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Europace : European Pacing,... Nov 2022While mexiletine has been used for over 40 years for prevention of (recurrent) ventricular arrhythmias and for myotonia, patient access has recently been critically...
AIMS
While mexiletine has been used for over 40 years for prevention of (recurrent) ventricular arrhythmias and for myotonia, patient access has recently been critically endangered. Here we aim to demonstrate the effectiveness and safety of mexiletine in the treatment of patients with (recurrent) ventricular arrhythmias, emphasizing the absolute necessity of its accessibility.
METHODS AND RESULTS
Studies were included in this systematic review (PROSPERO, CRD42020213434) if the efficacy or safety of mexiletine in any dose was evaluated in patients at risk for (recurrent) ventricular arrhythmias with or without comparison with alternative treatments (e.g. placebo). A systematic search was performed in Ovid MEDLINE, Embase, and in the clinical trial registry databases ClinicalTrials.gov and ICTRP. Risk of bias were assessed and tailored to the different study designs. Large heterogeneity in study designs and outcome measures prompted a narrative synthesis approach. In total, 221 studies were included reporting on 8970 patients treated with mexiletine. Age ranged from 0 to 88 years. A decrease in ventricular arrhythmias of >50% was observed in 72% of the studies for pre-mature ventricular complexes, 64% for ventricular tachycardia, and 33% for ventricular fibrillation. Electrocardiographic effects of mexiletine were small; only in a subset of patients with primary arrhythmia syndromes, a relative (desired) QTc decrease was reproducibly observed. As for adverse events, gastrointestinal complaints were most frequently observed (33% of the patients).
CONCLUSIONS
In this systematic review, we present all the currently available knowledge of mexiletine in patients at risk for (recurrent) ventricular arrhythmias and show that mexiletine is both effective and safe.
Topics: Humans; Infant, Newborn; Infant; Child, Preschool; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Mexiletine; Arrhythmias, Cardiac; Ventricular Fibrillation; Electrocardiography; Heart Ventricles
PubMed: 36036670
DOI: 10.1093/europace/euac087 -
Palliative Medicine Dec 2017Rectal tenesmus is a distressing symptom in patients with advanced cancer and challenging to treat. There is lack of consensus on the appropriate management of tenesmus... (Review)
Review
BACKGROUND
Rectal tenesmus is a distressing symptom in patients with advanced cancer and challenging to treat. There is lack of consensus on the appropriate management of tenesmus in this patient population.
AIM
To identify and examine the effectiveness of interventions to palliate rectal tenesmus caused by advanced cancer when surgery, radiotherapy or chemotherapy are no longer treatment options.
DESIGN
A systematic review of the literature following standard systematic review methodology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance.
DATA SOURCES
A comprehensive search of the electronic databases MEDLINE, EMBASE and the Cochrane Library was conducted from date of inception to April 2016. PubMed 'related articles' search, grey literature search and hand-searches of the bibliographies of relevant papers and textbooks were also performed. Non-cancer patients were excluded. Any studies involving surgery or radiotherapy to treat tenesmus were excluded. Studies involving interventions to treat pelvic pain syndromes without specific outcome measures on severity of tenesmus were excluded. The quality of the studies was assessed using a National Institute for Health and Clinical Excellence-recommended quality assessment tool.
RESULTS
From 861 studies, 9 met full criteria and were selected. All were case series investigating the use of pharmacological interventions (diltiazem, nifedipine, methadone, mexiletine hydrochloride, lidocaine and bupivacaine), anaesthetic interventions (lumbar sympathectomy, neurolytic superior hypogastric plexus block), and endoscopic laser interventions. The included studies showed substantial heterogeneity, and therefore, a meta-analysis was not feasible.
CONCLUSION
From this review, we identified a significant gap in research into the palliation of rectal tenesmus. A multimodal approach may be necessary due to the complexity of the pathophysiology of tenesmus. Future research should focus on randomised controlled trials of drug therapies whose potential effectiveness is suggested by case series.
Topics: Anesthesia; Anesthetics; Calcium Channel Blockers; Humans; Laser Therapy; Neoplasms; Palliative Care; Rectal Diseases
PubMed: 28590211
DOI: 10.1177/0269216317697897 -
The Cochrane Database of Systematic... Aug 2015Coronary artery disease is a major public health problem affecting both developed and developing countries. Acute coronary syndromes include unstable angina and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Coronary artery disease is a major public health problem affecting both developed and developing countries. Acute coronary syndromes include unstable angina and myocardial infarction with or without ST-segment elevation (electrocardiogram sector is higher than baseline). Ventricular arrhythmia after myocardial infarction is associated with high risk of mortality. The evidence is out of date, and considerable uncertainty remains about the effects of prophylactic use of lidocaine on all-cause mortality, in particular, in patients with suspected myocardial infarction.
OBJECTIVES
To determine the clinical effectiveness and safety of prophylactic lidocaine in preventing death among people with myocardial infarction.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 3), MEDLINE Ovid (1946 to 13 April 2015), EMBASE (1947 to 13 April 2015) and Latin American Caribbean Health Sciences Literature (LILACS) (1986 to 13 April 2015). We also searched Web of Science (1970 to 13 April 2013) and handsearched the reference lists of included papers. We applied no language restriction in the search.
SELECTION CRITERIA
We included randomised controlled trials assessing the effects of prophylactic lidocaine for myocardial infarction. We considered all-cause mortality, cardiac mortality and overall survival at 30 days after myocardial infarction as primary outcomes.
DATA COLLECTION AND ANALYSIS
We performed study selection, risk of bias assessment and data extraction in duplicate. We estimated risk ratios (RRs) for dichotomous outcomes and measured statistical heterogeneity using I(2). We used a random-effects model and conducted trial sequential analysis.
MAIN RESULTS
We identified 37 randomised controlled trials involving 11,948 participants. These trials compared lidocaine versus placebo or no intervention, disopyramide, mexiletine, tocainide, propafenone, amiodarone, dimethylammonium chloride, aprindine and pirmenol. Overall, trials were underpowered and had high risk of bias. Ninety-seven per cent of trials (36/37) were conducted without an a priori sample size estimation. Ten trials were sponsored by the pharmaceutical industry. Trials were conducted in 17 countries, and intravenous intervention was the most frequent route of administration.In trials involving participants with proven or non-proven acute myocardial infarction, lidocaine versus placebo or no intervention showed no significant differences regarding all-cause mortality (213/5879 (3.62%) vs 199/5848 (3.40%); RR 1.02, 95% CI 0.82 to 1.27; participants = 11727; studies = 18; I(2) = 15%); low-quality evidence), cardiac mortality (69/4184 (1.65%) vs 62/4093 (1.51%); RR 1.03, 95% CI 0.70 to 1.50; participants = 8277; studies = 12; I(2) = 12%; low-quality evidence) and prophylaxis of ventricular fibrillation (76/5128 (1.48%) vs 103/4987 (2.01%); RR 0.78, 95% CI 0.55 to 1.12; participants = 10115; studies = 16; I(2) = 18%; low-quality evidence). In terms of sinus bradycardia, lidocaine effect is imprecise compared with effects of placebo or no intervention (55/1346 (4.08%) vs 49/1203 (4.07%); RR 1.09, 95% CI 0.66 to 1.80; participants = 2549; studies = 8; I(2) = 21%; very low-quality evidence). In trials involving only participants with proven acute myocardial infarction, lidocaine versus placebo or no intervention showed no significant differences in all-cause mortality (148/2747 (5.39%) vs 135/2506 (5.39%); RR 1.01, 95% CI 0.79 to 1.30; participants = 5253; studies = 16; I(2) = 9%; low-quality evidence). No significant differences were noted between lidocaine and any other antiarrhythmic drug in terms of all-cause mortality and ventricular fibrillation. Data on overall survival 30 days after myocardial infarction were not reported. Lidocaine compared with placebo or no intervention increased risk of asystole (35/3393 (1.03%) vs 14/3443 (0.41%); RR 2.32, 95% CI 1.26 to 4.26; participants = 6826; studies = 4; I(2) = 0%; very low-quality evidence) and dizziness/drowsiness (74/1259 (5.88%) vs 16/1274 (1.26%); RR 3.85, 95% CI 2.29 to 6.47; participants = 2533; studies = 6; I(2) = 0%; low-quality evidence). Overall, safety data were poorly reported and adverse events may have been underestimated. Trial sequential analyses suggest that additional trials may not be needed for reliable conclusions to be drawn regarding these outcomes.
AUTHORS' CONCLUSIONS
This Cochrane review found evidence of low quality to suggest that prophylactic lidocaine has very little or no effect on mortality or ventricular fibrillation in people with acute myocardial infarction. The safety profile is unclear. This conclusion is based on randomised controlled trials with high risk of bias. However (disregarding the risk of bias), trial sequential analysis suggests that additional trials may not be needed to disprove an intervention effect of 20% relative risk reduction. Smaller risk reductions might require additional higher trials.
Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Bradycardia; Humans; Lidocaine; Myocardial Infarction; Randomized Controlled Trials as Topic; Ventricular Fibrillation
PubMed: 26295202
DOI: 10.1002/14651858.CD008553.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 -
Journal of Neuromuscular Diseases 2021Skeletal muscle ion channelopathies include non-dystrophic myotonias (NDM), periodic paralyses (PP), congenital myasthenic syndrome, and recently identified congenital...
BACKGROUND
Skeletal muscle ion channelopathies include non-dystrophic myotonias (NDM), periodic paralyses (PP), congenital myasthenic syndrome, and recently identified congenital myopathies. The treatment of these diseases is mainly symptomatic, aimed at reducing muscle excitability in NDM or modifying triggers of attacks in PP.
OBJECTIVE
This systematic review collected the evidences regarding effects of pharmacological treatment on muscle ion channelopathies, focusing on the possible link between treatments and genetic background.
METHODS
We searched databases for randomized clinical trials (RCT) and other human studies reporting pharmacological treatments. Preclinical studies were considered to gain further information regarding mutation-dependent drug effects. All steps were performed by two independent investigators, while two others critically reviewed the entire process.
RESULTS
For NMD, RCT showed therapeutic benefits of mexiletine and lamotrigine, while other human studies suggest some efficacy of various sodium channel blockers and of the carbonic anhydrase inhibitor (CAI) acetazolamide. Preclinical studies suggest that mutations may alter sensitivity of the channel to sodium channel blockers in vitro, which has been translated to humans in some cases. For hyperkalemic and hypokalemic PP, RCT showed efficacy of the CAI dichlorphenamide in preventing paralysis. However, hypokalemic PP patients carrying sodium channel mutations may have fewer benefits from CAI compared to those carrying calcium channel mutations. Few data are available for treatment of congenital myopathies.
CONCLUSIONS
These studies provided limited information about the response to treatments of individual mutations or groups of mutations. A major effort is needed to perform human studies for designing a mutation-driven precision medicine in muscle ion channelopathies.
Topics: Channelopathies; Humans; Hypokalemic Periodic Paralysis; Lamotrigine; Mexiletine; Muscle, Skeletal; Mutation; Myasthenic Syndromes, Congenital; Myotonic Disorders; Precision Medicine; Randomized Controlled Trials as Topic; Sodium Channel Blockers
PubMed: 33325393
DOI: 10.3233/JND-200582