Expert Consensus on the Diagnosis and Management of Digoxin Toxicity.

While there has been a decline in the use of digoxin in patients with heart failure and atrial fibrillation, acute and chronic digoxin toxicity remains a significant clinical problem. Digoxin's narrow therapeutic window and nonspecific signs and symptoms of toxicity create clinical challenges and uncertainty around the diagnostic criteria of toxicity and responsive treatment choices for the bedside clinician. A systematic review of published literature on digoxin toxicity (34,587 publications over 6 decades, with 114 meeting inclusion criteria) was performed to develop 33 consensus statements on diagnostic and therapeutic approaches which were then evaluated through a modified Delphi process involving a panel of experts in cardiology, nursing, emergency medicine, and medical toxicology. The results demonstrate agreement about the need to consider time of ingestion and nature of the exposure (ie, acute, acute-on-chronic, chronic) and the use of digoxin immune Fab for life-threatening exposure to decrease risk of death. While several areas of continued uncertainty were identified, this work offers formalized guidance that may help providers better manage this persistent clinical challenge.

Falling into complexity: A case of digitalis-induced fall, trauma, symptomatic bradycardia, and syncope.

Digoxin, a cardiac glycoside, functions by inhibiting the sodium potassium ATPase pump. It's crucial to note that digoxin has a very narrow therapeutic range. Its serum level vary due to changes in body weight, age, renal function, hepatic impairment and concomitant drug therapy. Chronic toxicity can lead to different types of arrrythmia,which span from heart blocks to ventricular tachycardia. This report present a case of an elderly male, where Digoxin toxicity resulted in syncope and mild traumatic brain injury. Initially upon patient's presentation ECG indicated myocardial infarction, subsequently bradycardia and complete heart block. The patient had a known history of chronic kidney disease and was prescribed 0.25mg of digoxin regularly without dose adjustment, which might have resulted in reduced digoxin elimination, leading to toxicity. Thus this case demonstrates a classic presentation of digoxin toxicity. Multiple risk factor such as old age, impaired renal function with continued digoxin treatment without dose adjustment was likely the cause of toxicity.

Stone heart syndrome: A curious case of digoxin toxicity and calcium infusion.

Stone heart syndrome has a complex interaction with digoxin toxicity, where, theoretically, the administration of intravenous calcium can worsen a patient's condition. Research on this subject is conflicting, so it is imperative to approach it cautiously.

Not only Van Gogh: a case of BRASH syndrome with concomitant digoxin toxicity.

BACKGROUND: Bradycardia, renal failure, atrioventricular (AV) node blocking, shock, and hyperkalemia syndrome is a potentially life-threatening clinical condition characterized by bradycardia, renal failure, atrioventricular (AV) node blocking, shock, and hyperkalemia. It constitutes a vicious circle in which the accumulation of pharmacologically active compounds and hyperkalemia lead to hemodynamic instability and heart failure. CASE PRESENTATION: A 66-year-old Caucasian female patient was admitted to the emergency department presenting with fatigue and bradycardia. Upon examination, the patient was found to be anuric and hypotensive. Laboratory investigations revealed metabolic acidosis and hyperkalemia. Clinical evaluation suggested signs of digoxin toxicity, with serum digoxin concentrations persistently elevated over several days. Despite the implementation of antikalemic measures, the patient's condition remained refractory, necessitating renal dialysis and administration of digoxin immune fab. CONCLUSION: Bradycardia, renal failure, atrioventricular (AV) node blocking, shock, and hyperkalemia syndrome is a life-threatening condition that requires prompt management. It is important to also consider potential coexisting clinical manifestations indicative of intoxication from other pharmacological agents. Specifically, symptoms associated with the accumulation of drugs eliminated via the kidneys, such as digoxin. These manifestations may warrant targeted therapeutic measures.

Plasma exchange for the management of digoxin toxicity in an individual with an acute kidney injury: A case report.

Digoxin toxicity can be life-threatening. Digoxin-specific antibody (DSA) fragments are used in severe digoxin toxicity, binding to serum-free digoxin and enabling increased renal excretion. In severe renal impairment, clearance of these complexes is prolonged, leading to rebound toxicity. Digoxin and DSA complexes are not dialysable. We present a case of a gentleman with severe digoxin toxicity and acute kidney injury (AKI). Despite receiving DSA doses, his digoxin levels rebounded and symptoms persisted. Based on published case reports, plasma exchange (PEX) after further dosing was arranged. PEX facilitated the removal of digoxin-DSA complexes, bypassing renal excretion. During PEX, clinical signs improved and were sustained. He did not require further dialysis or PEX, renal function recovered and he was discharged. This case highlights challenges in the management of severe digoxin toxicity in patients with a concurrent AKI. The use of PEX enabled digoxin-DSA complex removal and should be considered in these circumstances.

Feud, Flower, and Fatal Electrocardiograms.

Oleander is a prevalent tropical plant used in many parts of India for deliberate self-harm. The active ingredients act in a mechanism similar to cardiac glycosides; hence, the toxicological profile is similar to digoxin toxicity. Cardiac toxicity occurs in the form of a heart block with concomitant ventricular arrhythmia. Identifying the distinct electrocardiographic pattern for early diagnosis and initiating emergency management is imperative. Here, we present two such interesting cases of oleander intoxication, one with Nerium oleander and the other with Thevetia peruviana.

Safety profile of intravenous digoxin in Chinese patients with acute heart failure with reduced ejection fraction: a small-scale prospective cohort study.

Background: Adverse effects of intravenous digoxin vary from patients and disease status, which should be closely monitored. Aims: To explore the safety profile of intravenous digoxin in acute heart failure with reduced ejection fraction (HFrEF) among Chinese patients. Methods: A clinical prospective, single-center, single-arm, open-label exploratory clinical trial was performed in patients with acute HFrEF at Wuhan Asia Heart Hospital. A fixed dose of 0.5 mg digoxin was used intravenously once per day for 3 days. The normalized dosage of digoxin (NDD), toxic serum digoxin concentration (SDC), and adverse reactions of intravenous digoxin were recorded. Results: A total of 40 patients were recruited in the study. The SDC increased from 1.03 ± 0.34 ng/mL to 1.95 ± 0.52 ng/mL during treatment. 50% (20/40) patients reached a toxic SDC of 2.0 ng/mL, and toxic effects were seen in 30% (12/40) patients. Estimated glomerular filtration rate (eGFR) < 60 mL/min [HR: 5.269; 95% CI: 1.905-14.575, p = 0.001], NDD ≥7 µg/kg [HR: 3.028; 95% CI: 1.119-8.194, p = 0.029], and ischemic cardiomyopathy [HR: 2.658; 95% CI: 1.025-6.894, p = 0.044] were independent risk factors for toxic SDC. Toxic SDC was effectively identified [area under the receiver operating characteristic (ROC) curve = 0.85, p < 0.001] using this model, and patients would have a higher risk of toxicity with more risk factors. Conclusion: Intravenous digoxin of 0.5 mg was safe and effective for initial dose but not suitable for maintenance treatment in Chinese patients with acute HFrEF. Patients who had lower eGFR, received higher NDD, and had ischemic cardiomyopathy should be closely monitored to avoid digoxin toxicity.

Review: Failure of current digoxin monitoring for toxicity: new monitoring recommendations to maintain therapeutic levels for efficacy.

The current recommendations for monitoring digoxin, a narrow therapeutic index drug, are limited to confirming medication use or investigating suspicion of toxicity and fail our oath to do no harm. Numerous meta-analyses evaluating digoxin use consistently recommend frequent monitoring to maintain the level of 0.5 to ≤1.0 ng/ml because higher levels lead to increased morbidity and mortality without benefit. Data from the United States National Poison Control Center (2012-2020) show annual deaths due to digoxin of 18-36 compared to lithium's 1-7, and warfarin's 0-2 respectively. The latter drugs also have narrow therapeutic indexes like digoxin yet are more carefully monitored. Recognition of digoxin toxicity is impaired as levels are not being routinely checked after medications are added to a patient's regimen. In addition, providers may be using ranges to guide treatment that are no longer appropriate. It is imperative that monitoring guidelines and laboratory therapeutic levels are revised to reduce morbidity and mortality due to digoxin. In this review, we provide a comprehensive literature review of digoxin monitoring guidelines, digoxin toxicity, and evidence to support revising the ranges for serum digoxin monitoring.

Bidirectional Ventricular Tachycardia: Challenges and Solutions.

Bidirectional ventricular tachycardia (BiVT) is a rare form of ventricular tachycardia that manifests on surface electrocardiogram by dual QRS morphologies alternating on a beat-to-beat basis. It was first reported in the 1920s as a complication of digoxin, and since then, it has been reported in other conditions including fulminant myocarditis, sarcoidosis, catecholaminergic polymorphic ventricular tachycardia, and Andersen-Tawil syndrome. The mechanism for BiVT is not as well known as other forms of ventricular tachycardia but appears to include typical mechanisms including triggered activity from afterdepolarizations, abnormal automaticity, or reentry. This review will go beyond the definition, surface electrocardiogram, mechanisms, causes, and treatment of BiVT as per our current understanding.

A Case of Digoxin Toxicity Due to Acute Renal Failure.

Since the publication of the Digitalis Investigation Group trial in 1997, digoxin use has declined significantly. Medications such as angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) and beta-blockers that have been demonstrated to have a decrease in morbidity and mortality are prescribed in favor of digoxin. Despite the reduction in digoxin use and improved therapeutic monitoring, digoxin toxicity remains a significant cause of morbidity and mortality. When digoxin toxicity is suspected, patients should be managed with supportive care, including discontinuation of the medication, and consideration for administration of digoxin-specific antibody fragment. We present a case of digoxin toxicity precipitated by acute renal failure, with a discussion on the pathophysiology and diagnosis of digoxin toxicity, along with the indications for administration of digoxin-specific antibody fragments. While digoxin toxicity is prescribed less commonly, physicians need to maintain a high index of suspicion and be comfortable with administering digoxin-specific antibody fragment in these scenarios.

A Visual Resolution of Cardiotoxicity: A Case Report of Digoxin-Induced Bidirectional Ventricular Tachycardia.

Digoxin is rarely used in modern cardiovascular disease management. Therefore, digoxin toxicity has been infrequently encountered and it is paramount to diagnose in a timely fashion. Bidirectional ventricular tachycardia is an unusual arrhythmia wherein every other beat has a different QRS axis as it travels alternately down different conduction pathways. The arrhythmia can be a manifestation of myocarditis, myocardial infarct, Andersen-Tawil syndrome, arrhythmogenic right ventricular cardiomyopathy, catecholaminergic polymorphic ventricular tachycardia, herbal aconite poisoning, and digoxin toxicity. This case illustrates the importance of clinician awareness of rare electrocardiogram (EKG) patterns of digoxin toxicity and visual resolution of fatal arrhythmia with timely treatment.

Detecting Digoxin Toxicity by Artificial Intelligence-Assisted Electrocardiography.

Although digoxin is important in heart rate control, the utilization of digoxin is declining due to its narrow therapeutic window. Misdiagnosis or delayed diagnosis of digoxin toxicity is common due to the lack of awareness and the time-consuming laboratory work that is involved. Electrocardiography (ECG) may be able to detect potential digoxin toxicity based on characteristic presentations. Our study attempted to develop a deep learning model to detect digoxin toxicity based on ECG manifestations. This study included 61 ECGs from patients with digoxin toxicity and 177,066 ECGs from patients in the emergency room from November 2011 to February 2019. The deep learning algorithm was trained using approximately 80% of ECGs. The other 20% of ECGs were used to validate the performance of the Artificial Intelligence (AI) system and to conduct a human-machine competition. Area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were used to evaluate the performance of ECG interpretation between humans and our deep learning system. The AUCs of our deep learning system for identifying digoxin toxicity were 0.912 and 0.929 in the validation cohort and the human-machine competition, respectively, which reached 84.6% of sensitivity and 94.6% of specificity. Interestingly, the deep learning system using only lead I (AUC = 0.960) was not worse than using complete 12 leads (0.912). Stratified analysis showed that our deep learning system was more applicable to patients with heart failure (HF) and without atrial fibrillation (AF) than those without HF and with AF. Our ECG-based deep learning system provides a high-accuracy, economical, rapid, and accessible way to detect digoxin toxicity, which can be applied as a promising decision supportive system for diagnosing digoxin toxicity in clinical practice.

Transient bilateral chorea secondary to digoxin toxicity in a female with acute kidney injury: a case report.

BACKGROUND: Chorea secondary to digoxin toxicity is rare, with only three published cases describing the phenomenon. We report the case of a 78-year-old female presenting with intermittent vomiting and diarrhoea for 4 weeks. She had a history of chronic kidney disease and digoxin use for atrial fibrillation. CASE SUMMARY: A 78-year-old lady presented to the emergency department with a 4-week history of intermittent vomiting and diarrhoea. These symptoms commenced after a course of antibiotics prescribed by her general practitioner for a urinary tract infection. Her admission electrocardiogram demonstrated atrial fibrillation at a rate of 32, with evidence of digitalis toxicity. Her creatinine was 396 µmol/L (44-80 µmol/L) with digoxin level 8.1 nmol/L (0.77-1.5 nmol/L). Initially, treatment was with digoxin-specific antibody (FAB) and fluid resuscitation. Within 24 h, she developed transient head, neck, and bilateral upper limb chorea. Review of medications revealed no other likely causative agent. Neuroimaging showed no new ischaemia, but stable established bilateral infarcts of the basal ganglia. Haloperidol 0.5 mg twice daily was commenced. Three days later as digoxin levels normalized, the chorea resolved entirely without recurrence. DISCUSSION: We have identified three reported cases of digoxin-induced chorea. Our case resembles two of the published cases where a transient bilateral chorea, associated with digitalis toxicity and resolving within a few days of normalization of digoxin levels was demonstrated. There were no other focal neurological signs or symptoms. It has been postulated that an alteration to dopaminergic neuronal activity is a potential mechanism, as digoxin also demonstrates neuropsychiatric side effects such as psychosis and depression.

Maternal effects induced by oral digoxin during treatment of fetal tachyarrhythmia: Case series and literature review.

OBJECTIVES: The aim of this study is to evaluate the prevalence of maternal complications derived from digoxin treatment and its relationship with digoxinemia, as well as its occurrence in relation to the different treatment doses and therapeutic schemes used. STUDY DESIGN: This is a retrospective observational study of women who received digoxin for the treatment of fetal tachyarrhythmia over a 10-year period at the University Hospital Virgen del Rocío (Seville). Data corresponding to the digoxin dose, its duration, serum digoxin levels and electrocardiographic parameters during follow-up were collected. Maternal side effects were reported, and its relationship to the treatment dose as well as digoxinemia. The study is accompanied by a narrative review of related literature. RESULTS: There were 10 cases eligible. During treatment, as least one symptom or sign was present in 30 % of cases, being in all cases digestive symptoms. In all those cases, the digoxin level was higher than established as therapeutic threshold (2 ng/mL), and all reversed within a maximum of 48 h after the dose decrease. Digoxinemia overdosing (> 2 ng/mL) was observed in 6 women (60 %), one of which reached the toxicity range (> 3 ng/mL). In all cases, normal range was achieved decreasing the dose of digoxin 0.25 mg every 24 h. No patient developed side effects with digoxinemia below 2 ng/mL. No electrocardiographic abnormalities appeared during treatment. CONCLUSION: Digoxin is a safe treatment for management of fetal tachyarrhythmias. Side effects appear frequently when serum digoxin level is over 2 ng/mL, but they are usually mild and self-limited. However, it remains advisable to monitor electrocardiographic changes and digoxinemia through the whole therapy to prevent serious complications related to digoxin toxicity.

Continuous venovenous hemodialysis may be effective in digoxin removal in digoxin toxicity: A case report.

Digoxin is a cardiac glycoside that is used for the treatment of heart failure and atrial fibrillation. Besides its careful close follow-up, toxicity affects nearly 1% of congestive heart failure patients. Cessation of the drug, appropriate electrolyte and rhythm control and digoxin-Fab antibody are the mainstay for toxicity treatment in these patients. As known, hemodialysis and peritoneal dialysis are not effective by the means of digoxin removal. We present a 66-year-old patient who admitted to hospital with digoxin toxicity and severe acute kidney injury. The patient was treated with continuous venovenous hemodialysis because of her hypervolemia, hyperkalemia, cardiac instability, and the thought of probable decrease in digoxin levels concerning the continuous nature of solute clearance. Without the treatment using digoxin-specific Fab antibodies, the patient's digoxin level was decreased successfully with continuous venovenous hemodialysis. In conclusion, continuous venovenous hemodialysis may be a treatment option in digoxin toxicity especially those who suffer from severe renal dysfunction and cannot access digoxin antidote.

Tachycardia with alternating pacemaker spikes: Is it pacemaker malfunction?

A 67 year old female with diabetes mellitus type 2, chronic kidney disease, ischemic cardiomyopathy, status post biventricular implantable cardioverter-defibrillator presented to the Heart Failure clinic for routine follow up with a tachycardia with alternating pacemaker spikes.

Life-threatening digoxin toxicity due to drug-drug interactions in an HIV-positive man.

Drug-drug interactions with corticosteroids, causing Cushing's syndrome with secondary adrenal suppression, are well known in HIV patients. Corticosteroids are widely prescribed in the HIV-positive population. However, digoxin is rarely used in HIV patients; hence, digoxin toxicity due to drug-drug interaction is not widely recognised. Nevertheless, this practice might change in the future as HIV cohorts of patients are ageing, due to the successful treatment of HIV infection with combination antiretroviral therapy. We report a case of digoxin toxicity in an HIV-positive 51-year-old man, due to a combination of drug-drug interaction and renal impairment. The first case report of digoxin toxicity due to drug-drug interaction with ritonavir in an HIV-positive woman was published in 2003. To the best of our knowledge, no similar case report has since been published in the literature. This case alerts the profession to the importance of drug-drug interaction and highlights the clinical features of digoxin toxicity.

Digitalis toxicity: ECG vignette.

"Digitalis toxicity, often candidly indexed as poisoning, has plagued the medical profession for over 200 years. The situation qualifies as a professional disgrace on the basis of three items: the situation persists, physicians are often slow to recognize it and, over the decades, writers have been harsh in their denunciation of fellow physicians when toxicity has occurred…." These are the opening remarks of an essay published in 1983 on the 2nd centenary of William Withering's 'magic potion from foxglove's extract for dropsy.' Even today, after many decades, these words appear relevant! We present and discuss an interesting ECG of digitalis toxicity.

Severe suicidal digoxin and propranolol toxicity with insulin overdose.

We present a case of a 32-year-old male doctor, with type I diabetes mellitus on daily insulin therapy, who allegedly consumed large doses of digoxin and propranolol along with simultaneous administration of large dose of insulin with suicidal intent. Initial investigations revealed serum digoxin levels of 7.5 ng/ml, serum insulin 500 µIU/ml, and serum C-peptide 0.43 ng/ml. He was managed with charcoal-based hemoperfusion for digoxin overdose along with injection glucagon for propranolol overdose. His blood sugar levels were maintained with continuous infusion of 20% dextrose till the patient was allowed to take oral diet. Significant clinical improvement was noticed with this therapy which was evident by progressively declining serum digoxin levels, normalization of pulse rate, and adequate blood glucose levels. Finally, with a good hemodynamic profile and a serum digoxin level well within normal limits, he was discharged following consultation with a psychiatrist.