Digitalis Toxicity Research Articles

Cardiac Findings in Acute Yellow Oleander Poisoning

Background:—The Yellow Oleander is an ornamental tree that is common throughout the tropics. Ingestion of its seeds results in a clinical picture similar to digoxin toxicity.Objectives:—The aim of this study was to evaluate cardiac findings in acute Yellow Oleander poisoning.Methods and Materials: —A total of 21 patients with history of Yellow Oleander ingestion were enrolled in this study.Results:—All symptomatic patients had conduction defects affecting the sinus node, theatrio-ventricular node or both. Patients showing cardiac arrhythmias that required specific management had significantly higher serum potassium concentrations.Conclusion: —Most of the symptomatic patients had conduction defects affecting sinus or atrio-ventricular nodes but few had atrial or ventricular arrhythmias typical of digoxin poisoning.

Autopsy report on central pontine myelinolysis triggered by vomiting associated with digoxin intoxication

An 87-year-old male, prescribed digoxin and furosemide for congestive heart failure and Alzheimer disease, had dehydration and anemia due to poor food intake and hemorrhagic cystitis. Repeated vomiting due to an upper respiratory infection caused disturbance of consciousness and hypotension. The patient was admitted to hospital and diagnosed with digoxin intoxication and hypernatremia. The serum sodium (Na +) level was corrected, but the patient died 4 days after admission following uncontrollable seizure. A histologic examination after an autopsy revealed characteristic findings of central pontine myelinolysis (CPM). This is the first autopsy report on CPM triggered by vomiting in association with digoxin administration.

Bidirectional Ventricular Tachycardia

![Figure][1] Bidirectional ventricular tachycardia is a hallmark of severe digitalis toxicity. The 12-lead electrocardiogram obtained from a 54-year-old man with acute heart failure and digitoxin intoxication shows typical features of this potentially life-threatening arrhythmia: a regular

Type II bidirectional ventricular tachycardia in a patient with myocardial infarction

A 84-year-old man presented to the emergency department complaining of chest pain and palpitations. He had no history of coronary artery disease. The 12-lead electrocardiography showed bidirectional ventricular tachycardia (BVT). Coronary angiography revealed severe mid left anterior descending and mid left circumflex lesions. The BVT, in this case, was most likely due to myocardial ischema. The ethiology of published BVT cases are most commonly digitalis toxicity and rarely herbal aconitine poisoning, hypokalemic periodic paralysis, cathecolaminergic VT, myocarditis, and Anderson-Tawil syndrome. The patient had neither of these underlying conditions. To the best of our knowledge and research in the literature, there was no report of bidirectional VT in the patients with myocardial infarction.

Risk of digoxin intoxication caused by clarithromycin–digoxin interactions in heart failure patients: a population-based study

To quantify the effect of exposures to digoxin–clarithromycin interactions on the risk of digoxin toxicity requiring hospitalizations in a population-based manner in a Taiwanese population. This is a retrospective population-based nested case–control study. Data were retrieved from the National Health Insurance Research Database. Heart failure (HF) patients newly treated with digoxin between 1 January 2001 and 31 December 2004 were retrieved from the database as the study cohort. Case patients, admitted to the hospitals with the diagnosis of digoxin intoxication (ICD-9 code 972.1) were identified from the study cohort and compared with the matched controls for the receipt of clarithromycin. A total of 154,058 patients were identified as the study cohort; from these, 595 cases and 27,020 matched controls were selected for study. The prescription of clarithromycin at 7, 14, and 30 days prior to the index date was associated with a 4.36- (95% CI 1.28–14.79), 5.07- (95% CI 2.36–10.89), and 2.98-fold (95% CI 1.59–5.63) increase in hospitalization for digoxin intoxication, respectively. The results of the dose–response relationship also indicated that clarithromycin prescribed with a prescribed daily dose (PDD)/defined daily dose (DDD) ratio >2 led to a 55.41-fold (95% CI 9.31–329.9) increase of the risk, which is significantly greater than that prescribed with a 1–2 PDD/DDD ratio (adjusted OR 4.81; 95% CI 1.88–12.30) or with a <1 PDD/DDD ratio (adjusted OR 0.78; 95% CI 0.19–3.20). This study provides empirical evidence that digoxin–clarithromycin interactions do increase the risk of hospitalization for digoxin intoxication in HF patients and that this risk could reach as high as 55.4-fold. We strongly recommend that the combined use of digoxin with clarithromycin should be avoided and that digoxin concentrations should be monitored closely in situations where the combination can not be avoided.

Macrolide-Induced Digoxin Toxicity: A Population-Based Study

In this 15-year, population-based, nested case-control study, we investigated the association between hospitalization for digoxin toxicity and recent exposure to individual macrolide antibiotics. Clarithromycin was associated with the highest risk of digoxin toxicity (adjusted odds ratio (OR) 14.8; 95% confidence interval (CI) 7.9-27.9), whereas erythromycin and azithromycin were associated with much lower risk (adjusted OR 3.7; 95% CI 1.7-7.9; and adjusted OR 3.7; 95% CI 1.1-12.5, respectively). We found no increased risk with a neutral comparator, cefuroxime (adjusted OR 0.8; 95% CI 0.2-3.4).

The limitations of routine total digoxin immunoassay in patients with advanced chronic kidney disease

Sir, Digoxin is a commonly used drug in medicine. However, adverse events related to digoxin are one of the most frequent causes for emergency department visits related to medication, especially in older patients.1 The absorption of digoxin from the intestine is between 70% and 90% depending on the type of preparation used e.g. elixir, capsule, etc.2 Digoxin has a large volume of distribution and is concentrated in tissues like myocardium, skeletal muscle and red blood cells. Serum digoxin concentrations correlate best with lean rather than total body weight. Approximately 25% of the digoxin in the plasma is bound to protein.3 There is significant inter-individual variability in therapeutic range, but a generally accepted range is 0.5–2.0 µg/l. Digoxin is eliminated by first-order kinetics. It is primarily (∼70%) excreted unchanged by glomerular filtration and excretion by renal tubules and its excretion is proportional to glomerular filtration rate (GFR). In subjects with normal renal function, digoxin has a half-life of 1.5–2.0 days. The half-life in anuric patients is prolonged to between 3.5 and 5 days.4–7 Digoxin is not effectively removed from the body by dialysis or during exchange transfusion because most of the drug is bound to tissue and does not circulate in the blood.8 The common risk factors for digoxin toxicity are impaired renal function, advanced age and other medications. Co-administration of drugs like p-glycoprotein inhibitors (amiodarone, verapamil, quinidine and ciclosporin) can increase serum digoxin concentration between 20% and 60%.9 Electrolyte disturbances like hypokalaemia and hypomagnesaemia, induced by diuretic agents and hypercalcaemia can also increase digoxin toxicity. Clinical manifestations of digoxin toxicity include a wide range of signs and symptoms and its cardiac effect can be fatal. In life-threatening digoxin toxicity, treatment with digoxin-specific antibody fragments (Fab) is effective and safe.10 Fab is derived from …

Electrocardiographic manifestation of digoxin toxicity in a Pomeranian dog

This case report describes several electrocardiographic findings in an 8-years old female Pomeranian dog that was referred with a history of digoxin overdose. Electrocardiographic abnormalities detected in this case could be classified as primary electrocardiographic disturbances, reflecting cardiac chamber enlargement and secondary ECG changes, attributed to digoxin toxicity. ECG manifestations of digoxin toxicity such as first and second degree AV blocks completely disappeared following digoxin withdrawal. Therefore, veterinarians should be aware of the possibility of digoxin toxicity due to its narrow therapeutic margins. The purpose of this report is to increase awareness of small animal practitioners about adverse cardiotoxic effects of cardiac glycosides. It also highlights the significance of electrocardiographic monitoring for diagnosis and management of digoxin induced cardiac arrhythmias and conduction disturbances in small animal patients

Arrhythmogenic consequences of intracellular calcium waves

Intracellular Ca(2+) (Ca(i)(2+)) waves are known to cause delayed afterdepolarizations (DADs), which have been associated with arrhythmias in cardiac disease states such as heart failure, catecholaminergic polymorphic ventricular tachycardia, and digitalis toxicity. Here we show that, in addition to DADs, Ca(i)(2+) waves also have other consequences relevant to arrhythmogenesis, including subcellular spatially discordant alternans (SDA, in which the amplitude of the local Ca(i)(2+) transient alternates out of phase in different regions of the same cell), sudden repolarization changes promoting the dispersion of refractoriness, and early afterdepolarizations (EADs). Ca(i)(2+) was imaged using a charge-coupled device-based system in fluo-4 AM-loaded isolated rabbit ventricular myocytes paced at constant or incrementally increasing rates, using either field stimulation, current clamp, or action potential (AP) clamp. Ca(i)(2+) waves were induced by Bay K 8644 (50 nM) + isoproterenol (100 nM), or low temperature. When pacing was initiated during a spontaneous Ca(i)(2+) wave, SDA occurred abruptly and persisted during pacing. Similarly, during rapid pacing, SDA typically arose suddenly from spatially concordant alternans, due to an abrupt phase reversal of the subcellular Ca(i)(2+) transient in a region of the myocyte. Ca(i)(2+) waves could be visualized interspersed with AP-triggered Ca(i)(2+) transients, producing a rich variety of subcellular Ca(i)(2+) transient patterns. With free-running APs, complex Ca(i)(2+) release patterns were associated with DADs, EADs, and sudden changes in AP duration. These findings link Ca(i)(2+) waves directly to a variety of arrhythmogenic phenomena relevant to the intact heart.

Emergency step-by-step specific immunotherapy in severe digoxin poisoning: an observational cohort study

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

Inhibition of methyldigoxin-induced arrhythmias by pentadecapeptide BPC 157: A relation with NO-system

Pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419) reversed congestive heart failure and various arrhythmias, influenced the NO-system and showed no proarrhythmic effect. In therapy analogy, we challenged rats with digitalis, to show attenuation by BPC 157 and the relation between the NO-system and digitalis toxicity. (i). BPC 157 prophylactic effect. Development of cumulative intravenous digitalis toxicity, BPC 157 (50 µg, 10 µg, 10 ng/kg applied intravenously immediately before a methyldigoxin increment regimen (2.0/1.5/1.5/1.0 mg/kg at 15 min-intervals, total dose 6.0 mg/kg/45 min)) reduced the number of ventricular premature beats, prolonged the time before onset of ventricular tachycardia, reduced ventricular tachycardia and AV-block duration (µg-regimes) or reduced mainly the AV-block duration (ng-regimen). (ii). BPC 157 therapy. Advanced methyldigoxin toxicity (6.0 mg/kg i.v. bolus). BPC 157 applied at the 20th second of the grade 3 AV-block shortened AV-blocks, mitigated a further digitalis toxicity course. Ventricular tachycardias were either avoided (50 µg), or markedly reduced (10 µg, 10 ng). Fatal outcome was either avoided (50 µg), reduced (10 µg), or only delayed (10 ng) (iii) BPC 157, L-NAME, l-arginine, L-NAME + l-arginine application. L-NAME-application (5 mg/kg i.p.) aggravated methyldigoxin-arrhythmias. l-arginine (200 mg/kg i.p.) alone had no effect but blunted L-NAME-exaggeration (L-NAME + l-arginine). In this respect, BPC 157 (50 µg/kg i.p.) was prophylactically and therapeutically more effective: the antagonism of L-NAME with BPC 157 produced an effect similar to BPC 157 alone. In conclusion, digitalis-induced arrhythmias in rats could be prevented and counteracted by pentadecapeptide BPC 157, mainly through an interaction with the NO-system.

Inconsistent approach to the treatment of chronic digoxin toxicity in the United States

Evidence-based guidelines do not exist for the treatment of patients with chronic mild-moderate digoxin toxicity. We sought to evaluate differences among specialists in the use of digoxin-specific antibody fragments and the decision to admit these patients. A sample of cardiologists, emergency physicians, and medical toxicologists was surveyed. The survey detailed four hypothetical cases of chronic digoxin toxicity created by consensus among authors. All cases had the same digoxin concentration, but signs and symptoms varied in an attempt to explore four different thresholds. For each scenario, clinicians made decisions about admission and treatment. Survey response varied: cardiologists 17%, emergency physicians 6.7%, and toxicologists 39%. Statistically significant difference was found in the administration of Fab among cardiologists (67%), emergency physicians (82%), or toxicologists (91.5%) and admission rate (cardiologists 34%, emergency physicians 28%, and toxicologists 46%). Differences exist among clinicians of various specialties regarding treatment of chronic digoxin toxicity. These differences may reflect diverse perspectives or knowledge gaps and may translate into excess cost or less than ideal care. Exploring these differences may improve patient care, improve interactions among providers, and set the stage for development of consensus guidelines and research.

The Effects of Intravenous Calcium in Patients with Digoxin Toxicity

Digoxin is an inhibitor of the sodium-potassium ATPase. In overdose, hyperkalemia is common. Although hyperkalemia is often treated with intravenous calcium, it is traditionally contraindicated in digoxin toxicity. To analyze records from patients treated with intravenous calcium while digoxin-toxic. We reviewed the charts of all adult patients diagnosed with digoxin toxicity in a large teaching hospital over 17.5 years. The main outcome measures were frequency of life-threatening dysrhythmia within 1 h of calcium administration, and mortality rate in patients who did vs. patients who did not receive intravenous calcium. We use multivariate logistic regression to ensure that no relationship was overlooked due to negative confounders (controlling for age, creatinine, systolic blood pressure, peak serum potassium, time of development of digoxin toxicity, and digoxin concentration). We identified 161 patients diagnosed with digoxin toxicity, and were able to retrieve 159 records. Of these, 23 patients received calcium. No life-threatening dysrhythmias occurred within 1 h of calcium administration. Mortality was similar among those who did not receive calcium (27/136, 20%) compared to those who did (5/23, 22%). In the multivariate analysis, calcium was non-significantly associated with decreased odds of death (odds ratio 0.76; 95% confidence interval [CI] 0.24-2.5). Each 1 mEq/L rise in serum potassium concentration was associated with an increased mortality odds ratio of 1.5 (95% CI 1.0-2.3). Among digoxin-intoxicated humans, intravenous calcium does not seem to cause malignant dysrhythmias or increase mortality. We found no support for the historical belief that calcium administration is contraindicated in digoxin-toxic patients.

Beating to time: calcium clocks, voltage clocks, and cardiac pacemaker activity

the heartbeat arises in the sinoatrial node (SAN) and then spreads throughout the heart. SAN function is therefore essential for normal cardiac physiology. The function of the SAN decreases with age, and this has been correlated with changes of ion channel expression ([12][1]). It is therefore of

INFLUENCE OF ENALAPRIL, DIGOXIN, ATENOLOL AND DILTIAZEM ON LIPID PEROXIDATION IN EXPERIMENTAL MODEL OF COMPLEX METABOLIC DISORDERS

Aim. To study influence of enalapril, digoxin, atenolol and diltiazem on lipid peroxidation and antioxidative protection in experimental disorders of glucose and lipid metabolism. Material and methods. White nonlinear mice were used for modeling of the complex metabolic disorders by alloxan and cholesterol infusion. Evaluation of acute drug toxicity and indicators of lipid peroxidation and antioxidant protection was performed. Superoxide dismutase and catalase activity, malondialdehyde concentration were evaluated. Results. Toxicity of digoxin, diltiazem, atenolol in complex metabolic disorders was increased, and toxicity of enalapril was unchanged. Enalapril had antioxidant effect. Atenolol had prooxidative effect in myocardium and kidneys, and diltiazem - in kidneys. Conclusion. Enalapril showed antioxidant effect and decreased concentration of secondary products of lipid peroxidation in renal tissue. It may be considered as the first line drug in complex metabolic disorders.

Use of MDRD equation to detect occult renal failure and reduce the risk of digitalis overdose

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

From the Ryanodine Receptor to Cardiac Arrhythmias

Cardiac contraction is activated by an increase of intracellular calcium concentration ([Ca(2+)](i)), most of which comes from the sarcoplasmic reticulum (SR) where it is released, via the ryanodine receptor (RyR), in response to Ca(2+) entering the cell on the L-type Ca(2+) current. This phenomenon is termed Ca(2+)-induced Ca(2+) release (CICR). However, under certain circumstances, the SR can become overloaded with Ca(2+) and once a threshold SR Ca(2+) content is reached Ca(2+) is released spontaneously. Such spontaneous Ca(2+) release from the SR propagates as a Ca(2+) wave by CICR. Some of the Ca(2+) released during a wave is removed from the cell on the electrogenic Na - Ca exchanger resulting in depolarization. This is the cellular mechanism producing delayed afterdepolarizations and is common to those arrhythmias produced by digitalis toxicity and right ventricular outflow tract tachycardia. More recently it has been suggested that arrhythmogenic Ca(2+) waves can also occur if the properties of the RyR are altered, resulting in increase of RyR open probability, for example by phosphorylation. However, in this review experimental evidence will be presented to support the view that such arrhythmias still require a threshold SR Ca(2+) content to be exceeded and that this threshold is decreased by increasing RyR open probability.

A consideration of the qualities of a ‘good’ doctor with some help from the humanities

It is a reasonable generalisation that most doctors aim to be skilled in the practice of medicine; they try to be ‘good’ doctors. Also, despite frequent news stories illustrating the shortcoming of doctors, surveys show that contemporary society holds the medical profession in high regard;1 doctors are generally considered to be ‘good’ people despite obvious exceptions such as Dr Harold Shipman. But what do we mean by ‘goodness’ in medical practice? This essay uses sources from the arts and the humanities to explore this concept of ‘goodness’ and to consider the qualities of a ‘good’ doctor in a contemporary medical context. Let us start with a consideration of a picture of a ‘good’ doctor. Van Gogh (1853–1890), produced several portraits of his own physician, Dr Paul-Ferdinand Gachet. Van Gogh was a prolific artist, producing more than two thousand paintings, drawings, and sketches, also leaving detailed descriptions of his colourful life in letters and diaries. In a letter to his sister, Wilhemina Van Gogh, he wrote that in this painting he had tried to portray Gachet's ‘sad but gentle, yet clear and intelligent’ expression.2 A foxglove on the table represents Gachet's medical status and, possibly, the digitalis he prescribed for Van Gogh's mania. (It has been proposed that xanthopsia caused by digoxin poisoning explains Van Gogh's preoccupation with the colour yellow, though this seems unlikely.) Van Gogh started painting in Belgium moving to Paris in 1886 where he met the impressionist artists Pissarro, Monet, and Gauguin. Although his paintings now sell for millions of pounds he failed to make any money in his own lifetime, his penury a constant preoccupation. He was a heavy drinker with a taste for absinthe and had bursts of manic activity followed by periods of depression. To improve his health he moved south to …

Response to “Declining Public Health Burden of Digoxin Toxicity: Decreased Use or Safer Prescribing?”

Response to “Declining Public Health Burden of Digoxin Toxicity: Decreased Use or Safer Prescribing?”

Declining Public Health Burden of Digoxin Toxicity: Decreased Use or Safer Prescribing?

Declining Public Health Burden of Digoxin Toxicity: Decreased Use or Safer Prescribing?