Unintentional lethal overdose with metildigoxin in a 36-week-old infant--post mortem tissue distribution of metildigoxin and its metabolites by liquid chromatography tandem mass spectrometry.

A massive lethal overdose with beta-metildigoxin in a 36-week-old infant is presented. Determination of beta-metildigoxin and its metabolites digoxin, digoxigenin and digoxigenin-monodigitoxosid is achieved by a liquid chromatographic mass spectrometric (LC-MS/MS) method. Measured concentrations for beta-metildigoxin and digoxin in peripheral blood were 40.2 ng/ml and 25.6 ng/ml, respectively. Tissue distribution showed highest concentrations in kidney tissue and gastric content. The metabolite digoxigenin-monodigitoxosid could be detected in heart blood, duodenal content, gastric content and fat tissue while the metabolite digoxigenin could only be detected in gastric content since the drug was given by a stomach tube.

Free and total digoxin in serum during treatment of acute digoxin poisoning with Fab fragments: case study.

A woman ingested 10 mg of methyldigoxin in a suicide attempt and presented 19 hours after ingestion with clinical signs of glycoside intoxication. Her serum level of digoxin was 7.4 ng/mL, and antidotal therapy with Fab antibody fragments was started. The manufacturer's recommended dosing scheme was modified, with 80 mg Fab administered intravenously within 15 minutes followed by a continuous infusion at 30 mg/h. Total serum concentration of digoxin increased markedly within minutes after Fab therapy was started, while the level of free digoxin immediately decreased into the nontoxic range without recrudescent toxic effects of digoxin. The cumulative amounts of free and bound digoxin that were excreted in urine within 30 hours after ingestion were 900 microg and 1600 microg, respectively. Half-life of bound digoxin in urine was 9.9 hours; mean rate of clearance of bound digoxin in the urine was 7.0 mL/min. On the basis of these kinetic data, a smaller initial bolus dose of Fab followed by a continuous infusion may be a more tailored, cost-effective, and relatively safe therapy for patients who have overdosed on cardiac glycosides.

[Application of HPLC/MS for evaluation of fatal poisoning with digoxin in the aspect of medico-legal evidence]. / Zastosowanie techniki HPLC/MS w ocenie zatrucia smiertelnego digoksyna w aspekcie orzecznictwa sadowo-lekarskiego.

This paper presents a case of suicidal poisoning of a woman with digoxin administered by injection. The autopsy of the subject was performed in the Institute of Forensic Medicine CMUJ. Body fluids (blood, urine, perylimph) and tissues (kidney, liver, brain) were collected for toxicological investigation. Digoxin determination was carried out by means of high performance liquid chromatography with mass spectrometry (HPLC/MS) which revealed digoxin in extremely high concentrations in specimens examined. The method is especially useful for analysis of cardiac glycosides in fatal poisonings for medicolegal purposes.

[Percutaneous extracorporeal circulation in cardiogenic shock caused by combined poisoning with methyldigoxin, nifedipine and indapamide]. / Perkutane extrakorporale Zirkulation bei kardiogenem Schock aufgrund einer Mischintoxikation mit Metildigoxin, Nifedipin und Indapamid.

HISTORY AND FINDINGS: A 38-year-old man with endogenous depression was found comatose and with gasping respiration. Empty packets of tablets pointed to poisoning with methyldigoxin, nifedipine and indapamide. Pupils reacted slowly to light and no peripheral blood pressure could be measured. TREATMENT AND COURSE: Routine resuscitation measures (intubation, mechanical ventilation, external cardiac massage and drugs) were undertaken during transport to hospital where, in addition to further symptomatic treatment, digoxin antibodies were administered, but without noticeable effect. Percutaneous cardiopulmonary bypass was therefore undertaken. It achieved a cardiac output of 3.2l and a systolic pressure of 80 mm Hg: a stable rhythm and circulation were obtained within 15 hours indicating that electromechanical uncoupling had for the time being been overcome. The EEG suggested a midbrain syndrome. After another 18 hours of mechanical ventilation and symptomatic treatment asystole suddenly occurred. Renewed resuscitation procedures were not undertaken because of the very poor neurological state and prognosis. CONCLUSION: Although haemodynamic stabilization was only temporarily achieved and the patient's death could not be prevented because of adverse pretreatment conditions, the application of percutaneously implantable, transportable heart-lung machine appears to be justified in cases of intoxication with cardio- and vasodepressive substances.

[Blue color vision as a sign of digitalis poisoning]. / Cijanopsija kao znak intoksikacije digitalisom.

The paper deals with the course of the illness in a 66 years old male, who had taken an amount of 0.2 mg of medigoxin for an unknown period of time, because of chronic heart failure due to atherosclerotic heart disease and chronic atrial fibrillation. He have had a cholelithiasis also and reduced renal reserve. He was admitted by an emergency admittance because of nausea, vomiting, color vision disturbances: blue colored vision, and with other signs of digitalis toxicity: diffuse abdominal pain, an absolute arrhythmia with a slow ventricular rate, and with a short corrected Q-T interval in an electrocardiogram of 0.315 seconds and with high serum digoxin level reacted 3.8 nmol/L. After stopping of a digitalis treatment, in a period of time of four days, all signs of digitalis toxicity including blue color vision disturbances disappeared. In the paper that rare sign of digitalis toxicity is discussed.

[Acute psychoses caused by digitalis poisoning]. / Akutna psihoza kao posljedica intoksikacije digitalisom.

The course of illness in a 76-year-old woman with a history of dyspnea being treated with medigoxin, 0.1 mg daily, is presented. Five days before the symptoms of acute psychosis developed she had used medigoxin, 0.2 mg per day. On the fifth day of that therapy, the patient developed acute psychosis and was admitted to the Department of Psychiatry. An electrocardiogram recorded monomorphous ventricular premature beats at a frequency of 50%, the S-T segment depression of the anterolateral location with the diphasic T-wave and the corrected Q-T interval of 0.377 to 0.355 seconds. Five days after the discontinuation of medigoxin therapy, serum digoxin concentration was 2.2 nmol/L, out of which follows that two days after digitalis was stopped it was 4.0 nmol/L and that concentration was probably higher at the moment when acute psychosis developed. The patient was free of symptoms of acute psychosis after a single promazine dose and discontinuation of medigoxin.

[Course of chronic life-threatening digitalis poisoning in infancy with immunopharmacologic treatment using antidigoxin Fab of sheep]. / Verlauf einer chronischen lebensbedrohlichen Digitalis-Intoxikation im Säuglingsalter unter immunpharmakologischer Behandlung mit Antidigoxin Fab vom Schaf.

A 2 months old girl was given a tenfold increased dosage of Beta-Methyldigoxin for 2 weeks and subsequently developed severe symptoms of glycoside intoxication. In hospital she was treated by digoxin-specific Fab antibody fragments. 18 hours later the symptoms had totally disappeared. However, 48 hours from the beginning of the treatment free digoxin levels rose again to toxic ranges. In chronic intoxications the rediffusion of glycosides from tissues and interstitial space seems to be much more pronounced than in acute intoxications, and there is a higher risk of reintoxication.

Use of cholestyramine in three patients with beta-acetyldigoxin, beta-methyldigoxin and digitoxin intoxication.

The effect of cholestyramine (8 g every 6 h by oral administration) on glycoside plasma concentrations of three patients with suicidal and accidental digitalis intoxications were studied. During treatment with cholestyramine the plasma concentrations of beta-acetyldigoxin and beta-methyldigoxin declined with half-lives of 20.4 or 30.0 h. These values are significantly shorter than the therapeutic half-lives reported in the literature. The digitoxin plasma concentration decreased with a half-life of 74.5 h during the first 2 days. When the digitoxin plasma level dropped under 40 ng/ml, the half-life increased, similar to the half-life without cholestyramine administration. From these case reports cholestyramine seems to be helpful in managing intoxications with digoxin derivates as well as with digitoxin.

[Report of experiences in the treatment of 16 cases of severe glycoside poisoning with digitalis antibody fragments (Fab)]. / Erfahrungsbericht über die Behandlung von 16 schweren Glykosidvergiftungen mit Digitalis-Antikörper-Fragmenten (Fab).

To date, 16 patients with severe glycoside poisoning have been treated with Fab as part of the clinical trial for efficacy and tolerance. The ages of the patients ranged from 4 to 77 years. In 13 cases, the substance was taken with suicidal intent. The following were considered to be indications for the use of Fab: the appearance of life-threatening arrhythmias as high-grade atrioventricular conduction disorders, multifocal ectopic beats, ventricular tachycardia, and relapsing ventricular fibrillation in 5 cases. Serum digoxin concentrations were between 3.8 and 78 ng/ml before the start of treatment. The amount of Fab administered was 240-800 mg, in the majority of cases 480 mg. Regression of the arrhythmias was seen in all patients during or shortly after the Fab infusion. There was a rapid fall in the free digoxin in the serum to levels that were no longer measurable and a marked rise in bound digoxin with a simultaneous intensive excretion of bound digoxin in the urine. Fab therapy is considered to be a major advance in the treatment of severe, previously fatal, glycoside poisoning. No notable side effects were observed, nor were there any allergic reactions to foreign protein.

[Forensic aspects of digoxin-poisoning: toxicological and morphological findings (author's transl)]. / Toxikologische und morphologische Befunde bei Digosinvergiftung in forensischer Sicht.

Case report. A 82 year old woman died 80 min after accidental ingestion of 5 mg beta-methyl-digoxin. The autopsy and the histological examination revealed non-specific alterations due to shock and preexisting coronary heart disease. Digoxin levels in various fluids and tissues were estimated by radioimmunoassay: bloodplasma 20--25 ng/ml, liquor 10--13 ng/ml, liver 100--110 ng/g, kidney 130--145 ng/g; the gastric fluid contained 0,6 mg. Forensic aspects of glycosid-intoxication, especially of the varying concentrations in different tissues, are discussed.