Digitalis Intoxication Research Articles

Pharmacokinetic monitoring of chronic treatment with digoxin from Primary Health Care

ObjetiveTo assess the pharmacokinetic monitoring of SDC performed from primary healthcare (PH) in patients with chronic treatment. MethodsCross-sectional retrospective study of patients with chronic treatment with digoxin belonging to the department of a General University Hospital.Data were analized: age, sex, diagnosis, number of serum digoxin concentration determinations, date and origin of the request for monitoring, analytical result and pharmacokinetic assessment are collected. Results624 patients are undergoing chronic treatment with digoxin, 68% women, mean age 78.4 (39-98) years. 308 (49.4%) patients haven’t analytical determination of SDC (Group 1), 183 (29.3%) patients have a SDC occasionally performed with a request from specialist care (Group 2) and 133 (21,3%) patients have CSD performed with a request from primary healthcare doctors, with an average of 2.42 monitoring per patient and year (Group 3). These are those patients who have pharmacokinetic monitoring of chronic treatment with digoxin.Of the group 2.25 (13.6%) patientes were hospital admission from emergency department for presenting digitalis intoxication with CSD>2 ng/ml, and 39 (21.3%) patients for low dosing with CSD<0.5 ng/ml. Group 3.4 (3%) patients presented digitalis intoxication and 5 (3.8%) for insufficient dosing. ConclusionsA small proportion of patients undergoing chronic treatment with digoxin are under pharmacokinetic monitoring and a reduction in complications derived from inappropriate CSD compared to those not under pharmacokinetic follow-up is observed.

Case report on the interaction between furosemide and digoxin that caused digoxin toxicity

Toxicity from digitalis is a typical clinical issue. In this case, the interaction of digoxin and furosemide is becoming more widely recognised as a major cause of digitalis toxicity. We present an abnormal ECG that demonstrates digoxin-induced cardiotoxicity. We report a case of a Digoxin toxicity in a 79-year-old male patient admitted with complains of nausea, increase frequency of micturition, decrease appetite, increase nocturia, shortness of breathing. The patient is taking furosemide and digoxin as past medication for Heart block and Chronic kidney disease treatment. In patient, Serum digoxin level is high due to hypokalemia because of digoxin and furosemide drug interaction. The Electrocardiogram interpretation shows sinus bradycardia, ST segment depression, and T wave inversion which mainly due to digoxin toxicity. So for the management digoxin is omitted from the current treatment. The patient needs to be constantly monitored since digitalis poisoning is deadly. A digoxin-binding antibody is the only treatment for digoxin overdose that can reverse its effects by its antidote but it’s not available. So, the most successful course of treatment is symptomatic or efficient methods of extracorporeal drug removal.&#x0D; Keywords: Digoxin toxicity, furosemide, hypokalemia, cardiotoxicity, complete heart block, ST segment depression.

Bidirectional Ventricular Tachycardia Due to Digitalis Intoxication

Bidirectional ventricular tachycardia (BDVT) is defined by beat-to-beat alternation of the QRS axis on the electrocardiogram. Its diagnosis is uncommon, and the most characteristic etiology is digitalis intoxication (DI). We report the case of a patient with heart failure of valve origin admitted for sepsis that progressed to BDVT and death, associated with DI.

The effect of lidocaine when used as a local anesthetic or by intravenous injection

The efficacy profile of lidocaine as a local anesthetic is characterized by a rapid onset of action and an intermediate duration of efficacy. Longer-acting substances such as bupivacaine are sometimes given preference for spinal and peridural anesthesias, however, lidocaine, on the other hand, has the advantage of a rapid onset of action. Adrenaline supplements could delay the resorption and the duration of efficacy could be doubled. Lidocaine is the most important class 1B antiarrhythmic drug: it is used intravenously for the treatment of ventricular arrhythmias (for acute myocardial infarction, digitalis poisoning, cardioversion, or cardiac catheterization). Lidocaine has also been efficient in refractory cases of status epilepticus. Lidocaine may cause significant pain on initial injection due to the agent stimulating nociceptors before it exerts its effects on sodium channels; this can be counteracted by buffering the lidocaine with small volumes ofsodium bicarbonate shortly before use, making the solution less acidic. Pain can also be reduced by warming the solution to body temperature, injecting more slowly, using narrow cannulas, and injecting at 90 degrees to the skin.

Evaluating the Risk of Digitalis Intoxication Associated With Concomitant Use of Dronedarone and Digoxin Using Real-World Data

PurposeDronedarone may increase digoxin plasma levels through inhibition of P-glycoprotein. Using real-world data, we evaluated the risk of digitalis intoxication in concomitant users of dronedarone and digoxin compared digoxin-alone users. MethodsWe used the Clinformatics DataMart, a US claims database, to identify adult patients with atrial fibrillation (AF) or atrial flutter (AFL) who concomitantly used dronedarone and digoxin and those who used digoxin alone between July 2009 and March 2016. Digitalis intoxication during follow-up until March 2016 was ascertained using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM). Adjusted hazard ratios (HR) for digitalis intoxication in concomitant users versus users of digoxin alone were estimated, controlling for age, sex, cohort entry year, number of medical encounters for AF or AFL, history of congestive heart failure, diabetes, hypertension, stroke, myocardial infarction, renal failure, use of drugs interacting with digoxin, and digoxin dose. FindingsOverall, 524 concomitant users and 32,459 users of digoxin alone were identified, among which 3 and 301 events of digitalis intoxication occurred during follow-up, respectively. Incidence rates were 17.25 and 9.17 cases per 1000 person-years, respectively. The adjusted HR for digitalis intoxication in concomitant users versus users of digoxin alone was 1.56 (95% CI, 0.50-4.88; P = 0.45). When digitalis intoxication was defined by ICD-9-CM and ICD-10-CM codes accompanied by laboratory testing for digoxin/digitoxin or hospitalization within 30 days, no events occurred in the concomitant users and 40 events occurred in the users of digoxin alone (incidence rate of 1.22 cases per 1000 person-years). ImplicationsConcomitant use of dronedarone and digoxin was uncommon in this study, and no significant increase in the risk of digitalis intoxication with concomitant use was found.

Difficult Atrial Fibrilation Rate-Control and Digitalis Toxicity in Mitral-Valve Prolapse Patient with Hyperthyroidism

Rate-control is important management in patient with atrial fibrillation. The optimum rate control provides a decrease of symptoms, improves hemodynamics and prevents tachycardia-induced cardiomyopathy. Rate-control could be difficult to achieve because of patient's comorbidities and special treatment strategy is needed to resolve it. A-46-yo. male, came to ER with palpitation. Holosystolic murmur was heard at apex, radiating to axilla. ECG showed atrial fibrillation, with rapid ventricular response 180 bpm. Echocardiography showed dilated LA and LV, false-normal LV function with EF 59% and anterior mitral-valve prolapse with moderate mitral regurgitation. Acute treatment was administration of digoxin and beta blockers, but ventricular rate wasn’t controlled, until 1.5 mg doses of digoxin was administered. Then patient develops acute digitalis intoxication. After toxicity management, rapid ventricular rate recurs. Patient reevaluation showed hyperthyroidism with low TSH and high T4. Methimazole and propranolol was given and rate-control was achieved shortly after euthyroid state, in 2 months treatment. This patient suffered difficult rate-control despite guidelines-based management. Digitalis intoxication was developed after administration of several therapeutic doses. The diagnosis of hyperthyroidism is central in management of this case. Coexistent of hyperthyroidism and mitral-valve prolapse may be explained by genetic, autoimmune, and thyroid hormone effects in myocardium.

Unbalance Between Sarcoplasmic Reticulum Ca2 + Uptake and Release: A First Step Toward Ca2 + Triggered Arrhythmias and Cardiac Damage.

The present review focusses on the regulation and interplay of cardiac SR Ca2+ handling proteins involved in SR Ca2+ uptake and release, i.e., SERCa2/PLN and RyR2. Both RyR2 and SERCA2a/PLN are highly regulated by post-translational modifications and/or different partners’ proteins. These control mechanisms guarantee a precise equilibrium between SR Ca2+ reuptake and release. The review then discusses how disruption of this balance alters SR Ca2+ handling and may constitute a first step toward cardiac damage and malignant arrhythmias. In the last part of the review, this concept is exemplified in different cardiac diseases, like prediabetic and diabetic cardiomyopathy, digitalis intoxication and ischemia-reperfusion injury.

Anaphylaxis-induced atrial fibrillation and anesthesia: Pathophysiologic and therapeutic considerations.

Atrial fibrillation is the most common cardiac arrhythmia in western society affecting more than 35 million individuals worldwide annually. It is a common postoperative complication and may also occur spontaneously during general and local anesthesia administration. Aging, diabetes mellitus, hypertension, and cardiovascular diseases including cardiomyopathies, congenital cardiac anomalies, heart failure, myocardial ischemia, pericarditis, previous cardiac surgery, vascular disease, and valvular heart disease are some correlated factors. Beyond age, increased incidence of atrial fibrillation has been correlated to autoimmune system activation as it is the underlying mechanism of persistent atrial fibrillation development. Current research supports an association between the complement system activation and lymphocyte-pro-inflammatory cytokines release with the cardiac conduction system and atrial fibrosis. The loss of CD28 antigen from CD4+ CD28+ T lymphocytes seems to play a major role in atrial fibrillation development and prognosis. Except atrial fibrillation, a variety of additional electrocardiographic changes, resembling those with digitalis intoxication may accompany anaphylaxis and particularly Kounis syndrome. Histamine is one well-known mediator in allergic and inflammatory conditions as physiologically regulates several cardiovascular and endothelial functions with arrhythmogenic potential. The increased oxidative stress, measured by the redox potentials of glutathione, has been correlated with atrial fibrillation incidence and prevalence. The use of antazoline, a first-generation antihistamine agent used for rapid conversion of recent-onset atrial fibrillation in patients with preserved left ventricular function and for rapid atrial fibrillation termination during accessory pathway ablation denotes that anaphylaxis-induced histamine production could be the cause of atrial fibrillation at least in some instances. The anaphylaxis diagnosis in anesthesia can be challenging owing to the absence of cutaneous manifestetions such as flushing, urticaria, or angioedema. Anticoagulation for stroke prevention, rate and rhythm control medications, invasive methods such as radiofrequency ablation or cryoablation of pulmonary veins as well surgical ablation constitute the treatment basis of atrial fibrillation. Understanding the underlying mechanisms of atrial fibrillation by cardiologists, anesthesiologists and surgeons, as well as potential treatments, to optimize care is of paramount importance.

Analysis of electro-mechanical relationship in human iPS cell-derived cardiomyocytes sheets under proarrhythmic condition assessed by simultaneous field potential and motion vector recordings

We investigated the electro-mechanical relationship of human iPS cell-derived cardiomyocyte sheets under arrhythmic condition, which was induced by digitalis intoxication along with the electrical train stimulation (n = 4). We adopted motion vector analysis by high-speed video microscopy and extracellular field potential recording by 64-microelectrode array system. The motion vector analysis uncovered local contractile events at resting phase, at which the field potential analysis showed no deflection in any cell sheet. Thus, motion vector analysis may provide supplemental information over field potential recording in detecting Ca2+-triggered arrhythmias, which may become a new strategy for assessing arrhythmic liability of test articles.

Recognizing rare cardiac diseases by electrocardiogram

A number of rare cardiac diseases can be recognized by electrocardiogram (ECG). This article illustrates the clinical importance of ECG as a key diagnostic tool to detect Wolff-Parkinson-White syndrome and channelopathies, which are frequently diagnosed late after one or more affected family members have become victims of sudden cardiac death. These channelopathies include long QT syndrome, short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia. In addition, typical ECG findings are frequently present in patients with idiopathic ventricular tachycardia, arrhythmogenic right ventricular dysplasia, digitalis intoxication, hyperkalemia, acute cor pulmonale due to pulmonary embolism, as well as severe left ventricular hypertrophy as in hypertrophic cardiomyopathy.

REAÇÃO ADVERSA A MEDICAMENTOS COMO FATOR CONTRIBUINTE PARA A INTERNAÇÃO HOSPITALAR DE IDOSOS

Introduction: The increase in life expectancy and population aging are associated with a higher prevalence of chronic diseases and an increase in the number of drugs used. In this context, the occurrence of adverse drug reactions (ADR) in the elderly people is greater than the other individuals due to the vulnerability of their organism. Goals: To describe the occurrence of ADR related to home pharmacotherapy contributing to hospitalization for the elderly population. Methods: This is a Cross-sectional study involving patients older than 60 years old. The dependent variable was the occurrence of ADR related to drugs used at home. The ADRs were identified by analyzing the medical evolutions and laboratory examination results recorded in the medical record. Causality of ADR was verified employing the Naranjo algorithm. Results: The study included 183 elderly people, 22 of them (12%) had at least one ADR related to drugs used at home. There were 26 ADR identified, the most frequent were digitalis intoxication (n =4; 15.4%), raising the RNI (n = 2; 7.7%) and bradycardia (n = 2; 7.7%). The main drugs related to ADR were digoxin (n = 4), warfarin (n = 4) and amiodarone (n = 3). Regarding the causality, there were 21 (80.7%) of the ADR as probable and 5 (19.3%) as possible. Univariate analysis showed a statistically significant association with polypharmacy (OR: 3.05; IC95% 1.14-8.1; p= 0.021). Conclusions: The occurrence of ADR was positively associated with polypharmacy and it is an important issue for the health of the elderly population and should contribute to hospitalization.

ROLUL CALCIULUI ÎN INTOXICAŢIA ACUTĂ DIGITALICĂ – ÎNTRE MIT ŞI MEDICINA BAZATĂ PE DOVEZI

Digitalis poisoning is still frequently encountered in medical practice, either as acute or chronic overdosage. Toxic mechanism is represented by Na+/K+ ATP-ase blockade, followed by an increase in intracellular Na+ and hiperkalemia. Hiperkalemia increases mortality in digitalis poisoning, having a complementary effect to digitalis toxicity. Calcium salts are indicated for cardiac protection in hyperkalemia. Traditionlly, calcium was contraindicated in digitalis poisoning. A careful analisys of available studies demonstrates that calcium salts are useful in treatment of severe hyperkalemia, with electrocardiogram changes, associated with acute digitalis poisoning. Management issues for digitalis poisoning are presented in the end.

A medieval case of digitalis poisoning: the sudden death of Cangrande della Scala, lord of verona (1291–1329)

The natural mummy of Cangrande della Scala was exhumed from its tomb in the church of Santa Maria Antiqua in Verona and was submitted to a multidisciplinary study, that included archaeological, palaeopathological, palynological, toxicological and historical investigation. The body of Cangrande, still wearing his precious clothes, was in a good state of preservation. Palynological analyses demonstrated the presence of pollen grains of Digitalis sp./foxglove in the rectum content, along with Matricaria chamomilla/chamomille and Morus nigra/black mulberry. Toxicological analyses showed toxic concentrations of digoxin and digitoxin, two Digitalis glycosides, in the liver and faeces samples. Both palynological and toxicological data suggest an intoxication through the oral administration of an infusion or decoction of leaves and flowers of Digitalis.Cangrande died on July 22 1329, four day after his triumphal entrance in the city of Treviso. The sudden death was preceded by vomit and diarrhoea with fever that, according to written documents, he had contracted a few days before by “drinking from a polluted spring”. The gastrointestinal symptoms manifested by Cangrande in his last hours of life are compatible with the early phase of Digitalis intoxication and the hypothesis of poisoning is mentioned by some local historical sources. The palaeopathological analyses confirm a Digitalis poisoning. The most likely hypothesis on the causes of death is that of a deliberate administration of a lethal amount of Digitalis. Although several cases of poisoning through the use of organic substances are known from historical sources, no other direct evidences are documented in the palaeopathological literature.

Terapija poremećaja srčanog ritma u akutnom koronarnom sindromu

Acute myocardial infarction (AMI) is the worst acute syndrome of coronary heart diseases (CHD) with high morbidity and mortality, and it has become a serious threat to human health. A leading hypothesis for a major mechanism of arrhythmias in the acute phase of coronary occlusion is micro-reentry due to inhomogeneity of the electrical characteristics of ischemic myocardium. Arrhythmias could be of ventricular or supraventricular origin and the most often are: ventricular premature beats, accelerated idioventricular rhythm, ventricular tachycardia ventricular fibrillation and supraventricular premature beats and atrial fibrillation. Management of this arrhythmias consists not only of proper drug regime selection but also in their quick recognition or possible prediction and not less important, correction of variuos abnormalities such as: plasma electrolyte concentrations, acid-base balance disturbances, hypoxemia, anemia, and digitalis intoxication.

Therapeutic drug monitoring of digoxin in cardiac heart failure outpatients: comparisons of two analytical methods

Objective: To compare two analytical techniques used in the determination of plasma digoxin (LC-MS/MS and immunoassay) and to verify which one better answer the need of the clinical monitoring routine of patients with cardiac heart failure. Method: The clinical findings in 15 cardiac heart failure (CHF) outpatients of the Cardiac Heart Service of the Goias Federal University Clinical Hospital were investigated. Blood samples of the patients were collected and analysed by Immunoassay and by Liquid Chromatography coupled to Mass Spectrometry (LC-MS/MS). Results: The results of the statistic test (Student p = 0,05) showed a significant difference between the analytical methods: immunoassay concentrations were higher than the concentrations determined by LCMS/ MS. The explanation may be because immunoassay method measures digoxin plus other metabolites and endogenous substances, while the LC-MS/MS method measures only the digoxin molecule. None of the patients, showed relevant clinical data suggestive of digitalis intoxication, even several drugs with potential interaction were associated with treatment. Conclusion: It was concluded, therefore, that LC-MS/MS me thod is safer, more selective and specific than immunoassay, being an option for therapeutic drug monitoring of digoxin, since the reference values would be obtain for digoxinemia by LC-MS/MS.

Case 5 - A 73 Year-Old Man with Heart Failure, Preserved Systolic Function and Associated Renal Failure

Case 5 - A 73 Year-Old Man with Heart Failure, Preserved Systolic Function and Associated Renal Failure

Examining the Causes and Consequences of Calcium Overload in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Intracellular calcium overload has been linked to arrhythmias in conditions such as ischemia reperfusion, heart failure, catecholaminergic polymorphic ventricular tachycardia and digitalis intoxication. While this link has been extensively studied at the cellular level using animal models, there is a paucity of information on the causes and consequences of Ca2+ overload in healthy human myocytes. With the advent of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM), human myocytes are becoming more readily available. However, it remains unclear if these myocytes faithfully recapitulate all aspects of adult cardiomyocyte physiology. In order to determine if iPSC-CM will be a useful platform to study the causes and consequences of Ca2+ overload, we developed methodology to examine Ca2+ overload in beating clusters of iPSC-CM and in isolated myocytes. Spontaneous and field stimulated action potentials were measured with high resistance microelectrodes in spontaneously beating clusters of iPSC-CM while measuring cluster contraction with simultaneous video edge detection. Free intracellular Ca2+ was measured with fluo-4 and confocal microscopy in beating clusters and in isolated iPSC-CM. Ca2+ overload was induced in both preparations by treatment with ouabain (2.5-5 uM or with isoproterenol (1 uM) plus 5.4 mM extracellular Ca2+. Both maneuvers produced a rise in diastolic Ca2+ as well as the appearance of oscillatory action potentials, putative delayed afterdepolarizations and triggered activityies in beating clusters. These results indicate that iPS-derived cardiomyocytes provide a useful platform to study the mechanisms of Ca2+ overload-induced arrhythmias as well as possible treatments. However, given the spontaneous nature of iPS-derived cardiomyocytes, these cells may more readily recapitulate the effects of Ca2+ overload on sinoatrial or latent pacemaker cells.

Recurrent paroxysmal supraventricular tachycardia in the beach chair position for shoulder surgery under general anesthesia

Recurrent paroxysmal supraventricular tachycardia in the beach chair position for shoulder surgery under general anesthesia

Focus on digitalis intoxication in the elderly Report of a case treated with digoxin-specific Fab antibody fragments

The indications for digoxin are currently limited to rare cases of heart failure and/or atrial fibrillation. Its use should be even more rare in geriatrics its pharmacological characteristics, associated with age-related changes and comorbidities, particularly increase the risk of digoxin poisoning in the elderly. However, at least a third of aged patients suffering from heart failure and/or atrial fibrillation is treated by digitalis. Digoxin intoxication can provoke gastrointestinal troubles, neurological disturbances and, above all, cardiac conduction impairment and dysrythmias, which explain its severity and high mortality rate. Presently, first-line therapy is the administration of digoxin specific antibodies. Poor prognosis factors, frequently found in digoxin intoxications in the elderly, have been established for guiding the prescription of antibodies and their dosage. It is important for geriatricians to be able to recognize poisoning signs and the conditions in which an antidote treatment is necessary. This will permit a more effective management of the case, with the support of a poison control center and possible referral of the patient to an intensive care unit.

Taquicardia ventricular bidireccional atípica

A 75-year old male, with the sole cardiovascular risk factor of being an active smoker, was admitted with a several week history of progressive exertional dyspnea. He was not taking any medication on a regular basis. We performed a complete cardiological evaluation and diagnosed the patient with idiopathic dilated cardiomyopathy and severe left ventricular systolic dysfunction. Upon hospitalization, treatment was started with furosemide and captopril; an electrocardiogram revealed sinus rhythm with ventricular extrasystoles. Renal function parameters and serum ion concentrations were within normal limits from admission (creatinine: 0.7 mg/dL; sodium: 139 mEq/L; potassium: 4 mEq/L; magnesium: 1.6 mEq/L). We performed a continuous 24-h electrocardiogram in order to determine the density of ventricular extrasystoles as a possible cause for the cardiomyopathy, and 20% of the complexes corresponded to ventricular extrasystoles with two morphologies, as well as runs of 3-5 beats of nonsustained ventricular tachycardia. We documented one asymptomatic, at-rest episode of tachycardia at 113 bpm, which was a wide QRS tachycardia that alternated between the two morphological QRS types that had been observed in isolated extrasystoles (A). It was electrocardiographically compatible with bidirectional ventricular tachycardia. Although bidirectional ventricular tachycardia is characteristic of digitalis intoxication or familial forms of catecholaminergic ventricular tachycardia, this case was an atypical bidirectional tachycardia caused by a coupled continuous alternation of ventricular extrasystoles in the same patient (B). We started treatment with beta blockers and the ventricular extrasystole density decreased significantly (figure).