digoxin and Drug-Overdose

While relatively uncommon, an overdose of calcium channel blockers, beta blockers, or digoxin can result in significant morbidity and mortality, and management can be complex. An acute overdose will require different management strategies than chronic toxicity while on therapeutic dosing. Toxicity from these agents must be considered in bradycardic and hypotensive patients. This supplement provides an evidence-based overview of emergency department management of calcium channel blocker overdose, beta blocker overdose, and digoxin toxicity, and focuses on the caveats of treatment for each.

Topics: Adrenergic beta-Antagonists; Advanced Cardiac Life Support; Calcium Channel Blockers; Diagnosis, Differential; Digoxin; Drug Overdose; Emergency Service, Hospital; Evidence-Based Medicine; Humans

A review of the evidence behind the DigiFab® dosing calculator, which provides dosing for digoxin immune Fab in patients with confirmed digoxin poisoning or overdose.

Topics: Digoxin; Drug Overdose; Humans; Immunoglobulin Fab Fragments; Poisoning

The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup was formed to provide recommendations on the use of extracorporeal treatments (ECTR) in poisoning. Here, we present our results for digoxin.. After a systematic literature search, clinical and toxicokinetic data were extracted and summarized following a predetermined format. The entire workgroup voted through a two-round modified Delphi method to reach a consensus on voting statements. A RAND/UCLA Appropriateness Method was used to quantify disagreement, and anonymous votes were compiled and discussed in person. A second vote was conducted to determine the final workgroup recommendations.. Out of 435 articles screened, 77 met inclusion criteria. Only in-vitro, animal studies, case reports and case series were identified yielding a very low quality of evidence for all recommendations. Based on data from 84 patients, including six fatalities, it was concluded that digoxin is slightly dialyzable (level of evidence = B), and that ECTR is unlikely to improve the outcome of digoxin-toxic patients whether or not digoxin immune Fab (Fab) is administered. Despite the lack of robust clinical evidence, the workgroup recommended against the use of ECTR in cases of severe digoxin poisoning when Fab was available (1D) and also suggested against the use of ECTR when Fab was unavailable (2D).. ECTR, in any form, is not indicated for either suspected or proven digoxin toxicity, regardless of the clinical context, and is not indicated for removal of digoxin-Fab complex.

Topics: Animals; Cardiotonic Agents; Consensus; Delphi Technique; Digoxin; Disease Models, Animal; Drug Overdose; Drug-Related Side Effects and Adverse Reactions; Humans; Randomized Controlled Trials as Topic; Renal Dialysis

Accidental poisoning or overdoses occur frequently in children. These are difficult to recognise because young children cannot communicate their symptoms; this means that specific symptoms can be missed, which can delay the diagnosis. A 5-month-old boy was accidently given a tenfold dose of digoxin for 5 days. He developed feeding difficulties, vomiting, weight loss, elevated urea and creatinine levels, hyponatraemia, hyperkalaemia and ECG abnormalities. The digoxin plasma concentration was 7.6 µg/l. The patient was given digoxin antibodies, following which the digoxin concentration was < 0.3 µg/l; 12 hours later the digoxin concentration was 3.1 µg/l as a result of redistribution; 2 days after the administration of digoxin antibodies the plasma concentration was within the therapeutic range.

Topics: Antibodies; Cardiotonic Agents; Digoxin; Drug Overdose; Drug-Related Side Effects and Adverse Reactions; Humans; Hyperkalemia; Infant; Male; Medication Errors

While it is relatively uncommon, an overdose of calcium-channel blockers, beta blockers, or digoxin has a significant morbidity and mortality rate, and its management can be complex. Digoxin toxicity can present with an acute overdose or as chronic toxicity while a patient is on therapeutic dosing, which has implications for diagnosis and management. While the patient's specific clinical presentation may depend on factors such as the time of exposure and the type of agent ingested, the differential diagnosis of the bradycardic and hypotensive patient is narrow, and toxicity from these agents must be considered. This review provides an evidence-based overview of the emergency department management of calcium-channel blocker overdose, beta blocker overdose, and digoxin toxicity.

Topics: Adrenergic beta-Antagonists; Calcium Channel Blockers; Critical Pathways; Digoxin; Drug Overdose; Drug-Related Side Effects and Adverse Reactions; Electrocardiography; Emergency Service, Hospital; Humans; Risk Factors

Topics: Animals; Antidotes; Antivenins; Carbon Monoxide Poisoning; Digoxin; Drug Overdose; Emergency Treatment; Fat Emulsions, Intravenous; Hematologic Diseases; Humans; Hypoglycemic Agents; Immunoglobulin Fab Fragments; Immunoglobulin Fragments; Insulin; Poisoning; Shock, Cardiogenic; Snake Bites; Viperidae

Digitalis toxicity produces a toxidrome characterized by gastrointestinal, neurologic, electrolyte, and nonspecific cardiac manifestations. Chronic toxicity remains much more difficult to recognize compared with an acute presentation because of the nonspecific manifestations; therefore, serum glycoside levels are essential for diagnosis in this population. The mainstay of management continues to be rapid toxidrome identification followed by digoxin-specific antibody fragment therapy with supportive care. Several controversies still remain, including therapy for patients dependent on hemodialysis, appropriateness of calcium therapy for hyperkalemia, ideal agents for arrhythmia therapy, and the potential utility of plasmapheresis for removal of bound digoxin-antibody fragment complexes.

Topics: Anti-Arrhythmia Agents; Antidotes; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Drug Overdose; Humans; Hyperkalemia

Topics: Acetaminophen; Adrenergic beta-Antagonists; Analgesics, Non-Narcotic; Analgesics, Opioid; Anti-Arrhythmia Agents; Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents, Tricyclic; Aspirin; Benzodiazepines; Calcium Channel Blockers; Charcoal; Digoxin; Drug Overdose; Gastric Lavage; Humans; Ipecac; Practice Guidelines as Topic; Renal Dialysis

The treatment of poisoned patients is still largely defined by history, clinical assessment and interpretation of ancillary investigations. Measurement of drug concentrations is clinically important for relatively few compounds. Most measurements form an adjunct to and should not be considered a substitute for clinical assessment. Drug concentrations are particularly important for those compounds where the concentration is predictive of serious toxicity in an otherwise asymptomatic patient.

Topics: Acetaminophen; Digoxin; Drug Monitoring; Drug Overdose; Half-Life; Humans; Metabolic Clearance Rate; Pharmacokinetics; Prognosis; Theophylline

Topics: Antidotes; Cardiotonic Agents; Digoxin; Drug Overdose; Humans; Immunoglobulin Fab Fragments; Risk Factors

The treatment of poisoned patients is still largely defined by history, clinical assessment and interpretation of ancillary investigations. Measurement of drug concentrations is clinically important for relatively few compounds. Most measurements form an adjunct to and should not be considered a substitute for clinical assessment. Drug concentrations are particularly important for those compounds where the concentration is predictive of serious toxicity in an otherwise asymptomatic patient.

Topics: Acetaminophen; Anticonvulsants; Digoxin; Drug Monitoring; Drug Overdose; Ethanol; Ethylene Glycol; Humans; Iron; Lithium; Methanol; Paraquat; Prognosis; Salicylates; Theophylline

Topics: Antidotes; Digitalis; Digoxin; Drug Overdose; Humans; Plants, Medicinal; Plants, Toxic; Poisoning

To evaluate the efficacy and safety of a step-by-step fixed dose of specific immunotherapy protocol in case of severe digoxin poisoning in an open uncontrolled prospective study.. Twenty consecutive patients were admitted because of severe digoxin poisoning. The inclusion criteria were: digoxin overdose and either life-threatening arrhythmia; high-degree atrioventricular block, ventricular arrhythmia, or bradycardia less than 50 bpm and hyperkalaemia (>5.5 mmol/l). A two-step protocol of antidigoxin antibodies treatment was carried out. At admission, every patient received two vials of specific Fab-fragments. If after 1 h following infusion ECG signs regressed, no more treatment was given. If ECG signs did not regress, patients were given two more vials. At inclusion and 6 h after immunotherapy, clinical (cardiac rhythm, ECG records) and biological (serum digoxin concentration, potassium) findings were recorded.. Patients had a median (interquartile range) age of 83 (75-90) years. Four patients had acute poisoning and 16 chronic overdoses. Eleven patients showed ventricular arrhythmia, and five had high-degree atrioventricular block. Seventy percent of the patients needed only the first step. Significant decreases were observed in the number of cardiac dysrhythmia (16 vs. three patients), in the median (interquartile range) of serum digoxin concentration [5 microg/l (3.8-6.2) vs. 0.4 microg/l (0.3-2.2)] and in serum potassium [4.6 mmol/l (4.1-5.5) vs. 3.85 mmol/l (3.7-4.55)] before and after immunotherapy. The digoxin-related mortality was 5%.. This protocol of step-by-step digoxin-specific immunotherapy seems to be as effective as the equimolar treatment, and there was significant cost reduction in case of acute poisoning.

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Clinical Protocols; Digoxin; Drug Overdose; Electrocardiography; Emergencies; Female; Humans; Immunoglobulin Fab Fragments; Immunologic Factors; Male; Prospective Studies

Recommended doses of digoxin-specific antibody fragments (digoxin-Fab) for treatment of acute digoxin poisoning are pharmacokinetically unsubstantiated and theoretically excessive. Physiologically based pharmacokinetic (PBPK) modelling creates clinical simulations which are closely related to physiological and pharmacokinetic behaviour. This paper details the formulation of a PBPK model of digoxin and explores its use as a simulation tool for acute digoxin toxicity and its management.. A PBPK model of digoxin was constructed and validated for acute digoxin poisoning management by comparing simulations with observed individual acute overdose patients. These simulations were compared with standard two-compartment PK model simulations.. PBPK model simulations showed good agreement with post-absorption plasma concentrations of digoxin measured in 6 acute overdose patients. PBPK predictions were accurate to 1.5-fold or less of observed clinical values, proving to be more accurate than two-compartment simulations of the same patients which produced up to a 4.9-fold change.. Compared to conventional two-compartment modelling, PBPK modelling is superior in generating realistic simulations of acute digoxin toxicity and the response to digoxin-Fab. Simulation capacity provides realistic, continuous data which has the potential to substantiate alternative, less expensive, and safer digoxin-Fab dosing strategies for the treatment of acute digoxin toxicity.

Topics: Adult; Aged; Aged, 80 and over; Digoxin; Drug Overdose; Female; Humans; Immunoglobulin Fragments; Male; Middle Aged; Models, Biological

Topics: Aged; Atrial Fibrillation; Benzamides; Digoxin; Drug Interactions; Drug Overdose; Drug Substitution; Hematemesis; Humans; International Normalized Ratio; Male; Nitriles; Phenindione; Phenylthiohydantoin; Polypharmacy; Prostatic Neoplasms; Tinzaparin

Topics: Aged, 80 and over; Anti-Arrhythmia Agents; Antihypertensive Agents; Atorvastatin; Atrial Fibrillation; Bone Density Conservation Agents; Deprescriptions; Digoxin; Diltiazem; Diuretics; Drug Overdose; Factor Xa Inhibitors; Female; Furosemide; Heart Failure; Histamine H1 Antagonists, Non-Sedating; Histamine H2 Antagonists; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Ibandronic Acid; Lisinopril; Loratadine; Metoprolol; Polypharmacy; Pyrazoles; Pyridones; Ranitidine; Syncope

We hypothesized that in chronic digoxin toxicity, anti-digoxin antibodies (Fab) would be efficacious in binding digoxin, but this may not translate into improved clinical outcomes.. This study aims to investigate changes in free digoxin concentrations and clinical effects on heart rate and potassium concentrations in chronic digoxin poisoning when anti-digoxin Fab are given.. This is a prospective observational study. Patients were recruited if they have been treated with anti-digoxin Fab for chronic digoxin poisoning. Data was entered into a standardised prospective form, supplemented with medical records. Their serum or plasma was collected, analysed for free and bound digoxin and free anti-digoxin Fab concentrations.. From September 2013 to February 2015, 36 patients (median age, 78 years; 22 females) were recruited from 18 hospitals. Median heart rate (HR) was 49 beats/min. Initial median digoxin and potassium concentrations were 4.7 nmol/L (3.6 μg/L) (range: 2.3-11.2 nmol/L) and 5.3 mmol/L (range: 2.9-9.2 mmol/L) respectively. Beta-blockers (n = 18), calcium antagonists (n = 6), spironolactone and/or angiotensin blocking agents (n = 24) were also used concomitantly. Renal impairment and gastrointestinal symptoms were present in 31 (86%) and 22 (63%) patients respectively. Five patients died from conditions unrelated to digoxin toxicity. Median change in HR was 8 beats/min post-Fab with no effect on blood pressure; they were 4, 10 and 17 beats/min for the 1, 2 and ≥3 vials of anti-digoxin Fab groups respectively. Concomitant treatments with potassium lowering agents (12/36) and inotropic drugs (7/36) were used. Gastrointestinal effects resolved in all 22 patients. The median decrease for potassium was 0.3 mmol/L. Digoxin concentration reduced from 3.8 to 0 nmol/L post-Fab. There was a rebound observed in the free digoxin concentration in 25 patients but none had associated clinical deterioration.. One to two vials of anti-digoxin Fab initially bound all free digoxin confirming Fab efficacy. However, this was associated with only a moderate improvement in HR and potassium, suggesting bradyarrhythmia and hyperkalaemia may be from other co-morbidities.

Topics: Aged; Aged, 80 and over; Bradycardia; Cardiovascular Agents; Chronic Disease; Digoxin; Drug Overdose; Female; Heart Rate; Humans; Hyperkalemia; Immunoglobulin Fab Fragments; Male; Middle Aged; Poisoning; Potassium; Prospective Studies

BACKGROUND In 2011, following a period with delivery problems, the only registered digitoxin drug in Norway was replaced with digoxin. As a result, approximately 21 000 patients had to replace digitoxin with digoxin. There are important pharmacokinetic differences between digitoxin and digoxin (the general term for both drugs is digitalis), which must be taken into account when changing therapy. The aim of this study was to investigate compliance of drug security, during the transition from digitoxin to digoxin in Norway.MATERIAL AND METHOD Enquiries addressed to the Norwegian Poison Information Centre and reports of fatal adverse effects to the Regional Drug Information Centres (RELIS) regarding intake of digitalis were analysed. Serum concentrations of digitoxin and digoxin analyzed at Oslo University Hospital were reviewed. All data sources were reviewed for the years 2010-2014 and patients > 20 years were included.RESULTS The total number of enquiries addressed to the Norwegian Poison Information Centre, fatal adverse drug reactions reported to RELIS, and patient samples in the toxic range analyzed at Oslo University Hospital increased from 2012, timewise related to the transition to digoxin.INTERPRETATION Despite extensive information from the Norwegian Medicines Agency, a small, transient increase was observed in the number of overdoses and reported deaths from digitalis related to change in therapy. The cause of the overdose was in many cases unknown. This study revealed several cases of incorrect dosage, simultaneous use of digitoxin and digoxin, and washout time that was insufficient or lacking before initiation of digoxin.

Topics: Aged; Aged, 80 and over; Digitoxin; Digoxin; Drug Overdose; Drug Substitution; Female; Guideline Adherence; Humans; Male; Norway; Poison Control Centers

Topics: Antidotes; Bradycardia; Chemistry Techniques, Analytical; Digoxin; Drug Overdose; Female; Humans; Immunoglobulin Fab Fragments; Middle Aged; Polyethylene Glycols

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.

Topics: Cardiotonic Agents; Chromatography, Liquid; Digoxigenin; Digoxin; Drug Overdose; Forensic Toxicology; Humans; Hypertension, Pulmonary; Infant; Male; Medication Errors; Medigoxin; Tandem Mass Spectrometry; Tissue Distribution

We present case a male patient who attempted suicide by ingestion of 90 tablets of digoxin in total dose of 22.5 mg. A measured peak level of digoxin was 6,75 ng/ml. Temporary invasive cardiac pacing with single chamber ventricular pacer was performed for treatment of the life-threatening rhythm and conduction disturbances that revealed within few hours after admission. According to the authors, presented method of therapy should always be taken into consideration in case development of cardiovascular disturbances in acute poisoning with digoxin.

Topics: Adult; Arrhythmias, Cardiac; Cardiac Pacing, Artificial; Digoxin; Drug Overdose; Humans; Male; Suicide, Attempted

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Digoxin; Drug Overdose; Female; Glomerular Filtration Rate; Humans; Kidney Function Tests; Male; Renal Insufficiency; Retrospective Studies; Risk Assessment; ROC Curve

Neonatology and pediatrics are units where medication errors occur. Indeed, the complexity of nursing care, the lack of information and marketing authorization for drugs contribute to the occurrence of often underestimated iatrogenic events. Through a case of digoxin overdose in a neonatology unit, each stage of the drug circuit was analyzed. From prescription to administration to dispensation, the accumulation of individual errors put a newborn in danger. The analysis and declaration of such events can improve safety and the quality of patient care.

Topics: Cardiotonic Agents; Digoxin; Diuretics; Drug Overdose; Drug Prescriptions; Heart Septal Defects, Atrial; Humans; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Premature; Intensive Care Units, Neonatal; Medication Errors; Patient Safety; Quality of Health Care; Risk Factors

Digoxin overdose is closely related to Chronic Kidney Disease and creatinine dosage adjustment is usually needed. Our goal was to assess the advantages of serum creatinine and the MDRD equation to detect hidden renal insufficiency to reduce the overdose Digital risk.. We describe all digoxin samples processed and registered in our hospital laboratory database for a year. Patients under 18 years and samples below therapeutic ranges were excluded. Chi square (p<0.05), ROC curves and logistic regression analysis were conducted. SPSS software was used.. Between 1228 digoxin samples taken to 679 patients (273 men, 77 +/- 10 years old , and 406 women 82 +/- 8 years old), 14% were over therapeutic range (28 men and 67 women). Significant differences were observed in over dosage between high creatinine group regarding to normal creatinine group (31% vs. 10% in men, 44% vs. 15% in women). ROC curves showed that the most accurate levels to predict digoxin over dosage were MDRD<56 ml/min/1.73 m(2) in men and MDRD<52 ml/min/1.73 m(2) in women. 68% of over dosage men had declines of MDRD levels, compared to 61% with high creatinine levels, 81% of over dosage women had declines of MDRD compared to 51% with elevated creatinine levels.. Even in patients with normal creatinine levels, chronic kidney disease enhances digoxin over dose risk. Using the decline of glomerular filtration rate estimated by the MDRD equation is better than elevated creatinine levels to detect digoxin overdose, thus constituting a very useful tool to reduce the risk of overdose, especially among women.

Topics: Aged; Aged, 80 and over; Algorithms; Creatinine; Cross-Sectional Studies; Digoxin; Drug Overdose; Female; Glomerular Filtration Rate; Heart Failure; Humans; Kidney; Kidney Failure, Chronic; Male; Middle Aged; ROC Curve

In the case of severe digoxin intoxication, an antidote digoxin immune Fab (Digibind) is available. Digibind binds and inactivates digoxin. Measuring se-digoxin after administering Digibind (by standard measuring methods) is misleading as Digibind interferes with digitalis immunoassay measurements. The effect of Digibind must be estimated on the basis of the disappearance of the patient's symptoms and cardiac abnormalities. A case involving Fab therapy of a digoxin-overdosed patient is reported.

Topics: Aged; Anti-Arrhythmia Agents; Aortic Aneurysm, Abdominal; Digoxin; Drug Overdose; Humans; Immunoglobulin Fab Fragments; Male; Postoperative Complications; Renal Insufficiency

Topics: Digoxin; Drug Overdose; Florida; Humans; Infant, Newborn; Male; Medication Errors; Nursing

To evaluate the use of antidotal therapy in patients with an elevated digitalis concentration following chronic or acute exposure.. Retrospective review of patient records over 2 years in 20 city hospitals in France.. Overall 838 patients with an elevated serum digitalis concentration (digoxin > 1.95ng /ml or digitoxin > 23ng /ml) were included in the study. Of these, 67 (8%) had received antidotal therapy with Fab fragments.. The relationships between previously reported prognostic criteria and use of antidotal therapy were investigated. We identified five independent factors that were associated with the use of antidotal therapy: acute overdose (OR 15.74), Fab fragment availability in the hospital (11.06), serum potassium (1.81), and heart rate (0.96). Mortality was significantly lower in Fab-treated (6%, 4/67) than untreated patients (15%, 117/770).. Antidotal therapy is underused in patients with an elevated digitalis concentration especially in patients with chronic digitalis exposure. These patients in our series presented a higher mortality rate than patients with acute poisoning. Although they were older and tended to have a history of cardiac disease, they did not differ from patients with acute poisoning with regard to the main severity criteria and prognostic factors. The use of identical criteria for antidotal treatment after acute and chronic poisoning should help optimize outcomes. Fab fragment availability is insufficient in France but ranks only second after type of poisoning (acute or chronic) in the multivariate association with Fab treatment.

Topics: Aged; Aged, 80 and over; Antidotes; Cardiotonic Agents; Digoxin; Drug Overdose; Female; France; Hospital Mortality; Humans; Immunoglobulin Fab Fragments; Immunologic Factors; Intensive Care Units; Male; Middle Aged; Multicenter Studies as Topic; Retrospective Studies

We report here the successful treatment of a 16-year-old female who ingested 20 tablets of digoxin each containing 0.25 mg (total dose ingested equivalent to 0.1 mg/kg), 32 tablets of warfarin each containing 5mg (equivalent to 3.2 mg/kg), and approximately 15 tablets of propafenone each containing 300 mg (equivalent to 90 mg/kg). The patient developed hypotension and sinus bradycardia necessitating external cardiac pacing 17 hours after drug ingestion. In addition to gastric lavage, activated charcoal, blood alkalinisation, administration of vitamin K and temporary cardiac pacing, the authors performed plasma exchange for drug removal and administered rifampicin in order to increase the metabolism of digoxin, propafenone and warfarin. The patient was discharged without any sequelae. Plasma exchange may be lifesaving in drug ingestions where there is a low volume of distribution and high plasma protein binding. Rifampicin, an inducer of cytochrome p450, may be used in intoxications for elimination of drugs with inactive metabolites.

Topics: Adolescent; Anti-Arrhythmia Agents; Anticoagulants; Bradycardia; Cytochrome P-450 Enzyme System; Digoxin; Drug Overdose; Enzyme Induction; Female; Humans; Hypotension; Plasma Exchange; Propafenone; Rifampin; Warfarin

Topics: Aged; Cardiovascular System; Citalopram; Cyclohexanols; Digoxin; Drug Interactions; Drug Overdose; Female; Humans; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride

Topics: Aged; Digoxin; Drug Monitoring; Drug Overdose; Female; Fluorescence Polarization Immunoassay; Humans; Immunoenzyme Techniques; Reproducibility of Results

Topics: Digoxin; Drug Overdose; Humans; Infant, Newborn; Injections, Intravenous; Medication Errors; Syringes

Patients with digoxin intoxication may need transvenous temporary cardiac pacing (TCP) when symptomatic bradyarrhythmias are present. However, it has been reported that TCP might be associated with fatal arrhythmias in patients with acute digitalis intoxication caused by attempted suicide. The aim of this study was to assess the safety of TCP in patients with accidental digoxin-related symptomatic bradyarrhythmias.. Seventy patients (30 men; age 74 +/- 12 years) were enrolled in this retrospective study. Patients were divided into two groups: group 1 with TCP and group 2 without TCP. A digoxin overdose was defined as a serum digoxin level higher than 2.0 ng/ml combined with the presence of digoxin-related symptoms. Detailed clinical characteristics were reviewed on the basis of the medical records.. Group 1 included 24 patients (34.3%, 10 men). The rhythms prior to pacemaker insertion in group 1 included sinus arrest with junctional bradyarrhythmias (n = 9), atrial fibrillation with a slow ventricular rate (n = 11), and high-degree atrioventricular block (n = 4). The mean duration of pacemaker implantation was 5.8 +/- 2.9 days (2-12 days). There was no major arrhythmic event or mortality after TCP in group 1. Two patients in group 2 (4%) died of ventricular tachyarrhythmias. Group 1 had a higher level of blood urea nitrogen (45.1 +/- 26.0 vs. 33.4 +/- 19.3 mg/dl), of left ventricular ejection fraction (68 vs. 56%), and of digoxin (4.4 +/- 2.1 vs. 3.4 +/- 1.3 ng/ml) but a lower serum calcium level (8.7 +/- 0.6 vs. 9.1 +/- 0.8 mg/dl).. TCP was safe for patients with a digoxin overdose complicated by symptomatic bradycardia and should be recommended in such situations. However, this conclusion does not apply to acute digoxin intoxication as a result of attempted suicide.

Topics: Aged; Aged, 80 and over; Bradycardia; Cardiac Pacing, Artificial; Digoxin; Drug Overdose; Female; Humans; Male; Middle Aged; Retrospective Studies; Treatment Outcome

We present here a fatal poisoning case involving verapamil, metoprolol and digoxin. A 39-year-old male was found dead in his room, and a lot of empty packets of prescribed drugs were found near the corpse. The blood concentrations of verapamil, metoprolol and digoxin were 9.2 microg/ml, 3.6 microg/ml and 3.2 ng/ml, respectively. The cause of death was given as cardiac failure, hypotension and bradycardia due to a mixed drug overdose of verapamil, metoprolol and digoxin, based on the results of the autopsy and toxicological examination. We speculate that the toxicity of verapamil is potentiated by drug interaction with metoprolol and digoxin.

Topics: Adrenergic beta-Antagonists; Adult; Anti-Arrhythmia Agents; Calcium Channel Blockers; Digoxin; Drug Interactions; Drug Overdose; Humans; Male; Metoprolol; Suicide; Verapamil

We have recently developed a unique hybrid artificial kidney, where the proximal tubular cell line, over-expressing multidrug resistance protein, MDR-1 (PCTL-MDR), was cultured on hollow fibers. While this module efficiently removed digoxin in vitro, its efficacy in vivo remained to be determined.. The system was scaled up by connecting 10 similar modules in parallel, with the MDR-1 (PCTL-MDR) overexpressed proximal tubular cell line cultured as in our previous study. The system was connected to dogs intoxicated with digoxin, a representative substrate of MDR-1. Blood was circulated for 90 minutes through the system. Arterial and venous blood concentrations of digoxin and inulin were monitored. Complete blood cell count and granulocyte elastase were measured before and at the end of the study.. By using the system with PCTL-MDR, the arterial digoxin concentration was dramatically decreased from 2.89 +/- 0.10 to 0.92 +/- 0.11 ng/mL, but not by the system with PCTL alone. The clearance was 22.4 +/- 2.1 and 1.5 +/- 0.2 mL/min for the PCTL-MDR and PCTL equipment, respectively. Inulin was not transported in either system. White blood cell and platelet counts were slightly reduced by the treatment while hematocrit was unchanged; the granulocyte elastase concentration was slightly increased.. These data suggest that our new type of hybrid kidney can selectively remove digoxin sufficiently to reduce its systemic blood concentration in dogs with digoxin intoxication. Taking previous studies into consideration, this system may be a more powerful tool for the treatment of intoxication.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cardiotonic Agents; Cell Line; Digoxin; Dogs; Drug Overdose; Gene Expression; Kidney Tubules, Proximal; Kidneys, Artificial

Charles Bonnet syndrome (CBS) is characterized by the presence of visual hallucinations in elderly, mentally healthy people. We report a visually impaired 90-year-old woman suddenly complaining of visual hallucinations, suffering from hyperthyroidism and a relative digitalis overdose. The diagnosis of CBS could be made after the exclusion of an intoxication and other neurological and psychiatric syndromes. In this case, visual hallucinations ceased without specific psychopharmacological therapy. A brief review of this organic hallucinosis, differential diagnosis, especially hyperthyroidism-induced psychosis, and digitoxin-induced psychosis is given and current therapeutic strategies are suggested.

Topics: Aged; Aged, 80 and over; Delusions; Diagnosis, Differential; Digoxin; Drug Overdose; Female; Hallucinations; Herpes Zoster Ophthalmicus; Humans; Hyperthyroidism; Patient Care Team; Vision, Low

Topics: Arrhythmias, Cardiac; Depression; Digoxin; Drug Overdose; Electrocardiography; Enzyme Inhibitors; Humans; Hyperkalemia; Male; Middle Aged; Sodium-Potassium-Exchanging ATPase; Suicide, Attempted; Vomiting

Topics: Accidental Falls; Age Factors; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Brain Injuries; Digoxin; Drug Overdose; Electrocardiography; Female; Humans

Calcium chloride (CaCl(2)) is ineffective in severe calcium channel antagonist overdoses. Digoxin increases intracellular calcium by inhibiting the sodium-potassium adenosine triphosphatase enzymes.. To examine the effect of calcium and digoxin on the treatment of verapamil toxicity.. Sixteen dogs were instrumented to monitor hemodynamics. Verapamil toxicity (50% decrease in mean arterial pressure) was induced with verapamil (VER) at 6 mg/kg/hr and maintained for 30 minutes by titrating the VER rate. Following toxicity, the dogs received either digoxin (0.018 mg/kg) (DIG) (n = 8) or saline (No-DIG) (n = 8). Both groups received VER at three sequential rates (1 mg/kg/hr from 0 to 90 min, 6 mg/kg/hr from 90 to 130 min, and 18 mg/kg/hr from 130 to 170 min). Calcium boluses were given (500 mg at 0 and 15 min; 1 g at 140, 150, and 160 min). Data were analyzed using a repeated-measures analysis of covariance comparing DIG vs No-DIG across the infusion rates and time. Animal weight, does of VER administered during the toxicity phase, and baseline values were included as covariates. Mortality rates were compared at 230 minutes following a total dose of 500 mg of VER.. The DIG group had a higher systolic blood pressure (SBP) than the No-DIG group during the 1-mg/kg/hr (early p = 0.028, late p = 0.01), 6-mg/kg/hr (p = 0.051), and 18-mg/kg/hr (p = 0.038) VER infusion rates. There were no deaths in the DIG group and four deaths in the No-DIG group (Fisher = 0.08). Neither ventricular tachycardia nor ventricular fibrillation developed in either group. Other hemodynamic parameters did not show significant changes.. In a model of severe verapamil toxicity, digoxin plus calcium raised SBP and did not result in ventricular arrhythmias when compared with calcium alone.

Topics: Animals; Calcium; Calcium Channel Blockers; Chi-Square Distribution; Digoxin; Disease Models, Animal; Dogs; Drug Overdose; Drug Therapy, Combination; Male; Reference Values; Survival Rate; Treatment Outcome; Verapamil

67 year old patient with chronic heart failure and persistent atrial fibrillation had overdosed glycosides for several months. The symptoms of gastrointestinal system and nervous system appeared after long term therapy with toxic doses of glycosides. Originally depression was diagnosed based on the central nervous system disturbances. Even though overdose of glycosides was diagnosed the blood serum glycoside level was within the therapeutic limits. Based on the precise analysis of the data, it was concluded that the reason for normal blood serum glycoside level in this case was coexisting hyperthyreosis.

Topics: Aged; Atrial Fibrillation; Color Vision Defects; Depression; Digoxin; Drug Overdose; Heart Failure; Humans; Hyperthyroidism; Male

Measurement of unbound digoxin in presence of Fab fragments may be useful in management of overdoses. The analysis can be performed on serum directly or on ultrafiltrate of serum. The architecture of the immunoassay may influence the validity of results obtained using these two approaches. We tested this hypothesis by preparing serum mixtures containing various concentrations of digoxin and Digibind and analyzed them by the immunoassays before and after ultrafiltration. Four samples collected from Digibind-treated patients were also analyzed before and after ultrafiltration. The slopes and the y-intercepts of the measured versus the expected values for serum and its ultrafiltrate overlapped for the MEIA digoxin assay. For other three immunoassays tested (ACS:180, Stratus, and On-Line), either the slope or the intercept for measured versus the expected results for serum were significantly different (P < 0.05) than those for ultrafiltrate. Following addition of digoxin and Digibind, differences in results for serum analyzed directly or after ultrafiltration were < 0.50 ng/ml. Comparable samples from digoxin-overdosed patients treated with Digibind had differences of > 1.0 ng/ml. Previous claims reporting direct analysis of digoxin in presence of antidote but not having used patient samples for validation should be revisited. To date, analysis of serum ultrafiltrate by an immunoassay proven not to have matrix bias remains the most accurate approach in measuring unbound digoxin in presence of antidote.

Topics: Adult; Antidotes; Digoxin; Drug Overdose; Female; Humans; Immunoassay; Immunoglobulin Fab Fragments; Male; Middle Aged; Regression Analysis; Reproducibility of Results; Ultrafiltration

Topics: Cardiotonic Agents; Digitoxin; Digoxin; Drug Administration Schedule; Drug Overdose; Heart Failure; Humans; Risk Factors; Tachycardia, Supraventricular

Topics: Digoxin; Drug Overdose; Fatal Outcome; Humans; Infant; Male; Medication Errors

A 79-year 65 kg male called the ambulance service 4 h after ingestion of 100 tablets of digoxin 0.1 mg complaining of nausea and vomiting. The ECG showed an idioventricular escape rhythm with a heart rate of 30/min. After 0.5 mg atropine, heart rate increased to 80/min. Soon after admission to the emergency department, the patient developed electromechanical dissociation. Due to persistent cardiac arrest, percutaneous cardiopulmonary bypass was started, and the ECG rhythm changed to ventricular fibrillation. Several attempts to terminate ventricular fibrillation by electrical defibrillation failed. Fifty-eight minutes after cardiac arrest, antidigoxin-Fab was administered and 1 h 25 min after cardiac arrest, ventricular fibrillation was terminated by the tenth electrical defibrillation attempt. Initially, the patient's overall status improved over the next 2 days, but then he developed a severe adult respiratory distress syndrome and died of unresponsive septic shock 12 days after ingestion of digoxin. This case demonstrates that percutaneous cardiopulmonary bypass may provide support in patients with cardiac arrest due to massive digoxin overdose. This temporary support can maintain adequate tissue perfusion during the time required for drug neutralization in order to achieve successful defibrillation. Percutaneous cardiopulmonary bypass should be considered in patients with severe, but temporary cardiac dysfunction due to a life-threatening drug overdose.

Topics: Aged; Anti-Arrhythmia Agents; Cardiopulmonary Bypass; Digoxin; Drug Overdose; Electric Countershock; Fatal Outcome; Heart Arrest; Humans; Male; Retreatment

Topics: Atrial Fibrillation; Cardiotonic Agents; Digoxin; Drug Administration Schedule; Drug Overdose; Humans

Topics: Aged; Anti-Arrhythmia Agents; Digoxin; Drug Overdose; Humans; Male; Mental Disorders; Nervous System Diseases

Two chronic haemodialyzed patients with digitalis intoxication are reported. One of them took digoxin 0.25 mg three times daily for an unknown period and the other took digitoxin 0.1 mg twice daily for two weeks. The symptoms of intoxication were mainly concealed by uremic syndrome. The diagnosis was established by noticed sinus bradycardia, first- and second-degree atrioventricular block in ECG and the determination of sera levels of glycosides (serum digoxin concentration was 7.36 ng/ml, serum digitoxin concentration was 46.5 ng/ml) in both cases. Considering the probable long elimination period of digitalis and the potentially life-threatening situation the patients were given digoxin-specific antibody (Fab) fragments with potassium replacement therapy. The symptoms disappeared within a few hours after therapy, side effects and rebound toxicity did not develop. In connection with these cases the aim of this report is to publish a method which can reverse the life-threatening digitalis intoxication in patients suffering from renal failure as well. As to the above method, the authors have not found any similar case reports in the Hungarian medical literature.

Topics: Aged; Antidotes; Digoxin; Drug Overdose; Female; Humans; Immunoglobulin Fragments; Potassium; Renal Dialysis; Self Administration; Uremia

Topics: Adolescent; Digoxin; Drug Overdose; Electrocardiography; Female; Humans; Suicide, Attempted

Digitalis intoxication is a common problem, mainly because of the narrow margin of safety of digoxin. These patients may have concomitant renal failure. In patients who have renal failure and who have been treated with digoxin-Fab, the elimination of the digoxin-Fab complex is significantly delayed, and there is a risk of dissociation of the complex with rebound of free digoxin and recurrence of toxicity. The high molecular weight of digoxin and digoxin-Fab complex prevents its elimination by hemodialysis or continuous arteriovenous hemofiltration. A 3-day-old newborn with digoxin overdose and acute renal failure was treated with digoxin immune Fab and peritoneal dialysis. Low levels of total digoxin were measured in the dialyzate, indicating poor elimination of the digoxin-Fab complex through peritoneal dialysis.

Topics: Acute Kidney Injury; Adult; Child; Digoxin; Drug Overdose; Female; Humans; Immunoglobulin Fab Fragments; Infant, Newborn; Peritoneal Dialysis; Pregnancy

Topics: Aged; Aged, 80 and over; Digoxin; Drug Overdose; Female; Heart Failure; Humans; Immunoglobulin Fab Fragments; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Ischemia; Suicide, Attempted; Ultrafiltration

Topics: Aged; Aged, 80 and over; Caregivers; Communication; Digoxin; Drug Overdose; Female; Humans; Patient Compliance

Topics: Acute Disease; Digoxin; Drug Overdose; Female; Humans; Infant, Newborn

Digitalis intoxication is a frequent iatrogenic effect in patients on treatment with digoxin. In the present study we evaluated the pharmacokinetic behaviour of digoxin and the factors responsible for intoxication by this drug in monitored patients exhibiting clinical signs of overdosing with serum levels > 2 ng/ml. A control group of patients was used as a reference whose population pharmacokinetic parameters obtained by a maximum likelihood method were: Vd = 542.92 +/- 274.53 (litre); Cl = 8.73 +/- 1.55 (litre/h) (mean +/- SD). Statistically significant differences (P < 0.001) were found between the mean Cl values in both groups of patients. The difference between the dose-level ratios established in both populations studied also proved to be significant (P < 0.001). Calculation of the optimum dose for each patient showed that the doses recommended in intoxicated patients should be three times lower than those used in the control population. A good correlation was found between the concentrations observed 24 h after administration and the mean concentrations observed at steady state predicted for both population groups. Multiple regression analysis showed that the variables with the greatest predictive value for clearance in intoxicated patients were age and renal function. The modifications observed in the pharmacokinetic behaviour and in the response to digoxin in this type of patient suggest systematic monitoring using pharmacokinetic and clinical criteria jointly.

Topics: Adult; Digoxin; Drug Overdose; Humans; Iatrogenic Disease; Middle Aged; Retrospective Studies

Prompted by animal studies reporting the accumulation of digitalis-glycosides in ocular tissues, we investigated whether measurement of digoxin levels in human ocular tissues can improve the postmortem diagnosis of lethal digoxin intoxication. Digoxin was measured in the vitreous humor and choroid-retina of patients who had received in-patient treatment with digoxin prior to death (therapeutic group) and in a single case of suicidal intoxication. The results were compared with the digoxin levels in the femoral vein blood, myocardium, kidney and liver, and evaluated in light of the medical history of each patient. In the therapeutic group the mean digoxin level was higher in the choroid-retina than in other tissues and body fluids. The range of variation in levels in the choroid-retina following therapeutic doses was comparable to that in the other tissues. An extremely high level of digoxin was present in the choroid-retina in the case of suicidal intoxication. In all cases, levels in the vitreous humor were very low compared to those in the choroid-retina. Hence, it is unlikely that significant distortion of choroid-retinal levels occurs due to postmortem diffusion of digoxin into the vitreous body. Our results indicate that measurement of digoxin levels in the choroid-retina can aid the postmortem diagnosis of lethal digoxin intoxication.

Topics: Aged; Aged, 80 and over; Aqueous Humor; Choroid; Digoxin; Drug Overdose; Evaluation Studies as Topic; Female; Forensic Medicine; Humans; Kidney; Liver; Male; Middle Aged; Myocardium; Poisoning; Postmortem Changes; Retina

The ability of digitalis compounds to counteract calcium antagonist overdose was studied in anesthetized dogs (n = 6, 13.5 +/- 0.7 kg) and isolated trabeculae from human hearts (n = 7). Digitalis caused by increasing intracellular cytosolic Ca2+ concentration through Na+/Ca(2+)-exchange across the cell membrane, was postulated to overcome the detrimental effects of excessive slow calcium-channel blockade. In anesthetized dogs, an infusion of verapamil (40 mg/30 min, i.v.) decreased mean arterial pressure from 88 +/- 6 to 66 +/- 6 mm Hg (P < 0.05), reduced systemic vascular resistance (SVR) from 3838 +/- 916 to 2200 +/- 669 dyne.s/cm5 (P < 0.05), and induced total atrio-ventricular (A-V) block in three animals. Stroke volume (SV) remained unchanged. Administration (i.v.) of NaCl (0.9%, 200 ml) and calcium gluconate (100 mg)--to increase the availability of Na+ and Ca(2+)--together with atropine (0.2 mg)--to block the parasympathetic effects of digoxin on A-V conduction--increased left ventricular contractility (15%) but had no significant effects on blood pressure, SV, or A-V block. Digoxin (0.125 mg) returned sinus rhythm in all dogs and, by increasing SVR (P < 0.05) and left ventricular contractility (P < 0.05), returned arterial pressures to baseline. Because of increased afterload, SV decreased slightly (15%) despite increased cardiac contractility. In experiments with isolated trabeculae from diseased human hearts, TA 3090 (Clentiazem) depressed contractile force and ouabain, another glycoside, restored contractile force within 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Atropine; Calcium; Calcium Channel Blockers; Calcium Gluconate; Depression, Chemical; Digoxin; Diltiazem; Dogs; Drug Overdose; Electrocardiography; Female; Hemodynamics; Humans; Male; Myocardium; Verapamil

Life-threatening digitalis intoxication is treated using digoxin specific antibody fragments (Fab) that bind and inactivate the drug. The free digoxin serum concentration could be useful in the management of Fab-treated patients, but the standard methods of measurement can be clinically misleading because Fab anti-digoxin interferes with digitalis immunoassay measurements. A case involving Fab therapy of a digoxin overdosed patient, in which two laboratory methods gave very different results, is reported. The radioimmunologic assay (RIA), widely used in laboratories, yielded high values without relation to true serum free digoxin concentration. On the contrary, the recently introduced fluoroenzymatic sequential immunoassay (FEIA), which accurately measures free glycoside concentration, was a valuable aid in monitoring Fab treatment. Therefore, cardiologists' knowledge of a possible interference of specific anti-digoxin fragment treatment with many immunoassays may greatly enhance the rational management of these patients.

Topics: Acute Disease; Aged; Digitalis; Digoxin; Drug Overdose; Female; Humans; Immunoglobulin Fab Fragments; Monitoring, Physiologic; Plants, Medicinal; Plants, Toxic; Poisoning

A 50-year-old, previously healthy, woman swallowed 1 g digoxin powder, dissolved in water, with suicidal intent. On admission to hospital one hour later, having vomited three times at home, the prominent signs were somnolence and hypersalivation. Serum digoxin level was 3.37 ng/ml. There followed repeated episodes of asystole alternating with ventricular fibrillation requiring cardiopulmonary resuscitation over 90 min and adrenaline administration. Repeated electrical defibrillation, administration of dopamine, phenytoin and lidocaine, as well as transitory transvenous electrical stimulation became necessary. Anti-digoxin antibody fragments were administered, initially 80 mg, to a total of 3,280 mg over 24 hours. After 3 days of intensive care and a further 21 days in hospital she was discharged and referred to psychiatric treatment. This case demonstrates that even severe digoxin poisoning can be successfully treated without sequelae by the appropriate administration of digoxin antidote. The main problems in this case were regulation of the dosage and acquiring the necessary amount of antidote which greatly exceeded the hospital's own depot.

Topics: Acute Disease; Antidotes; Combined Modality Therapy; Digitalis; Digoxin; Drug Overdose; Drug Therapy, Combination; Female; Gastric Lavage; Humans; Middle Aged; Plants, Medicinal; Plants, Toxic; Poisoning; Powders; Suicide, Attempted; Ventricular Fibrillation

Interpretation of postmortem serum digoxin levels is made difficult above all by a possible prefinal or postmortem rise in digoxin concentrations in the blood. To compensate for this postmortem increase, Eriksson et al. (1984) divided the level of postmortem digoxin in femoral venous blood by a factor of 1.5; in the opinion of these authors, postmortem digoxin levels still exceeding "therapeutic levels" after division by 1.5 are an index of digoxin overdose. The diagnostic value of this "correction factor" was investigated. In 56 cases with documented digoxin medication, samples of postmortem femoral venous blood were taken and the level of digoxin determined. In none of the cases had there been a clinical diagnosis of digoxin intoxication. Fifty percent of the measured values were above "therapeutic levels" (0.7 ng/ml to 2.2 ng/ml). Following division by 1.5, 20% of the cases still showed levels exceeding 2.2 ng/ml; the highest "corrected" value was 4.44 ng/ml. Taking into account the length of time between final dosage and death, individual differences in sensitivity to digitalis glycoside, and the complexity of ante- and postmortem dispersion processes, we concluded for the cases we studied that an (undetected) digoxin overdose was not even likely in those cases whose postmortem values after division by 1.5 lie above "therapeutic levels". The "correction factor" proposed by Eriksson et al. (1984) is only of limited diagnostic value; at best the "corrected" values can give an approximate indication of the corresponding antemortem serum digoxin concentrations. In particular, "corrected" values only a little above "therapeutic levels" could not confirm suspicion of an overdose with sufficient certainty.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Digoxin; Dose-Response Relationship, Drug; Drug Overdose; Female; Humans; Male; Middle Aged; Postmortem Changes