Serum Digoxin Concentration Research Articles

Digoxin Loading Doses and Serum Digoxin Concentrations for Rate Control of Atrial Arrhythmias in Critically Ill Patients.

Intravenous (IV) digoxin loading dose recommendations for rate control of atrial arrhythmias in critically ill patients are not well studied. When using digoxin in the setting of atrial fibrillation/atrial flutter (AF/AFL), a loading dose (LD) in either a fixed-dose regimen, weight-based dose, or pharmacokinetic-based calculation to target a serum digoxin concentration (SDC) of 0.8-1.5 ng/mL is recommended. The objective of this study was to assess the safety and effectiveness of digoxin LD used in critically ill patients for rate control of AF/AFL and to assess the SDC achieved. This single center retrospective cohort study included patients who received IV digoxin and had a SDC drawn. The primary endpoint was the median SDC achieved after a digoxin LD. Secondary outcomes included the frequency of SDCs ≥1.5 ng/mL and heart rate (HR) control. A total of 92 patients were included. The median total LD of digoxin for the entire cohort was 11mcg/kg (750 mcg). For 61% of the cohort, the LD was distributed over six-hour intervals. The median SDC after completion of the IV digoxin LD was 1.3 ng/mL (0.9, 1.7). The incidence of supratherapeutic SDC was 36% for the total cohort. A target HR < 110 beats per minute within 24 hours from digoxin LD was achieved in 60% of the cohort. In conclusion, a median total digoxin LD of 750 mcg in critically ill patients with AF/AFL, targeting a SDC < 1.5ng/mL may be considered for acute rate control, taking into account drug-drug interactions in the cardiac intensive care unit. Future studies are necessary to confirm our findings.

Efficacy and safety of low-dose digoxin in patients with heart failure. Rationale and design of the DECISION trial.

Digoxin is the oldest drug in cardiovascular (CV) medicine, and one trial conducted >25 years ago showed a reduction in heart failure (HF) hospitalizations but no effect on mortality. However, later studies suggested that the dose of digoxin used in that trial (and other studies) may have been too high. The DECISION (Digoxin Evaluation in Chronic heart failure: Investigational Study In Outpatients in the Netherlands) trial will examine the efficacy and safety of low-dose digoxin in HF patients with reduced or mildly reduced left ventricular ejection fraction (LVEF) with a background of contemporary HF treatment. The DECISION trial is a randomized, double-blind, parallel-group, placebo-controlled event-driven outcome trial which will investigate the efficacy and safety of low-dose digoxin in patients with chronic HF and LVEF <50%. Both patients with sinus rhythm and atrial fibrillation will be enrolled and will be randomized (1:1) to low-dose digoxin or matching placebo. To maintain a target serum digoxin concentration of 0.5-0.9 ng/ml, dose adjustments are made throughout follow-up based on serum digoxin measurements with dummy values for the placebo group. The primary endpoint is a composite of CV mortality and total HF hospitalizations or total urgent hospital visits for worsening HF, and all endpoints are adjudicated blindly by a Clinical Event Committee. The estimated sample size was 982 patients who will be followed for a median of 3 years, and in December 2023 enrolment was completed after 1002 patients. The DECISION trial will provide important evidence regarding the effect of (low-dose) digoxin on CV mortality and total HF hospitalizations and urgent hospital visits when added to contemporary HF treatment of patients with reduced or mildly reduced LVEF. ClinicalTrials.gov identifier: NCT03783429.

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

BackgroundBradycardia, 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 presentationA 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.ConclusionBradycardia, 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.

Characterizing Utilization and Outcomes of Digoxin Immune Fab for Digoxin Toxicity.

Digoxin is a widely prescribed drug for congestive heart failure and atrial fibrillation. Digoxin has a narrow therapeutic index and toxicity can develop quite easily. Digoxin immune fab (DIF) is an effective treatment for toxicity, however there are limited studies characterizing its impact on clinical outcomes in real-world clinical practice. The aim of this study was to identify factors and healthcare outcomes associated with digoxin immune fab (DIF) treatment in patients with confirmed/suspected digoxin toxicity. An IRB-approved retrospective chart review of digoxin toxic patients (2011-2020) presenting at an academic healthcare system was conducted. Demographic and clinical data were collected. Patients were stratified by DIF treatment versus non-DIF treatment. DIF utilization patterns (appropriate, use when not indicated, or underutilized) were determined using pre-defined criteria. Severe digoxin toxicity was defined as having one or more of the following: mental status disturbances, antiarrhythmic therapy, acute renal impairment or dehydration, serum digoxin concentration (SDC) > 4ng/mL, or serum K+ > 5mEq/mL. Logistic multivariable regression analysis evaluated factors associated with DIF use. All statistical analyses were performed in R version 4.1. Data from 96 patients (non-DIF treated group = 49; DIF treated group = 47) were analyzed. DIF was used appropriately in 70 patients (73%), underutilized in 19 (20%), and administered to 7 (7%) patients when it was not indicated. Several clinical parameters differentiated the DIF from the non-DIF group (p<0.05) including higher mean SDC (3.41±1.63 vs 2.87±1.17), higher mean potassium (5.33±1.48 vs 4.55±0.87), more toxicity severity (85% vs 49%), and more likely to require cardiac pacing (26% vs 4%). Digoxin toxicity resolved sooner in the DIF group (coefficient - 0.702, 95% CI - 1.137 to - 0.267) (p<0.01) and they had shorter intensive care unit lengths of stay (12.4±20.3 vs 24.4±28.7 days; p=0.018). The all-cause mortality rate in patients appropriately managed with DIF therapy versus those patients where DIF was underutilized was 11% and 21%, respectively. Based on our study population, DIF therapy appears to be beneficial in limiting duration of toxicity and intensive care unit lengths of stay in digoxin toxic patients. Although DIF was appropriately utilized in most cases, there was a relatively high proportion of cases in which DIF treatment was either underutilized or not indicated.

Evaluation of therapeutic and toxic levels of serum digoxin concentration: a cross-sectional study from a tertiary hospital.

Digoxin is a cardiac glycoside for treating heart failure and atrial fibrillation. Despite its limited therapeutic range and complex pharmacokinetic properties, this medication continues to be frequently prescribed. This study aimed to evaluate the serum digoxin concentration (SDC) at therapeutic, subtherapeutic, and toxic levels and explore the factors affecting these levels in patients receiving digoxin therapy for heart failure. In this descriptive and cross-sectional study, the data were obtained from the electronic system of patients who presented to Afyonkarahisar Health Sciences University. For the SDC, the reference range was accepted as 0.5-0.9 ng/mL, and the upper limit was 2.0 ng/mL. The patient's demographic characteristics, comorbidities, and laboratory findings were evaluated. The Mann-Whitney U test, Chi-square test, and logistic regression analysis were used. p<0.05 was considered statistically significant. The data of 419 patients (mean age: 65.9±16.1 years, 68.5% women) were evaluated. The mean SDC was 1.11±1.01 ng/mL, and it was below 0.5 ng/mL in 24.3% of the patients, 0.5-0.9 ng/mL in 23.4%, 0.9-2 ng/mL in 41.3%, and over 2 ng/mL in 11.1%. Age, male gender, the presence of diabetes mellitus, and high HbA1c values were found to be associated with greater SDC levels, but this was not statistically significant. The presence of renal failure, elevated creatinine and magnesium levels, and potassium, sodium, and calcium levels outside the normal limits significantly increased the SDC. High creatinine and low/high potassium values significantly affected the detection of SDC at the toxic level. The measurement of SDC levels holds significance not only in the monitoring of toxicity but also in ensuring adherence to the recommended therapeutic range during therapy. It is recommended to exercise caution in terms of risk factors such as age, kidney function test results, and blood electrolyte levels.

MITRAL REGURGITATION IN SADDLE-BILLED STORKS (EPHIPPIORHYNCHUS SENEGALENSIS) IN HUMAN CARE: DIAGNOSIS, ECHOCARDIOGRAPHIC MEASUREMENTS, AND MANAGEMENT.

The asymptomatic and slow progressive nature of cardiopathies represents a risk to the welfare of avian species in human care. Diagnosis and treatment of cardiac disease in birds pose a challenge due to unique anatomic and physiologic characteristics. Comprehensive cardiac assessments with diagnostic tools such as echocardiography, color-Doppler, the biomarker cardiac troponin I (cTn1), and cholesterol serum concentrations have been utilized in different bird species with varying success. Saddle-billed storks (Ephippiorhynchus senegalensis) have been maintained in human care for over 80 yrs and several institutions have noted heart murmurs and cardiomegaly. Despite these findings, peer-reviewed literature describing cardiopathies is lacking for this species. This case series documents the identification of mitral valve regurgitation in saddle-billed storks in a breeding center. Transcoelomic echocardiography using a ventromedial approach with a two-chambered view and color Doppler was utilized. Echocardiographic measurements were taken and compared 1 yr later in most of the birds. There was left atrial enlargement and worsened mitral regurgitation in one geriatric patient, and no progression of the disease in two young birds. Serum samples showed that cTn1 had different concentrations depending on the severity of the disease, whereas cholesterol was within reference range for all birds. Treatment with digoxin and pimobendan was recommended in one bird, serum concentrations of digoxin were tested in a 6-mon span, results were within therapeutic range, and there were no overt adverse effects. There was a suspected genetic component in this population, as four of the five birds with confirmed mitral regurgitation were related.

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 0.5mg digoxin was used intravenously once per day for 3days. 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 ± 0.34ng/mL to 1.95 ± 0.52ng/mL during treatment. 50% (20/40) patients reached a toxic SDC of 2.0ng/mL, and toxic effects were seen in 30% (12/40) patients. Estimated glomerular filtration rate (eGFR) < 60mL/min [HR: 5.269; 95% CI: 1.905-14.575, p = 0.001], NDD ≥7μg/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 0.5mg 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.

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.

Digitalis in heart failure: declining use and ongoing outcome trials.

Reasons for the decline in use of digitalis in heart failure, importance of serum digoxin concentrations, and characteristics of two ongoing trials with digitalis in heart failure.

Evaluation of Safety and Efficacy of Intravenous Digoxin Loading Doses Based on Ideal Body Weight.

Intravenous digoxin loading dose recommendations differ between clinical guidelines and Food and Drug Administration packaging for acute rate control. The objective of this study was to assess the safety and efficacy of intravenous digoxin loading in patients who received ≤12 µg/kg and >12 µg/kg of digoxin using ideal body weight (IBW). This single center retrospective cohort study with exempt status from the local Institutional Review Board included patients who received intravenous digoxin and had a serum digoxin concentration (SDC) drawn. Digoxin doses >36 hours after the first dose were excluded. Patients who received a total of >12 µg/kg and ≤12 µg/kg IBW were compared. The primary endpoint was frequency of SDCs ≥1.2 ng/mL, which have been shown to be associated with increased mortality. A total of 244 patients were included (144 receiving >12 µg/kg and 100 receiving ≤12 µg/kg). There were significantly more SDC ≥1.2 ng/mL in the >12 µg/kg group than the ≤12 µg/kg group (50.6% vs. 30.0%; adjusted odds ratio, 3.19; 95% confidence interval [CI]: 1.79-5.84), with no difference in rate control failure. Major limitations of the study include retrospective nature and possible selection bias. Compared to patients who received digoxin doses ≤12 µg/kg IBW, patients who received >12 µg/kg IBW had higher rates of SDC ≥1.2 ng/mL. This suggests that appropriate weight-based dosing with 8 to 12 µg/kg IBW has the potential to be a safer approach to digoxin loading, rather than frequently used dosing strategies that result in doses >12 µg/kg.

Forage and You Shall Find: Cardiac Glycoside Poisoning and the Danger of Foraging.

Amateur foraging, which can be described as the gathering of uncultivated plants for sustenance or recreation, supports many benefits for the forager and the environment; however, it can also present the hazard of unintentional poisoning. Asclepias syriaca, or common milkweed, is a potentially edible plant that also contains cardioactive steroids akin to digoxin. A 38-year-old female amateur forager boiled and sautéed 8-10 milkweed pods before ingesting them. She developed vomiting and heart palpitations within 1 hour and presented to an emergency department 3 hours after ingestion. Her exam was within normal limits with exception of heart rate in the 40-50s without hypotension. ECG was notable for sinus bradycardia. Laboratory analysis was notable for a detectable serum digoxin concentration. Life-threatening toxicity did not occur. Recently, some military services have advocated for foraging as a means to sustain far-forward troops. However, misidentification of plants by inexperienced foragers can result in severe toxicity or death. If mass foraging becomes part of expeditionary operations, military clinicians must be trained and prepared for the potentially severe plant-related poisonings.

Characteristics and Outcomes of Suspected Digoxin Toxicity and Immune Fab Treatment Over the Past Two Decades—2000-2020

The role of digoxin in clinical practice has narrowed over time. Data on digoxin toxicity trends and outcomes are variable and lack granularity for treatment outcomes. This study aimed to address data gaps in digoxin toxicity trends and outcomes in patients treated with or without digoxin immune fab (DIF). This single-center analysis examined patients with signs/symptoms concerning digoxin toxicity, defined as hospital admission or emergency department visit with elevated digoxin serum concentrations (>2ng/ml) and/or a primary diagnosis code of digoxin toxicity and/or DIF order. Between 2000 and 2020, 727 patients were identified with signs concerning for digoxin toxicity with a mortality rate of 12.7% during admission and 42.7% at 1year. DIF was ordered in 9% of cases. Incidence of digoxin toxicity per 1,000 patients with a digoxin prescription and frequency of DIF treatment fluctuated over time without a clear trend toward increase or reduction. DIF-treated patients demonstrated a heavier co-morbidity burden and lower presenting heart rates (median 53 [39.5 to 69.5] vs 77 [64.0 to 91.5]beats/min, p <0.001), worse renal function (median estimated glomerular filtration rate, 30.3 [14.8 to 48.6] vs 40.0 [24.2 to 61.2]ml/min/1.73m2, p=0.013), and higher potassium (median 4.5 [4.0 to 5.3] vs 4.3 [3.9 to 4.8]mEq/L, p=0.022). Compared with a matched cohort, DIF-treated patients experienced a nonsignificant, numerically lower in-hospital mortality (8.2% vs 15.8%, p=0.199) and 30-day all-cause hospitalization (14.3% vs 24.7%, p=0.112) and similar 6-month and 1-year hospitalization and mortality. In conclusion, digoxin toxicity remains a pertinent public health issue despite reduction in digoxin utilization. DIF therapy is used in a medically complex population with a high-acuity illness at presentation and is associated with nonsignificant trends toward reduced in-hospital mortality and early readmission that are attenuated over time.

Population pharmacokinetic analysis and dosage recommendations for digoxin in Japanese patients with atrial fibrillation and heart failure using real-world data

BackgroundDigoxin is an important treatment option for reducing the ventricular rate in patients with atrial fibrillation (AF) and heart failure (HF). Digoxin has a narrow therapeutic window and large interindividual variability. A low target blood concentration, especially ≤0.9 ng/mL, is recommended for patients with HF who are taking digoxin. This study aimed to develop a population pharmacokinetic model and to identify clinical factors that affect digoxin exposure and an optimal digoxin dosing regimen in Japanese patients with AF and HF.MethodsA population pharmacokinetic analysis was performed by using a nonlinear mixed effects model based on 3465 concentration points from 391 patients (>18 years) who were receiving oral digoxin. Using trough serum digoxin concentrations and clinical data, a population pharmacokinetic model was developed for determining covariates of clearance. A 1-compartment model was used to examine the interindividual variability of the oral clearance (CL/F) of digoxin. An appropriate dosage of digoxin was identified using Monte Carlo simulation.ResultsThe final model demonstrated that creatinine clearance (CLCR) and the use of amiodarone were factors that contributed to the CL/F of digoxin. Monte Carlo simulation results showed that with a daily maintenance dose of 0.25 mg, the intoxication risk window of a trough serum concentration of ≥0.9 ng/mL could be reached in more than half of patients regardless of renal function category or concurrent use of amiodarone. The appropriate maintenance dosage was 0.125 mg daily for most Japanese patients with AF and HF. However, with a daily dose of 0.125 mg, a trough serum concentration of ≥0.9 ng/mL could be reached in more than half of patients with renal impairments (CLCR 30 mL/min) or concurrent use of amiodarone. A daily maintenance dose of 0.0625 mg was acceptable for these patients.ConclusionsCLCR and the use of amiodaron were found to contribute to digoxin clearance using a population pharmacokinetic methodology. For Japanese patients with AF and HF, 0.125 mg is an appropriate daily digoxin maintenance dose, but a dose reduction is required for patients with CLCR <30 mL/min or concurrent amiodarone use.

Serum digoxin concentrations in dogs with atrial fibrillation under long term digoxin treatment.

Background:Atrial fibrillation (AF) is the most common arrhythmia in dogs, most frequently diagnosed as chronic AF associated with a structural heart disease. The therapeutic strategy, in these cases, is based on the heart rate control and digoxin is one of the most used drugs.Aim:The aim of this work was to study the serum digoxin concentration changes in dogs with AF under long-term treatment with digoxin. Furthermore, the remission of clinical signs and the correlation between digoxinemia and other clinical and laboratory variables were retrospectively evaluated.Methods:The prospective study was conducted on seven large breed dogs from the time of reaching the definitive digoxin dosage. Digoxinemia was determined at month: 1, 3, 6, 9, 12, then twice a year. A post hoc statistical analysis investigated the influence of selected clinical and laboratory variables on the risk to develop spikes in digoxinemia. Clinical data, heart rate, digoxin dosage (mg/m2), and digoxinemia (ng/ml) at all available follow-ups were retrospectively evaluated from the medical records of 17 further dogs and a linear regression analysis was performed on the whole data set. The relation between the time of remission of AF clinical signs and variables was also investigated.Results:An unexpected increase in digoxin serum concentration was recorded in three dogs after one year monitoring, in absence of digoxin dosage changes. No statistical significance of all the studied variables on the risk to develop spikes of digoxinemia was registered. Two dogs, reaching digoxinemia 4.46 and 5.24 ng/ml, showed symptoms that reversed after digoxin withdrawal. From retrospective data, 88% of dogs reached complete reverse of AF clinical signs in 2.1 months from digoxin treatment starting, regardless of digoxin initial dosage, digoxinemia, and heart rate.Conclusion:Digoxin in monotherapy remain a good option to treat AF in dogs, anyway digoxin toxicity could emerge during long-term therapy, similarly to what happen in human medicine. Life-threatening spikes of digoxinemia could occur, especially after 1-year treatment with digoxin. It is very important that practitioners be aware of this possibility and encourage the owners to monitor digoxinemia during long-term treatment to avoid dangerous and toxic effects.

Impact of autoantibodies against the M2-muscarinic acetylcholine receptor on clinical outcomes in peripartum cardiomyopathy patients with standard treatment

ObjectivesTo evaluate the impact of autoantibodies against the M2-muscarinic receptor (anti-M2-R) on the clinical outcomes of patients receiving the standard treatment for peripartum cardiomyopathy (PPCM).MethodsA total of 107 PPCM patients who received standard heart failure (HF) treatment between January 1998 and June 2020 were enrolled in this study. According to anti-M2-R reactivity, they were classified into negative (n = 59) and positive (n = 48) groups, denoted as the anti-M2-R (−) and anti-M2-R (+) groups. Echocardiography, 6-min walk distance, serum digoxin concentration (SDC), and routine laboratory tests were performed regularly for 2 years. The all-cause mortality, cardiovascular mortality, and rehospitalisation rate for HF were compared between the two groups.ResultsA total of 103 patients were included in the final data analysis, with 46 in the anti-M2-R (+) group and 57 in the anti-M2-R (−) group. Heart rate was lower in the anti-M2-R (+) group than in the anti-M2-R (−) group at the baseline (102.7 ± 6.1 bpm vs. 96.0 ± 6.4 bpm, p < 0.001). The initial SDC was higher in the anti-M2-R (+) group than in the anti-M2-R (−) group with the same dosage of digoxin (1.25 ± 0.45 vs. 0.78 ± 0.24 ng/mL, p < 0.001). The dosages of metoprolol and digoxin were higher in the anti-M2-R (−) patients than in the anti-M2-R (+) patients (38.8 ± 4.6 mg b.i.d. vs. 27.8 ± 5.3 mg b.i.d., p < 0.0001, respectively, for metoprolol; 0.12 ± 0.02 mg/day vs. 0.08 ± 0.04 mg/day, p < 0.0001, respectively, for digoxin). Furthermore, there was a greater improvement in cardiac function in the anti-M2-R (−) patients than in the anti-M2-R (+) patients. Multivariate analysis identified negativity for anti-M2-R as the independent predictor for the improvement of cardiac function. Rehospitalisation for HF was lower in the anti-M2-R (−) group, but all-cause mortality and cardiovascular mortality were the same.ConclusionsThere were no differences in all-cause mortality or cardiovascular mortality between the two groups. Rehospitalisation rate for HF decreased in the anti-M2-R (−) group. This difference may be related to the regulation of the autonomic nervous system by anti-M2-R.

Closing the Digitalis Divide: Back to the Basics of Randomized Controlled Trials.

Publishe d decades after several randomized controlled trials (RCT) demonstrating decreased hospitalizations and no effect on all-cause mortality with digoxin use, a series of meta-analyses linking digoxin treatment and mortality have contributed to a narrower application of this medication for the management of heart failure (HF) and atrial fibrillation (AF). Given the conflicting data from the earlier RCTs and more recent meta-analyses, there is a growing polarization among providers for and against the use of digoxin in managing these conditions. To help close this divide, we provide a perspective on the literature with special attention to the quality of both older and more recent studies on this subject. The data from the highest quality studies we have, RCTs, suggest that digoxin use in patients with HF and/or AF is associated with improvement in several areas of outcomes including functional capacity, symptom management, reduced hospitalizations, fewer deaths due to HF, and treatment of refractory chronic heart failure with rEF, and may even have overall mortality benefit when serum digoxin concentrations are within therapeutic range. These effects are more pronounced in patients with EF < 25% and NYHA Class II-IV and at highest risk for hospitalization. As the risk of confounding factors was minimized by the study design, the likelihood that positive outcomes were identified with digoxin use increased. Clinicians and researchers need further adequately designed and powered RCTs exploring the connection between digoxin therapy and mortality, hospitalizations, and symptom management.

Clinical experience with titrating doses of digoxin antibodies in acute digoxin poisoning. (ATOM-6)

Introduction 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. Methods 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. Results 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. Conclusions 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.

Evaluating high serum digoxin concentration risk factors interaction between direct oral anticoagulant agents and digoxin

Aim:Digoxin is an anti-arrhythmic drug that also has a positive inotropic property. It is mainly used to control heart rate in nonvalvular atrial fibrillation, and improve ejection fraction in heart failure. In recent years, the frequency of digoxin and a combination of new drug using has been increasing. Therefore, to assess the pharmacokinetic interaction between direct oral anticoagulant agents and cardiovascular drugs is necessary for intoxications. Material and Methods:Patients Serum Digoxin Concentrations levels and digoxin intoxications were evaluated according to risk factors investigated retrospectively Patients Serum Digoxin Concentrations levels &amp;lt;1 ng/ml is accepted as low, 1-2 ng/ml therapeutic range, 2.1-2.4 ng/ml is high and &amp;gt;2.4 ng/ml toxicity. Results:The study consisted of 248 females (60.2%) and 160 males (39.2%). The mean age of the patients was 70.5 years. The average age of patients was 70.5 years. Serum digoxin concentrations of 408 patients; 44.81% were detected in the low therapeutic range, 34.41% in the therapeutic range, 6.23% in the high therapeutic range, 14.55% in the toxic therapeutic range. The mean glomerular filtration rate was 58.45, and the mean Serum Digoxin Concentration was 1.36 ng/ml. The statistically significant relationship between age and Patients Serum Digoxin Concentration was 16.3% (p &amp;lt;0.05). There was a statistically significant relationship between Glomerular Filtration Rate and Serum Digoxin Concentrations; one increased and the other decreased (p &amp;lt;0.05). In patients without atherosclerotic heart disease, Serum Digoxin Concentration was significantly lower than those with atherosclerotic heart disease(p&amp;lt; 0.05). Serum Digoxin Concentrations were significantly higher in patients treated with rivaroxaban, the proportions of which differ significantly from each other at the 0.05 level. Conclusion:Nowadays, the frequency of using digoxin and direct oral anticoagulants together is increasing. The narrow therapeutic level of digoxin necessitates close monitoring due to drug-drug interactions.

Evaluating plasma Digoxin concentration after an intravenous loading dose in patients with renal failure

Background: Digoxin is a medication of Glycoside family which is commonly prescribed for patients with atrial fibrillation, atrial flutter, and heart failure. With a narrow therapeuticlevel(0.5–2 ng/mL), careful monitoring of digoxin blood level is necessary. Symptoms of digoxin toxicity include nausea, vomiting, visual changes, altered mental status, hyperkalemia, and cardiovascular collapse. As renal failure decreases the clearance of digoxin, and impaired renal function is common in heart failure, this population is at higher risk of toxicity. Methods & materials: In this prospective study, patients with chronic kidney disease- nondialysis (CKD-ND) who were admitted with heart failure or atrial fibrillation at university hospital, were enrolled. Digoxin-naive patients were treated with a 10 mcg/kg intravenous digoxin loading dose. Serum digoxin level was measured 6 to 12 hours after the last loading dose. Patients were followed for 48 hours for signs of toxicity. Correlation between therapeutic digoxin level and degree of renal failure was evaluated. The effect of serum electrolyte (magnesium, calcium, and potassium) concentration on digoxin level was determined. Pregnant women were excluded from study. Results: From 2018 to 2020, 87 CKD patients, (60 (69%) men and 27 (31%) women) aged from 31 to 92 years old, with a mean age of 70.51 ± 14.06 years were admitted to the cardiac unit. Near 80% of the cohort were CKD stage 3 and 4 patients. About half of patients had digoxin levels in therapeutic range (45 cases = 51.7%), followed by 24.1% with supra therapeutic and the other 24.1% with toxic levels. There was significant relationship between GFR and serum digoxin concentration (p-value = 0.038); the lower the GFR was, the higher was the digoxin level and also between serum creatinine and digoxin level (p value: .04). Serum digoxin concentration had significant correlation with serum magnesium level (p-value = 0.006). Conclusion: this study demonstrated that monitoring plasma Digoxin concentration after an intravenous loading dose in patients with renal failure can be very helpful to prevent digoxin toxicity. The lower the GFR was, the higher the digoxin level and the risk for toxicity if the bolus and even maintenance do not monitor meticulously.

Persistence of High Serum Digoxin Concentrations.

Persistence of High Serum Digoxin Concentrations.