Aspectos novedosos de la intoxicación digitálica / New aspects on digitalis toxicity

Los digitálicos son fármacos con capacidad de aumentar la contractilidad miocárdica (inotrópico positivo), que han desempeñado un rol primordial en el tratamiento de pacientes con insuficiencia cardiaca; su uso inapropiado puede traer complicaciones serias a estos pacientes, incluso, hasta la muerte. La más importante de estas complicaciones es la intoxicación digitálica, originada por la sobredosis de dichos fármacos, a causa de la combinación del efecto inhibitorio en la conducción nodal y la estimulación sobre las fibras individuales auriculares y ventriculares. Debido al uso frecuente de estos medicamentos en todos los niveles de atención de salud y lo difícil que resulta diagnosticar dicha complicación por la complejidad de su cuadro clínico y de su expresión electrocardiográfica, se realizó una revisión bibliográfica exhaustiva sobre el tema para brindar amplia información, que permita una atención adecuada a los pacientes con este diagnóstico

Digitalis are drugs with the capacity of increasing myocardial contractility (inotropic positive agents) which have carried out an important role in the treatment of heart failure; their inappropriate use can bring severe complications to the patient, even, to death. The most important in these complications is the digitalis toxicity, originated by the overdose of these drugs, caused by the combination of the inhibitory effect in the nodal conduction and stimulation on the individual atrial and ventricular fibers. Due to the frequent use of these medications at all levels of medical care and to the difficulty in diagnosing this complication caused by the complexity of their clinical pattern and of their electrocardiographic expression, an exhaustive literature review was carried out on the topic to give a wide information that allows an appropriate care to the patients with this diagnosis

Epidemiology of overdose episodes from the period prior to hospitalization for drug poisoning until discharge in Japan: An exploratory descriptive study using a nationwide claims database.

BACKGROUND: Little is known about the nationwide epidemiology of the annual rate, causative substance, and clinical course of overdose-related admission. We aimed to describe the epidemiology of overdose episodes from the period prior to hospitalization for drug poisoning until discharge to home. METHODS: We assessed all cases of admission due to overdose (21,663 episodes) in Japan from October 2012 through September 2013 using the National Database of Health Insurance Claims and Specific Health Checkups of Japan. RESULTS: The annual rate of overdose admission was 17.0 per 100,000 population. Women exhibited two peaks in admission rates at 19-34 years (40.9 per 100,000) and ≥75 years (27.8 per 100,000). Men exhibited one peak in the admission rate at ≥75 years (23.7 per 100,000). Within 90 days prior to overdose, ≥60% and ≥9% of patients aged 19-49 years received a prescription for benzodiazepines and barbiturates, respectively. In addition, 59% of patients aged ≥75 years received a prescription for benzodiazepines prior to overdose, 47% had a history of congestive heart failure, and 24% had a diagnosis of poisoning by cardiovascular drugs. The proportion of patients with recent psychiatric treatments decreased with age (65.1% in those aged 35-49 years and 13.9% in those aged ≥75 years). CONCLUSIONS: The findings emphasize the need for overdose prevention programs that focus on psychiatric patients aged 19-49 years who are prescribed benzodiazepines or barbiturates and on non-psychiatric patients aged ≥75 years who are prescribed benzodiazepines or digitalis.

Respuesta al ECG de enero de 2016 / Response to ECG, January 2016

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Tratamiento de la intoxicación digitálica. Bases para el uso de los anticuerpos antidigital / Digitalis poisoning: the basis for treatment with antidigoxin antibodies

La intoxicación digitálica, sobre todo asociada a un tratamiento crónico con este fármaco, es un motivo recurrente de consulta a los servicios de urgencias españoles. La intoxicación aguda es excepcional y podría presentarse tanto en una tentativa de suicidio como por la ingesta de plantas presentes en nuestro medio y que contienen glucósidos digitálicos. La insuficiencia renal, al modificar la cinética de la digoxina, es un importante factor precipitante de reacciones adversas y graves a este medicamento. Las manifestaciones clínicas son inespecíficas, y predominan las digestivas (náuseas, vómitos, diarreas, dolor abdominal) y circulatorios (inestabilidad, mareos, síncope, lipotimia). Las bradiarritmias (fibrilación auricular lenta, bloqueos de conducción) son frecuentes y pueden acabar en asistolia. Las taquiarritmias podrían conducir a la fibrilación ventricular. En las intoxicaciones agudas, la hiperpotasemia es un factor de riesgo de parada cardiaca. La concentración plasmática de digoxina permite evaluar la gravedad de una intoxicación, siempre y cuando se haya alcanzado el equilibrio de distribución entre las concentraciones plasmáticas y tisulares. El tratamiento de la intoxicación aguda precisa la administración de carbón activado en las primeras horas tras la ingesta. En las intoxicaciones agudas o por tratamiento crónico, es necesaria la monitorización electrocardiográfica continua y normalizar, en caso necesario, las concentraciones de potasio y magnesio. Las bradiarritmias se tratan con atropina como fármaco de primera elección y las arritmias ventriculares con fenitoína o lidocaína. Las situaciones de riesgo vital requieren eluso de anticuerpos antidigital, y se recomienda la disponibilidad de este antídoto en loshospitales considerados de referencia o alta tecnología, el cual deberá dosificarse en función de la carga corporal total de digoxina (AU)

Digitalis poisoning, particularly in persons under long-term digoxin therapy, is a reason for repeated visits to Spanish emergency departments. Acute poisoning is rare but may occur as a result of attempted suicide or the intake of plants that contain cardiac glycosides. Kidney failure modifies digoxin pharmacokinetics and is an important trigger for severe adverse reactions to the drug. Clinical manifestations are nonspecific but usually include gastrointestinal events (nausea, vomiting, diarrhea, and abdominal pain) along with circulatory effects (hemodynamic instability, dizziness or lightheadedness, and syncope). Bradycardia (slow atrial fibrillation, conduction blocks) is common and may cause systole. Tachyarrhythmias may lead to ventricular fibrillation. In acute digitalis poisoning, hyperkalemia is a risk factor for cardiac arrest. The digoxin plasma concentration can indicate the severity of the poisoning, provided the tissue-to plasma ratio is at steady state. To treat acute poisoning, administer activated charcoal within the first few hours after digitalis intake. In such cases, or in poisoning during long-term digoxin therapy, continuous electrocardiographic monitoring is essential and potassium and magnesium concentrations should be brought within the normal range. The first-line treatment for bradycardia is atropine. Ventricular arrhythmias are treated with phenytoin or lidocaine. In life threatening situations, antidigox in antibodies must be used. They should be available in all referral or high-level tertiary care facilities and are administered according to the total digoxin body load (AU)

Cardiac glycoside toxicity: more than 200 years and counting.

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

Digitalis toxicity: a fading but crucial complication to recognize.

Digoxin usage has decreased in the treatment of congestive heart failure and atrial fibrillation as a result of its inferiority to beta-adrenergic inhibitors and agents that interfere with the deleterious effects of the activated renin-angiotensin-aldosterone system. As a result of reduction of usage and dosage, glycoside toxicity has become an uncommon occurrence but may be overlooked when it does occur. Older age, female sex, low lean body mass, and renal insufficiency contribute to higher serum levels and enhanced risk for toxicity. Arrhythmias suggesting digoxin toxicity led to its recognition in the case presented here.

Clinical manifestations of elderly patients with digitalis intoxication in the emergency department.

This study aimed to determine the clinical characteristics of elderly patients diagnosed with digitalis intoxication, on the Emergency Department, University Hospital Complex, A Coruña, Spain. During the study period (January-September 2008) cases were included in which digitalis intoxication was confirmed by plasma digoxin levels. We collected data on age, gender, base-line diseases, therapeutic indications for digoxin, functional classification, ejection fraction, plasma digoxin levels, creatinine clearance, ions, gasometry, electrocardiogram, concomitant medication, symptomatology and treatment. The results were: mean age 82.0 ± 6.6 years, predominantly female subjects (83.7%). The most prevalent pathologies were cardiac valvulopathy (81.0%), hypertension (68.3%) and ischemic cardiopathy (46.3%), 95.1% had a background of cardiac insufficiency, and 52.6% were in functional grade III. The mean digoxin level was 2.7 ± 0.69 ng/ml, 23.1% of the patients had a creatinine clearance of less than 60 ml/min/1.73 m(2) and 2.6% had a severely reduced glomerular filtration rate (GFR) (clearance<30 ml/min/1.73 m(2)). A negative correlation was found between digoxin levels and clearance (r = -0.22; p = 0.18) and between the levels and cardiac frequency (r = -0.35; p = 0.026). Of the patients, 47.5% presented bradycardia and 87.8% arrhythmias, most frequently auricular fibrillation. The most frequent symptoms were nausea (54.8%), fatigue (42.9%), vomiting (33.3%) and anorexia (28.6%). We conclude that clinical digestive symptoms in elderly women who are taking digitalis, with bradycardia and impaired renal functioning, should lead us to suspect digitalis intoxication.

A case of angiographically verified non-occlusive mesentery ischemia induced by digitalis.

Here we present a case of non-occlusive mesentery ischemia induced by digitalis, which was verified angiographically. Nonocclusive mesentery ischemia, a subgroup of "acute mesentery ischemia", is known as a period of intestinal ischemic hypoperfusion without a demonstrable vascular occlusion in the mesentery bed. It can be caused by factors leading to splanchnic hypoperfusion, which can be of cardiac, renal or hepatic origin. In addition, it can be induced by certain drugs such as digitalis, ergotamines and vasoactive agents. In clinical practice, digitalis toxicity is commonly seen. In contrast, non-occlusive mesentery ischemia secondary to digitalis is quite rare. However, nonocclusive mesentery ischemia should be included in the differential diagnosis for patients who develop sudden and diffuse abdominal pain while on digitalis therapy.

Digoxin-specific Fab fragments as single first-line therapy in digitalis poisoning.

OBJECTIVE: 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. DESIGN: Retrospective chart review (January 1990 to January 2004). SETTING: University hospital intensive care unit. PATIENTS: Consecutive patients admitted for cardiac glycoside poisoning. INTERVENTION: First-line therapy with Fab fragments (with or without atropine) in either curative or prophylactic doses. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: First-line therapy with Fab fragments in patients with digitalis poisoning was associated with a low mortality rate.

Electrocardiographic abnormalities associated with poisoning.

This article will review the cardiovascular toxicities of various medications, stressing the electrocardiographic presentation--both rhythm and morphological issues--and emphasizing recognition and management issues. Cardiovascular toxins are grouped into categories causing similar electrocardiographic effects, including the potassium efflux blockers, sodium channel blockers, sodium-potassium adenosine triphosphatase blockers (ie, digitalis compounds), calcium channel blockers, and beta-adrenergic blockers. This article reviews the various electrocardiographic abnormalities associated with these 5 classes of agents, ranging from morphological abnormalities and conduction blocks to brady- and tachyarrhythmias.

Taquicardia ventricular bidireccional por intoxicación digitálica / Bidirectional ventricular tachycardia due to digitalis poisoning

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[Digitalis intoxication secondary to treatment with clarithromycin]. / Original Breve Intoxicación digitálica secundaria al tratamiento con claritromicina.

OBJECTIVE: The goal of this study was to investigate the percentage of patients concurrently receiving digoxin and clarithromycin who exhibited serum digoxin concentrations above the therapeutic range because of a likely interaction between both drugs, and whether digitalis intoxication ensued. METHOD: A descriptive, retrospective study carried out from January 2002 to December 2003 in all inpatients concurrently receiving digoxin and clarithromycin whose serum digoxin concentrations were monitored by the Pharmacy Department s Pharmacokinetics Section. RESULTS: Twenty-six patients having received digoxin and clarithromycin concurrently during their hospital stay were included in the study. Of these, 12 patients (46.2%) had serum digoxin concentrations above the therapeutic range: 7 received digoxin in doses unsuited for their age and/or renal function, and 2 fell short of the mean period of time considered adequate for an interaction to occur. Therefore, only 3 patients had serum digoxin concentrations above the therapeutic range, probably because of an interaction with clarithromycin, and all three had digitalis intoxication symptoms. CONCLUSIONS: According to the results of our study, 11.5% of patients concurrently receiving digoxin and clarithromycin had serum digoxin concentrations above the therapeutic range because of a likely interaction between these two drugs, with digitalis intoxication ensuing. Thus, we deem it necessary to monitor serum digoxin concentrations in patients receiving clarithtomycin.

Intoxicación digitálica mortal / Fatal digitalis poisoning

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