-
Minerva Cardiology and Angiology Dec 2023To evaluate the clinical outcomes of oral mexiletine (oMXT) to treat ventricular tachyarrhythmias (VTAs) in the era of implantable cardioverter-defibrillator (ICD)...
INTRODUCTION
To evaluate the clinical outcomes of oral mexiletine (oMXT) to treat ventricular tachyarrhythmias (VTAs) in the era of implantable cardioverter-defibrillator (ICD) technology.
EVIDENCE ACQUISITION
A systematic search was conducted using PubMed, Embase and Cochrane databases following the PRISMA guidelines to collect literature data reporting oMXT efficacy and safety outcomes in treating VTAs in ICD recipients.
EVIDENCE SYNTHESIS
Final analysis included four studies accounting for a total of 91 patients with recurrent VTAs treated with oMXT. Amiodarone therapy was initially attempted in most patients (91.2%), while catheter ablation was performed in one-third of patients. VTA recurrences were observed in 55/91 patients (60.4%) during oMXT treatment compared to 91/91 (100%) before treatment (P<0.001). Appropriate therapies occurred in 55/88 ICD patients (62.5%) during oMXT treatment compared to 80/88 (90.9%) before treatment (P<0.001). After oMXT introduction, there was a significant reduction of the individual burden of VTA episodes and appropriate ICD therapies per patient, showing Hedges'g values of -1.103 (P=0.002) and -1.474 (P=0.008), respectively. Safety analysis showed a sample-weighted overall side-effect rate of 30%, while 21% of patients required drug reduction or discontinuation. Aggregated meta-regression analysis of the included studies and remote literature revealed a linear correlation between oMXT dosage and the overall side effects rate (r = 0.48; P=0.014).
CONCLUSIONS
Oral mexiletine provides an adjunctive treatment to manage VTAs and reduces appropriate therapies in ICD patients with moderate efficacy and acceptable safety profiles. These observations await confirmation through randomised clinical trials.
Topics: Humans; Mexiletine; Defibrillators, Implantable; Anti-Arrhythmia Agents; Treatment Outcome; Tachycardia, Ventricular
PubMed: 36305779
DOI: 10.23736/S2724-5683.22.06176-2 -
The Cochrane Database of Systematic... Oct 2019Lidocaine, mexiletine, tocainide, and flecainide are local anesthetics which give an analgesic effect when administered orally or parenterally. Early reports described... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Lidocaine, mexiletine, tocainide, and flecainide are local anesthetics which give an analgesic effect when administered orally or parenterally. Early reports described the use of intravenous lidocaine or procaine to relieve cancer and postoperative pain. Interest reappeared decades later when patient series and clinical trials reported that parenteral lidocaine and its oral analogs tocainide, mexiletine, and flecainide relieved neuropathic pain in some patients. With the recent publication of clinical trials with high quality standards, we have reviewed the use of systemic lidocaine and its oral analogs in neuropathic pain to update our knowledge, to measure their benefit and harm, and to better define their role in therapy.
OBJECTIVES
To evaluate pain relief and adverse effect rates between systemic local anesthetic-type drugs and other control interventions.
SEARCH METHODS
We searched MEDLINE (1966 through 15 May 2004), EMBASE (January 1980 to December 2002), Cancer Lit (through 15 December 2002), Cochrane Central Register of Controlled Trials (2nd Quarter, 2004), System for Information on Grey Literature in Europe (SIGLE), and LILACS, from January 1966 through March 2001. We also hand searched conference proceedings, textbooks, original articles and reviews.
SELECTION CRITERIA
We included trials with random allocation, that were double blinded, with a parallel or crossover design. The control intervention was a placebo or an analgesic drug for neuropathic pain from any cause.
DATA COLLECTION AND ANALYSIS
We collected efficacy and safety data from all published and unpublished trials. We calculated combined effect sizes using continuous and binary data for pain relief and adverse effects as primary and secondary outcome measurements, respectively.
MAIN RESULTS
Thirty-two controlled clinical trials met the selection criteria; two were duplicate articles. The treatment drugs were intravenous lidocaine (16 trials), mexiletine (12 trials), lidocaine plus mexiletine sequentially (one trial), and tocainide (one trial). Twenty-one trials were crossover studies, and nine were parallel. Lidocaine and mexiletine were superior to placebo [weighted mean difference (WMD) = -11; 95% CI: -15 to -7; P < 0.00001], and limited data showed no difference in efficacy (WMD = -0.6; 95% CI: -7 to 6), or adverse effects versus carbamazepine, amantadine, gabapentin or morphine. In these trials, systemic local anesthetics were safe, with no deaths or life-threatening toxicities. Sensitivity analysis identified data distribution in three trials as a probable source of heterogeneity. There was no publication bias.
AUTHORS' CONCLUSIONS
Lidocaine and oral analogs were safe drugs in controlled clinical trials for neuropathic pain, were better than placebo, and were as effective as other analgesics. Future trials should enroll specific diseases and test novel lidocaine analogs with better toxicity profiles. More emphasis is necessary on outcomes measuring patient satisfaction to assess if statistically significant pain relief is clinically meaningful.
Topics: Administration, Cutaneous; Anesthesia, Local; Anesthetics, Local; Humans; Neuralgia; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31684682
DOI: 10.1002/14651858.CD003345.pub2 -
Frontiers in Cardiovascular Medicine 2022Brugada syndrome (BrS) is associated with ventricular tachyarrhythmias. However, the presence of electrical strom (ES) and its management still debated.
BACKGROUND
Brugada syndrome (BrS) is associated with ventricular tachyarrhythmias. However, the presence of electrical strom (ES) and its management still debated.
OBJECTIVES
We present the outcome and management of 44 BrS patients suffering from ES.
METHODS
A systematic literature review and pooled analysis Through database review including PubMed, Web of Science, Cochrane Libary and Cinahl studies were analyzed. Evidence from 7 reports of 808 BrS patients was identified.
RESULTS
The mean age of patients suffering from ES was 34 ± 9.5 months (94.7% males, 65.8% spontaneous BrS type I). Using electrophysiological study ventricular tachycardia/ventricular fibrillation were inducible in 12/23 (52.2%). Recurrence of ES was documented in 6.1%. Death from ES was 8.2% after a follow-up of 83.5 ± 53.4. In up to 27 ES resolved without treatment. External shock was required in 35.6%, internal ICD shock in 13.3%, Overdrive pacing, left cardiac sympathetic block and atropin in 2.2%. Short-term antiarrhythmic management was as the following: Isopreterenol or Isopreterenol in combination with quinidine 35.5%, orciprenaline in 2.2%, quinidine 2.2%, disopyramide 2.2% or denopamide 2.2%. However, lidocaine, magensium sulfate, mexiletine and propanolol failed to control ES.
CONCLUSION
Although ES is rare in BrS, this entity challenges physicians. Despite its high mortality rate, spontaneous termination is possible. Short-term management using Isoproterenol and/or quinidine might be safe. Prospective studies on management of ES are warranted.
PubMed: 36386327
DOI: 10.3389/fcvm.2022.981715 -
The Cochrane Database of Systematic... Jul 2013Chronic pain can often occur after surgery, substantially impairing patients' health and quality of life. It is caused by complex mechanisms that are not yet well... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic pain can often occur after surgery, substantially impairing patients' health and quality of life. It is caused by complex mechanisms that are not yet well understood. The predictable nature of most surgical procedures has allowed for the conduct of randomized controlled trials of pharmacological interventions aimed at preventing chronic postsurgical pain.
OBJECTIVES
The primary objective was to evaluate the efficacy of systemic drugs for the prevention of chronic pain after surgery by examining the proportion of patients reporting pain three months or more after surgery. The secondary objective was to evaluate the safety of drugs administered for the prevention of chronic pain after surgery.
SEARCH METHODS
We identified randomized controlled trials (RCTs) of various systemically administered drugs for the prevention of chronic pain after surgery from CENTRAL, MEDLINE, EMBASE and handsearches of other reviews and trial registries. The most recent search was performed on 17 July 2013.
SELECTION CRITERIA
Included studies were double-blind, placebo-controlled, randomized trials involving adults and evaluating one or more drugs administered systemically before, during or after surgery, or both, which measured pain three months or more after surgery.
DATA COLLECTION AND ANALYSIS
Data collected from each study included the study drug name, dose, route, timing and duration of dosing; surgical procedure; proportion of patients reporting any pain three months or more after surgery, reporting at least 4/10 or moderate to severe pain three months or more after surgery; and proportion of participants dropping out of the study due to treatment-emergent adverse effects.
MAIN RESULTS
We identified 40 RCTs of various pharmacological interventions including intravenous ketamine (14 RCTs), oral gabapentin (10 RCTs), oral pregabalin (5 RCTs), non-steroidal anti-inflammatories (3 RCTs), intravenous steroids (3 RCTs), oral N-methyl-D-aspartate (NMDA) blockers (3 RCTs), oral mexiletine (2 RCTs), intravenous fentanyl (1 RCT), intravenous lidocaine (1 RCT), oral venlafaxine (1 RCT) and inhaled nitrous oxide (1 RCT). Meta-analysis suggested a modest but statistically significant reduction in the incidence of chronic pain after surgery following treatment with ketamine but not gabapentin or pregabalin. Results with ketamine should be viewed with caution since most of the included trials were small (that is < 100 participants per treatment arm), which could lead to the overestimation of treatment effect.
AUTHORS' CONCLUSIONS
Additional evidence from better, well designed, large-scale trials is needed in order to more rigorously evaluate pharmacological interventions for the prevention of chronic pain after surgery. Furthermore, available evidence does not support the efficacy of gabapentin, pregabalin, non-steroidal anti-inflammatories, intravenous steroids, oral NMDA blockers, oral mexiletine, intravenous fentanyl, intravenous lidocaine, oral venlafaxine or inhaled nitrous oxide for the prevention of chronic postoperative pain.
Topics: Adrenal Cortex Hormones; Adult; Amines; Analgesics; Chronic Pain; Cyclohexanecarboxylic Acids; Female; Gabapentin; Humans; Ibuprofen; Ketamine; Male; Mexiletine; Pain, Postoperative; Pregabalin; Randomized Controlled Trials as Topic; gamma-Aminobutyric Acid
PubMed: 23881791
DOI: 10.1002/14651858.CD008307.pub2 -
Complementary Therapies in Medicine Dec 2016To evaluate the efficacy and safety of the Chinese herbal extract Wenxin Keli, alone or in combination with Western medicine, for ventricular premature beats. (Meta-Analysis)
Meta-Analysis
BACKGROUND
To evaluate the efficacy and safety of the Chinese herbal extract Wenxin Keli, alone or in combination with Western medicine, for ventricular premature beats.
METHODS
This systematic review was registered at PROSPERO (registration number CRD42013003200). A systematic literature search of 8 core electronic databases and 3 clinical trial registries in Chinese and English, yielded 10 trials whose randomness verified by contacting the authors. The included trials were assessed by the Cochrane risk of bias tool.
RESULTS
Wenxin Keli might be more efficacious than placebo (Change of VPBs numbers, RR, 1.61, 95%CI, 1.48-1.76, P<0.00001, I=0%;VPBs- related symptom, RR, 2.10, 95%CI, 1.91-2.30, P<0.00001, I=0%), and the dual therapy of Wenxin Keli plus amiodarone might also be more effective than the monotherapy of amiodarone (Change of VPBs numbers, RR, 1.23, 95%CI, 1.10-1.39, P=0.0005, I=0%; VPBs- related symptom, RR, 1.51., 95%CI, 1.30-1.76, P<0.00001, I=0%), whereas Wenxin Keli might be comparable to metoprolol, propafenone or mexiletine (Change of VPBs numbers: metoprolol, RR, 1.01, 95%CI, 0.91-1.11, P=0.88, I=0%; propafenone, RR, 1.05, 95%CI, 0.93-1.19, P=0.44, I=0%; mexiletine, RR, 1.06, 95%CI, 0.96-1.17, P=0.28. VPBs- related symptom: metoprolol, RR, 0.95, 95%CI, 0.87-1.04, P=0.27, I=0%, propafenone. RR, 1.10, 95%CI, 0.93-1.30, P=0.29, I=29%, mexiletine,RR, 0.94, 95%CI, 0.78-1.12, P=0.47). Participants with ventricular premature beats' numbers<360 beats/h or with coronary heart disease benefited the most of the Wenxin Keli therapy (Change of VPBs numbers:RR, 1.10, 95%CI, 1.02-1.20, P=0.02, I=44%; RR, 1.71, 95%CI, 1.18-2.49, P=0.005, I=54%, respectively). The safety analysis revealed that Wenxin Keli did not statistically significant differed from the Western medicine in respect of the incidence of total adverse drug reactions (RR, 0.59, 95%CI, 0.35-1.01, P=0.05, I=0%), but Wenxin Keli might be associated with a reduced risk of proarrhythmic reactions (P=0.007). The quality of the methodology of included trials was generally low. Several limitations existed that affected the validity of the findings, including the small sample size, insufficient randomization methods, poorly defined eligibility criteria, short duration of follow-up, absence of hard endpoints, and high risk of publication bias(P=0.013).
CONCLUSIONS
Wenxin Keli might be a promising alternative and complementary medicine for ventricular premature beats.
Topics: Aged; Complementary Therapies; Coronary Artery Disease; Drugs, Chinese Herbal; Humans; Middle Aged; Prospective Studies; Ventricular Premature Complexes
PubMed: 27912945
DOI: 10.1016/j.ctim.2016.10.007 -
Regional Anesthesia and Pain Medicine Apr 2022In an attempt to aggregate observations from clinical trials, several meta-analyses have been published examining the effectiveness of systemic, non-opioid,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In an attempt to aggregate observations from clinical trials, several meta-analyses have been published examining the effectiveness of systemic, non-opioid, pharmacological interventions to reduce the incidence of chronic postsurgical pain.
OBJECTIVE
To inform the design and reporting of future studies, the purpose of our study was to examine the quality of these meta-analyses.
EVIDENCE REVIEW
We conducted an electronic literature search in Embase, MEDLINE, and the Cochrane Database of Systematic Reviews. Published meta-analyses, from the years 2010 to 2020, examining the effect of perioperative, systemic, non-opioid pharmacological treatments on the incidence of chronic postsurgical pain in adult patients were identified. Data extraction focused on methodological details. Meta-analysis quality was assessed using the A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) critical appraisal tool.
FINDINGS
Our search yielded 17 published studies conducting 58 meta-analyses for gabapentinoids (gabapentin and pregabalin), ketamine, lidocaine, non-steroidal anti-inflammatory drugs, and mexiletine. According to AMSTAR 2, 88.2% of studies (or 15/17) were low or critically low in quality. The most common critical element missing was an analysis of publication bias. Trends indicated an improvement in quality over time and association with journal impact factor.
CONCLUSIONS
With few individual trials adequately powered to detect treatment effects, meta-analyses play a crucial role in informing the perioperative management of chronic postsurgical pain. In light of this inherent value and despite a number of attempts, high-quality meta-analyses are still needed.
PROSPERO REGISTRATION NUMBER
CRD42021230941.
Topics: Adult; Chronic Pain; Gabapentin; Humans; Ketamine; Pain, Postoperative; Pregabalin
PubMed: 35027479
DOI: 10.1136/rapm-2021-102981 -
European Journal of Pain (London,... Mar 1998Basic research indicates that systemic local-anaesthetic-type drugs that block sodium channels are effective in pain due to nerve damage. These drugs were first used as...
Basic research indicates that systemic local-anaesthetic-type drugs that block sodium channels are effective in pain due to nerve damage. These drugs were first used as analgesics in the 1950s and they are still commonly used to try to relieve neuropathic pain and incident pain caused by cancer. As they are potentially toxic, these drugs should not be used without proven effectiveness. For these reasons, a systematic review of randomized controlled trials of systemically administered local-anaesthetic-type drugs in chronic pain was performed. Main outcomes were pain relief or pain intensity difference and adverse effects. Twenty-one reports were found, and four publications were excluded. In the remaining 17 studies (450 patients), 10 used intravenous lignocaine, two used intranasal lignocaine, four used oral mexiletine and one used oral tocainide. The best documented effective dose of intravenous lignocaine was 5 mg/kg, and when infused over 30 min it was well tolerated. Intravenous lignocaine was effective in all four studies in non-cancer-related neuropathic pain. In migraine, lignocaine produced an inconsistent effect. Lignocaine was without effect in all three studies in cancer-related pain. Oral mexiletine showed some efficacy in all three studies in pain due to peripheral nerve damage, but lacked effect in the only study in central pain. Only minor dose-related adverse effects were reported in the 85 patients given mexiletine 225-750 mg. Local-anaesthetic-type drugs are effective in pain due to nerve damage, but there is little or no evidence to support their use in cancer-related pain. Copyright 1998 European Federation of Chapters of the International Association for the Study of Pain.
PubMed: 10700296
DOI: 10.1016/s1090-3801(98)90041-6 -
International Journal of Cardiology Mar 2019The most common cardiac feature of Kearns-Sayre syndrome (KSS) is atrioventricular block (AVB), and pacemaker implantations (PMIs) are recommended for KSS patients with...
The most common cardiac feature of Kearns-Sayre syndrome (KSS) is atrioventricular block (AVB), and pacemaker implantations (PMIs) are recommended for KSS patients with advanced AVB. However, some KSS patients develop fatal arrhythmias such as polymorphic ventricular tachycardia (PMVT) and ventricular fibrillation (VF) and die suddenly even after PMIs. We report a patient with KSS who developed PMVT, VF, and QT prolongation, and was treated with mexiletine and successfully managed with an implantable cardioverter defibrillator (ICD). We reviewed the literature on arrhythmias in KSS published from 1975 to 2018. There were 112 patients with arrhythmia-associated KSS, 10 died, and 6 died suddenly after the PMI. The first manifestation of an arrhythmia was bundle branch block, then it progressed to AVB, and developed into complete AVB (CAVB) in about half the KSS patients. Ventricular arrhythmias were documented in 12 patients, and 8 were implanted with defibrillators afterwards. One patient after the implantation of a cardiac resynchronization therapy defibrillator (CRT-D) was treated for VF by an appropriate shock. This fact suggested that VF occurred even under proper pacing, and that defibrillators were effective. Pacemakers may suppress early afterdepolarizations (EADs) associated with a QT prolongation due to bradycardia. Similarly, mexiletine may suppress EADs by blocking the late sodium and Ca currents. Ventricular arrhythmias observed under suppression of EADs may be caused by delayed afterdepolarization (DADs) via an increasing intracellular Ca concentration due to mitochondrial dysfunction. Therefore, a PMI alone may not be sufficient to prevent sudden death, and an ICD implantation should be necessary.
Topics: Adolescent; Cardiac Resynchronization Therapy; Death, Sudden, Cardiac; Defibrillators, Implantable; Electrocardiography; Female; Humans; Kearns-Sayre Syndrome; Tachycardia, Ventricular; Ventricular Fibrillation
PubMed: 30642644
DOI: 10.1016/j.ijcard.2018.12.064