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Item Buffered vs. Unbuffered Local Anesthesia in Mandibular Molars Diagnosed with Symptomatic Irreversible Pulpitis: A Controlled, Randomized, Double-Blind Study(2022) Alena, Peter; Spolnik, Kenneth; Ehrlich, Ygal; Warner, NedIntroduction: Profound pulpal anesthesia is not always adequate in mandibular teeth after the administration of local anesthesia, especially in the presence of irreversible pulpitis. Failure to achieve anesthesia has been seen in 30–80% of patients in teeth with a diagnosis of irreversible pulpitis. Onpharma™ developed an FDA-approved device that uses sodium bicarbonate to buffer a standard local anesthetic (LA) solution so that its pH may become closer to its pKa. Claims have been made that buffering a local anesthetic increases the anesthetic’s effect. Previous studies on the anesthetic efficacy of Onpharma’s Onset buffering system were inconclusive and may be dependent on the techniques used. Objectives: The aim of this study is to determine whether a buffered local anesthetic can lead to more profound and faster pulpal anesthesia in mandibular molars diagnosed with symptomatic irreversible pulpitis as compared to a standard, unbuffered local anesthetic. Materials and Methods: 40 total subjects completed the study. Screened and eligible subjects with a mandibular molar diagnosed with symptomatic irreversible pulpitis were randomly allocated into 2 groups so 1 group received a total of 3 cartridges of a standard, unbuffered 2% lidocaine with 1:100,000 epinephrine via inferior alveolar nerve block (IANB) followed by supplemental buccal and lingual infiltrations, while the other received the equivalent yet buffered formulation. An electronic pulp tester (EPT) was used to objectively determine baseline pulpal status of the affected tooth, followed by 2-minute interval testing following the administration of all local anesthesia. The onset of pulpal anesthesia was defined by the first of 2 consecutive EPT=80 readings, and the endodontic treatment could begin. Profound pulpal anesthesia was ultimately determined if the patient reported a comfortable pulpotomy as reflected on the Wong-Baker FACES Visual Analog Scale. Null Hypothesis 1: Subjects possessing mandibular molars diagnosed with symptomatic irreversible pulpitis will not achieve pulpal anesthesia more profoundly using buffered 2% lidocaine w/ 1:100,000 epinephrine in comparison to the standard, unbuffered anesthetic formulation. Null hypothesis 2: Subjects possessing mandibular molars diagnosed with symptomatic irreversible pulpitis will not achieve pulpal anesthesia faster using buffered 2% lidocaine w/ 1:100,000 epinephrine in comparison to the standard, unbuffered anesthetic formulation. Results: We observed a local anesthetic success rate of 45% in the buffered group, 70% in the unbuffered group, and ultimately 57.5% between both groups. The findings further indicate that the VAS scores after pulpotomy is significantly different between the 2 groups (p=0.019), with the unbuffered group having a more profound mean VAS score of 1.2 (as opposed to a buffered mean of 3.1). Regarding the time of onset for pulpal anesthesia, there was no statistically significant difference noted between the buffered and unbuffered groups. Conclusion: Based on the findings of this study, the null hypothesis 1 cannot be rejected since unbuffered 2% lidocaine with 1:100,000 epinephrine had a statistically significant increase in profound pulpal anesthesia compared to the buffered equivalent. The null hypothesis 2 cannot be rejected since there was no evidence of a significant difference in the time to pulpal anesthesia between the buffered and unbuffered groups.Item Efficacy, safety, and impact on procedural outcomes of local anesthesia in endoscopic submucosal dissection: a systematic review and meta-analysis(Taylor & Francis, 2024-07-29) Abosheaishaa, Hazem; Abdelghany, Abdelmalek; Abdallfatah, Abdallfatah; Mohamed, Doha; Bahbah, Ammar Ayman; Mohamed, Islam; Elfert, Khaled; Salem, Ahmed E.; Beran, Azizullah; Madkour, Ahmad; Al-Haddad, Mohammad; Medicine, School of MedicineBackground: Endoscopic submucosal dissection (ESD) has revolutionized the treatment of early stage gastrointestinal cancers. However, ESD can be associated with increased postprocedural pain and higher complication rates. This systematic review and meta-analysis evaluated the efficacy and safety of local anesthesia. Methods: A comprehensive search was conducted to identify relevant randomized controlled trials investigating the effect of local anesthesia in ESD procedures. The Cochrane risk of bias tool for randomized trials was used to assess study quality. A meta-analysis was performed using Review Manager 5.4, with summary measures expressed as pooled odds ratios (OR) or mean differences with corresponding 95% confidence intervals (CI). Results: Four randomized controlled trials with 296 patients undergoing ESD procedures were included. The use of local anesthesia did not significantly impact procedural time (mean difference = -2.05, 95% CI = -9.29, 5.18, I2 = 30%, P = 0.58). Lastly, the use of local anesthesia did not increase the risk of bleeding or other adverse events (P > 0.05) and decreased the incidence of bradycardia (OR = 0.16, 95% CI = 0.03, 0.95; I2 = 0%; P = 0.04). Conclusion: Our study found that the use of local anesthesia did not significantly affect the procedural time of ESD. However, it effectively reduced postoperative pain in some trials with no risk of increased incidence of adverse events.Item Human Nav1.5 F1486 deletion associated with long-QT syndrome leads to deficiency in inactivation and reduces lidocaine sensitivity(2012-03-19) Song, Weihua; Shou, Weinian; Cummins, Theodore R.; Chen, Peng-Sheng; Hudmon, Andrew; Nass, Richard; Khanna, RajeshThe cardiac voltage-gated sodium channel α subunit Nav1.5 generates the cardiac sodium current, which is essential for the initiation and propagation of the cardiac action potentials. Mutations of SCN5A, the gene that encodes Nav1.5, have been well documented to cause long-QT syndrome (LQTs) by disrupting channel inactivation and increasing late sodium current. Previous studies have revealed the importance of the intracellular loop region between transmembrane domain III and IV of sodium channel α subunit in regulating the fast inactivation. A recent clinical case study reported an infant patient with LQTs carrying a phenylalanine (F) deletion at amino acid 1486 of the Nav1.5 channel. This study reported that the patient showed severe cardiac arrhythmia reflected as LQTs and subsequent ventricular tachycardia, which was refractory to antiarrhythmic drug lidocaine treatment. Therefore, it was hypothesized that the deletion of F1486 on Nav1.5 would substantially alter electrophysiological properties of the channel and reduce the potency of lidocaine on sodium channel. Using HEK293 cells and neonatal rat cardiomyocytes, the F1486del channel was functionally characterized by whole-cell patch clamp techniques. Studies revealed that the deletion of F1486 causes a combination of changes including a loss-of-function alteration reflected as a substantial reduction of peak current density and a number of gain-of-function alterations including reduced channel inactivation, substantial augmentation of late sodium current, and an increase in ramp current. In addition, lidocaine sensitivity was dramatically reduced. By contrast, the voltage for half maximal activation (V1/2) and the time constant for channel deactivation for the F1486del channel were identical to the wild type channels. Using neonatal rat cardiomyocytes, we were able to study the functional consequence of F1484del on action potential duration (APD). Cardiomyocytes expressing F1486del channel have substantial APD prolongation and prominent spontaneous early afterdepolarizations, which likely underlie the subsequent LQTs in the patient. Taken together, despite the reduction in peak current density, the substantial gain-of-function changes are sufficient to cause the APD prolongation, which is a prominent characteristic of LQTs. These findings provide knowledge for understanding the relationships between sodium channel structure, pharmacology and the physiological consequence of sodium channel mutations that underlie LQT3.Item Intravenous Lidocaine Infusion for the Management of Early Postoperative Pain: A Comprehensive Review of Controlled Trials(MedWorks Media, 2020-10-15) Chu, Robert; Umukoro, Nelly; Greer, Tiashi; Roberts, Jacob; Adekoya, Peju; Odonkor, Charles A.; Hagedorn, Jonathan M.; Olatoye, Dare; Urits, Ivan; Orhurhu, Mariam Salisu; Umukoro, Peter; Viswanath, Omar; Hasoon, Jamal; Kaye, Alan D.; Orhurhu, Vwaire; Medicine, School of MedicinePreviously used as anti-arrhythmic, intravenous lidocaine infusion is becoming popular for use in management of acute pain. There is still much to be understood about its pharmacokinetics and pharmacodynamics, especially with regard to optimal dosing to avoid side effects. In this article, we selected and reviewed randomized controlled trials to summarize the pharmacokinetics, antinociceptive effects, anti-hyperalgesic effects, anti-inflammatory effects, side effects, and role of intravenous lidocaine in the management of early postoperative pain. The mechanisms of action of lidocaine are still unclear but there are many theories postulated. Optimal dosing of lidocaine is not known but general consensus indicates that a loading dose of 1-2 mg/kg, followed by 1-2 mg/kg/hr continuous infusion during early postoperative pain control while recovering from anesthesia to achieve therapeutic levels of 0.5-5 mcg/kg clearly improves analgesia in the immediate postoperative period. Although lidocaine was initially studied and proven to have clear analgesic effects following laparoscopic and open abdominal surgeries, it has now been shown to be applicable in different clinical settings perioperatively including following spinal, breast, ENT and other surgeries. It is generally safe, with hypotension, headache and vomiting being the more common side effects. Serious adverse effects include cardiovascular block and arrhythmias, neuro-excitability and hypersensitivity, although the frequency of these are not known.