Hemodialysis as an alternative treatment of mexiletine intoxication.

Mexiletine is a class IB antiarrhythmic agent. Although it is primarily used in treating ventricular arrhythmias, recent indications for use of mexiletine include chronic and neuropathic pains. At high doses, mexiletine causes drowsiness, confusion, nausea, hypotension, sinus bradycardia, paresthesia, seizures, bundle branch block, atrioventricular heart block, ventricular arrhythmias, asystole, cardiovascular collapse, and coma. A 23-year-old male patient presented to the emergency department with intentional ingestion of high-dose mexiletine. Despite decontamination and supportive treatment, his vitals deteriorated during the observation period; and he developed stupor and dysarthria. Patient then underwent hemodialysis. His vital signs and overall condition improved rapidly following hemodialysis treatment. In this case report, we aimed to emphasize hemodialysis as a useful alternative therapy for severe mexiletine intoxications.

[Determination of mexiletine in human blood by liquid chromatography-tandem mass spectrometry].

OBJECTIVE: To establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for detection of mexiletine by liquid chromatography tandem mass spectrometry. METHODS: After simple protein precipitation of the blood sample with acetonitrile, the organic solvent layer diluted with LC mobile solvent was separated by Allure PFP Propyl column, confirmed and quantified by MS/MS in the multi-reaction monitoring (MRM) mode via positive electrospray ionization. RESULTS: Mexiletine and naloxone (internal standard) got ideal resolution under the selected analytical condition. The correlation coeficient of linear calibration curve was over 0.9999 within the mexiletine concentration range 0.02-10 microg/mL. The relative standard deviations were under 10% for intra-day and under 15% for inter-day, and the detection limit was 0.01 microg/mL. CONCLUSION: The established LC-MS/MS method is simple, rapid, sensitive, unaffected by matrix effect and appropriate for detection of mexiletine in blood in the field of therapeutic drug monitoring and forensic toxicology.

Determination of mexiletine in human blood by liquid chromatography-tandem mass spectrometry / 法医学杂志

OBJECTIVE@#To establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for detection of mexiletine by liquid chromatography tandem mass spectrometry.@*METHODS@#After simple protein precipitation of the blood sample with acetonitrile, the organic solvent layer diluted with LC mobile solvent was separated by Allure PFP Propyl column, confirmed and quantified by MS/MS in the multi-reaction monitoring (MRM) mode via positive electrospray ionization.@*RESULTS@#Mexiletine and naloxone (internal standard) got ideal resolution under the selected analytical condition. The correlation coeficient of linear calibration curve was over 0.9999 within the mexiletine concentration range 0.02-10 microg/mL. The relative standard deviations were under 10% for intra-day and under 15% for inter-day, and the detection limit was 0.01 microg/mL.@*CONCLUSION@#The established LC-MS/MS method is simple, rapid, sensitive, unaffected by matrix effect and appropriate for detection of mexiletine in blood in the field of therapeutic drug monitoring and forensic toxicology.

[A case of fatal poisoning with the anti-arrhythmia agents Katen and Neo-Gilurytmal]. / Letálny prípad intoxikácie antiarytmikami Katen a Neo-Gilurytmal.

The case is presented on 17-year-old student who ingested larger doses of tablets and capsules in privacy. She ingested antiarrhythmics Katen and Neo-Gilurytmal without clinical therapy by these drugs and without history of suicidal attempt. The imminent case of death was asphyxiation by aspiration of vomits from gastric contents after ingestion of excessive doses of drugs. The secondary findings as brain edema, petechiae under the serous membranes and congestion of the abdominal cavity, were relieved at autopsy. Noxae was identified by the postmortem toxicological analysis of blood, liver, kidney, gastric contents and intestinal contents. Mexiletine and prajmaline were analysed by the capillary gas chromatography with FID detection. Retention time of mexiletine was 6.66 minutes, prajmaline 15.15 minutes, respectively. Blood alcohol concentration was 0.21 mg.g-1. Concentration of prajmaline in gastric contents was 3.03 mg.g-1, mexiletine 0.11 mg.g-1, respectively.

A mexiletine intoxication.

A case is presented of a 26-year-old white male with a history of depression and previous suicide attempts. No anatomic cause of death was determined at the autopsy. Comprehensive toxicological analysis of the blood and urine specimens identified mexiletine, a class 1B antiarrhythmic drug. Mexiletine was detected by gas chromatography and confirmed by gas chromatography-mass spectrometry. Quantitations were as follows: heart blood, 38 mg/L; subclavian blood, 14 mg/L; urine, 370 mg/L; liver, 190 mg/kg; kidney, 170 mg/kg; vitreous humor, 17 mg/L; and bile, 440 mg/L. The medical examiner ruled that the cause of death was mexiletine intoxication and the manner of death was suicide.

Postmortem distribution of mexiletine in a fatal overdose.

A case involving a fatal overdose of mexiletine is presented. Quantitation of the drug was accomplished by gas chromatography with a flame-ionization detector. The presence of mexiletine was confirmed by gas chromatography-mass spectrometry. Toxicological analysis revealed the following tissue distribution of mexiletine: heart blood, 44.8 micrograms/mL; femoral blood, 10.0 micrograms/mL; vitreous, 8.6 micrograms/mL; liver, 171.6 micrograms/g; brain, 84.0 micrograms/g; and gastric contents, 1464 mg.

Mexiletine overdose producing status epilepticus without cardiovascular abnormalities.

Few cases of mexiletine overdose have been reported in the literature. The available case reports have invariably noted significant hemodynamic or electrocardiographic abnormalities. A 41-year-old woman, on mexiletine for arrhythmia control, ingested up to 90 of her 200 mg mexiletine tablets in a suicide attempt. She presented to the emergency department awake with a normal blood pressure and pulse. Shortly afterwards, the patient had a generalized motor seizure, which responded after 40 minutes to intravenous diazepam 100 mg, phenobarbital 1 g and pyridoxine 5 g. Recurrent status epilepticus at one hour required an additional 40 mg of diazepam and a loading dose of pentobarbital. During the entire episode, her electrocardiogram remained normal. The patient's mexiletine level was 20 micrograms/mL (therapeutic 1-2 micrograms/mL) and the patient's urine screen was negative for cocaine. Mexiletine is a group Ib antidysrhythmic agent with electrophysiologic effects similar to lidocaine. Mexiletine has a little first pass hepatic metabolism and a large volume of distribution along with a high lipid solubility, and prolonged central nervous system toxicity may be expected. As with lidocaine, the toxic deaths from mexiletine have resulted from hypotension and bradycardia. The patient reported had a significant mexiletine overdose which resulted in convulsive status epilepticus, but was devoid of hemodynamic or electrocardiographic abnormalities.

Adsorption of mexiletine onto activated charcoal in macrogol-electrolyte solution.

Adsorption studies in vitro of mexiletine onto activated charcoal were performed in macrogol (polyethylene glycol)-electrolyte solution (PEG-ELS) and JP XII disintegration medium No. 2 (second medium). Mexiletine was adsorbed more extensively onto activated charcoal in PEG-ELS than that in JP XII second medium. The maximum adsorptive capacity of activated charcoal for the drug was 328 and 284 mg per gram of charcoal in PEG-ELS and JP XII second medium, respectively. In addition, the equilibrium constant of activated charcoal estimated according to the Langmuir equation was 0.079 and 0.034 l per gram of charcoal in PEG-ELS and JP XII second medium, respectively. Adsorption of mexiletine onto activated charcoal was decreased by omitting macrogol, sodium sulfate or sodium bicarbonate from a standard PEG-ELS formulation. Oral activated charcoal will be useful in combination with whole bowel irrigation with PEG-ELS in mexiletine overdose because of its excellent adsorbability in the solution.

Survival following severe overdose with mexiletene, nifedipine, and nitroglycerine.

Survival following attempted suicide in a 50-year-old man by ingestion of 12.4 g of mexiletine, 620 mg of nifedipine and 50 to 100 tablets of sublingual nitroglycerine 1:150 is reported. Initial presentation was that of mental obtundation, vomiting, tonic-clonic seizure, high-degree atrioventricular block, profound vasodilation and cardiovascular collapse. Treatment consisted of intravenous calcium gluconate and aggressive fluid management. Maintenance of cardiovascular stability required continuous infusion phenylephrine, dopamine and epinephrine. The patient made a full recovery and was medically discharged on the fourth hospital day. This case represents the largest overdose of mexiletine to date to end in patient survival.

Poisoning due to class 1B antiarrhythmic drugs. Lignocaine, mexiletine and tocainide.

Since most of the toxicity associated with class 1B antiarrhythmic drugs is dose-related, this review examines adverse effects seen in both therapeutic practice and accidental or premeditated overdose. Toxicity is very common with these agents and can be life-threatening. A high percentage of patients must discontinue therapy because of adverse effects. Mexiletine and tocainide are structural analogues of lignocaine (lidocaine) and toxicity is similar with all 3 drugs. With gradual intoxication (the most common form) central nervous system effects such as lightheadedness, dizziness, drowsiness and confusion are seen first. Seizures and respiratory arrest can occur. Cardiovascular toxicity is manifested by progressive heart block, reduced cardiac contraction, hypotension and asystole. Both mexiletine and tocainide may have proarrhythmic effects. Gastrointestinal toxicity is also common. Shock, hypotension, cardiac failure and beta-blocker therapy reduce lignocaine clearance and enhance the risk of intoxication during routine therapy. Both lignocaine and mexiletine elimination is impaired in severe liver disease while tocainide clearance is reduced in renal failure. Management of toxicity is largely supportive and symptomatic. Lignocaine infusion must be discontinued and decontamination of the gut in the case of oral preparations is recommended. Serious intoxication requires intensive care unit admission. Haemodialysis or haemoperfusion may be helpful in serious lignocaine and tocainide poisoning. In institutions where extracorporeal circulatory assistance is available, massive lignocaine poisoning has been successfully treated with this intervention. In the therapeutic setting serious toxicity can be prevented by close clinical surveillance and appropriate dose reduction in patients with reduced drug clearance. Because of the large interindividual variation in lignocaine pharmacokinetic parameters, therapeutic drug monitoring is recommended if results can be reported quickly. Mexiletine and tocainide have stereoselective metabolism and assays do not distinguish the more active isomers. Therapeutic drug monitoring is less useful in this situation.

[Treatment with mexiletine. Clinical and pharmacokinetic studies]. / Behandlung mit Mexiletin. Klinische und pharmakokinetische Untersuchungen.

Pharmacokinetics of the antiarrhythmic agent mexiletine were found to be highly variable. Ineffective or toxic doses can be avoided by monitoring mexiletine concentrations in patients plasma. However, the success of antiarrhythmic therapy is mainly determined by the severity of the underlying disease. Therefore, the efficacy of treatment with mexiletine should be controlled by Holter monitoring.