well known side effects. However, there has been no report of bupivacaine-induced myocardial injury. We present a case of bupivacaine cardiac toxicity mimicking an acute non-ST segment elevation myocardial infarction, which was eventually diagnosed as bupivacaine-induced cardiac toxicity without CNS toxicity. As soon as a healthy young woman at a private clinic was given a spinal anesthesia of 6mg bupivacaine for hemorrhoidectomy, she developed arrhythmia and hypotension. She was transferred to our emergency room. There was an accelerated idioventricular rhythm with ST segment depression on electrocardiogram, coarse breathing sounds with rales on whole lung field and a butterfly sign on the chest radiograph. 2D transthoracic echocardiography (TTE) revealed reduced left ventricle systolic ejection fraction (approximately 27%). There was regional wall motion abnormality of the left ventricle on 2D TTE and the cardiac marker was increased. We diagnosed the patient as having acute non-ST segment elevation myocardial infarction but her impaired cardiac function improved gradually. On the seventh day from admission, there was a complete spontaneous recovery of cardiac function, and coronary angiography revealed a normal coronary artery. Therefore, we firmly believe that bupivacaine directly injures the cardiac cell.
Myocardium/*pathology ; Myocardial Infarction/chemically induced/*diagnosis/etiology ; Humans ; Heart/*drug effects ; Female ; Electrocardiography ; Diagnosis, Differential ; Bupivacaine/*adverse effects ; Adult

PURPOSE: Intravenous lipid emulsions have been used to treat the systemic toxicity of local anesthetics. The goal of this in vitro study was to examine the effects of lipid emulsions on the norepinephrine-mediated reversal of vasodilation induced by high doses of levobupivacaine, ropivacaine, and mepivacaine in isolated endothelium-denuded rat aorta, and to determine whether such effects are associated with the lipid solubility of local anesthetics. MATERIALS AND METHODS: The effects of lipid emulsions (0.30, 0.49, 1.40, and 2.61%) on norepinephrine concentration-responses in high-dose local anesthetic (6x10-4 M levobupivacaine, 2x10-3 M ropivacaine, and 7x10-3 M mepivacaine)-induced vasodilation of isolated aorta precontracted with 60 mM KCl were assessed. The effects of lipid emulsions on local anesthetic- and diltiazem-induced vasodilation in isolated aorta precontracted with phenylephrine were also assessed. RESULTS: Lipid emulsions (0.30%) enhanced norepinephrine-induced contraction in levobupivacaine-induced vasodilation, whereas 1.40 and 2.61% lipid emulsions enhanced norepinephrine-induced contraction in both ropivacaine- and mepivacaine-induced vasodilation, respectively. Lipid emulsions (0.20, 0.49 and 1.40%) inhibited vasodilation induced by levobupivacaine and ropivacaine, whereas 1.40 and 2.61% lipid emulsions slightly attenuated mepivacaine (3x10-3 M)-induced vasodilation. In addition, lipid emulsions attenuated diltiazem-induced vasodilation. Lipid emulsions enhanced norepinephrine-induced contraction in endothelium-denuded aorta without pretreatment with local anesthetics. CONCLUSION: Taken together, these results suggest that lipid emulsions enhance the norepinephrine-mediated reversal of local anesthetic-induced vasodilation at toxic anesthetic doses and inhibit local anesthetic-induced vasodilation in a manner correlated with the lipid solubility of a particular local anesthetic.
Amides/adverse effects ; Anesthetics, Local/*adverse effects ; Animals ; Bupivacaine/adverse effects/analogs & derivatives ; Emulsions/*chemistry/*therapeutic use ; Lipids/*chemistry ; Male ; Mepivacaine/adverse effects ; Norepinephrine/*therapeutic use ; Rats ; Rats, Sprague-Dawley ; Vasodilation/*drug effects

OBJECTIVETo observe the intervention effect of electroacupuncture (EA) at "Weizhong" (BL 40) on rats with bupivacaine-induced multifidus muscle injury, so as to explore the action mechanism.

METHODSA total of 72 rats were randomly divided into a control group, a model group, a Weizhong group and a Shenshu group, 18 rats in each group. Each group was again randomly divided into a 4-day subgroup, a 7-day subgroup and a 14-day subgroup, 6 rats in each subgroup. Rats in the model group, Weizhong group and Shenshu group were treated with intramuscular injection of 0.5% bupivacaine (BPVC) to establish the model of multifidus muscle injury. Rats in the Weizhong group and Shenshu group were treated with EA at "Weizhong" (BL 40) and "Shenshu" (BL 23), 20 min per treatment, once a day. Each subgroup was treated for 4 days, 7 days and 14 days respectively. Rats in the control group and model group were treated with immobilization. The morphology and cross sectional area (CSA) changes of multifidus with HE and Masson staining at different time points were observed; the expression of insulin like growth factor 1 (IGF-1) and myogenic differentiation antigen (MyoD) was measured by immunohistochemical method.

RESULTSAfter the modeling, there were significant morphology changes of multifidus at different time points, which was not fully recovered after 14 days. The morphological observation in the Weizhong group and Shenshu group was superior to that in the model group. At 7th day, the CSA in the Weizhong group was higher than that in the model group (P < 0.05); at 14th day, the CSA in the Weizhong group and Shenshu group was higher than that in the model group (P < 0.01, P < 0.05). At 4th day and 7th day, the expression of IGF-1 in the model group was higher than that in the control group (both P < 0.01); at 4th day, that in the Weizhong group was higher than that in the model group (P < 0.01), and that in the Weizhong group was higher than that in the Shenshu group (P < 0.05), and that in the Shenshu group was as higher than that in the model group (P < 0.05); at 14th day, that in the Shenshu group was higher than that in the model and Weizhong group (P < 0.01). At 4th day, the expression of MyoD in the Weizhong group and Shenshu group was higher than that in the model group (P < 0.01), which was more significant in the Weizhong group (P < 0.01).

CONCLUSIONElectroacupuncture at "Weizhong" (BL 40) and "Shenshu" (BL 23) can both promote the regeneration of multifidus muscle injury. EA at "Weizhong" (BL 40) has a better effect at early phase, which may be related to the up-regulation of IGF-1 and MyoD and the completion of the proliferation of myoblast in advance.

Acupuncture Points ; Anesthetics, Local ; adverse effects ; Animals ; Bupivacaine ; adverse effects ; Electroacupuncture ; Humans ; Male ; Muscles ; injuries ; physiopathology ; Muscular Diseases ; chemically induced ; physiopathology ; therapy ; Rats ; Rats, Sprague-Dawley ; Regeneration

A 49-year-old female presented with bilateral abducens nerve palsies. She had 75 prism diopter esotropia. The extraocular movement of the lateral rectus was -1 limitation for the right eye and -4 limitations for the left. After performing orbital magnetic resonance imaging (MRI), 2 mL of bupivacain (5 mg/mL) was injected into the left lateral rectus (LR). One month after injection, a further orbital MRI was performed. Subsequently, recession of both medial rectus (6 mm) and resection of the left LR (9 mm) were performed. After one month, bupivacaine had no hypertrophic effects. There was little change in angle of deviation. The orbital MRI scan showed a 1.91% increase in volume compared to the muscle prior to the injection. Histological findings showed no muscle fibers of the left LR muscle, only the fiber nucleus and the collagen that replaced the fibers. We report on the changes in stiffness and muscle volume and on the histology of the muscle one month after injecting bupivacaine into the paralyzed left LR muscle combined with standard surgical treatment.
Abducens Nerve/*pathology ; Abducens Nerve Diseases/*drug therapy/pathology ; Anesthetics, Local/*administration & dosage/adverse effects ; Bupivacaine/*administration & dosage/adverse effects ; Female ; Humans ; Magnetic Resonance Imaging ; Middle Aged

OBJECTIVETo investigate the effects, side-effects and security of bupivacaine, ropivacaine combined with fentanyl in postoperative continuous epidural analgesia.

METHODSA total of 1 600 postoperative continuous epidural analgesia patients receiving different agents in SICU were divided into two groups: 0.1% bupivacaine +5 microg/ml fentanyl group (group B, n = 920) and 0.2% ropivacaine +2 microg/ml fentanyl group (group R, n = 680). The effects (visual analog-scale score and content to analgesia), side effects were analyzed retrospectively in the two groups.

RESULTSCompared with group B, patients in group R had higher analgesia contentment (P < 0.05), but no difference in visual analog-scale score was found in the two groups. The incidences of urinary retention, nausea and vomiting, skin itching in group B were significantly higher than those in group R (P < 0.05). In each group, patients over sixty had higher ratio of hypotension than those under sixty (P < 0.05); The female patients had a higher incidence of nausea and vomiting than male patients (P < 0.05); The incidence of debility and numbness of lower limbs in patients with lumbar segments epidural analgesia was higher than those with thoracic analgesia (P < 0.05).

CONCLUSIONS0.1% bupivacaine +5 microg/ml fentanyl and 0.2% ropivacaine +2 microg/ml fentanyl can provide adequate pain relief in postoperative continuous epidural analgesia, and 0.2% ropivacaine +2 microg/ml fentanyl comes with less side effects. The incidence of complication is related with analgesics, age, gender and the position of epidural puncture.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Amides ; administration & dosage ; adverse effects ; Analgesia, Epidural ; adverse effects ; methods ; Analgesia, Obstetrical ; adverse effects ; methods ; Analgesics, Opioid ; administration & dosage ; adverse effects ; Anesthetics, Local ; administration & dosage ; adverse effects ; Bupivacaine ; administration & dosage ; adverse effects ; Female ; Fentanyl ; administration & dosage ; adverse effects ; Humans ; Male ; Middle Aged ; Pain, Postoperative ; prevention & control ; Retrospective Studies

BACKGROUNDSpinal anesthesia was considered as a reasonable anesthetic option in severe preeclampsia when cesarean delivery is indicated, and there is no indwelling epidural catheter or contraindication to spinal anesthesia. However, the ideal dose of intrathecal bupivacaine has not been quantified for cesarean delivery for severe preeclamptic patients. This study aimed to determine the ED 50 and ED 95 of intrathecal bupivacaine for severely preeclamptic patients undergoing elective cesarean delivery.

METHODSTwo hundred severely preeclamptic patients are undergoing elective cesarean delivery under combined spinal-epidural anesthesia enrolled in this randomized, double-blinded, dose-ranging study. Patients received 4 mg, 6 mg, 8 mg, or 10 mg intrathecal hyperbaric bupivacaine with 2.5 μg sufentanil. Successful spinal anesthesia was defined as a T6 sensory level achieved within 10 minutes after intrathecal drug administration and/or no epidural supplement was required during the cesarean section. The ED 50 and ED 95 were calculated with a logistic regression model.

RESULTSED 50 and ED 95 of intrathecal bupivacaine for successful spinal anesthesia were 5.67 mg (95% confidence interval [CI]: 5.20-6.10 mg) and 8.82 mg (95% CI: 8.14-9.87 mg) respectively. The incidence of hypotension in Group 8 mg and Group 10 mg was higher than that in Group 4 mg and Group 6 mg (P < 0.05). The sensory block was significantly different among groups 10 minutes after intrathecal injection (P < 0.05). The use of lidocaine in Group 4 mg was higher than that in other groups (P < 0.05). The use of phenylephrine in Group 8 mg and Group 10 mg was higher than that in the other two groups (P < 0.05). The lowest systolic blood pressure before the infant delivery of Group 8 mg and Group 10 mg was lower than the other two groups (P < 0.05). The satisfaction of muscle relaxation in Group 4 mg was lower than other groups (P < 0.05). There was no significant difference in patients' satisfaction and the newborns' Apgar score and the blood gas analysis of umbilical artery serum (P > 0.05).

CONCLUSIONOur study showed that the ED 50 and ED 95 of intrathecal bupivacaine for severely preeclamptic patients undergoing elective cesarean delivery were 5.67 mg and 8.82 mg, respectively. In addition, decreasing the dose of intrathecal bupivacaine could reduce the incidence of maternal hypotension.

Adult ; Anesthesia, Epidural ; Anesthesia, Spinal ; adverse effects ; methods ; Blood Pressure ; physiology ; Bupivacaine ; administration & dosage ; adverse effects ; therapeutic use ; Cesarean Section ; Double-Blind Method ; Female ; Humans ; Male ; Sufentanil ; administration & dosage ; adverse effects ; therapeutic use

OBJECTIVETo investigate the effect of KN93, a calmodulin-dependent protein kinase II (CaMK II) inhibitor, on SH-SY5Y cell injury induced by bupivacaine hydrochloride.

METHODSSH-SY5Y cells exposed for 24 h to 1 mmol/L KN93, 1 mmol/L bupivacaine hydrochloride, or both were examined for morphological changes and Cav3.1 protein expressions using Western blotting. The vitality and apoptosis rate of the cells at different time points during the exposures were assessed with MTT assay and flow cytometry, respectively.

RESULTSBupivacaine hydrochloride exposure caused obvious cell morphologial changes, reduced cell viability, increased cell apoptosis, and enhanced Cav3.1 protein expression. All these changes were partly reversed by treatment of the cells with 1 mmol/L KN93.

CONCLUSIONSCaMKII may play a role in bupivacaine hydrochloride-induced SH-SY5Y cells injury, which is related with upregulated Cav3.1 protein expression.

Apoptosis ; Bupivacaine ; adverse effects ; Calcium Channels, T-Type ; metabolism ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; antagonists & inhibitors ; metabolism ; Cell Line ; Cell Survival ; Humans ; Up-Regulation

OBJECTIVETo compare efficacy and side effects of patient-controlled epidural analgesia (PCEA) with levobupivacaine, ropivacaine and racemic bupivacaine after cesarean section.

METHODSIn this prospective, randomized double-blind study, 90 ASA I-II full-term nulliparous women (aged 25-38 years with body weight of 59-87 kg) undergoing elective cesarean section under spinal-epidural anesthesia equally allocated into 3 groups. PCEA was administered with 0.125% levobupivacaine and 20 microg/ml morphine (group L, n=30), 0.125% ropivacaine and 20 microg/ml morphine (group R, n=30), and 0.125% bupivacaine and 20 microg/ml morphine (group B, n=30), respectively. The Visual Analog Scale (VAS) score, satisfaction rate, patients' overall impression of treatment, modified Bromage motor score, and incidence of side effects were recorded at regular intervals after operation.

RESULTSThe three groups were comparable with respect to the efficacy of analgesia, patients' overall impression of treatment, motor blockade and side effects. There was significant difference in patients' satisfaction rate between group R (70%) and the other two groups (93.3% in group L and 96.6% in group B, P<0.05).

CONCLUSIONPCEA with 0.125% levobupivacaine and morphine 20 microg/ml produces better analgesic effect with little side effects after cesarean section.

Adult ; Amides ; administration & dosage ; adverse effects ; Analgesia, Epidural ; Analgesia, Obstetrical ; Analgesia, Patient-Controlled ; Bupivacaine ; administration & dosage ; adverse effects ; analogs & derivatives ; Cesarean Section ; Double-Blind Method ; Drug Therapy, Combination ; Female ; Humans ; Morphine ; administration & dosage ; Nausea ; chemically induced ; Pregnancy ; Prospective Studies ; Pruritus ; chemically induced ; Treatment Outcome ; Vomiting ; chemically induced

Although levobupivacaine (LBUP) is less cardiotoxic than racemic bupivacaine (RBUP), the resuscitation from the LBUP-induced cardiovascular collapse (CVC) has not been easy as expected. Following the recent reports that proposed the resuscitative action of insulin for the RBUP-induced CVC, a controlled trial was performed to assess the feasibility of insulin for the LBUP-induced CVC. Fourteen dogs were randomly allocated into two groups: the RBUP and LBUP groups. Each group received continuous intravenous infusions of RBUP or LBUP until the mean arterial pressure (MAP) reached 40 mmHg. Then, an intravenous bolus of insulin (2 U/kg) was administered. Both groups were successfully resuscitated. At CVC, a decrease of cardiac output and an increase of systemic vascular resistance were observed but to a lesser degree in the LBUP group (p<0.05). After insulin injection, the MAP further declined to under 40 mmHg for several minutes, which was more protracted in the LBUP group (p<0.05). The CVCs induced by LBUP or RBUP in anesthetized dogs could be successfully resuscitated by insulin. Compared with RBUP, however, the less degree of vasoconstriction by LBUP and the innate vasodilatory property of insulin yielded a delayed increment of MAP during the immediate resuscitation period in the LBUP-induced CVC.
Treatment Outcome ; Overdose ; Male ; Insulin/*administration & dosage ; Heart Arrest/*chemically induced/physiopathology/*prevention & control ; Drug Combinations ; Dose-Response Relationship, Drug ; Dogs ; Cardiopulmonary Resuscitation/methods ; Cardiac Output/*drug effects ; Bupivacaine/*adverse effects/analogs & derivatives ; Blood Pressure/*drug effects ; Blood Flow Velocity/drug effects ; Animals ; Anesthetics, Local