digoxin and Poisoning

Digoxin is a cardiac glycoside used as drug in case of heart problems, including congestive heart failure, atrial fibrillation or flutter, and certain cardiac arrhythmias. It has a very narrow therapeutic window of the medication. Digoxin is toxic substance with well known cardiotoxic effect. In this work, pharmacology and toxicology of digoxin are summarized; Its pharmacokinetics, pharmacodynamics, available acute toxicity data (different species, different administration routes) are summarized in this article. Moreover, its treatment side effect and human poisonings are thoroughly discussed. Finally, appropriate therapy regimen is proposed.

Topics: Animals; Digoxin; Drug Interactions; Humans; Poisoning

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

Topics: Acetaminophen; Aspirin; Barbiturates; Digoxin; Drug Monitoring; Humans; Inorganic Chemicals; Lithium; Organic Chemicals; Pesticides; Poisoning; Theophylline

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

This review provides current information on the use of antigen-binding fragments (Fab) from cleaved antibodies to treat poisoning with digoxin and other potent, low formula mass poisons, such as colchicine and tricyclic antidepressants. Anti-digoxin Fab fragments have been used successfully for many years in the management of severe poisoning with digoxin, digitoxin, and a range of other structurally related compounds, including cardiotoxins from Nerium and Thevetia sp. (oleander) and Bufo sp. (toads). However, their main use remains treating digoxin poisoning. Equimolar doses of anti-digoxin Fab fragments completely bind digoxin in vivo. The approximate dose of Fab fragments (mg) is 80 times the digoxin body burden (mg). If neither the dose ingested nor the plasma digoxin/digitoxin concentration is known, in an adult 380 mg of anti-digoxin Fab fragments should be given. The dose for elderly patients or those with renal impairment should be similar to that for those with normal renal function. Fab fragments have a plasma half-life of 12-20 hours, but this can be prolonged in patients with renal impairment. Analysis of serum ultrafiltrate using an immunoassay shown not to have matrix bias remains the most accurate approach to measuring free digoxin in the presence of anti-digoxin Fab fragments. The antibody fragments are given intravenously over 15-30 minutes after dilution to at least 250 mL with plasma protein solution, 0.9% (w/v) sodium chloride, or deionised water, except in infants where the volume infused can be reduced. Factors limiting the efficacy of Fab fragments are the dose, the duration of the infusion and any delay in administration. Guidelines for Fab fragment administration in children include (i) dilution to a final Fab concentration of 10 g/L in either 5% (w/v) dextrose or 0.9% (w/v) sodium chloride; (ii) infusion through a 0.22 microm filter; (iii) administration of the total dose over a minimum of 30 minutes; and (iv) avoiding coadministration of other drugs and/or electrolyte solutions. Fab fragments are generally well tolerated. Adverse effects attributable to Fab treatment include hypokalaemia and exacerbation of congestive cardiac failure; renal function could be impaired in some patients. Fab fragment preparations for treating acute colchicine and tricyclic antidepressant poisoning have been developed, but are not available commercially. Colchicine poisoning is rare in Western countries, and pharmacological management together with

Topics: Digoxin; Humans; Immunoglobulin Fab Fragments; Infusions, Intravenous; Poisoning

Digitalis glycoside poisoning is an important clinical problem and the development of digoxin-specific antibody fragments (Fab) 30 years ago has changed clinical practice. Nevertheless, doubts still exist as to the appropriate dose indications for therapy. This paper reviews relevant literature, describes the difficulties associated with current treatment protocols and proposes an approach to therapy, which is based on theoretical principles and evidence gleaned from currently available clinical data sets. In patients with 'acute' poisoning, serum digoxin concentrations do not equate to the total body burden, as tissue distribution will not have occurred, and the calculations for present protocols, which use serum concentrations, are therefore likely to result in too much antibody being administered. Since a therapeutic quantity of digoxin will have little effect in a normal individual, complete neutralisation of all digoxin is also unnecessary. The pharmacokinetic and dynamic logic of using a smaller initial loading dose than predicted from total body calculations is rational. It is recommended that half the calculated loading dose, either based on serum concentration or history, should be administered and the impact on clinical features observed. If a clinical response is not seen within 1-2 hours, a further similar dose should be given. In the event of a full response, patients should be monitored for 6-12 hours; a second dose should only be given in the event of recurrence of toxicity. In patients with 'chronic' digoxin poisoning, the serum digoxin concentration will reflect the total body load. However, since such patients are invariably receiving digoxin for therapeutic purposes, full neutralisation is again not indicated. In addition, tissue redistribution of digoxin from deeper stores will occur following the binding of biologically active digoxin in the circulation. This process will occur over a number of hours and if the total calculated dose of antibody is administered in a single bolus, significant quantities will be excreted prior to redistribution of digoxin. Pharmacokinetic logic, therefore, suggests that half the calculated loading dose, based on serum concentration, should be administered and the impact on clinical features observed; a second dose should be given in the event of recurrence of toxicity.

Topics: Digoxin; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Immunoglobulin Fab Fragments; Poisoning

Topics: 2-Propanol; Adrenergic beta-Antagonists; Carbon Monoxide Poisoning; Child; Cocaine; Cyanides; Digoxin; Ethylene Glycol; Humans; Hypoglycemic Agents; Insecticides; Isoniazid; Lysergic Acid Diethylamide; Methanol; N-Methyl-3,4-methylenedioxyamphetamine; Nicotine; Organophosphorus Compounds; Poisoning

Cardiac glucoside intoxication is a frequent medical problem given the following: the very narrow therapeutic range, its use in advanced aged patients, in patients with altered renal function, and because of interaction with other drugs. There are two types of digitalis intoxication: one that appears as a complication of the treatment with digitalis, and the other as a result of an accidental ingestion or in suicide attempt. The objective of this study was to review and assess the level of scientific evidence on the effectiveness and the indications of use of Fab fragments of antidigoxine antibodies.. A systematic bibliographic search in the following databases was made: MEDLINE, The Cochrane Library, The Iowa Drug Information Service, Embase, LMS/R&D Insight, and Indice Médico Español. The selected papers were classified according to their level of scientific evidence.. Abstracts of 252 references were reviewed. In the reviewed bibliography no controlled, randomized trials were found. Most of the studies found are descriptions of case series or single cases that were treated with antidigoxin Fab fragments. These types of studies provide little or no scientific evidence to speak of. None of the treatment regimes with antidigoxin antibody Fab fragments so far proposed have proven to be valid in a controlled, randomized clinical trial.. There is a very high level of concordance among the studies reviewed with regards to the efficacy and the indications for the use of Fab fragments in severe acute accidental digitalis intoxication and in suicide attempts. Regarding those intoxications that result in patients undergoing digitalis therapy, usual therapeutic approach is traditional treatment and the monitorization of the severity of the intoxication.

Topics: Digitalis; Digoxin; Humans; Immunoglobulin Fab Fragments; Plants, Medicinal; Plants, Toxic; Poisoning

In our environment, the use of Fab antibodies for digoxin intoxication is often difficult due to the low availability of this drug in most centers. We present a case of massive digoxin intoxication that was successfully managed with the classic treatment. Later, we discuss the need to individualize the management of this kind of intoxications in order to reduce, when possible, sanitary costs.

Topics: Acute Disease; Aged; Anti-Arrhythmia Agents; Combined Modality Therapy; Digoxin; Female; Humans; Immunoglobulin Fab Fragments; Poisoning; Suicide, Attempted

Although most acute pediatric ingestions of digoxin or other related cardiac glycosides result in minimal or no symptoms, occasionally a child is symptomatic. Gastrointestinal complaints or first-degree AV block are the most common presenting symptoms. Children can generally be given a single dose of activated charcoal, observed, and discharged without any subsequent problems. However, some patients will be toxic and require monitoring, medication, and possibly digoxin-specific antibody fragments. The most important role of the clinician is to recognize the clinical manifestations and institute the appropriate therapy. As in the case presented, the history of an ingestion may not always be obtained initially. Thus, the physician should maintain a high index of suspicion for acute digoxin ingestion and order the appropriate confirmatory tests (eg, a digoxin level, a potassium level, and a 12-lead ECG) when necessary.

Topics: Acute Disease; Cardiotonic Agents; Digitalis; Digoxin; Humans; Infant; Male; Plants, Medicinal; Plants, Toxic; Poisoning; United States

Topics: Digitoxin; Digoxin; Drug Interactions; Drug Monitoring; Humans; Poisoning

Topics: Charcoal; Digoxin; Humans; Immunoglobulin Fab Fragments; Poisoning

Significant digitalis toxicity, although uncommon, is a medical emergency. Recognition of the problem and good supportive care (eg, administration of activated charcoal and binding resins, correction of potassium levels, restoration of heart rhythm) are the cornerstones of treatment. If indicated, immunotherapy with digoxin immune Fab (Digibind) is a valuable and effective tool.

Topics: Arrhythmias, Cardiac; Charcoal; Digitalis Glycosides; Digoxin; Emergencies; Humans; Hypokalemia; Immunoglobulin Fab Fragments; Poisoning

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

The development of the radioimmunoassay for digoxin by Smith and coworkers in 1969 was a landmark in digitalis therapy. Since then, the complex pharmacokinetics of digoxin have been defined. As a result, the incidence of digitalis toxicity has markedly decreased. To use the digoxin assay properly, however, the relation of this pharmacokinetic parameter to digoxin pharmacodynamics must be known and the limitations of the assay itself understood. Systolic time intervals (STI) are uniquely useful to quantitate the inotropic effect of digitalis preparations. This technique can demonstrate the onset and magnitude of the inotropic effect for both oral and intravenous digitalis administration. By defining the mathematical relation between STI and simultaneous serum digoxin concentrations following intravenous administration of 1 mg digoxin, computer simulations can be made of the effect of dosing changes on blood and tissue concentrations. The serum digoxin assay has technical problems relating to quality control, interference by metabolites, and cross-reactions with endogenous digitalis-like substances. Further, a standard time for measurement following dosing has not been established. Physical activity can significantly after the serum digoxin concentrations by increasing skeletal muscle binding. Numerous drugs can interfere with digoxin absorption or elimination. Using the serum digoxin assay is the only way to assess these interactions. Computer surveillance (ideally with physician or pharmacist interaction) has been used to monitor digitalis but has not yet gained widespread acceptance. This is clearly a method in need of further testing.

Topics: Digoxin; Drug Monitoring; Heart Failure; Humans; Poisoning; Radioimmunoassay

The incidence of digoxin toxicity increases with age, largely because the two most common conditions that benefit from use of digoxin, congestive heart failure and atrial fibrillation, are markedly more prevalent in old age. Whether the elderly are more sensitive to the effects of digoxin because of age per se is unclear. However, several other factors render the elderly more susceptible to digoxin toxicity. These include an age-related decline in renal function and a decrease in volume of digoxin distribution. There is also an increase in the number of comorbid conditions, including cardiovascular and chronic obstructive pulmonary disease, which heighten susceptibility to digoxin toxicity. Moreover, treatment of these diseases with such interactive medications as quinidine and calcium channel blockers may increase the serum level of digoxin. Similarly, such electrolyte imbalances as hypokalemia and hypomagnesemia occur more frequently in the elderly as a result of diuretic therapy. However, recent data suggest that manifestations of digoxin toxicity among younger and older patients do not differ. Similar incidences of cardiac toxicity, gastrointestinal toxicity, and altered mental status are found in both patient populations. Treatment of digitalis toxicity in the elderly is the same as for younger patients. Response rates to Digibind are not diminished in the elderly.

Topics: Age Factors; Aged; Causality; Digoxin; Drug Interactions; Humans; Immunoglobulin Fab Fragments; Incidence; Poisoning

Digitalis glycosides have a narrow margin between therapeutic and toxic levels. Although the incidence of digitalis toxicity appears to be decreasing, continuation of digoxin therapy in the face of overt toxicity carries a substantial risk of life-threatening cardiac rhythm disturbances. This review will focus primarily on toxicity produced by digoxin and discuss the mechanisms, clinical manifestations, and current management of digitalis toxicity. The appropriate methodology for measurement and interpretation of serum digoxin levels is emphasized. The varied cardiac dysrhythmias induced by digoxin are detailed and their specific management outlined. Immunological (antibody) treatment has now been established and approved for the therapy of advanced, life-threatening digitalis toxicity and the multicenter trial of digitalis antibodies is described. Proper understanding of the pharmacokinetics of digitalis glycosides and careful followup of digitalis treated patients for early evidence of toxicity should help to decrease further the prevalence of toxic reactions.

Topics: Arrhythmias, Cardiac; Digitoxin; Digoxin; Humans; Poisoning

Topics: Adult; Antibodies; Body Temperature; Charcoal; Child; Digoxin; Diuresis; Half-Life; Heart Massage; Hemoperfusion; Humans; Poisoning; Poisons; Quinine; Renal Dialysis; Resuscitation

Topics: Acetaminophen; Acetylcysteine; Antidotes; Charcoal; Chemical and Drug Induced Liver Injury; Child Abuse; Child, Preschool; Digitoxin; Digoxin; Emetics; Female; Gastric Lavage; Humans; Hydrocarbons; Immunoglobulin Fab Fragments; Infant; Male; Naloxone; Narcotics; Poisoning

The use of antibodies in the diagnosis and treatment of drug poisoning is becoming an important aspect of emergency medicine. Digoxin-specific antibodies selectively inhibit the pharmacologic and toxic effects of the digitalis glycosides. Digoxin-specific Fab fragments rapidly reverse digitalis toxicity in animals and man. Furthermore, these Fab fragments are eliminated in the urine and are less immunogenic than whole antibodies. Anti-digoxin Fab fragments have been approved by the Food and Drug Administration for the treatment of digitalis intoxication. Alternative ways of using antidrug antibodies in the treatment of poisoning are being explored. Studies that demonstrate that antidrug antibodies immobilized on solid matrices remain functional have been conducted. Such immobilized antidrug antibodies are being evaluated for their ability to remove drugs from the circulation by extracorporeal perfusion. These areas of research promise to provide significant advances in the treatment of poisoning.

Topics: Animals; Antibodies; Digoxin; Humans; Poisoning

Topics: Biological Transport; Digoxin; Hemoperfusion; Humans; Hydrogen-Ion Concentration; Ions; Lipid Metabolism; Peritoneal Dialysis; Poisoning; Probenecid; Protein Binding; Renal Dialysis; Solubility; Tissue Distribution

Topics: Arrhythmias, Cardiac; Digoxin; Drug Synergism; Heart Diseases; Humans; Poisoning; Potassium; Vision Tests

Topics: Acrylates; Blood Urea Nitrogen; Charcoal; Creatinine; Digoxin; Embolism; Female; Gels; Hemoperfusion; Humans; Middle Aged; Poisoning; Renal Dialysis; Uremia; Uric Acid; Water-Electrolyte Balance

Topics: Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Heart Failure; Humans; Kidney Failure, Chronic; Poisoning; Vision Disorders

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Atrioventricular Node; Diagnosis, Differential; Digitalis Glycosides; Digitoxin; Digoxin; Heart Diseases; Heart Rate; Heart Ventricles; Humans; Myocardium; Poisoning; Radioimmunoassay

Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Atrioventricular Node; Digitalis Glycosides; Digoxin; Diuretics; Electrocardiography; Fatigue; Female; Gastrointestinal Diseases; Glucose; Heart Block; Humans; Lidocaine; Male; Middle Aged; Phenytoin; Poisoning; Potassium; Procainamide; Saliva; Tachycardia; Time Factors; Vision Disorders

Topics: Animals; Antibodies; Arrhythmias, Cardiac; Cardiac Glycosides; Digoxin; Erythrocytes; Haptens; Heart; Heart Rate; Humans; Immunoglobulin G; Immunotherapy; Kidney Cortex; Myocardium; Poisoning; Rabbits

Topics: Anorexia Nervosa; Color Vision Defects; Digitalis Glycosides; Digitoxin; Digoxin; Eye Manifestations; Fatigue; Humans; Medication Errors; Mental Disorders; Muscular Diseases; Nausea; Neurologic Manifestations; Poisoning; Vision Disorders

Topics: Absorption; Chemical Phenomena; Chemistry; Child; Child, Preschool; Digoxin; Humans; Infant; Infant, Newborn; Poisoning; Radioimmunoassay

Topics: Age Factors; Arrhythmias, Cardiac; Calcium; Child; Coronary Care Units; Digitalis Glycosides; Digoxin; Electric Countershock; Electrocardiography; Endocrine System Diseases; Heart Diseases; Heart Failure; Heart Rate; Heart Valve Diseases; Humans; Kidney Failure, Chronic; Liver Diseases; Lung Diseases; Magnesium; Obesity; Ouabain; Poisoning; Potassium; Psychophysiologic Disorders; Pulmonary Heart Disease; Thyroid Diseases; Time Factors

Because life-threatening digitalis intoxication is unusual in children, treatment with digoxin-specific-antibody Fab fragments (Fab) has rarely been reported. We describe the efficacy of Fab in the treatment of children with severe digitalis intoxication.. Twenty-nine children with intoxication due to digoxin (28) or digitoxin (1) received Fab at 21 participating hospitals between 1974 and 1986. Data were gathered about the patients' medical illnesses, doses and serum concentrations of digitalis, responses to Fab therapy, and outcomes.. In the infants and young children with acute digoxin intoxication, the digoxin doses ranged from 0.30 to 0.96 mg per kilogram of body weight; two adolescents had severe intoxication after doses of only 0.20 and 0.26 mg per kilogram. The serum digoxin concentrations ranged from 3.0 to greater than 100 ng per milliliter (mean, 13.8). Atrioventricular block (present in 22 patients [76 percent]) was the most common sign of toxicity. All the patients in this series had severe disturbances of cardiac rhythm, hyperkalemia (mean serum potassium concentration, 5.4 mmol per liter), or both. In 27 patients (93 percent), digitalis toxicity resolved after the administration of Fab. Of the 19 patients for whom data were available on the timing of the response to Fab, 15 responded within 180 minutes. Three patients required retreatment with Fab. Seven died of complications unrelated to the administration of Fab.. We recommend that Fab be used in the treatment of digitalis poisoning in infants and young children who have ingested greater than or equal to 0.3 mg of digoxin per kilogram, who have underlying heart disease, or who have a serum digoxin concentration of greater than or equal to 6.4 nmol per liter (greater than or equal to 5.0 ng per milliliter) in the elimination phase; and who also have a life-threatening arrhythmia, hemodynamic instability, hyperkalemia, or rapidly progressive toxicity. Adolescents, who are more sensitive to the toxic effects of digoxin than younger children, may require treatment with Fab after ingesting lower doses.

Topics: Acute Disease; Adolescent; Arrhythmias, Cardiac; Child, Preschool; Digitoxin; Digoxin; Female; Heart Block; Heart Diseases; Humans; Hyperkalemia; Immunoglobulin Fab Fragments; Infant; Infant, Newborn; Male; Poisoning

Minimal pharmacokinetic data on digoxin immune Fab are currently available, especially in patients with impaired renal function. The serum concentration-time profiles of total digoxin, free digoxin, and digoxin immune Fab in four patients with moderate to severe renal impairment who received digoxin immune Fab are presented. The calculated elimination half-life of digoxin immune Fab was 25-73 hours. The calculated elimination half-life of total digoxin was 24-72 hours. Free digoxin concentrations rebounded to a peak of 1-2.9 ng/mL 44-97 hours after the administration of digoxin immune Fab. The areas under the curve for digoxin immune Fab were 213-1026 micrograms.h/mL, and total body clearances were 2.3-7.1 mL/min. The total digoxin concentrations peaked at 14-33 times the pre-Fab digoxin concentrations 5-30 hours after digoxin immune Fab administration. In comparing these data with data available from patients with normal renal function, the half-life of digoxin immune Fab and total digoxin was longer, the peak total digoxin concentration occurred later, the ratio of the peak total digoxin concentration to pre-Fab digoxin concentration was larger, and the rebound in free digoxin occurred later in patients with renal impairment. The Fab dose should not be reduced in patients with renal impairment; however, post-Fab monitoring should be extended to compensate for the prolonged half-life of Fab and later rebound of free digoxin.

Topics: Adult; Aged; Digoxin; Female; Humans; Immunoglobulin Fab Fragments; Kidney Failure, Chronic; Poisoning; Time Factors

Following the development of methods for eliciting and purifying digoxin-specific Fab fragments with high affinity and specificity for cardiac glycosides, clinical studies were undertaken as a multicenter, open-label trial to test safety and efficacy in patients with advanced and potentially life-threatening digitalis toxicity that failed to respond to conventional therapeutic measures. One-hundred fifty such patients were treated with digoxin-specific antibody fragments purified from immunoglobulin G (IgG) produced in sheep. Doses of Fab were equivalent to the amount of digoxin or digitoxin in the patient's body, as estimated from the medical history or serum concentration measurements. Of 150 patients included in this trial, detailed information is available on 148. One-hundred nineteen (80%) had resolution of all signs and symptoms of digitalis toxicity following specific Fab fragment infusions, 14 (10%) improved, and 15 (10%) showed no response. Among 14 patients with adverse events possibly or probably caused by Fab, the most common events were development of hypokalemia and exacerbation of congestive heart failure. Analysis of the available clinical data indicates that a treatment response was observed in at least 90% of patients with convincing evidence of advanced and potentially life-threatening digitalis toxicity. The data from this multicenter trial have been augmented by findings from an observational surveillance study conducted to monitor the safety and effectiveness of treatment with digoxin immune Fab (ovine) following commercial availability. In this experience, 74% of patients were judged to have a complete or partial response to treatment, and 12% no response. The response for the remaining 14% was not reported or reported as uncertain. In this clinical experience, digoxin-specific Fab was generally well tolerated and clinically effective in patients with potentially life-threatening digitalis toxicity.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Child; Child, Preschool; Digoxin; Female; Humans; Immunoglobulin Fab Fragments; Infant; Infant, Newborn; Infusions, Intravenous; Male; Metabolic Diseases; Middle Aged; Poisoning; Product Surveillance, Postmarketing

Topics: Charcoal; Digoxin; Humans; Male; Poisoning; Suicide Prevention

Topics: Cardiovascular Agents; Digoxin; Drug-Related Side Effects and Adverse Reactions; Humans; Immunoglobulin Fab Fragments; Poisoning

For acute digoxin poisoning, it has been recommended to give bolus doses of 10-20 vials or potentially larger than needed doses calculated from dose ingested or the measured concentration. However, a recent revision of internal Poisons Information Centre guidelines prompted a change of our recommendations, specifically instead of large boluses, to use titrating repeated low doses of digoxin antibodies(Digoxin-Fab) based on bedside assessment of cardiac toxicity.. This is a prospective observational study of patients with acute digoxin poisoning identified through two Poisons Information Centres and three toxicology units. Patient demographics, signs and symptoms of digoxin toxicity, doses and response to Digoxin-Fab, free and bound serum digoxin concentrations. Outcomes were recorded and analysed.. From September 2013 to September 2020, 23 patients with 25 presentations (median age 56 years, females 56%) were recruited. Median dose ingested was 13 mg(IQR: 9.5-25). Median heart rate (HR) was 41 beats/min before treatment. Initial median digoxin and potassium concentrations were 14.5 nmol/L (IQR: 10.9-20) [11.2 µg/L(IQR: 8.4-15.4)] and 5 mmol/L (IQR: 4.5-5.4 mmol/L), respectively. Gastrointestinal symptoms and acute kidney injury were present in 22 patients (88%) and 5 patients (20%), respectively. Four patients received an initial bolus dose of Digoxin-Fab of 5-20 vials. Twenty-one patients received repeated titrated doses (1-2 vials) of Digoxin-Fab and the median total dose was 4 vials (IQR: 2-7.5). Median maximal change in HR post-Digoxin-Fab was 19 beats/min. The median potassium concentration decrease post-Digoxin-Fab was 0.3 mmol/L. Total dose used in the titration group was 25% and 35% of the predicted doses based on the amount of digoxin ingested or measured serum concentration, respectively. Twelve had free digoxin concentrations measured. Free digoxin concentrations dropped to almost zero after any dose of Digoxin-Fab. Ten patients had a rebound of digoxin >2.6 nmol/L (2 µg/L). There were no deaths from acute digoxin toxicity.. The new practice of using small, titrated doses of Digoxin-Fab led to a considerable reduction in total usage and major savings. The clinical response to titrated doses was safe and acceptable in acute digoxin poisoning.

Topics: Cardiovascular Agents; Digoxin; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Immunoglobulin Fab Fragments; Middle Aged; Poisoning; Potassium

Topics: Digoxin; Emulsions; Humans; Immunoglobulin Fab Fragments; Poisoning

The use of extracorporeal treatments (ECTRs) for poisonings with four non-traditionally dialysed toxins (NTDTs) is increasing in the United States. This study evaluated whether ECTRs are prescribed for toxin removal or the treatment of other medical illnesses or complications. We performed a 2-Phase retrospective analysis evaluating the main indication for ECTRs in patients with poisoning from a NTDT (defined for this study as acetaminophen, opioids, tricyclic antidepressants (TCAs) or digoxin) and ECTR. The first phase assessed all cases from a single site (New York City Poison Control Center) between the years 2000 and 2016, and the second phase surveyed all United States Poison Control Centers (PCCs). In Phase 1, demographics, toxin ingested and main indication for ECTR were extracted. In Phase 2, a query to the National Poison Data System using the a pragmatic subset of inclusion criteria from Phase 1 restricted to single toxin ingestions over a narrower time frame (2014-2016) provided the cases for study. A structured online questionnaire was sent to all United States PCCs to request their database review regarding the indication for ECTR for their cases. In Phase 1, 92 cases met inclusion criteria. In Phase 2, 519 cases were screened and 425 met inclusion criteria. In Phase 1 91/92 (98.9%) and Phase 2 411/425 (96.7%), of extracorporeal treatments were used to treat underlying medical conditions or poisoning-related complications rather than accelerate toxin removal. The increasing number of ECTRs reported in patients who ingested one of the four NTDTs thus appears to be for medical indications rather than attempts at toxin removal, a distinction that is important.

Topics: Acetaminophen; Analgesics, Opioid; Antidepressive Agents, Tricyclic; Databases, Factual; Digoxin; Humans; New York City; Poison Control Centers; Poisoning; Renal Dialysis; Retrospective Studies; Surveys and Questionnaires; United States

Digoxin poisoning is a frequent reason for seeking emergency care. This study aimed to assess mortality related to digoxin poisoning.. Descriptive observational study of digoxin poisonings attended in the emergency departments of 4 hospitals in Catalonia from 2013 through 2015. We gathered data relevant to the poisonings and recorded immediate and 30-day mortality. Factors possibly related to mortality were explored.. A total of 171 digoxin poisonings were attended. Seven (4.1%) were acute and 164 (95.9%) were chronic. The immediate and 30-day mortality rates were 6.4% and 13.4%, respectively. Bivariate analysis did not identify factors related to immediate mortality. However, the variables more often associated with 30-day mortality in this analysis were acute poisoning (after which 13% died vs 2.7% of those with chronic poisoning, P=.05), suicide attempts (8.7% of whom died vs 0.7%, P=.048), more compromised renal function (21.7% vs 9.5%, P=.037), fewer neurologic symptoms (4.3% vs 17.8% with more symptoms, P=.005), higher mean digoxin concentrations (4.7 mg/dL in those who died vs 3.7 mg/dL, P=.027), and a lower Barthel index (mean [SD] 49.1 [33.4] in those who died vs 70.3 [28.5]; P=.006). Logistic regression analysis identified serum digoxin concentration to be independently associated with immediate mortality. A lower Barthel index was associated with 30-day mortality.. Immediate mortality is related to a high digoxin concentration in serum, and 30-day mortality to a low Barthel index.. La intoxicación digitálica es un motivo frecuente de consulta en los servicios de urgencias hospitalarios (SUH). El objetivo de este estudio es conocer la mortalidad asociada a dicha intoxicación.. Estudio descriptivo y observacional de las intoxicaciones digitálicas atendidas en los SUH de 4 hospitales de Cataluña durante los años 2013-15. Se recogieron datos relativos a la intoxicación, la mortalidad inmediata y a los 30 días. Se analizó la existencia de posibles factores asociados a la mortalidad.. Se registraron 171 intoxicaciones digitálicas. Siete eran agudas (4,1%) y 164 (95,9%) crónicas. La mortalidad inmediata fue del 6,4% y a los 30 días fue del 13,4%. El análisis binario no identificó ningún factor relacionado con la mortalidad inmediata. En cuanto a la mortalidad a 30 días, los pacientes que fallecieron tenían con mayor frecuencia una intoxicación aguda (13% vs 2,7%; p = 0,05), había más intoxicaciones con intencionalidad suicida (8,7% vs 0,7%; p = 0,048), más afectación renal (21,7% vs 9,5%; p = 0,037), menos sintomatología neurológica (4,3% vs 17,8%; p = 0,005), mayor digoxinemia (4,7 mg/dl vs 3,7 mg/dl; p = 0,027) y menor puntuación en el índice de Barthel (IB) (49,1 (33,4) vs 70,3 (28,5); p = 0,006). El análisis de regresión logística identificó la digoxinemia como un factor independiente de mortalidad inmediata y la puntuación en el IB en la mortalidad a 30 días.. La digoxinemia se relaciona con la mortalidad inmediata y el IB se relaciona con la mortalidad a 30 días.

Topics: Adult; Aged; Aged, 80 and over; Digoxin; Emergency Service, Hospital; Enzyme Inhibitors; Female; Follow-Up Studies; Humans; Male; Middle Aged; Poisoning; Spain

Treatment of chronic digitalis intoxication includes suspension of drug intake, which may be sufficient in case of mild manifestations, and supportive measures. Severe bradycardia requires the administration of atropine or isoproterenol; placement of a temporary pacemaker may be required in case of absent response to pharmacological therapy. Severe and life-threatening manifestations should be treated with digoxin-specific fragment antigen binding antibodies (Fab). Therapeutic plasma exchange has been suggested, in addition to Fab therapy, to maximize the clearance of Fab-digoxin complexes in patients with renal failure. To date, few case reports have described the use of such a therapeutic approach; currently, extracorporeal methods are not recommended as part of the treatment of digitalis intoxication, and stronger evidence is required to establish their benefit.

Topics: Aged; Bradycardia; Digoxin; Female; Humans; Immunoglobulin Fab Fragments; Metabolic Clearance Rate; Plasma Exchange; Poisoning; Renal Insufficiency

Topics: Alprazolam; Antidotes; Digoxin; Diltiazem; Extracorporeal Membrane Oxygenation; Fat Emulsions, Intravenous; Fatal Outcome; Female; Hemofiltration; Humans; Middle Aged; Multiple Organ Failure; Poisoning

Topics: Acute Kidney Injury; Aged, 80 and over; Atrial Fibrillation; Confusion; Delirium; Diagnosis, Differential; Digoxin; Electrocardiography; Female; Heart Failure; Humans; Immunoglobulin Fab Fragments; Lung Diseases; Medically Uninsured; Nausea; Poisoning; Radiography, Thoracic; Vomiting

The aim of the study was to compare the adsorption ability of two adsorbent materials, namely diosmectite and activated charcoal towards selected model compounds that are most commonly involved in acute intoxication. Eleven model compounds were selected: acetylsalicylic acid, α-amanitin, amlodipine, digoxin, phenobarbital, ibuprofen, imipramine, carbamazepine, oxazepam, promethazine, and theophylline. Of the tested compounds, promethazine and imipramine were the most effectively adsorbed to diosmectite. Their adsorption to diosmectite (0.356±0.029mg promethazine/mg diosmectite and 0.354±0.019mg imipramine/mg diosmectite, respectively) was significantly higher than their adsorption to activated charcoal. The effect of temperature and pH on the adsorption efficiencies was also evaluated. In the case of experiments with mixture of both adsorbents, they mostly behaved in a solution independently or in a slightly antagonistic way. Using various methods such as N

Topics: Adsorption; Alpha-Amanitin; Amlodipine; Antidotes; Aspirin; Carbamazepine; Charcoal; Digoxin; Ibuprofen; Imipramine; Oxazepam; Phenobarbital; Poisoning; Promethazine; Silicates; Theophylline

The filter has been approved by the Food and Drug Administration for the removal of beta-2 microglobulin in patient undergoing hemodialysis. We used the filter (the patient agrees) off label, in the course of digitalis intoxication and we have shown that the filter is capable of removing the drug effectively.

Topics: Aged; Anti-Arrhythmia Agents; Atrial Flutter; Diabetic Nephropathies; Digoxin; Humans; Male; Poisoning; Renal Dialysis

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

Cardiac glycosides of plant origin are implicated in toxic ingestions that may result in hospitalization and are potentially lethal. The utility of commonly available digoxin serum assays for detecting foxglove and oleander ingestion has been demonstrated, but no studies have evaluated the structurally similar convallatoxin found in Convallaria majalis (lily of the valley) for rapid laboratory screening, nor has digoxin immune Fab been tested as an antidote for this ingestion.. We aimed to (1) evaluate multiple digoxin assays for cross-reactivity to convallatoxin, (2) identify whether convallatoxin could be detected in vivo at clinically significant doses, and (3) determine whether digoxin immune Fab could be an effective antidote to convallatoxin.. Cross-reactivities of purified convallatoxin and oleandrin with five common digoxin immunoassays were determined. Serum from mice challenged with convallatoxin was tested for apparent digoxin levels. Binding of convallatoxin to digoxin immune Fab was determined in vitro.. Both convallatoxin and oleandrin were detectable by a panel of commonly used digoxin immunoassays, but cross-reactivity was variable between individual assays. We observed measurable apparent digoxin levels in serum of convallatoxin intoxicated mice at sublethal doses. Convallatoxin demonstrated no binding by digoxin immune Fab.. Multiple digoxin immunoassays detect botanical cardiac glycosides including convallatoxin and thus may be useful for rapid determination of severe exposures, but neutralization of convallatoxin by digoxin immune Fab is unlikely to provide therapeutic benefit.

Topics: Animals; Animals, Outbred Strains; Cardenolides; Cardiotonic Agents; Convallaria; Cross Reactions; Digoxin; Dose-Response Relationship, Drug; Female; Immunoassay; Immunoglobulin Fab Fragments; Lethal Dose 50; Mice; Plant Poisoning; Poisoning; Strophanthins; Vasodilator Agents

Topics: Antidotes; Digoxin; Humans; Immunoglobulin Fab Fragments; Male; Middle Aged; Nerium; Plants, Toxic; Poisoning; Suicide, Attempted

Oleander poisoning can be detected by digoxin immunoassays and for last two decades the fluorescence polarization immunoassay (FPIA) has been used for rapid detection of oleander poisoning in clinical laboratories. Recently, Abbott Laboratories (Abbott Park, IL) discontinued this assay. Therefore, we explored the possibility of using another digoxin assay (Dimension Vista Flex Reagent Cartridge, Tina Quant, EMIT 2000 and old FPIA assay for comparison) for rapid detection of oleander poisoning. When aliquots of drug-free serum pools were supplemented with pure oleandrin or oleander extract, we observed the highest apparent digoxin values using Dimension Vista digoxin assay (Flex Reagent Cartridge). We also observed significant apparent digoxin values in vivo in sera of mice both 1 and 2  hr after feeding with oleander extract. When a serum pool prepared from patients taking digoxin was further supplemented with various amounts of oleander extract, the highest falsely elevated digoxin values were observed with Dimension Vista digoxin assay. Monitoring free digoxin using Dimension Vista digoxin assay (Flex Reagent Cartridge) did not eliminate this interference. Digibind neutralized digoxin-like factors of oleander extract and such effect can be monitored by observing significant reduction in apparent free digoxin levels in the presence of Digibind as measured in the protein-free ultrafiltrate using Dimension Vista digoxin assay (Flex Reagent Cartridge).

Topics: Animals; Digoxin; Disease Models, Animal; Fluorescence Polarization Immunoassay; Humans; Mice; Mice, Inbred BALB C; Nerium; Plant Extracts; Plant Leaves; Poisoning; Reproducibility of Results; Substance Abuse Detection

Topics: Calcium; Digoxin; Humans; Infusions, Intravenous; Poisoning

Topics: Age Factors; Cardiac Pacing, Artificial; Charcoal; Digoxin; Disease Susceptibility; Gastric Lavage; Humans; Hyperkalemia; Immunization, Passive; Poisoning; Risk Factors

Topics: Acute Kidney Injury; Antidotes; Bromazepam; Digoxin; Female; Fluid Therapy; Humans; Hydroxyethyl Starch Derivatives; Hyperkalemia; Immunization, Passive; Immunoglobulin Fab Fragments; Middle Aged; Poisoning; Polygeline; Suicide, Attempted; Time Factors; Ventricular Premature Complexes

Despite administration of Fab fragments in digitalis poisoning, high mortality rates are consistently reported. A previous study suggested that Fab fragments prescribed as first-line therapy might improve mortality rate. Our objective was to evaluate this approach.. Retrospective chart review (January 1990 to January 2004).. University hospital intensive care unit.. Consecutive patients admitted for cardiac glycoside poisoning.. First-line therapy with Fab fragments (with or without atropine) in either curative or prophylactic doses.. A total of 141 patients were admitted for digitalis poisoning of whom 66 received first-line Fab fragment therapy. Their median age was 74 years (25th to 75th percentiles: 51-83); 76% were women. Half were intoxicated by digitoxin and half by digoxin. Median serum concentration was 168 (108-205) ng/mL for digitoxin and 6.2 (4.3-13.5) ng/mL for digoxin. Conduction disturbances were reported in 45 cases (68%) and ventricular arrhythmia in six cases (9%). Fab fragments were administered as curative treatment in 21 patients (32%) and prophylactically in 45 patients (68%). The median cumulative dose was 4 (4-6) vials. No adverse effects were reported. Five patients (7.6%) died.. First-line therapy with Fab fragments in patients with digitalis poisoning was associated with a low mortality rate.

Topics: Aged; Aged, 80 and over; Arrhythmias, Cardiac; Atropine; Cardiotonic Agents; Critical Care; Digitalis Glycosides; Digitoxin; Digoxin; Female; Humans; Immunoglobulin Fab Fragments; Male; Middle Aged; Poisoning; Retrospective Studies

We studied the potential for detecting oleander with a new immunoassay (Digoxin III, Abbott Laboratories, Abbott Park, IL) by comparing results with those from the fluorescence polarization immunoassay (FPIA) and Digoxin II assay (Abbott). In aliquots of drug-free serum pools supplemented with pure oleandrin or oleander extract, we observed apparent digoxin values using all 3 immunoassays, but values obtained by the Digoxin III were higher than obtained by the other assays. We also observed significant apparent digoxin values in vivo in serum samples of mice 1 and 2 hours after feeding oleander extract. The average half-life of digoxin-like factors was 1.1 hours. In a serum pool (prepared from patients taking digoxin) supplemented with oleander extract, the observed digoxin values were falsely lowered when measured by the Digoxin II but falsely elevated when measured by the Digoxin III and FPIA. Monitoring free digoxin using the Digoxin III cannot eliminate this interference. Digibind neutralized digoxin-like factors of oleander extract; the effect can be monitored by observing a significant reduction in apparent free digoxin levels in the presence of Digibind as measured in protein-free ultrafiltrate using the Digoxin III. The Digoxin III is highly sensitive for measuring oleander.

Topics: Administration, Oral; Animals; Digoxin; Disease Models, Animal; Dose-Response Relationship, Drug; Immunoassay; Mice; Nerium; Plant Extracts; Plant Leaves; Poisoning; Reproducibility of Results; Substance Abuse Detection

Omeprazole is a commonly prescribed inhibitor of the gastric proton pump and has numerous indications in the treatment of gastrointestinal diseases. It is primarily metabolized through the CYP2C19 enzyme, a member of the P450 mixed-function oxidase group, although a minor pathway of metabolism is through CYP3A4, another P450 enzyme. Digoxin is primarily metabolized outside the P450 system, but a minor pathway of metabolism is by CYP3A4. To our knowledge, this is the first known case of digoxin toxicity associated with omeprazole. The possible pathways for such an interaction are reviewed, including increased stomach absorption, p-glycoprotein activity and interactions in the P450 system.

Topics: Aged; Atrial Fibrillation; Cardiotonic Agents; Digoxin; Drug Interactions; Enzyme Inhibitors; Female; Follow-Up Studies; Gastroesophageal Reflux; Humans; Immunoglobulin Fab Fragments; Omeprazole; Poisoning; Tachycardia, Paroxysmal

Gastric decontamination with single-dose activated charcoal (SDAC) is a mainstay in emergency department (ED) treatment of ingestions. Guidelines updated in 2005 encourage practitioners to use SDAC only in toxic ingestions presenting within 1 hour. Despite these guidelines, adult studies demonstrate a significant lack of consensus. This study examined the proposed use of SDAC for gastric decontamination in common pediatric ingestion scenarios by emergency physicians working in Canadian pediatric EDs.. A standardized survey consisting of 5 clinical scenarios was mailed to all physicians with a primary clinical appointment to the ED at 9 Canadian children's hospitals.. One hundred thirty-one physicians were surveyed, and 95 (72%) responded. The majority of respondents were pediatricians (68.1%) with a mean of 15.0 years of experience (SD, 6.8 years). Of those surveyed; 91 (97.8%) would use SDAC for a toxic ingestion presenting in less than 1 hour; 35 (36.8%) would use SDAC for a toxic ingestion presenting after 3 hours; 61 (64.9%) would use SDAC for a nontoxic exploratory ingestion presenting in less than 1 hour; and 29 (30.5%) would use SDAC for a mildly symptomatic intentional ingestion presenting at an unknown time. Eleven (11.7%) would use SDAC for an ingestion of a substance that does not adsorb to SDAC.. There is variation in the use of SDAC among emergency physicians working in Canadian pediatric EDs. This variation suggests that optimal management is not clear and that continued education and research are required.

Topics: Acetaminophen; Adolescent; Antidotes; Canada; Charcoal; Child, Preschool; Cross-Sectional Studies; Digoxin; Emergency Service, Hospital; Guideline Adherence; Health Care Surveys; Humans; Ibuprofen; Iron Compounds; Lorazepam; Male; Paroxetine; Poisoning; Time Factors

We report the first case of a child with known cardiac disease who presented in full cardiac arrest secondary to digoxin poisoning and was successfully resuscitated. A 12-week-old female presented 1-week status post surgical repair of a congenital heart anomaly in asystolic cardiac arrest. The patient was successfully resuscitated with standard Advanced Pediatric Life Support. A toxic digoxin level returned, Digoxin-specific antibody fragments (Digibind, Fab) were administered, and all signs and symptoms of toxicity resolved. The patient was discharged 6 days after presentation with full neurological recovery.

Topics: Child; Diagnosis, Differential; Digoxin; Electrocardiography; Emergency Treatment; Female; Heart Arrest; Humans; Poisoning

Acute digitalis overdosage is characterized by high electric instability, its mortality may reach 10-15 percent even nowadays.. To detect the possible risk factors which might predict severe intoxication.. Data of 50 patients treated at authors' department with acute digoxin poisoning over the past 8 years could be retrospectively evaluated. Cases were classified according to the Poison Severity Score (PSS). The following parameters were taken into consideration: age, sex, diseases influencing the severity of intoxication, dose of the drug, heart frequency, serum potassium and digoxin levels and vomiting. For statistical analysis a Kruskal-Wallis test and a chance-quotient calculation was applied.. From 50 patients 30 were mild (PSS 1, 2), 20 were severely poisoned, which subgroup included 8 deaths (PSS 4) and 12 patients who recovered (PSS 3). Based on Kruskal-Wallis test significant differences were found in the following items: greater number of primary diseases PSS 4 vs other subgroups (p < 0.05); bradycardia PSS 4 vs PSS 2 (p < 0.05) and PSS 3 vs PSS 2 (p < 0.05); hyperkalaemia PSS 3 vs PSS 2 (p < 0.01); elevated serum digoxin level PSS 3 vs PSS 2 (p < 0.05). The risk of severe poisoning (PSS 3-4) was increased in case of hyperkalaemia, bradycardia, vomiting (p < 0.001), and if the patients' age and if the drug dose exceeded 65 years or 10 mg, respectively (p < 0.05).. The predictive risk factors concerning severe acute digoxin poisoning are profuse vomiting, hyperkalaemia and bradycardia. The predictive risk factors of fatal outcome are age over 65 years associated with primary disease, vomiting and bradycardia.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Bradycardia; Cardiotonic Agents; Digoxin; Female; Heart Rate; Humans; Hyperkalemia; Male; Middle Aged; Poisoning; Predictive Value of Tests; Prognosis; Retrospective Studies; Risk Assessment; Risk Factors; Severity of Illness Index; Vomiting

The administration of intravenous (IV) calcium to treat hyperkalemia resulting from digoxin poisoning is considered potentially dangerous, based on a body of older literature which, in sum, reported increased cardiac glycoside toxicity with calcium administration (increased arrhythmias, higher rate of death).. This pilot study sought to determine if the administration of calcium chloride when compared to normal saline would affect time to death when given to hyperkalemic, digoxin toxic swine.. Digoxin IV at 0.25 mg/kg was determined to be appropriately toxic for this study. When arrhythmias consistent with hyperkalemia developed, animals were given either IV calcium chloride (CaCl) bolus (10 mg/kg, Group 1, n=6) or normal saline volume equivalent (Group 2, n=6). Three intervals were observed: Interval 1: time interval from digoxin administration (T0) to when ECG changes consistent with hyperkalemia developed (at which point calcium chloride or normal saline was administered); Interval 2: time interval from the development of ECG changes consistent with hyperkalemia to asystole; Interval 3: time interval from digoxin administration to asystole. Both groups were monitored for changes in heart rhythms, serum potassium levels, and time to asystole.. The intravenous digoxin dose of 0.25 mg/kg induced hyperkalemia, arrhythmias, and death approximately 1 h after administration in all animals studied. Group 1: Interval 1 averaged 18.75 (S.D. +/-7.96) min, Interval 2 averaged 16.75 (S.D. +/-17.17) min, and Interval 3 averaged 35.5 (S.D. +/-14.49) min range; Group 2: average Interval 1 24.8 (S.D. +/-4.71) min, Interval 2 averaged 19.5 (S.D.+/-15.92), Interval 3 averaged 44.3 (S.D. +/-13.80) minutes. There was no statistically significant difference between the groups at any time interval, Interval 1 (p=0.43), Interval 2 (p=0.65), Interval 3 (p=0.40). There was no difference in serum potassium throughout the study period.. The administration of intravenous CaCl in the setting of hyperkalemia from acute digoxin toxicity did not affect mortality or time to death at the dose administered.

Topics: Animals; Calcium Chloride; Cardiotonic Agents; Digoxin; Disease Models, Animal; Electrocardiography; Hyperkalemia; Injections, Intravenous; Pilot Projects; Poisoning; Potassium; Random Allocation; Swine

To quantify and analyze suspected and actual digoxin intoxications.. A drug-use study has been carried out of digoxinaemia requests and results in patients treated chronically with digoxin.. Digoxin intoxication (presence of symptoms and typical signs) was suspected in 31.3% of the patients. The percentage analytically confirmed intoxications (digoxinaemia >2 ng/mL) was 16.6%. Sex, age, and dosage had no significant effect in the suspicion or confirmation of digoxin intoxication. Hospitalization and the association of hypokalaemic drugs or those increasing digoxinaemia had no effect in the suspicion of digoxin intoxication. In analytically confirmed intoxications, no significant differences were found between suspected and non-suspected cases.. The suspicion of this intoxications is not usually related with digoxin serum levels, and thus, the toxic limit is imprecise.

Topics: Aged; Aged, 80 and over; Cardiotonic Agents; Digoxin; Female; Humans; Male; Middle Aged; Poisoning

This study considers the clinical manifestations and risk factors of digoxin toxicity and establishes an appropriate cut-off serum level for the diagnosis of toxicity. A retrospectivestudy of 125 hospitalized patients whose serum digoxin was assayed in 1998 was conducted. Of the 125 subjects, 42 (33.6%) were classified as having definite digoxin toxicity, 9 (7.2%) were classified as having probable digoxin toxicity, and 74 (59.2%) were classified as non-toxicated. Of the patients with definite digoxin toxicity, 24 (57.1%) had cardiac manifestations, seven (16.7%) had non-cardiac manifestations, and 11 had manifestations of both types. The commonest manifestation was atrial fibrillation with block. Average daily doses of digoxin in the patients with definite digoxin toxicity and those without intoxication varied from 0.125 to 0.5 ng/ml. There was no significant statistical difference in digoxin dosage between those with and those without digoxin toxicity. Seven univariate factors of digoxin toxicity were examined: logistic regression analysis showed that, serum BUN and serum chloride were independent associated factors of digoxin toxicity: the finding suggests that renal impairment and volume contraction are strong determinants of digoxin toxicity. Mean (SD) serum digoxin levels among the patients with and without toxicity were 2.28 (1.3) and 1.05 (0.6) ng/ml respectively (p = 0.000). The best cut-off level determined by Receiver Operating Characteristic (ROC) analysis was 1.97 ng/ml. However, a low sensitivity and a high specificity make serum digoxin levels a diagnostic rather than a screening tool. The manifestations of digoxin toxicity among Thai inpatients are no different from those of other populations. The best cut-off level of serum digoxin for the diagnosis of toxicity is 2 ng/ml.

Topics: Analysis of Variance; Digoxin; Drug Monitoring; Female; Humans; Logistic Models; Male; Middle Aged; Poisoning; Radioimmunoassay; Reference Values; Retrospective Studies; Sensitivity and Specificity; Thailand

Life-threatening digoxin toxicity may be effectively treated with digoxin-specific antibody fragments (Fab). However, in end-stage renal disease, the digoxin-Fab complexes persist in the circulation and dissociate, potentially resulting in rebounding free digoxin levels and the recurrence of symptomatic toxicity. To prevent this rebound phenomenon, plasma exchange (PE) has been implemented for the removal of the digoxin-Fab complexes in renal failure. However, there is only one case report describing its use in this setting. To better determine the optimal timing of PE after Fab administration, we performed two PE treatments (each preceded by Fab) in a patient with acute renal failure and acute digoxin poisoning. The admission serum digoxin level was 21 ng/mL. The timing of the PE treatments relative to Fab dosing was as follows: the first PE was performed 26 hours post-Fab, and the second PE was performed 2.5 hours post-Fab. The plasma ultrafiltrate digoxin concentration was 2.5-fold greater when PE was performed 2.5 hours versus 26 hours after Fab administration (19.9 versus 8.1 ng/mL). The combined total amount of digoxin removed in the ultrafiltrate plasma was minimal (0.13 mg), less than 1% of the total amount of ingested drug. We conclude that the optimal timing of PE is within the first 3 hours after Fab administration. Although PE is efficacious for removing digoxin-Fab complexes, thus preventing rebound digoxin toxicity, it is not efficacious for improving total digoxin clearance because of the large apparent volume of distribution of digoxin (5 to 8 L/kg).

Topics: Acute Kidney Injury; Digoxin; Humans; Immunoglobulin Fab Fragments; Male; Middle Aged; Plasma Exchange; Poisoning; Suicide, Attempted

Topics: Aged; Cardiotonic Agents; Digoxin; Female; Humans; Nursing Assessment; Poisoning

Chan Su, a traditional Chinese medication, and Love Stone, a topical aphrodisiac, are both made from dried venom of the toad bufo bufo gargarizans and contain bufalin, cinobufotalin, cinobufagin, and other cardioactive steroids of the bufadienolide class. Deaths have occurred following ingestion of these products and the clinical course resembles digoxin toxicity. The purpose of this study was to determine the efficacy of digoxin specific Fab fragments in treating Chan Su poisoning. An ethanolic extract was prepared from Chan Su. Digoxin specific Fab fragments were reconstituted in normal saline to a concentration of 80 mg/ml. An approximate LD90 dose was determined in preliminary experiments. Mice were then randomly divided into a treatment group of 15 mice and a control group of 30 mice. The treatment group was pretreated with 20 ml/kg of digoxin specific Fab fragment solution by intraperitoneal injection at t = 0, followed by 10 ml/kg of digoxin specific Fab fragments intraperitoneal at t = 30 min. The control group was pretreated with equal volumes of intraperitoneal normal saline at the same times. Immediately following the 30 min injection, both groups were given the estimated LD90 dose of Chan Su extract by subcutaneous injection. An endpoint of survival at 6 h was chosen after preliminary results showed that all deaths occurred in the first 4 h. All 30 of the control mice had seizures followed by death compared to 11 seizures and 7deaths in the 15 treatment mice. These results were statistically significant by Fisher's exact test (p = 0.00003 for mortality and p = 0.009 for seizures). Digoxin specific Fab fragments are effective in the treatment of Chan Su poisoning in mice and may be effective for poisoning by other cardioactive steroids of the bufadienolide class.

Topics: Amphibian Venoms; Animals; Aphrodisiacs; Bufanolides; Bufonidae; Bufotenin; Cardenolides; Digoxin; Dose-Response Relationship, Drug; Gas Chromatography-Mass Spectrometry; Immunoglobulin Fab Fragments; Medicine, Chinese Traditional; Mice; Poisoning; Seizures; Survival Rate

Topics: Antidotes; Blood Proteins; Digoxin; Humans; Immunoassay; Immunoglobulin Fab Fragments; Poisoning; Protein Binding

Contrary to cardiac glycoside poisoning often seen in medical practice, intentional digoxin poisoning is rather rare and its course is serious only if very high doses have been ingested. Ventricular arrhythmias and severe conduction disturbances are the most threatening sings may need the use of antiarrhythmic agents, temporally endocardial stimulation or digoxin specific antibody Fab fragments. The course and the management of digitalis poisoning is described in two young patients (female aged 37 and male aged 26). Before admission to the hospital they were healthy, without any heart problem. Only one patient (female) had short spell of nausea and vomiting as well as green vision phenomenon. This patient developed transitory non-life threatening conduction disturbances (degree and II degree a-v block). The second patient had nausea and vomiting but no serious cardiac symptoms. In both patients very high digoxin plasma levels were found (19.88 ng/ml and 9.63 ng/ml), but no one of them had serious poisoning symptoms and did not require any specific therapy. After 3 (male) and 4 (female) days both patients left the hospital.

Topics: Adult; Arrhythmias, Cardiac; Digoxin; Female; Heart Block; Humans; Male; Nausea; Poisoning; Suicide, Attempted; Vomiting

Topics: Adult; Antibodies, Monoclonal; Antidepressive Agents, Tricyclic; Antivenins; Arrhythmias, Cardiac; Binding Sites, Antibody; Colchicine; Digoxin; Female; Humans; Immunization, Passive; Immunoglobulin Fab Fragments; Immunotherapy; Lipopolysaccharides; Poisoning; Sepsis; Venoms

This is the first report in the forensic literature of a combination of fatal digoxin poisoning with endocardial fibroelastosis (EFE). Typical morphological features of EFE as the cause of clinically diagnosed cardiomyopathy were present in the autopsy of a 3-year-old girl, including cardiac hypertrophy and marked thickening of the left-sided endocardium, consisting of numerous elastic and collagenic fibres. After exclusion of cardiac and cerebral causes of death, accidental digoxin intoxication was proved. Postmortem toxicological analyses by fluorescence polarization immunoassay (FPIA) disclosed digoxin levels of 71 micrograms/kg (femoral vein blood), 77 micrograms/kg (cardiac blood), 255 and 221 micrograms/kg (cardiac muscle of the right and left chamber), 163 micrograms/kg (psoas muscle), 91 micrograms/kg (lung), 222 micrograms/kg (liver) and 520 micrograms/kg (kidney). The results are compared with the antemortem digoxin concentration of 39 ng/ml serum. The case is discussed from its unusual morphological and toxicological aspects, with special consideration of possible medical malpractice.

Topics: Cardiotonic Agents; Child, Preschool; Digoxin; Endocardial Fibroelastosis; Fatal Outcome; Female; Humans; Poisoning

Topics: Aphrodisiacs; Bufanolides; Digoxin; Humans; Poisoning

Topics: Animals; Antidotes; Child, Preschool; Digoxin; Humans; Immunoglobulin Fab Fragments; Immunotherapy; Poisoning

A 15-year-old-female admitted after ingesting 5 milligrams of digoxin, presented atrial tachycardia with 2.0 degree atrioventricular block and frequent ventricular premature complexes. Serum digoxin determination at admission was 16 ng/ml. Two hours following the administration of 2 amp of Fab antidigoxin (160 milligrams) the arrhythmias disappeared and remained asymptomatic until discharge.

Topics: Adolescent; Digoxin; Electrocardiography; Female; Humans; Immunoglobulin Fab Fragments; Poisoning; Suicide, Attempted

The role of the parasympathetic autonomic nervous system (ANS) in digoxin intoxication was investigated in atropine pretreated conscious rabbits. Both the electrocardiographic registration and the histologic analysis indicated possible prevention of lethal arrhythmias by atropine pretreatment. The hearts of animals pretreated with atropine appeared less damaged, since they presented only a light cytoplasmic vacuolization. It was evident that the administration of digoxin without atropine pretreatment provoked dramatic signs of digitalis intoxication followed by animal death. Myocardia of these rabbits were highly damaged. On the other hand, our experimental data indicated that the abolishment of the vagal tone by atropine blockade caused only signs (i.e. inversion of the T wave) due to myocardial ischemia, to which the light cytoplasmic vacuolation could be correlated. Myocardial ischemia could be caused by constriction of coronary blood vessels, which could be consequential to both the prevalent activity of the orthosympathetic ANS, following parasympathetic blockade, and direct digoxin effects on vascular fibrecells, which both produce vasoconstriction. Therefore, it is reasonable to assume that the parasympathetic ANS plays a major role in digitalis intoxication in rabbits.

Topics: Animals; Anti-Arrhythmia Agents; Atropine; Digoxin; Electrocardiography; Heart; Myocardium; Parasympathetic Nervous System; Parasympatholytics; Poisoning; Rabbits

Topics: Adult; Cardiotonic Agents; Digoxin; Emergency Nursing; Female; Humans; Immunoglobulin Fab Fragments; Poisoning

We describe two cases of digoxin toxicity presenting with clinical and electroencephalographic evidence of encephalopathy without other features of digoxin toxicity.

Topics: Aged; Brain Diseases; Diagnosis, Differential; Digoxin; Female; Humans; Poisoning

Topics: Amphibian Venoms; Antibodies, Monoclonal; Cardiac Glycosides; Cross Reactions; Digoxin; Humans; Immunoassay; Immunoglobulin Fab Fragments; Male; Middle Aged; Poisoning

Gitaloxin is a digitalis glycoside used for the same indications as digoxin and digitoxin. The successful outcome for a 2 1/2-year-old boy who accidentally ingested 3 mg of gitaloxin (100 times the normal therapeutic dose) is reported. At admission the child presented with irregular heart rhythm. He subsequently started vomiting, even after continuous gastric feeding. Only 48 h after ingestion of gitaloxin he became somnolent and developed bradyarrhythmia. The symptoms disappeared 96 h later; the bradyarrhythmia, however, (second-degree atrioventricular block) decreased progressively only after 120 h. The initial clinical presentation of gitaloxin poisoning may be misleading and careful observation in a pediatric intensive care unit is mandatory. A cross-reaction between the fluorescence polarization immunoassay for digitoxin and the radioimmunoassay for gitaloxin was found and was used as a helpful, but rough, estimate of the severity of gitaloxin poisoning, in the absence of a specific measurement of gitaloxin.

Topics: Bradycardia; Child, Preschool; Critical Care; Digoxin; Electrocardiography; Fluorescence Polarization Immunoassay; Humans; Male; Poisoning; Vomiting

During February 1993-May 1995, the New York City Poison Control Center (NYCPCC) was informed about onset of illness in five previously healthy men after they ingested a substance marketed as a topical aphrodisiac; four of the men died. These cases were investigated by the New York City Department of Health, the New York City Department of Environmental Protection, and the Food and Drug Administration (FDA). Four cases were referred to the NYCPCC and one case to the New York City medical examiner's office. The decedents died from cardiac dysrhythmias, and all five patients had measurable levels of digoxin* detected in their serum. Digoxin had not been prescribed for therapeutic purposes for any of these patients, and none had medical conditions associated with endogenous digoxin-like immunoreactive substances. The purported aphrodisiac contains bufadienolides, naturally occurring cardioactive steroids that have digoxin-like effects. This report describes three of the five case reports, summarizes the investigations of the five cases, and underscores the health risks associated with inappropriate use of preparations containing digoxin-like substances.

Topics: Adolescent; Adult; Aphrodisiacs; Arrhythmias, Cardiac; Bufanolides; Digoxin; Fatal Outcome; Heart Arrest; Humans; Hyperkalemia; Hypotension; Male; New York City; Poisoning

Topics: Adolescent; Adult; Arrhythmias, Cardiac; Bufanolides; Digoxin; Fatal Outcome; Heart Arrest; Humans; Hyperkalemia; Hypotension; Male; New York City; Poisoning

Topics: Atrial Fibrillation; Cardiac Complexes, Premature; Diagnosis, Differential; Digoxin; Electrocardiography; Female; Heart Failure; Humans; Middle Aged; Poisoning; Rheumatic Heart Disease

Topics: Aged; Aged, 80 and over; Digoxin; Drug Monitoring; Female; Humans; Immunoglobulin Fab Fragments; Poisoning

Cholestyramine, a bile acid sequestering resin, has been reported to bind digitalis in vitro. We gave 4 g every 6 hours to 3 patients with non-life threatening digoxin intoxication. In all 3 serum digoxin concentrations and digoxin half-life decreased: from 50 to 32 hours, from 50 to 10 hours and from 46 to 16 hours in the 3 cases, respectively. Cholestyramine is potentially useful and safe adjunct medication for non-life threatening digoxin intoxication.

Topics: Aged; Aged, 80 and over; Cholestyramine Resin; Digoxin; Female; Half-Life; Humans; Male; Poisoning

To evaluate an animal model of multiple-dose activated charcoal (MDAC) therapy and correlate the pharmacokinetic properties of four drugs with the efficacy of MDAC.. Prospective, randomized, controlled, crossover design.. A university animal research facility.. Seven female pigs (15 to 22 kg) with an indwelling central venous line and gastrostomy tube.. Acetaminophen (30 mg/kg), digoxin (30 micrograms/kg), theophylline (8.9 mg/kg), and valproic acid (18 mg/kg) were simultaneously administered intravenously over 12 minutes. In the experimental arm, 25 g activated charcoal was administered at 0, 2, 4, 6, 12, 18, 24, and 30 hours through the gastric tube. In the control arm, an equal volume of water was given at the same times. Blood specimens were obtained over 36 hours to measure serum drug concentrations.. Each drug exhibited enhanced elimination (P < .01) in the MDAC group except valproic acid. Lower intrinsic clearance was correlated (P < .05) with increased systemic elimination during the charcoal arm. Volume of distribution, half-life, and protein binding were not significantly correlated with charcoal-enhanced systemic drug elimination.. The response of a drug to MDAC may be affected by its intrinsic clearance. The restrictive nature of the protein binding of valproic acid may be responsible for its lack of response. Results with the porcine model are consistent with the effects observed in human beings.

Topics: Acetaminophen; Animals; Charcoal; Digoxin; Disease Models, Animal; Drug Administration Schedule; Female; Half-Life; Linear Models; Metabolic Clearance Rate; Pharmacokinetics; Poisoning; Poisons; Prospective Studies; Random Allocation; Swine; Theophylline; Valproic Acid

The incidence of digoxin toxicity among patients in hospitals has declined in recent years. To evaluate whether a similar decline has occurred in ambulatory care, we reviewed randomly selected medical records for 183 outpatients receiving ongoing treatment with digoxin at 10 urban and rural Department of Veterans Affairs Medical Centers in the Rocky Mountain region. The prevalence of traditional risk factors for digoxin toxicity--elevated serum digoxin and serum creatinine levels, hypokalemia, and a new prescription of an interacting drug-was established from computerized laboratory and pharmacy records. Of the 183 patients, 50 (27.3%) had one or more risk factors for digoxin toxicity: serum digoxin levels were elevated in 13.6% of patients in whom a level was obtained, with hypokalemia in 14.3%, elevated creatinine levels in 17.9%, and possible drug interactions in 5.5% of patients over a 1-year period. Nevertheless, digoxin toxicity occurred in only 2 persons (1.1% or 1.4 per 100 patient-years of treatment). We conclude that digoxin toxicity was rare in this group of outpatients, even in persons presumed to be at high risk because of metabolic abnormalities, increased digoxin concentrations, or the use of interacting drugs. The low rate of digoxin toxicity in outpatients parallels the decline in the incidence of toxicity observed in hospital-based studies.

Topics: Aged; Digoxin; Humans; Middle Aged; Outpatients; Poisoning; Prevalence; Risk Factors; Southwestern United States

Topics: Aged; Aged, 80 and over; Digoxin; Female; Humans; Nursing Assessment; Poisoning; Syncope

A concurrent audit was made of 92 patients with plasma or serum digoxin levels of 3.0 ng/ml or more. Evidence of digoxin toxicity was present in 44 of these patients, and premature blood sampling accounted for the high levels in 30 nontoxic patients. Another 14 patients tolerated high digoxin levels without apparent adverse effects. Impaired renal function appeared to increase the risk of digoxin toxicity, even though digoxin levels were similar in patients with and without toxicity. Pharmacokinetic predictions based on patient weight and creatinine clearance often deviated considerably from measured digoxin levels even when these were drawn appropriately.

Topics: Aged; Aged, 80 and over; Chicago; Concurrent Review; Creatinine; Digoxin; Female; Hospital Bed Capacity, 500 and over; Hospitals, Teaching; Humans; Male; Medical Audit; Middle Aged; Poisoning; Risk Factors

Topics: Arrhythmias, Cardiac; Digoxin; Electrocardiography; Female; Humans; Middle Aged; Poisoning

A 22-year-old man presented to our emergency department after an intentional overdose of a homemade foxglove extract. Clinical symptoms with symptomatic bradyarrhythmia and ECG changes were consistent with cardiac glycoside poisoning. Treatment with digoxin-specific Fab fragments resulted in transient clinical and ECG improvement. Serum immunoassay demonstrated a digitoxin-like glycoside. The serum levels showed no evidence of altered elimination or distribution with Fab therapy despite temporary improvements in the clinical course. The use of Fab did not result in a shortened clinical course in this episode of foxglove poisoning, as one would expect in the setting of commercial glycoside product poisoning.

Topics: Adult; Digitalis; Digitoxin; Digoxin; Half-Life; Humans; Immunoglobulin Fab Fragments; Male; Plant Extracts; Plants, Medicinal; Plants, Toxic; Poisoning; Suicide, Attempted

Topics: Aged; Atrial Flutter; Digoxin; Female; Humans; Hypothyroidism; Poisoning; Risk Factors

Topics: Aged; Aged, 80 and over; Digoxin; Female; Humans; Immunoglobulin Fab Fragments; Poisoning; Radioimmunoassay; Reproducibility of Results

Topics: Adult; Aged; Aged, 80 and over; Digoxin; Electrocardiography; Female; Heart Failure; Humans; Male; Middle Aged; Poisoning

Digoxin is a toxic drug with a narrow therapeutic index that is mostly used by the elderly. Although it is accepted that toxicity of digoxin occurs more frequently in elderly than in younger patients, there is dispute about its prevalence and associated mortality. A study was therefore set up to, on the one hand, find the prevalence and associated mortality of digoxin toxicity in patients admitted onto two geriatric wards in London and, on the other hand, to study the relationship between serum digoxin level and age, serum urea, serum potassium and serum calcium in geriatric patients with digoxin toxicity. Over a period of three years 1438 patients (age 75-93) were admitted of whom 452 (31%) were on digoxin. Thirty-five patients (7.7%) were diagnosed as having digoxin toxicity. Eight patients (22.9%) with digoxin toxicity died during admission. Mortality was higher although not statistically significant for the patients with toxicity than for the patients who were on digoxin without toxicity. The fatal outcome was not predicted by age, serum urea, serum potassium or serum calcium. The serum digoxin level of the eight patients who died was lower than the level of those (n = 23) who survived. Four patients (11%) had a normal serum digoxin level and clinical features of digoxin toxicity that disappeared on stopping digoxin. A hypothesis is put foreward to explain the weak association between serum digoxin level and digoxin toxicity in geriatric patients.

Topics: Aged; Aged, 80 and over; Calcium; Digoxin; Electrocardiography; Hospital Departments; Humans; London; Poisoning; Potassium; Prevalence; Urea

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

Topics: Animals; Antidotes; Digitalis; Digoxin; Humans; Plants, Medicinal; Plants, Toxic; Poisoning; Rats

Topics: Antibodies; Digitalis Glycosides; Digoxin; Humans; Poisoning

Digoxin toxicity occurs most commonly among the elderly. While the clinical syndrome of digoxin toxicity is well understood, how toxic manifestations change with age is not known.. We performed secondary analysis of data from a postmarketing surveillance study of patients with life-threatening digoxin toxicity treated with digoxin antibody therapy. Patients receiving long-term maintenance digoxin therapy and aged 55 years or older were divided into four age groups: 55 to 64, 65 to 74, 75 to 84, and 85 years and older (n = 45, 167, 183, and 83, respectively) and compared with regard to presenting manifestations, digoxin dosing, serum potassium and digoxin levels, and renal function.. The prevalence of high-degree atrioventricular block showed an increasing but nonsignificant trend with age (40%, 40%, 42%, and 47%, respectively). Age-related trends in high-degree atrioventricular block were stronger among men than women and even stronger among men with underlying cardiac ischemia. The proportion of subjects with nausea/vomiting as a toxic manifestation did not consistently change with age (42%, 48%, 48%, and 46%, respectively). There were no age-related differences in degree of renal impairment or maintenance dose, but maintenance dose decreased with increasing renal impairment.. Among patients with life-threatening digoxin toxicity, there is no age-related difference in clinical presentation.

Topics: Age Factors; Aged; Aged, 80 and over; Arrhythmias, Cardiac; Digoxin; Female; Heart Block; Humans; Immunoglobulin Fab Fragments; Male; Middle Aged; Nausea; Poisoning; Prevalence; Product Surveillance, Postmarketing; Vomiting

Intoxications with drugs, household products and plants include approximately 70% of all cases reported to the STIZ. Among drugs the most frequent severe intoxications occur with benzodiazepines and antidepressives; therefore, the toxicological risk of these substances are investigated in more detail. In children, accidental intoxications with household products are most frequent. In these cases special emphasis must be put on preventive measures. Plants only rarely lead to severe intoxications; however, if toxic symptoms do occur, the analysis of their causality and overall risk for the patient can be a difficult task and frequently requires the involvement of a plant specialist.

Topics: Adult; Aged; Antidepressive Agents; Benzodiazepines; Child; Digoxin; Household Products; Humans; Pharmaceutical Preparations; Plant Poisoning; Poisoning; Switzerland

The treatment of digoxin intoxication has been revolutionized by digoxin specific antibody fragments (Fab). Serum digoxin concentrations may be inaccurate after this treatment. We report a case of digoxin intoxication where the results of serum concentration determinations were strikingly disparate depending on the assay used. To investigate this discrepancy we compared serum samples spiked with digoxin from 0-50 ng/mL in the presence of increasing concentrations of digoxin specific Fab-fragments. Samples were measured using the Abbott TDx assay with and without ultrafiltration of the sample and the Dade-Stratus radial partition assay. The TDx assay was statistically reduced by the Fab-fragments although the magnitude of the effect was small. The radial partition assay was dramatically affected by the addition of Fab-fragments. The predicted non-Fab bound concentration correlated highly with the measured concentration. When samples were ultrafiltered prior to TDx assay, the measured concentration was dramatically depressed but the regression of predicted non-Fab bound concentration versus observed had a significantly lower slope than for the radial partition assay. We hypothesize that this difference is due to serum protein binding in addition to Fab-fragment binding. We conclude that the radial partition assay gives the best approximation of digoxin concentration remaining unbound to Fab-fragments. Ultrafiltration followed by TDx assay gives an acceptable approximation.

Topics: Antigen-Antibody Reactions; Digoxin; False Negative Reactions; Humans; Immunoassay; Immunoglobulin Fab Fragments; Infant; Poisoning

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

Each year many people have digitalis toxicity severe enough to require extensive hospital treatment. Digoxin immune Fab[ovine]-Fab fragments (Digibind) have been shown to reverse digitalis toxicity and substantially reduce the risk of death. Data were used from uncontrolled studies of patients treated with Fab fragments as well as clinical, medical care and pharmacokinetic data from symptomatically treated patients to derive estimates of the difference in clinical outcomes and medical care costs when treating with this new drug. Estimates are derived separately for treatment of patients with toxicity that is immediately life-threatening and patients whose manifestations are not immediately life-threatening. Treatment with Fab fragments reduces the probability of dying more for the seriously toxic than for the less seriously toxic patient. Such treatment is generally associated with an increase in total medical care costs for the seriously toxic patients because more of them survive the toxic episode and require additional medical care before discharge from the hospital. For these patients, the estimated cost per life-year saved is between $1,900 and $5,400. When Fab fragments are used to treat less seriously toxic patients, total medical care costs decrease because of an estimated decreased number of days in the coronary care unit and decreased use of pacemakers and other aggressive treatments.

Topics: Accidents; Adult; Arrhythmias, Cardiac; Cardiac Pacing, Artificial; Cause of Death; Child, Preschool; Cost-Benefit Analysis; Costs and Cost Analysis; Digoxin; Electric Countershock; Heart Massage; Humans; Immunoglobulin Fab Fragments; Length of Stay; Life Expectancy; Poisoning; Probability; Suicide, Attempted; Survival Rate; Treatment Outcome

A case report of severe digitalis poisoning in a patient with prosthetic heart valve is presented. He complained of nausea, vomiting, drowsiness, temporal disorientation and lethargy. The electrocardiogram showed idioventricular rhythm, and plasma levels of digoxin were 6.78 ng/ml. Predisposing factors por digitalis poisoning were prerenal failure and concomitant quinidine therapy. Treatment with digoxin-immune antibody fragments (FAB) promptly lead to abolition of the ventricular arrhythmia and disappearance of every clinical symptoms in hours. Plasma digoxin levels showed a steep decrease until normal values at the fifth day. The favourable course of either clinical and electrocardiographic response to IV administration of FAB are discussed, stressing the fact of the high morbidity of digitalis poisoning in opposition to the relative safety of Fabs use in its therapy.

Topics: Digitalis Glycosides; Digoxin; Humans; Immunoglobulin Fab Fragments; Male; Middle Aged; Poisoning

Measurement of serum digoxin concentrations (SDCs) is used routinely in the diagnosis of digoxin toxicity. Following administration of the antidote, digoxin immune antigen binding fragments (Fab), SDC monitoring is hampered by assay-related problems because of the presence of Fab in the serum. Recent evidence has suggested several available methods to monitor free SDC during Fab therapy. This report describes the utility of monitoring free SDC following Fab administration. Free SDCs were obtained using an ultrafiltration and fluorescence polarization immunoassay system in three patients over periods of up to 204 hours after Fab administration. In each case, the decline in free SDC was temporally related to the resolution of digoxin toxicity; in one case, digoxin intoxication recurred and was associated with a rebound increase in free SDC. In addition to the therapeutic benefits, prospective monitoring of free SDC in two of the patients also may have resulted in cost savings secondary to reduced hospital stay or less use of Fab.

Topics: Adult; Aged; Digoxin; Female; Humans; Immunoglobulin Fab Fragments; Male; Middle Aged; Monitoring, Physiologic; Poisoning; Time Factors

Topics: Adolescent; Aged; Aged, 80 and over; Digoxin; Female; Half-Life; Humans; Immunoglobulin Fab Fragments; Male; Poisoning; Suicide, Attempted

Topics: Aged; Digoxin; Female; Humans; Immunoglobulin Fragments; Poisoning

Digoxin excess can produce characteristic bradyarrhythmias, tachyarrhythmias, and hyperkalemia. The bradyarrhythmias, which consist of disturbances in conduction and block at the level of the atrioventricular and sinus nodes, are mediated by a direct and vagotonic effect. The vagotonic effect of excess digoxin may also result in a marked slowing of the sinus rate in the setting of severe toxicity. Digoxin increases automatic and triggered electrical activity in atrial muscle, His-Purkinje system, and ventricular muscle, which predisposes to tachycardias. Many of the tachyarrhythmias are relatively specific for the toxic effects of digoxin. Atrial tachycardias with variable atrioventricular block, accelerated junctional rhythms (especially in the setting of atrial fibrillation), and fascicular tachycardias are characteristic digoxin toxic rhythms. Digoxin-specific antibody fragments should be considered the treatment of choice for any digoxin toxic arrhythmia associated with hemodynamic compromise or the threat of hemodynamic compromise. Hyperkalemia, when due to acute severe digoxin toxicity, is also an appropriate indication for digoxin-specific Fab fragment therapy. When assessing the risk:benefit ratio for using digoxin-specific Fab fragment therapy, one needs to determine, in addition to the electrocardiographic manifestations and patient's hemodynamic status (1) the severity of toxicity, as indexed by the amount ingested and/or the serum digoxin concentration; (2) the expected time course for reversal of toxicity, which is usually determined by the status of renal function; (3) the need for digoxin to provide ventricular rate control or improved ventricular contractility and therapeutic alternatives to digoxin; (4) the presence of a strong allergy history; (5) the presence of such factors as increased age and severity of heart disease that may predispose to digoxin toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Arrhythmias, Cardiac; Causality; Clinical Protocols; Digoxin; Electrocardiography; Hemodynamics; Humans; Hyperkalemia; Immunoglobulin Fab Fragments; Poisoning

A patient with renal failure due to myeloma kidney and coincident digitalis intoxication due to prescribed daily digoxin administration was treated with digoxin-specific antibody fragments and plasmapheresis. Rapid response to therapy was noted, removal of digoxin-antidigoxin antibody complexes was confirmed, and prevention of delayed rebound toxicity was documented. We suggest that this is the therapy of choice in similar individuals.

Topics: Acute Kidney Injury; Aged; Digoxin; Female; Humans; Immunoglobulin Fab Fragments; Multiple Myeloma; Plasmapheresis; Poisoning; Renal Dialysis

Digoxin intoxication has been reported to be a common adverse drug reaction with an in-hospital incidence of 6% to 23% and an associated mortality rate as high as 41%. A retrospective review was conducted to assess the accuracy of diagnosis, the morbidity and mortality of digoxin intoxication, and its incidence in hospitalized patients with heart failure. We reviewed the medical records of 219 patients discharged with the diagnosis of digoxin intoxication between 1980 and 1988. Patients were classified as follows: (1) Definite intoxication--patients with symptoms and/or arrhythmias suggestive of digoxin intoxication that resolved after discontinuation of digoxin; (2) possible intoxication--patients with symptoms and/or arrhythmias suggestive of digoxin intoxication in the absence of documented resolution after discontinuation of digoxin, or the presence of other clinical illnesses that could possibly account for those findings; (3) no intoxication--patients whose symptoms or ECG abnormalities were clearly explained by other associated clinical illnesses and persisted after withdrawal of digoxin. We identified only 43 patients (20%) with definite intoxication. The majority of patients discharged with the diagnosis of digoxin intoxication (133 or 60%) were classified as possibly digoxin intoxicated, and 43 patients (20%) had no clinical evidence to support this diagnosis. To estimate the incidence of digoxin intoxication, we also reviewed the medical records of 994 patients admitted in 1987 with heart failure. Of these, 563 were receiving digoxin and in 27 the diagnosis of digoxin intoxication was made by their clinicians. Our review showed that only four were definitely intoxicated (0.8%), and the diagnosis could not be excluded in another 16 (4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Aged, 80 and over; Arrhythmias, Cardiac; Digoxin; Female; Hospitals, Urban; Humans; Male; Michigan; Poisoning; Retrospective Studies

Although elevated digitalis concentrations are often observed, symptomatic intoxications occur less frequently. We report the course in three patients with extremely elevated digitalis concentrations as examples of the poor correlation between measured serum levels and symptoms. In view of the cost of treatment by fab-fragments and the lack of a close dose-related effect of digitalis, we suggest restricting the use of fab-fragment therapy to patients with severe hyperkalemia or hemodynamically relevant arrhythmias.

Topics: Adult; Aged; Aged, 80 and over; Combined Modality Therapy; Digitoxin; Digoxin; Female; Humans; Immunoglobulin Fab Fragments; Male; Poisoning; Suicide, Attempted

Topics: Aged; Body Weight; Digoxin; Female; Humans; Immunoglobulin Fab Fragments; Poisoning

Serious digoxin toxicity due to accidental or deliberate overdose is uncommon, but more than half of the cases reported in 1985 involved children. Toxicity can occur acutely, as with accidental overdose, or with long-term maintenance dosing. In children it is almost always acute. Conventional treatment includes gastric lavage or ipecac-induced emesis, and activated charcoal or nonabsorbable resins and cathartics to reduce absorption. Although children appear to tolerate massive ingestions without specific therapy, serum digoxin levels must be reduced quickly and safely when conventional measures have failed. Fab fragments of digoxin-specific antibodies have been successfully used to treat refractory digoxin toxicity. Indications for use should be limited to life-threatening digoxin toxicity when conventional therapy has failed.

Topics: Antibody Specificity; Child; Digoxin; Gastric Lavage; Humans; Immunoglobulin Fab Fragments; Immunoglobulin Fragments; Ipecac; Poisoning

The use of digoxin-specific fragments, antigen-binding (Fab) for antidotal therapy of severe digitalis intoxication is rapidly becoming a treatment of choice. Furthermore, studies with this mode of drug-specific therapy using Fab specific for desipramine and for phencyclidine suggest that this treatment may be applicable to a variety of other drugs or drug classes. As Fab technology has advanced, so have laboratory methods for monitoring the efficacy of treatment.

Topics: Antidotes; Desipramine; Digoxin; Humans; Immunoglobulin Fab Fragments; Phencyclidine; Poisoning

Topics: Acetylcysteine; Antidotes; Digoxin; Ethanol; Glucagon; Humans; Immunoglobulin Fab Fragments; Methylene Blue; Naloxone; Poisoning; Pyridoxine

Hemoperfusion through Amberlite XAD-4 resin column has been shown to effectively remove sedative-hypnotics, analgesics and other drugs causing acute intoxication. There is no appreciable clinical toxicity and dramatic shortening of coma time and possible decrease in mortality may be achieved. Thrombocytopenia and clotting may be diminished by pre-perfusion coating with 2.5% albumin. Albumin coating may facilitate the repeated use of hemoperfusion without any complications. More recently, resin hemoperfusion has been used for procainamide, N-acetylprocainamide and theophylline intoxication achieving exceptionally high clearance rates.

Topics: Acecainide; Digoxin; Glutethimide; Hemoperfusion; Humans; Ion Exchange Resins; Poisoning; Polystyrenes; Polyvinyls; Procainamide; Theophylline

Acute massive digoxin overdose may result in life-threatening arrhythmias, with reported mortality of up to 20% prior to the introduction of digitalis-specific antibodies. Digitalis-specific Fab antibody fragments remain under experimental protocol and are not widely available. Interpretation of serum digoxin levels and indications for the use of Fab are not clearly established. The authors report a case of massive digoxin overdose in an 18-month-old child with the highest reported digoxin level (48 ng/ml) with which a victim survived without the need for Fab administration. She developed only mild manifestations of digitalis intoxication, and her serum potassium never exceeded 5.2 mEq/l. Her course may be explained by the distribution kinetics of digoxin, which follows a two-compartment model, and the relative resistance of children to digitalis intoxication. This case emphasizes the need for better criteria than the digoxin level for the administration of Fab. The serum potassium concentration, which is usually elevated in acute type digitalis intoxication, may be a better predictor of the need for Fab in acute massive digitalis ingestion.

Topics: Digoxin; Female; Humans; Immunoglobulin Fab Fragments; Infant; Metabolic Clearance Rate; Poisoning; Potassium

Topics: Adult; Amiodarone; Antibody Specificity; Benzofurans; Digoxin; Female; Humans; Immunoglobulin Fab Fragments; Poisoning; Ventricular Fibrillation

A case of massive digoxin ingestion with multiple arrhythmias, consisting of high grade A-V block and ventricular ectopy not responsive to lidocaine, is described. The arrhythmias ceased following administration of digoxin-specific Fab fragments. The patient improved and was transferred to the psychiatric unit.

Topics: Antibodies; Digoxin; Female; Humans; Immunoglobulin Fab Fragments; Immunotherapy; Middle Aged; Poisoning; Substance-Related Disorders

The usefulness of a new biocompatible, specific immunosorbent, Agarose-Polyacrolein Microsphere Beads--Antidigoxin antibodies (APAMB-AD) for hemoperfusive removal of digoxin in digoxin intoxicated dogs is described. The sorbent contains antidigoxin antibodies covalently bound to polyacrolein microspheres, 0.2 micron in diameter. Thousands of microspheres are matrix-encapsulated in cross-linked agarose to form beads 500 to 800 micron in diameter. The sorbent removes digoxin specifically, leaving other components of the blood intact, in contrast to the nonspecific sorbents (charcoal and ion exchange resins) currently in use. Digoxin-intoxicated dogs looked ill, vomited, and their ECGs showed malignant arrhythmias which were reversed during the first hour of hemoperfusion. By 2 hours of hemoperfusion, the ECG tracings returned to the preintoxication state. Up to 27% of the total body digoxin burden was removed. The sorbent is biocompatible. Neither the formed elements nor a battery of the routinely assayed soluble components of the blood or complement (C'4) were altered significantly during the hemoperfusion trials. The dogs tolerated the hemoperfusion well and all survived the intoxication. Nonhemoperfused dogs or dogs whose blood was hemoperfused through beads lacking antidigoxin did not survive the digoxin intoxication.

Topics: Acrolein; Animals; Antibodies; Digoxin; Dogs; Hemoperfusion; Microspheres; Poisoning; Polymers; Sepharose

Topics: Adult; Age Factors; Aged; Biological Availability; Cardiac Glycosides; Digitalis Glycosides; Digitoxin; Digoxin; Dose-Response Relationship, Drug; Heart Failure; Humans; Middle Aged; Poisoning; Risk

Topics: Digitoxin; Digoxin; Female; Hemoperfusion; Humans; Middle Aged; Poisoning; Protein Binding

Plasma levels of digoxin were measured in a patient after massive intoxication. Pharmacokinetic analysis of the data as compared with other cases of digoxin intoxication reveals that in these situations oral administration of cholestyramine may be of benefit to the patient.

Topics: Cholestyramine Resin; Digoxin; Humans; Male; Middle Aged; Poisoning

Topics: Digoxin; Hemoperfusion; Humans; Poisoning

Digitalis therapy is frequently accompanied by adverse drug reactions. Severe digitalis intoxications are still a problem. Therapeutical methods, which could be used in the case of a life threatening digoxin intoxication, are known, but not yet generally available. Hemodialysis has only a minor effect on digoxin excretion. This study was planned to test the hypothesis that hemoperfusion across dextran-cocoated charcoal or the resin Amberlite XAD 4 could be more effective in the therapy of digoxin intoxications. The ability of hemoperfusion to eliminate digoxin was tested in a patient who had to undergo treatment beacuse of a severe bromcarbamide intoxication. Additionally we compared the effect of several modifications on this method in 12 dogs, which had received 0.05 mg/kg body weight per day for three days prior to the experiment. Although hemoperfusion across Amberlite XAD 4 may eliminate as much digoxin as normal human kidneys during the few hours of treatment, the amount of digoxin removed after all is only a small percentage of the total body pool. Thus compared to the risks of hemoperfusion as an invasive treatment its effect is small. According to our results, hemoperfusion cannot be recommended as a standard therapy of severe digoxin intoxications.

Topics: Adult; Animals; Digoxin; Dogs; Female; Hemoperfusion; Humans; Kidney; Poisoning

Topics: Animals; Digitalis Glycosides; Digoxin; Glucosephosphate Dehydrogenase; Guinea Pigs; L-Lactate Dehydrogenase; Liver; Malate Dehydrogenase; Oxidoreductases; Poisoning; Rabbits

Topics: Biguanides; Clonidine; Digoxin; Drug-Related Side Effects and Adverse Reactions; Humans; Pharmaceutical Preparations; Poisoning; Radiography; Time Factors; Toxicology

Topics: Barbiturates; Digoxin; Hemoperfusion; Humans; Inactivation, Metabolic; Poisoning; Renal Dialysis

Since there is no widely used causal means of reducing the severity of massive digitalis intoxication the capability of hemoperfusion with coated activated charcoal to remove toxicologically relevant amounts of digoxin and digitoxin was evaluated in vitro and in man. At a blood flow rate of 100 ml/min the digoxin clearance by hemoperfusion in vitro was 51 +/- 8 ml/min in comparison to 24.3 +/- 11.3 ml/min by hemodialysis. The average hemoperfusion clearance of digitoxin was 31.7 +/- 13.4 ml/min, whereas almost no digitoxin was removed by hemodialysis. These clearance values point to the ability of hemoperfusion of eliminating digitalis glycosides from the blood. They do not clarify the essential question whether it is possible to lower the toxic concentrations in the tissues.

Topics: Charcoal; Digitoxin; Digoxin; Hemoperfusion; Humans; Poisoning

The diagnostically relevant data of 1164 patients under digitalis were stored in a computer and compared statistically for toxic and nontoxic patients. Resulting from this a questionnaire was developed in which each item was weighted according to its own diagnostic value. In a prospective study 77 suspected cases of digitalis intoxication were classified according to their scoring in the questionnaire. In 92% of the patients this classification was confirmed by the final diagnosis (after withdrawal of the glycoside). Mean score and mean serum digoxin concentration (SDC) of the toxic patients were significantly higher. There was a high consensus between the final diagnosis, the classification by the questionnaire and the SDC. The questionnaire proved to be a useful aid in the bedside diagnosis of digitalis intoxication.

Topics: Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Humans; Poisoning; Risk; Surveys and Questionnaires

6 patients with severe digitalis intoxication were studied while hospitalised in a coronary care unit. 2 and 4 patients had ingested high doses of lanatosid C and digoxin, respectively. In three cases ventricular arrhythmias, in one of these and two further cases SA blocking and an additional A-V-block in one case were observed. Maximum blood levels of digoxin between 3.4 and 20 ng/ml were determined several hours after the ingestion. The maximal blood levels were achieved in one patient only 52 h after ingesting lanatosid C and in one patient taking digoxin after 12.5 h. Potassium concentrations in plasma were elevated in 4 patients. Antiarrhythmic and electrolyte therapy is discussed and the usefulness of a stomach lavage for diminishing the quantity of absorbed lanatosid C is shown in one patient who had a maximal blood level of 3.4 ng/ml after taking 23.7 mg of lanatosid C. Cumulative urinary excretion of this patient was 0.68 mg within 5.5 days. This result confirms the minimal enteral absorption under the therapy chosen.

Topics: Adult; Aged; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Female; Heart Block; Humans; Intestinal Absorption; Kinetics; Lanatosides; Male; Middle Aged; Poisoning

Consideration of the interactions of drugs and dialysis must include an understanding of the mechanisms of transport during dialysis, i.e., diffusion, ultrafiltration and membrane-protein binding effects. Clearance is a function of molecular size, blood and dialysate flow, membrane area and permeability, and dialyzer support geometry. Protein binding and hematocrit decrease the in vivo clearances in comparison to those measured in vitro with aqueous solutions. The effect on the serum half-life is also determined by the distribution space and clearance by other routes. Other factors such as metabolic alterations of dialysis can affect pharmacologic activity, and the clinical response is the end product of many determinants. Numerous drugs are effectively removed by hemodialysis or at a slower rate by peritoneal dialysis, which occasionally allows considerable influx. The influence of intestinal contents on elimination rates by peritoneal dialysis is unknown. Peritoneal dialysis can be influenced considerably by vasoactive drugs.

Topics: Animals; Barbiturates; Capillary Permeability; Digoxin; Half-Life; Humans; Kidney Failure, Chronic; Metabolic Clearance Rate; Peritoneal Dialysis; Pharmaceutical Preparations; Poisoning; Potassium; Protein Binding; Renal Dialysis

Purified Fab fragments of ovine digoxin-specific antibodies reversed severe digoxin intoxication in a patient who had taken 22.5 mg of the drug with suicidal intent. Atrioventricular block with extreme bradycardia was temporarily managed by pacing, but progressive, intractable hyperkalemia (serum potassium of 8.7 meq per liter) with increasing pacing threshold and progressive intraventricular conduction delay was controlled only after infusion of 1100 mg of Fab. Sinus rhythm returned 10 minutes after completion of Fab infusion. Within five hours, the serum potassium concentration fell to 4.0 meq per liter. Free digoxin concentrations in serum fell sharply to undetectable levels, whereas total serum digoxin concentration concomitantly increased 12-fold. Renal excretion of digoxin bound to Fab was documented. Reversal of toxicity was not accompanied by hemodynamic instability, and antibodies to sheep Fab fragments were not detected in the patient's serum after treatment. Thus, purified digoxin-specific Fab fragments are capable of rapid reversal of advanced digoxin toxicity.

Topics: Adult; Animals; Antibody Specificity; Digoxin; Electrocardiography; Heart Block; Humans; Hyperkalemia; Immunoglobulin Fab Fragments; Male; Poisoning; Sheep; Suicide, Attempted

Topics: Aged; Digitalis Glycosides; Digoxin; Female; Humans; Male; Middle Aged; Poisoning

Digoxin overdose leading to toxicity causes a variety of symptoms ranging from cardiovascular, gastrointestinal and central nervous system effects. Toxicity occurs at a serum level of 3.0ng/ml. The value of phenytoin sodium in treatment of digoxin toxicity is discussed.

Topics: Child, Preschool; Digoxin; Female; Humans; Phenytoin; Poisoning

A case is reported in which a Digoxin intoxication led to irregularities in atrial rhythm. This case, which was diagnosed by an intraatrial cardiogram, shows the usefulness of this method which is easy to practise and leads to special therapeutic aid.

Topics: Arrhythmia, Sinus; Arrhythmias, Cardiac; Diagnosis, Differential; Digoxin; Electrocardiography; Heart Atria; Heart Block; Heart Valve Prosthesis; Humans; Male; Middle Aged; Mitral Valve; Poisoning; Postoperative Complications; Tachycardia

Topics: Adult; Digoxin; Female; Humans; Male; Poisoning; Prospective Studies; Radioimmunoassay

A case of digoxin overdosage is presented in which hemodialysis and forced diuresis were employed in the treatment. Hemodialysis was found to be ineffective in removing significant amounts of the drug and additional experimental work using a dog confirmed that forced diuresis failed to alter the rate of digoxin excretion.

Topics: Animals; Digoxin; Disease Models, Animal; Diuresis; Dogs; Humans; Male; Middle Aged; Poisoning; Radioimmunoassay; Renal Dialysis; Tritium

4 patients tried to commit suicide by ingestion of 45 to 100 tablets of digoxin (Lanicor 0,25 mg) and acteyldigoxin (Novodigal 0,2 mg) respectively. In all patients cardiac arrhythmias occurred including 3 rd degree av-block, tachyarrhythmias and ventricular fibrillation which was lethal in two patients. After a short period hyperkaliaemia a rapid decrease of potassium in the serum was observed 3-12 hours after administration of digoxin. This loss of potassium was due to an increased excretion of potassium and sodium in the urine. It is thought that a reversible tubular leakage is responsible for the loss of electrolytes by the kidney rather than an inhibition of the ATPase in kidney tissue. From our observations the following therapy scheme for digitalis-intoxication is recommended: 1. Gastric lavage and administration of absorbents (charcoal, cholestyramin) in order to decrease the absorption of the glycosides and to interrupt the enterohepatic circulation. 2. Substitution of electrolytes by infusions and by oral route to balance sodium and potassium levels in the serum. 3. Administration of diphenylhydantoin for treatment of cardiac arrhythmias. 4. Implantation of a temporary pacemaker for treatment of cardiac arrhythmias especially for the management of bradycardias. 5. Plasmapheresis to lower the glycosid concentration in the heart muscle and in other tissues.

Topics: Adult; Arrhythmias, Cardiac; Charcoal; Digoxin; Female; Gastric Lavage; Humans; Hyperkalemia; Hypokalemia; Kidney; Male; Middle Aged; Pacemaker, Artificial; Phenytoin; Plasmapheresis; Poisoning; Potassium; Sodium; Suicide; Water-Electrolyte Balance

Topics: Alcoholic Intoxication; Antidepressive Agents, Tricyclic; Aspirin; Atropine; Child; Digoxin; Household Products; Humans; Iron; Poisoning

One hundred ten individuals were divided into patients with digoxin intoxication; patients treated with digoxin; patients treated with digoxin and diuretics; patients treated with diuretics; and control subjects. Measurement of salivary potassium and calcium levels showed that 81% of the patients with digoxin intoxication had noticeable elevation of the salivary calcium level. In 22%, elevation of the salivary calcium level preceded clinical manifestations of intoxication. The high calcium level in the saliva was not accompanied by changes in serum or urinary calcium levels. The elevation of salivary calcium levels can be used not only as an additional indicator of digoxin intoxication but also for detecting impending intoxication in patients treated with this drug.

Topics: Adult; Aged; Calcium; Digoxin; Drug Therapy, Combination; Electrocardiography; Furosemide; Heart Failure; Humans; Middle Aged; Poisoning; Potassium; Saliva

Topics: Aged; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Electrocardiography; Female; Humans; Male; Middle Aged; Poisoning

Topics: Adenosine Triphosphatases; Aged; Color Perception Tests; Color Vision Defects; Digitalis Glycosides; Digoxin; Female; Humans; Male; Middle Aged; Poisoning

Topics: Digitoxin; Digoxin; Heart Diseases; Humans; Magnesium; Poisoning; Radioimmunoassay; Spectrum Analysis; Uremia

Topics: Acute Disease; Adult; Atropine; Bradycardia; Digoxin; Electrocardiography; Female; Furosemide; Humans; Hyperkalemia; Intensive Care Units; Pacemaker, Artificial; Poisoning; Radioimmunoassay; Suicide

Topics: Administration, Oral; Adolescent; Digoxin; Electrocardiography; Female; Half-Life; Heart Block; Humans; Hyperkalemia; Phenytoin; Poisoning; Potassium; Suicide

Topics: Adult; Aged; Digoxin; Female; Humans; Male; Middle Aged; Myocardium; Poisoning; Suicide

Topics: Digoxin; Humans; Peritoneal Dialysis; Poisoning; Renal Dialysis

Topics: Alcoholic Intoxication; Barbiturates; Carbon Monoxide Poisoning; Clinical Laboratory Techniques; Digitoxin; Digoxin; Humans; Lead Poisoning; Poisoning; Salicylates

Topics: Antigen-Antibody Reactions; Digoxin; Female; Humans; Immune Sera; Methods; Poisoning; Pregnancy; Radioimmunoassay; Time Factors; Tritium

Topics: Animals; Digoxin; Dogs; Dose-Response Relationship, Drug; Drinking Behavior; Electrocardiography; Feeding Behavior; Female; Heart Rate; Hemorrhage; Isosorbide Dinitrate; Leukocyte Count; Male; Osmolar Concentration; Poisoning; Time Factors

Topics: Administration, Oral; Adult; Age Factors; Body Weight; Child, Preschool; Digoxin; Electrocardiography; Humans; Infant; Infant, Newborn; Infant, Premature; Poisoning; Radioimmunoassay

Topics: Acute Disease; Biological Transport, Active; Digoxin; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature; Infant, Premature, Diseases; Magnesium; Male; Phenytoin; Poisoning; Potassium; Respiratory Distress Syndrome, Newborn; Sodium; Vomiting

Topics: Digoxin; Electrocardiography; Female; Gastric Lavage; Half-Life; Heart; Heart Block; Humans; Male; Middle Aged; Poisoning; Radioimmunoassay; Suicide; Ventricular Fibrillation

Topics: Administration, Oral; Adolescent; Adult; Age Factors; Aortic Valve Stenosis; Child; Child, Preschool; Digitalis Glycosides; Digoxin; Heart Defects, Congenital; Heart Septal Defects; Humans; Infant; Injections, Intramuscular; Poisoning; Radioimmunoassay; Tritium

Topics: Adult; Arrhythmias, Cardiac; Coumarins; Digoxin; Electrocardiography; Female; Follow-Up Studies; Glycolates; Heart Block; Humans; Poisoning; Prognosis; Suicide; Time Factors

Topics: Arrhythmias, Cardiac; Digoxin; Humans; Poisoning

Topics: Age Factors; Aged; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Electrocardiography; Female; Humans; Male; Poisoning

Topics: Aged; Cardiac Glycosides; Digitalis Glycosides; Digoxin; Humans; Male; Middle Aged; Neurologic Manifestations; Poisoning; Potassium; Ventricular Fibrillation

Topics: Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Electrocardiography; Humans; Poisoning; Potassium; Radioimmunoassay; Time Factors; Tritium; Urea

Topics: Adult; Chlorides; Digoxin; Electrocardiography; Ephedrine; Female; Humans; Poisoning; Potassium; Rest

Topics: Accidents; Adolescent; Adult; Aged; Cardiac Complexes, Premature; Child, Preschool; Coronary Disease; Digoxin; Female; Half-Life; Humans; Male; Middle Aged; Poisoning; Radioimmunoassay; Suicide; Tachycardia, Paroxysmal; Ventricular Fibrillation

Topics: Digoxin; Electrocardiography; Evaluation Studies as Topic; Humans; Methods; Poisoning; Radioimmunoassay; Tritium

Topics: Administration, Oral; Arrhythmias, Cardiac; Cardiac Glycosides; Diet Therapy; Digitoxin; Digoxin; Diuresis; Drug Tolerance; Edetic Acid; Electrocardiography; Gastrointestinal Diseases; Heart Failure; Heart Rate; Humans; Injections, Intravenous; Lanatosides; Nervous System Diseases; Phytotherapy; Plants, Medicinal; Poisoning; Potassium; Rest; Strophanthins

Topics: Acute Disease; Aged; Arrhythmias, Cardiac; Coronary Disease; Digitalis Glycosides; Digitoxin; Digoxin; Electrocardiography; Female; Humans; Lung Diseases; Male; Myocardial Infarction; Poisoning; Prognosis; Prospective Studies; Radioimmunoassay

Topics: Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Cardiac Complexes, Premature; Diagnosis, Differential; Digoxin; Electrocardiography; Heart Block; Humans; Middle Aged; Poisoning; Tachycardia

Topics: Adolescent; Adult; Aged; Arrhythmias, Cardiac; Atropine; Digoxin; Electrocardiography; Female; Humans; Male; Pacemaker, Artificial; Poisoning; Potassium Chloride; Propranolol; Suicide

Topics: Adenine Nucleotides; Animals; Digoxin; Glucose; Guinea Pigs; Lactates; Myocardium; Phosphates; Phosphocreatine; Poisoning; Rats; Uremia; Ureter

Topics: Animals; Antibodies; Antibody Formation; Antidotes; Digoxin; Dogs; Heart Block; Poisoning; Rabbits; Tachycardia

Topics: Arrhythmias, Cardiac; Bronchitis; Brugada Syndrome; Cardiac Conduction System Disease; Digitalis; Digoxin; Electrocardiography; Geriatrics; Heart Conduction System; Heart Failure; Humans; Hypertension; Poisoning; Toxicology

Topics: Adams-Stokes Syndrome; Arrhythmias, Cardiac; Barbiturates; Digoxin; Electrocardiography; Heart Block; Humans; Myocardial Infarction; Pacemaker, Artificial; Poisoning; Quinidine; Resuscitation; Toxicology