BACKGROUND: People with the Ehlers-Danlos Syndromes (EDS), a group of heritable disorders of connective tissue, often report experiencing dental procedure pain despite local anesthetic (LA) use. Clinicians have been uncertain how to interpret this apparent LA resistance, as comparison of EDS and non-EDS patient experience is limited to anecdotal evidence and small case series. The primary goal of this hypothesis-generating study was to investigate the recalled adequacy of pain prevention with LA administered during dental procedures in a large cohort of people with and without EDS. A secondary exploratory aim asked people with EDS to recall comparative LA experiences. METHODS: We administered an online survey through various social media platforms to people with EDS and their friends without EDS, asking about past dental procedures, LA exposures, and the adequacy of procedure pain prevention. Among EDS respondents who both received LA and recalled the specific LA used, we compared agent-specific pain prevention for lidocaine, procaine, bupivacaine, mepivacaine, and articaine. RESULTS: Among the 980 EDS respondents who had undergone a dental procedure LA, 88% (n = 860) recalled inadequate pain prevention. Among 249 non EDS respondents only 33% (n = 83) recalled inadequate pain prevention (P < 0.001 compared to EDS respondents). The agent with the highest EDS-respondent reported success rate was articaine (30%), followed by bupivacaine (25%), and mepivacaine (22%). CONCLUSIONS: EDS survey respondents reported nearly three times the rate of LA non-response compared to non-EDS respondents, suggesting that LAs were less effective in preventing their pain associated with routine office dental procedures.
Anesthesia, Local ; Anesthetics, Local ; Bupivacaine ; Carticaine ; Cohort Studies ; Connective Tissue ; Dental Care ; Ehlers-Danlos Syndrome ; Friends ; Humans ; Lidocaine ; Mepivacaine ; Procaine ; Social Media ; Surveys and Questionnaires

No abstract available.
Brachial Plexus Block* ; Brachial Plexus* ; Mepivacaine* ; Myoclonus* ; Upper Extremity*

BACKGROUND: The goal of this in vitro study was to investigate the effect of lipid emulsion on vasodilation caused by toxic doses of bupivacaine and mepivacaine during contraction induced by a protein kinase C (PKC) activator, phorbol 12,13-dibutyrate (PDBu), in an isolated endothelium-denuded rat aorta. METHODS: The effects of lipid emulsion on the dose-response curves induced by bupivacaine or mepivacaine in an isolated aorta precontracted with PDBu were assessed. In addition, the effects of bupivacaine on the increased intracellular calcium concentration ([Ca²⁺]ᵢ) and contraction induced by PDBu were investigated using fura-2 loaded aortic strips. Further, the effects of bupivacaine, the PKC inhibitor GF109203X and lipid emulsion, alone or in combination, on PDBu-induced PKC and phosphorylation-dependent inhibitory protein of myosin phosphatase (CPI-17) phosphorylation in rat aortic vascular smooth muscle cells (VSMCs) was examined by western blotting. RESULTS: Lipid emulsion attenuated the vasodilation induced by bupivacaine, whereas it had no effect on that induced by mepivacaine. Lipid emulsion had no effect on PDBu-induced contraction. The magnitude of bupivacaine-induced vasodilation was higher than that of the bupivacaine-induced decrease in [Ca²⁺]ᵢ. PDBu promoted PKC and CPI-17 phosphorylation in aortic VSMCs. Bupivacaine and GF109203X attenuated PDBu-induced PKC and CPI-17 phosphorylation, whereas lipid emulsion attenuated bupivacaine-mediated inhibition of PDBu-induced PKC and CPI-17 phosphorylation. CONCLUSIONS: These results suggest that lipid emulsion attenuates the vasodilation induced by a toxic dose of bupivacaine via inhibition of bupivacaine-induced PKC and CPI-17 dephosphorylation. This lipid emulsion-mediated inhibition of vasodilation may be partly associated with the lipid solubility of local anesthetics.
Anesthetics, Local ; Animals ; Aorta ; Blotting, Western ; Bupivacaine* ; Calcium ; Fura-2 ; In Vitro Techniques ; Mepivacaine* ; Muscle, Smooth, Vascular ; Myosin-Light-Chain Phosphatase ; Phorbol 12,13-Dibutyrate ; Phosphorylation ; Protein Kinase C ; Rats ; Solubility ; Vasodilation*

BACKGROUND: The goal of this in vitro study was to investigate the effect of lipid emulsion on vasodilation caused by toxic doses of bupivacaine and mepivacaine during contraction induced by a protein kinase C (PKC) activator, phorbol 12,13-dibutyrate (PDBu), in an isolated endothelium-denuded rat aorta. METHODS: The effects of lipid emulsion on the dose-response curves induced by bupivacaine or mepivacaine in an isolated aorta precontracted with PDBu were assessed. In addition, the effects of bupivacaine on the increased intracellular calcium concentration ([Ca²⁺]ᵢ) and contraction induced by PDBu were investigated using fura-2 loaded aortic strips. Further, the effects of bupivacaine, the PKC inhibitor GF109203X and lipid emulsion, alone or in combination, on PDBu-induced PKC and phosphorylation-dependent inhibitory protein of myosin phosphatase (CPI-17) phosphorylation in rat aortic vascular smooth muscle cells (VSMCs) was examined by western blotting. RESULTS: Lipid emulsion attenuated the vasodilation induced by bupivacaine, whereas it had no effect on that induced by mepivacaine. Lipid emulsion had no effect on PDBu-induced contraction. The magnitude of bupivacaine-induced vasodilation was higher than that of the bupivacaine-induced decrease in [Ca²⁺]ᵢ. PDBu promoted PKC and CPI-17 phosphorylation in aortic VSMCs. Bupivacaine and GF109203X attenuated PDBu-induced PKC and CPI-17 phosphorylation, whereas lipid emulsion attenuated bupivacaine-mediated inhibition of PDBu-induced PKC and CPI-17 phosphorylation. CONCLUSIONS: These results suggest that lipid emulsion attenuates the vasodilation induced by a toxic dose of bupivacaine via inhibition of bupivacaine-induced PKC and CPI-17 dephosphorylation. This lipid emulsion-mediated inhibition of vasodilation may be partly associated with the lipid solubility of local anesthetics.
Anesthetics, Local ; Animals ; Aorta ; Blotting, Western ; Bupivacaine* ; Calcium ; Fura-2 ; In Vitro Techniques ; Mepivacaine* ; Muscle, Smooth, Vascular ; Myosin-Light-Chain Phosphatase ; Phorbol 12,13-Dibutyrate ; Phosphorylation ; Protein Kinase C ; Rats ; Solubility ; Vasodilation*

BACKGROUND: Mepivacaine induces contraction or decreased blood flow both in vivo and in vitro. Vasoconstriction is associated with an increase in the intracellular calcium concentration ([Ca2+]i). However, the mechanism responsible for the mepivacaine-evoked [Ca2+]i increase remains to be determined. Therefore, the objective of this in vitro study was to examine the mechanism responsible for the mepivacaine-evoked [Ca2+]i increment in isolated rat aorta. METHODS: Isometric tension was measured in isolated rat aorta without endothelium. In addition, fura-2 loaded aortic muscle strips were illuminated alternately (48 Hz) at two excitation wavelengths (340 and 380 nm). The ratio of F340 to F380 (F340/F380) was regarded as an amount of [Ca2+]i. We investigated the effects of nifedipine, 2-aminoethoxydiphenylborate (2-APB), gadolinium chloride hexahydrate (Gd3+), low calcium level and Krebs solution without calcium on the mepivacaine-evoked contraction in isolated rat aorta and on the mepivacaine-evoked [Ca2+]i increment in fura-2 loaded aortic strips. We assessed the effect of verapamil on the mepivacaine-evoked [Ca2+]i increment. RESULTS: Mepivacaine produced vasoconstriction and increased [Ca2+]i. Nifedipine, 2-APB and low calcium attenuated vasoconstriction and the [Ca2+]i increase evoked by mepivacaine. Verapamil attenuated the mepivacaine-induced [Ca2+]i increment. Calcium-free solution almost abolished mepivacaine-induced contraction and strongly attenuated the mepivacaineinduced [Ca2+]i increase. Gd3+ had no effect on either vasoconstriction or the [Ca2+]i increment evoked by mepivacaine. CONCLUSIONS: The mepivacaine-evoked [Ca2+]i increment, which contributes to mepivacaine-evoked contraction, appears to be mediated mainly by calcium influx and partially by calcium released from the sarcoplasmic reticulum.
Animals ; Aorta* ; Calcium* ; Endothelium* ; Fura-2 ; Gadolinium ; Mepivacaine ; Nifedipine ; Rats* ; Sarcoplasmic Reticulum ; Vasoconstriction ; Verapamil

BACKGROUND: To improve residual pain management in acute cervical radiculopathy treated with NSAIDs, the feasibility of early and repeated low-dose interscalene brachial plexus block (IS-BPB) needs to be assessed. METHODS: This was a prospective study on patients receiving NSAIDs (loxoprofen) for cervical radiculopathy of < or = 2-week onset. Pain was assessed using the visual analogue scale (VAS). A low-dose ultrasonography (USG)-guided IS-BPB (dexamethasone [1.65 mg; 0.5 ml] and mepivacaine [1%; 3.0 ml]) was performed at baseline and weekly thereafter for 4 weeks in an outpatient setting for the intervention group. All patients were evaluated using a visual satisfaction score (VSS) at week 4. Patients with baseline VAS scores < 70 (mild to moderate pain; MM group) and > or = 70 (severe pain; SE group) were compared to the controls receiving NSAIDs. RESULTS: A total of 316 IS-BPBs were performed in the intervention group. There was a significant difference in the decline in the VAS from week 0 to week 3 in the MM and SE groups (P < 0.05); however, from week 3 to week 4, the therapeutic effect exhibited no significant difference. Thirteen patients at week 2 (15.5%; MM: 27.7%; SE: 0%), 43 at week 3 (51.2%; MM: 83.0%; SE: 10.8%), and 47 at week 4 (56.0%; MM: 85.1%; SE: 18.9%) achieved a VAS score of < or = 20. Patient satisfaction was high, and the decrease in VAS scores in both groups was significant (P < 0.05) compared to the controls. CONCLUSIONS: Weekly, low-dose, USG-guided IS-BPB can be implemented for early pain relief in acute cervical radiculopathy, with high patient satisfaction.
Anti-Inflammatory Agents, Non-Steroidal* ; Brachial Plexus* ; Humans ; Mepivacaine ; Nerve Block ; Outpatients ; Pain Management ; Patient Satisfaction ; Prospective Studies ; Radiculopathy* ; Ultrasonography

BACKGROUND: Dexmedetomidine extends the duration of nerve block when administered perineurally together with local anesthetics by central and/or peripheral action. In this study, we compared the duration of nerve block between dexmedetomidine and epinephrine as an adjuvant to 1% mepivacaine in infraclavicular brachial plexus block. METHODS: Thirty patients, scheduled for upper limb surgery were assigned randomly to 3 groups of 10 patients each. We performed brachial plexus block using a nerve stimulator. In the control group (group C), patients received 40 ml of 1% mepivacaine. In group E, patients received 40 ml of 1% mepivacaine containing 200 microg of epinephrine as an adjuvant. In group D, patients received 40 ml of 1% mepivacaine containing 1 microg/kg of dexmedetomidine as an adjuvant. Sensory block duration, motor block duration, time to sense pain, and onset time were assessed. We also monitored blood pressure, heart rate, oxygen saturation and bispectral index. RESULTS: In group D and group E, sensory block duration, motor block duration and time to sense first pain were prolonged significantly compared to group C. However, there was no significant difference between group D and group E. CONCLUSIONS: Perineural 1 microg/kg of dexmedetomidine similarly prolonged nerve block duration compared to 200 microg of epinephrine, but slowed heart rate. Thus, dexmedetomidine is expected to be a good alternative as an adjuvant to local anesthesia in patients who are cautioned against epinephrine.
Anesthesia, Local ; Anesthetics, Local ; Blood Pressure ; Brachial Plexus* ; Dexmedetomidine* ; Epinephrine* ; Heart Rate ; Humans ; Mepivacaine* ; Nerve Block ; Oxygen ; Upper Extremity

Although local anesthetics can cause adverse drug reactions (ADRs), most ADRs to local anesthetics are from vasovagal, toxic, or anxiety reactions, while immunoglobulin E (IgE)-mediated anaphylaxis is extremely rare. We report a case of IgE-mediated anaphylactic reaction to lidocaine. A 27-year-old male patient who had two episodes of anaphylactic reactions after local injection of lidocaine was referred to our clinic for the safe use of local anesthetics for the subsequent dental procedure. Skin prick and intradermal tests were performed with amide local anesthetics; lidocaine, bupivacaine, mepivacaine, and ropivacaine. Lidocaine and mepivacaine showed positive response in prick test, and lidocaine, mepivacaine, and bupivacaine showed positive reactions in intradermal test. Only ropivacaine showed negative response both in prick and in intradermal test, and the patient was successfully treated with it. To detect serum-specific IgE, we prepared lidocaine-human serum albumin (HSA) conjugate. Enzyme-linked immunosorbent assay result showed high level of specific IgE to lidocaine-HSA conjugate in serum of the patient. This case suggests that local anesthetics can elicit specific IgE-mediated allergic reactions, and both skin prick and intradermal test should be performed in case of suspected IgE-mediated allergic response to local anesthetics.
Amides ; Anaphylaxis ; Anesthetics, Local ; Anxiety ; Bupivacaine ; Drug Toxicity ; Enzyme-Linked Immunosorbent Assay ; Humans ; Hypersensitivity ; Immunoglobulin E ; Immunoglobulins ; Intradermal Tests ; Lidocaine ; Male ; Mepivacaine ; Serum Albumin ; Skin

BACKGROUND: Laryngopharyngeal reflux (LPR) disease has many symptoms such as globus pharyngeus, excessive throat clearing and hoarseness. The aim of this study was to investigate the effect of stellate ganglion block (SGB) in addition to proton pump inhibitors (PPI) on LPR. METHODS: Fifty patients complaining of more than 3 typical LPR symptoms for over 3 months were enrolled in the study. The P group took PPI for 8 weeks. The SP group took PPI and interwent a series of 8 SGB procedure once a week during the period of treatment. The blocks were performed one at a time unilaterally on the right and left stellate ganglions by injecting 1% mepivacaine 6 ml. We evaluated the reflux symptom index (RSI) before treatment and following 4 weeks and 8 weeks of treatment in both groups. RESULTS: After 4 weeks of treatment, the RSI of the P group decreased, but not significantly, to 16.6 +/- 6.8 compared with the baseline value of 19.2 +/- 2.7 (P = 0.093), whereas the RSI of the SP group decreased significantly to 9.8 +/- 3.3 compared with the baseline value of 19.0 +/- 4.7 (P = 0.000). After 8 weeks of treatment, the RSI of the P group decreased significantly to 13.7 +/- 6.7 (P = 0.001) and the RSI of the SP group also decreased significantly to 7.7 +/- 3.4 (P = 0.000). There were significant differences in the RSI between the two groups after 4 weeks (P = 0.000) and 8 weeks (P = 0.001) of treatment. CONCLUSIONS: The symptoms of LPR improved earlier when PPI therapy was combined with SGB compared with PPI therapy alone.
Hoarseness ; Humans ; Laryngopharyngeal Reflux ; Mepivacaine ; Pharynx ; Proton Pump Inhibitors ; Stellate Ganglion

BACKGROUND: Intravenous lipid emulsion has been used to treat systemic toxicity of local anesthetics. The goals of this in vitro study were to determine the ability of two lipid emulsions (Intralipid(R) and Lipofundin(R) MCT/LCT) to reverse toxic dose local anesthetic-induced vasodilation in isolated rat aortas. METHODS: Isolated endothelium-denuded aortas were suspended for isometric tension recording. Vasodilation was induced by bupivacaine (3 x 10(-4) M), ropivacaine (10(-3) M), lidocaine (3 x 10(-3) M), or mepivacaine (7 x 10(-3) M) after precontraction with 60 mM KCl. Intralipid(R) and Lipofundin(R) MCT/LCT were then added to generate concentration-response curves. We also assessed vasoconstriction induced by 60 mM KCl, 60 mM KCl with 3 x 10(-4) M bupivacaine, and 60 mM KCl with 3 x 10(-4) M bupivacaine plus 1.39% lipid emulsion (Intralipid(R) or Lipofundin(R) MCT/LCT). RESULTS: The two lipid emulsions reversed vasodilation induced by bupivacaine, ropivacaine, and lidocaine but had no effect on vasodilation induced by mepivacaine. Lipofundin(R) MCT/LCT was more effective than Intralipid(R) in reversing bupivacaine-induced vasodilation. The magnitude of lipid emulsion-mediated reversal of vasodilation induced by high-dose local anesthetics was as follows (from highest to lowest): 3 x 10(-4) M bupivacaine-induced vasodilation, 10(-3) M ropivacaine-induced vasodilation, and 3 x 10(-3) M lidocaine-induced vasodilation. CONCLUSIONS: Lipofundin(R) MCT/LCT-mediated reversal of bupivacaine-induced vasodilation was greater than that of Intralipid(R); however, the two lipid emulsions equally reversed vasodilation induced by ropivacaine and lidocaine. The magnitude of lipid emulsion-mediated reversal of vasodilation appears to be correlated with the lipid solubility of the local anesthetic.
Amides ; Anesthetics, Local ; Animals ; Aorta ; Bupivacaine ; Emulsions ; Lidocaine ; Mepivacaine ; Rats ; Solubility ; Vasoconstriction ; Vasodilation