RESUMEN
Digoxin, the oldest known cardiovascular drug, is still used today to treat heart failure and atrial fibrillation. Because it has a narrow therapeutic index and multiple interactions, it frequently causes toxicity with a wide range of symptoms and cardiac arrhythmias. More importantly, elevated serum digoxin levels have been linked to a higher risk of death in patients with heart failure or atrial fibrillation, even without signs or symptoms of toxicity. This article reviews the current state of digoxin use, its pharmacologic principles, and the mechanisms, clinical presentation, and management of toxicity.
Asunto(s)
Fibrilación Atrial , Digoxina , Insuficiencia Cardíaca , Digoxina/efectos adversos , Digoxina/sangre , Humanos , Fibrilación Atrial/tratamiento farmacológico , Insuficiencia Cardíaca/inducido químicamente , Cardiotónicos/uso terapéutico , Cardiotónicos/efectos adversos , Cardiotónicos/farmacología , Antiarrítmicos/efectos adversosRESUMEN
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.
Asunto(s)
Bradicardia , Digoxina , Hiperpotasemia , Diálisis Renal , Humanos , Femenino , Anciano , Digoxina/efectos adversos , Hiperpotasemia/inducido químicamente , Bradicardia/inducido químicamente , Insuficiencia Renal/inducido químicamente , Antiarrítmicos/efectos adversos , Síndrome , Acidosis/inducido químicamente , Choque/inducido químicamente , Bloqueo Atrioventricular/inducido químicamente , Fragmentos Fab de InmunoglobulinasRESUMEN
IMPORTANCE: Trimethoprim-sulfamethoxazole (TMP-SMX) may increase digoxin concentration, a medication with a narrow therapeutic index. Small changes in digoxin concentration could predispose individuals to the risk of toxicity. OBJECTIVE: To characterize the risk of digoxin toxicity in older adults taking digoxin following co-prescription of TMP-SMX compared with co-prescription of amoxicillin. DESIGN, SETTINGS, AND PARTICIPANTS: Retrospective population-based cohort study in Ontario, Canada (2002-2020) using linked health care data. Participants comprised 47,961 older adults taking digoxin (58% women; median age 80 years [interquartile range 74-86]) who were newly treated with TMP-SMX (n = 10,273) compared with those newly treated with amoxicillin (n = 37,688). EXPOSURE: Co-prescription of TMP-SMX versus amoxicillin in older adults concurrently taking digoxin. MAIN OUTCOME AND MEASURE: The primary outcome was a hospital encounter (i.e., hospital admission or emergency department visit) with digoxin toxicity within 30 days of the antibiotic prescription. Inverse probability of treatment weighting on the propensity score was used to balance comparison groups on indicators of baseline health. Weighted risk ratios (RR) were obtained using modified Poisson regression and weighted risk differences (RD) using binomial regression. The number needed to harm (NNH) was calculated as 1/RD. RESULTS: A hospital encounter with digoxin toxicity occurred in 49/10,273 (0.48%) patients treated with TMP-SMX versus 32/37,688 (0.08%) in those treated with amoxicillin (weighted RR, 5.71 [95% confidence interval (CI), 3.19 to 10.24]; weighted RD, 0.39% [95% CI, 0.25% to 0.53%]; NNH 256 [95% CI, 233 to 400]). CONCLUSION AND RELEVANCE: In older adults taking digoxin, the 30-day risk of a hospital encounter with digoxin toxicity was nearly 6 times higher in those co-prescribed TMP-SMX versus amoxicillin, although the absolute risk difference was low (0.4%). Physicians should prescribe an alternative antibiotic when clinically appropriate. If TMP-SMX must be co-prescribed with digoxin (if the benefit is believed to outweigh the risk), digoxin should be dose-reduced on an individual basis.
Asunto(s)
Amoxicilina , Antibacterianos , Digoxina , Combinación Trimetoprim y Sulfametoxazol , Humanos , Digoxina/efectos adversos , Digoxina/administración & dosificación , Anciano , Femenino , Masculino , Anciano de 80 o más Años , Estudios Retrospectivos , Amoxicilina/efectos adversos , Amoxicilina/administración & dosificación , Combinación Trimetoprim y Sulfametoxazol/efectos adversos , Combinación Trimetoprim y Sulfametoxazol/administración & dosificación , Antibacterianos/efectos adversos , Antibacterianos/administración & dosificación , Estudios de Cohortes , Interacciones Farmacológicas , Ontario/epidemiología , Cardiotónicos/efectos adversos , Cardiotónicos/uso terapéutico , Cardiotónicos/administración & dosificaciónRESUMEN
BACKGROUND: Some studies have shown digoxin use to be associated with adverse outcomes, including increased mortality. There are limited data on whether digoxin use is associated with increased risk of ventricular tachycardia/ventricular fibrillation (VT/VF) in heart failure patients with an implantable cardioverter-defibrillator (ICD). OBJECTIVES: This study sought to assess whether digoxin use is associated with increased risk of VT/VF in patients with heart failure with reduced ejection fraction with a primary prevention ICD in landmark clinical trials. METHODS: The study cohort consisted of patients with an ICD or cardiac resynchronization therapy-defibrillator who were enrolled in 4 landmark MADIT trials (Multicenter Automatic Defibrillator Implantation Trials). We employed propensity score quintile stratification for treatment with digoxin as well as additional multivariable adjustment to assess the risk of digoxin vs no-digoxin therapy for the endpoints of first and recurrent VT/VF and all-cause mortality. The proportional hazards regression models for arrhythmia-specific endpoints incorporated adjustments for the competing risk of death. RESULTS: At baseline, 1,155 of 4,499 patients were on digoxin (26%). After propensity score quintile stratification, patients prescribed digoxin were shown to exhibit a statistically significant 48% increased risk of VT/VF (P < 0.001), 42% increased risk of the composite of VT/VF or death (P < 0.001), and a 37% increased risk of all-cause mortality (P = 0.006). Digoxin use was also associated with increased risk of appropriate ICD shocks (HR: 1.91; P < 0.001) and with increased burden of VT/VF events (HR: 1.46; P = 0.001). CONCLUSIONS: Our findings suggests that digoxin use is associated with ventricular tachyarrhythmia and death in heart failure with reduced ejection fraction patients with an ICD.
Asunto(s)
Desfibriladores Implantables , Digoxina , Insuficiencia Cardíaca , Taquicardia Ventricular , Humanos , Digoxina/uso terapéutico , Digoxina/efectos adversos , Desfibriladores Implantables/efectos adversos , Femenino , Taquicardia Ventricular/mortalidad , Masculino , Persona de Mediana Edad , Anciano , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/tratamiento farmacológico , Puntaje de Propensión , Fibrilación Ventricular/mortalidad , Antiarrítmicos/uso terapéutico , Antiarrítmicos/efectos adversos , Estudios de Cohortes , Factores de RiesgoRESUMEN
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.
Asunto(s)
Lesión Renal Aguda , Intercambio Plasmático , Humanos , Masculino , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/terapia , Digoxina/efectos adversos , Diálisis Renal , Anciano de 80 o más AñosRESUMEN
OBJECTIVE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Asunto(s)
Fibrilación Atrial , Insuficiencia Cardíaca , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Digoxina/efectos adversos , Estudios Transversales , Cardiotónicos/uso terapéutico , Centros de Atención Terciaria , Creatinina , Fibrilación Atrial/tratamiento farmacológico , PotasioRESUMEN
This case report describes a patient in their 70s with hypertension and heart failure presenting to the emergency department with chest discomfort, nausea, anorexia, and weakness.
Asunto(s)
Digoxina , Insuficiencia Cardíaca , Humanos , Digoxina/efectos adversos , Cardiotónicos/efectos adversos , Insuficiencia Cardíaca/inducido químicamente , Insuficiencia Cardíaca/tratamiento farmacológicoRESUMEN
BACKGROUND: Atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF) are common cardiovascular conditions linked to significant health burdens. This review aims to study the relationship of serum digoxin concentration and mortality and morbidity outcomes in defined population. METHODS: We conducted a thorough search of databases such as PubMed, Google Scholar, and Cochrane Library, from inception until 20th Aug 2023. Studies that explored the relationship between serum digoxin concentration and mortality, morbidity, or other clinical endpoints in AF and HFrEF patients (ejection fraction ≤45 %) were eligible for inclusion. RESULTS: The selected studies exhibited a wide range of designs, patient cohorts, and measured outcomes. The association between serum digoxin concentration, mortality and morbidity endpoints like hospitalization rates and cardiovascular events were assessed in these studies. Despite the methodological diversity, our systematic review uncovered consistent trends across the studies, suggesting that elevated serum digoxin concentrations may correlate with higher mortality and morbidity in AF and HFrEF patients. CONCLUSION: This systematic review emphasizes the need for cautious management of serum digoxin levels in patients with concurrent AF and HFrEF. While digoxin remains a valuable treatment for heart failure, its potential adverse effects on outcomes in this specific patient subgroup call for vigilant monitoring and individualized treatment approaches. Further research is required to elucidate the dose-response relationship and potential confounding factors influencing outcomes associated with serum digoxin concentration in AF and HFrEF patients. Clinicians should consider these findings when making therapeutic decisions to enhance patient care and outcomes.
Asunto(s)
Fibrilación Atrial , Insuficiencia Cardíaca , Humanos , Digoxina/efectos adversos , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/epidemiología , Fibrilación Atrial/complicaciones , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/complicaciones , Volumen Sistólico/fisiología , MorbilidadRESUMEN
BACKGROUND: The optimal loading dose of digoxin in patients with reduced kidney function is unknown. Tertiary references recommend reduced loading doses; however, these recommendations are based on immunoassays that are falsely elevated by the presence of digoxin-like immunoreactive substances, a problem that is minimized in modern assays. OBJECTIVE: To determine whether chronic kidney disease (CKD) or acute kidney injury (AKI) is associated with supratherapeutic digoxin concentrations after a digoxin loading dose. METHODS: A retrospective analysis on patients who received an intravenous loading dose of digoxin with a digoxin concentration collected 6 to 24 hours after the end of the dose. Patients were stratified into 3 groups: AKI, CKD, and non-AKI/CKD (NKI) based on glomerular filtration rate and serum creatinine. The primary outcome was frequency of supratherapeutic digoxin concentrations (>2 ng/mL) and secondary outcomes included frequency of adverse events. RESULTS: A total of 146 digoxin concentrations were included (AKI = 59, CKD = 16, NKI = 71). Frequencies of supratherapeutic concentrations were similar between groups (AKI: 10.2%, CKD: 18.8%, NKI: 11.3%; P = 0.61). Pre-planned logistic regression demonstrated no significant relationship between kidney function group and the development of a supratherapeutic concentration (AKI: odds ratio [OR]: 1.3, 95% confidence interval [CI]: 0.4-4.5; CKD: OR 4.3, 95% CI: 0.7-23). CONCLUSION AND RELEVANCE: This is the first study in routine clinical practice evaluating the relationship between kidney function and digoxin peak concentrations that differentiates AKI from CKD. We did not find a relationship between kidney function and peak concentrations; however, the group with CKD was underpowered.
Asunto(s)
Lesión Renal Aguda , Insuficiencia Renal Crónica , Humanos , Estudios Retrospectivos , Digoxina/efectos adversos , Lesión Renal Aguda/inducido químicamente , Factores de Riesgo , Tasa de Filtración GlomerularRESUMEN
Objetivos: Analizar los factores relacionados con el uso de digoxina en urgencias en pacientes con insuficiencia cardiaca aguda (ICA) y el impacto pronóstico a corto plazo. Método: Se incluyeron pacientes diagnosticados de ICA en 45 servicios de urgencias españoles sin tratamiento crónico con digoxina, los cuales se dividieron según recibiesen digoxina endovenosa en urgencias o no. Se recogieron 51 variables relativas al paciente o al episodio de descompensación y se investigó el perfil del paciente tratado con digoxina en urgencias. Como variables evolutivas se investigaron la necesidad de ingreso, la estancia en urgencias prolongada (> 24 horas) en dados de alta y la hospitalización prolongada (> 7 días) en ingresados, y la mortalidad intrahospitalaria y a 30 días por cualquier causa. Se analizó si el tratamiento con digoxina se asoció a diferencias evolutivas, de forma cruda y ajustada a las características del paciente y el episodio de ICA. Resultados: Se analizaron 15.549 pacientes (mediana = 83 años, mujeres = 55%), de los que 1.430 (9,2%) fueron tratados con digoxina. La digoxina se utilizó más en mujeres, pacientes jóvenes, en mejor clase funcional de la New York Heart Association (NYHA), pero con descompensaciones más graves y, sobre todo, cuando existía una fibrilación auricular (FA) con respuesta ventricular rápida como desencadenante. Se hospitalizó el 75,4% de pacientes (más frecuente en tratados con digoxina; 81,6% vs 74,8%, p < 0,001), tuvo estancia prolongada en urgencias el 38,3% (52,9% vs 37,2%, p < 0,001), hospitalización prolongada el 48,1% (49,3% vs 47,9%, p = 0,385), mortalidad intrahospitalaria el 7,2% (6,9% vs 7,2%, p = 0,712) y a 30 días el 9,7% (9,3% vs 9,7%, p = 0,625). El modelo ajustado mostró que el uso de digoxina en urgencias sólo se asoció con estancia prolongada en urgencias (OR = 1,883, IC 95% = 1,359-2,608), pero no con la necesidad de ingreso, hospitalización prolongada o mortalidad. (AU)
Objectives: To analyze factors related to the use of digoxin to treat patients with acute heart failure (AHF) in emergency departments (EDs) and the impact of digoxin treatment on short-term outcomes. Methods: We included patients diagnosed with AHF in 45 Spanish EDs. The patients, who were not undergoing long-term treatment for heart failure, were classified according to whether or not they were given intravenous digoxin in the ED. Fifty-one patient or cardiac decompensation episode variables were recorded to profile ED patients treated with digoxin. Outcome variables studied were the need for hospital admission, prolonged stay in the ED (> 24 hours) for discharged patients, prolonged hospitalization (> 7 days) for admitted patients, and all-cause in-hospital or 30-day mortality. The associations between digoxin treatment and the outcomes were studied with odds ratios (ORs) adjusted for patient and AHF episode characteristics. Results: Data for 15 549 patients (median age, 83 years; 55% women) were analyzed; 1430 (9.2%) were treated with digoxin. Digoxin was used more often in women, young patients, and those with better New York Heart Association (NYHA) classifications but more severe cardiac decompensation, especially if the trigger was atrial fibrillation with rapid ventricular response. Admissions were ordered for 75.4% of the patients overall (81.6% of digoxin-treated patients vs 74.8% of nontreated patients; P < .001). The ED stay was prolonged in 38.3% of patients discharged from the ED (52.9% of digoxin-treated patients vs 37.2% of nontreated patients; P < .001). The duration of hospital stay was prolonged in 48.1% (digoxin-treated, 49.3% vs 47.9%; P = .385). In-hospital mortality was 7.2% overall (6.9% vs 7.2%, P= .712), and 30-day mortality was 9.7% (9.3% vs 9.7%, P = .625). ED use of digoxin was associated with a prolonged stay in the department (adjusted OR, 1.883; 95% CI, 1.359-2.608) but not with hospitalization or mortality. (AU)
Asunto(s)
Humanos , Masculino , Femenino , Anciano , Anciano de 80 o más Años , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/diagnóstico , Digoxina/efectos adversos , Digoxina/uso terapéutico , España , Servicio de Urgencia en HospitalRESUMEN
OBJECTIVES: To analyze factors related to the use of digoxin to treat patients with acute heart failure (AHF) in emergency departments (EDs) and the impact of digoxin treatment on short-term outcomes. MATERIAL AND METHODS: We included patients diagnosed with AHF in 45 Spanish EDs. The patients, who were not undergoing long-term treatment for heart failure, were classified according to whether or not they were given intravenous digoxin in the ED. Fifty-one patient or cardiac decompensation episode variables were recorded to profile ED patients treated with digoxin. Outcome variables studied were the need for hospital admission, prolonged stay in the ED (> 24 hours) for discharged patients, prolonged hospitalization (> 7 days) for admitted patients, and all-cause in-hospital or 30-day mortality. The associations between digoxin treatment and the outcomes were studied with odds ratios (ORs) adjusted for patient and AHF episode characteristics. RESULTS: Data for 15 549 patients (median age, 83 years; 55% women) were analyzed; 1430 (9.2%) were treated with digoxin. Digoxin was used more often in women, young patients, and those with better New York Heart Association (NYHA) classifications but more severe cardiac decompensation, especially if the trigger was atrial fibrillation with rapid ventricular response. Admissions were ordered for 75.4% of the patients overall (81.6% of digoxin-treated patients vs 74.8% of nontreated patients; P .001). The ED stay was prolonged in 38.3% of patients discharged from the ED (52.9% of digoxin-treated patients vs 37.2% of nontreated patients; P .001). The duration of hospital stay was prolonged in 48.1% (digoxin-treated, 49.3% vs 47.9%; P = .385). In-hospital mortality was 7.2% overall (6.9% vs 7.2%, P= .712), and 30-day mortality was 9.7% (9.3% vs 9.7%, P = .625). ED use of digoxin was associated with a prolonged stay in the department (adjusted OR, 1.883; 95% CI, 1.359-2.608) but not with hospitalization or mortality. CONCLUSION: Digoxin continues to be used in one out of ten ED patients who are not already on long-term treatment with the drug. Digoxin use is associated with cardiac decompensation triggered by atrial fibrillation with rapid ventricular response, younger age, women, and patients with better initial NYHA function status but possibly more severe decompensation. Digoxin use leads to a longer ED stay but is safe, as it is not associated with need for admission, prolonged hospitalization, or short-term mortality.
OBJETIVO: Analizar los factores relacionados con el uso de digoxina en urgencias en pacientes con insuficiencia cardiaca aguda (ICA) y el impacto pronóstico a corto plazo. METODO: Se incluyeron pacientes diagnosticados de ICA en 45 servicios de urgencias españoles sin tratamiento crónico con digoxina, los cuales se dividieron según recibiesen digoxina endovenosa en urgencias o no. Se recogieron 51 variables relativas al paciente o al episodio de descompensación y se investigó el perfil del paciente tratado con digoxina en urgencias. Como variables evolutivas se investigaron la necesidad de ingreso, la estancia en urgencias prolongada (> 24 horas) en dados de alta y la hospitalización prolongada (> 7 días) en ingresados, y la mortalidad intrahospitalaria y a 30 días por cualquier causa. Se analizó si el tratamiento con digoxina se asoció a diferencias evolutivas, de forma cruda y ajustada a las características del paciente y el episodio de ICA. RESULTADOS: Se analizaron 15.549 pacientes (mediana = 83 años, mujeres = 55%), de los que 1.430 (9,2%) fueron tratados con digoxina. La digoxina se utilizó más en mujeres, pacientes jóvenes, en mejor clase funcional de la New York Heart Association (NYHA), pero con descompensaciones más graves y, sobre todo, cuando existía una fibrilación auricular (FA) con respuesta ventricular rápida como desencadenante. Se hospitalizó el 75,4% de pacientes (más frecuente en tratados con digoxina; 81,6% vs 74,8%, p 0,001), tuvo estancia prolongada en urgencias el 38,3% (52,9% vs 37,2%, p 0,001), hospitalización prolongada el 48,1% (49,3% vs 47,9%, p = 0,385), mortalidad intrahospitalaria el 7,2% (6,9% vs 7,2%, p = 0,712) y a 30 días el 9,7% (9,3% vs 9,7%, p = 0,625). El modelo ajustado mostró que el uso de digoxina en urgencias sólo se asoció con estancia prolongada en urgencias (OR = 1,883, IC 95% = 1,359-2,608), pero no con la necesidad de ingreso, hospitalización prolongada o mortalidad. CONCLUSIONES: La digoxina continúa utilizándose en uno de cada 10 pacientes con ICA atendidos en urgencias que no utilizaban este fármaco de manera habitual. Su uso se relaciona con un paciente cuya ICA ha sido descompensada por una FA con respuesta ventricular rápida, más joven y más frecuentemente mujer, en mejor clase funcional de la NYHA basal y con una descompensación posiblemente más grave. El uso de digoxina conlleva una estancia en urgencias más prolongada, pero su uso es seguro, pues no se asocia a la necesidad de ingreso, hospitalización prolongada o mortalidad a corto plazo.
Asunto(s)
Fibrilación Atrial , Insuficiencia Cardíaca , Humanos , Femenino , Anciano de 80 o más Años , Masculino , Digoxina/efectos adversos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/diagnóstico , Servicio de Urgencia en Hospital , HospitalizaciónRESUMEN
BACKGROUND: Digoxin related retinal toxicity causes blurred vision, photophobia, central scotoma, color vision abnormality, and electroretinography (ERG) abnormalities. Here, we report a case with transient abnormalities in vison, in which fundus autofluorescence (FAF), optical coherence tomography (OCT), and ERG findings resembled those in KCNV2 (potassium voltage-gated channel modifier subfamily V member 2)-associated retinopathy. CASE REPORT: An 89-year-old woman presented with complaints of acute blurred vision, nyctalopia, photophobia, and color vision abnormality. She received digoxin for tachycardia induced by atrial fibrillation for a month. The fundi showed a faint white ring at the fovea, which showed hyperfluorescence in FAF. OCT showed a thickened EZ in the macula. A dark-adapted (DA)-30 ERG showed a reduced and "squaring (trough-flattened)" a-wave, and a delayed, supernormal b-wave, resulting in a high b/a-wave amplitude ratio. The digoxin dose was reduced following an elevation in serum levels. Five weeks later, her visual acuities improved, and abnormal hyperfluorescence on FAF disappeared. After 6 months, no visual symptoms were reported. The ellipsoid-zone thickening in OCT improved; however, the b/a-wave amplitude ratio on DA-30 ERG remained high. The b-wave in LA-long-flash ERG was initially reduced, which improved after correction of serum level of digoxin. CONCLUSIONS: The patient's clinical findings resembled those of patients with KCNV2-associated retinopathy or temporal hyperkalemia. These disorders appear to have a common pathogenesis, which may be related to abnormal extracellular potassium levels in the retina. The on-bipolar cells seemed to be more affected than the off-bipolar cells in digoxin related retinal toxicity.
Asunto(s)
Canales de Potasio con Entrada de Voltaje , Enfermedades de la Retina , Humanos , Femenino , Anciano de 80 o más Años , Electrorretinografía , Tomografía de Coherencia Óptica/métodos , Digoxina/efectos adversos , Fotofobia , Enfermedades de la Retina/inducido químicamente , Enfermedades de la Retina/diagnóstico , Potasio , Canales de Potasio con Entrada de Voltaje/genéticaRESUMEN
Importance: Serum creatinine-based estimated glomerular filtration rate (eGFRcr) may overestimate the glomerular filtration rate (GFR) in patients with cancer. Cystatin C-based eGFR (eGFRcys) is an alternative marker of GFR. Objective: To determine whether the therapeutic drug levels and adverse events (AEs) associated with renally cleared medications were higher in patients with cancer whose eGFRcys was more than 30% lower than their eGFRcr. Design, Setting, and Participants: This cohort study analyzed adult patients with cancer at 2 major academic cancer centers in Boston, Massachusetts. These patients had their creatinine and cystatin C measured on the same day between May 2010 and January 2022. The date of the first simultaneous eGFRcr and eGFRcys measurement was considered to be the baseline date. Exposure: The primary exposure was eGFR discordance, defined as an eGFRcys that was more than 30% lower than the eGFRcr. Main Outcomes and Measures: The primary outcome was risk of the following medication-related AEs within 90 days of the baseline date: (1) supratherapeutic vancomycin trough level greater than 30 µg/mL, (2) trimethoprim-sulfamethoxazole-related hyperkalemia (>5.5 mEq/L), (3) baclofen toxic effect, and (4) supratherapeutic digoxin level (>2.0 ng/mL). For the secondary outcome, a multivariable Cox proportional hazards regression model was used to compare 30-day survival of those with vs without eGFR discordance. Results: A total of 1869 adult patients with cancer (mean [SD] age, 66 [14] years; 948 males [51%]) had simultaneous eGFRcys and eGFRcr measurement. There were 543 patients (29%) with an eGFRcys that was more than 30% lower than their eGFRcr. Patients with an eGFRcys that was more than 30% lower than their eGFRcr were more likely to experience medication-related AEs compared with patients with concordant eGFRs (defined as eGFRcys within 30% of eGFRcr), including vancomycin levels greater than 30 µg/mL (43 of 179 [24%] vs 7 of 77 [9%]; P = .01), trimethoprim-sulfamethoxazole-related hyperkalemia (29 of 129 [22%] vs 11 of 92 [12%]; P = .07), baclofen toxic effects (5 of 19 [26%] vs 0 of 11; P = .19), and supratherapeutic digoxin levels (7 of 24 [29%] vs 0 of 10; P = .08). The adjusted odds ratio for vancomycin levels more than 30 µg/mL was 2.59 (95% CI, 1.08-7.03; P = .04). Patients with an eGFRcys more than 30% lower than their eGFRcr had an increased 30-day mortality (adjusted hazard ratio, 1.98; 95% CI, 1.26-3.11; P = .003). Conclusions and relevance: Results of this study suggest that among patients with cancer with simultaneous assessment of eGFRcys and eGFRcr, supratherapeutic drug levels and medication-related AEs occurred more commonly in those with an eGFRcys more than 30% lower than their eGFRcr. Future prospective studies are needed to improve and personalize GFR estimation and medication dosing in patients with cancer.
Asunto(s)
Hiperpotasemia , Neoplasias , Masculino , Adulto , Humanos , Anciano , Tasa de Filtración Glomerular , Creatinina , Estudios de Cohortes , Cistatina C , Baclofeno , Combinación Trimetoprim y Sulfametoxazol , Vancomicina , Digoxina/efectos adversos , Neoplasias/tratamiento farmacológicoRESUMEN
OBJECTIVES: To investigate the effect of induced fetal demise on the induction to expulsion interval during later trimester medication abortion. STUDY DESIGN: This retrospective cohort was conducted at St. Paul's Hospital Millennium Medical College, Ethiopia. Later medication abortion cases that had induced fetal demise were compared to matching cases with no induced fetal demise. Data were collected by reviewing maternal charts and analyzed using SPSS version 23. Simple descriptive analysis, χ2 test, and multiple logistic regression analysis were used as appropriate. Odds ratio, 95% CI, and p-value<0.05 were used to present the significance of the findings. RESULTS: A total of 208 patient charts were analyzed. Seventy-nine patients were provided with intra-amniotic digoxin, 37 patients were provided with intracardiac lidocaine, and 92 had no induced demise. The mean induction to expulsion interval was 17.8 hours in the intra-amniotic digoxin group, which is not statistically different than 19.3 hours in the intracardiac lidocaine and 18.5 hours in the group without induced fetal demise (p-value = 0.61). Expulsion rate after 24 hours was not statistically different among the three groups (5.1% in the digoxin group vs 10.6% intracardiac lidocaine group vs 7.8% in the no induced fetal demise group, p-value = 0.82). Multivariate regression analysis demonstrated that inducing fetal demise was not associated with successful expulsion at<24 hours (adjusted odds ratio [AOR] = 0.19, 95% CI, 0.03-1.29 and AOR = 0.62, 95% CI, 0.11-3.48, for digoxin and lidocaine, respectively) from induction. CONCLUSIONS: In this study, inducing fetal demise using digoxin or lidocaine prior to later medication abortion was not associated with a reduction in the induction to expulsion interval. IMPLICATIONS: During later medication abortion with mifepristone and misoprostol, inducing fetal demise may not be associated with a change in the length of the procedure. Induced fetal demise may be required for other reasons.
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Abortivos no Esteroideos , Aborto Inducido , Misoprostol , Embarazo , Femenino , Humanos , Aborto Inducido/métodos , Estudios Retrospectivos , Segundo Trimestre del Embarazo , Muerte Fetal , Misoprostol/efectos adversos , Mifepristona , Digoxina/efectos adversos , LidocaínaRESUMEN
Digoxin toxicity (plasma digoxin concentration ≥0.9 ng/mL) is associated with worsening heart failure (HF). Decision tree (DT) analysis, a machine learning method, has a flowchart-like model where users can easily predict the risk of adverse drug reactions. The present study aimed to construct a flowchart using DT analysis that can be used by medical staff to predict digoxin toxicity. We conducted a multicenter retrospective study involving 333 adult patients with HF who received oral digoxin treatment. In this study, we employed a chi-squared automatic interaction detection algorithm to construct DT models. The dependent variable was set as the plasma digoxin concentration (≥ 0.9 ng/mL) in the trough during the steady state, and factors with p < 0.2 in the univariate analysis were set as the explanatory variables. Multivariate logistic regression analysis was conducted to validate the DT model. The accuracy and misclassification rates of the model were evaluated. In the DT analysis, patients with creatinine clearance <32 mL/min, daily digoxin dose ≥1.6 µg/kg, and left ventricular ejection fraction ≥50% showed a high incidence of digoxin toxicity (91.8%; 45/49). Multivariate logistic regression analysis revealed that creatinine clearance <32 mL/min and daily digoxin dose ≥1.6 µg/kg were independent risk factors. The accuracy and misclassification rates of the DT model were 88.2 and 46.2 ± 2.7%, respectively. Although the flowchart created in this study needs further validation, it is straightforward and potentially useful for medical staff in determining the initial dose of digoxin in patients with HF.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Insuficiencia Cardíaca , Adulto , Humanos , Estudios Retrospectivos , Volumen Sistólico , Creatinina , Función Ventricular Izquierda , Digoxina/efectos adversos , Insuficiencia Cardíaca/inducido químicamente , Aprendizaje Automático , Cardiotónicos/efectos adversosRESUMEN
PURPOSE: To perform a systematic umbrella review with meta-analysis to evaluate the certainty of evidence on mortality risk associated with digoxin use in patients with atrial fibrillation (AF) with or without heart failure (HF). METHODS: We systematically searched MEDLINE, Embase, and Web of Science databases from inception to 19 October 2021. We included systematic reviews and meta-analyses of observational studies investigating digoxin effects on mortality of adult patients with AF and/or HF. The primary outcome was all-cause mortality; secondary outcome was cardiovascular mortality. Certainty of evidence was evaluated by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool and the quality of systematic reviews/meta-analyses by the A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR2) tool. RESULTS: Eleven studies accounting for 12 meta-analyses were included with a total of 4,586,515 patients. AMSTAR2 analysis showed a high quality in 1, moderate in 5, low in 2, and critically low in 3 studies. Digoxin was associated with an increased all-cause mortality (hazard ratio [HR] 1.19, 95% confidence interval [95%CI] 1.14-1.25) with moderate certainty of evidence and with an increased cardiovascular mortality (HR 1.19, 95%CI 1.06-1.33) with moderate certainty of evidence. Subgroup analysis showed that digoxin was associated with all-cause mortality both in patients with AF alone (HR 1.23, 95%CI 1.19-1.28) and in those with AF and HF (HR 1.14, 95%CI 1.12-1.16). CONCLUSION: Data from this umbrella review suggests that digoxin use is associated with a moderate increased risk of all-cause and cardiovascular mortality in AF patients regardless of the presence of HF. TRIAL REGISTRATION: This review was registered in PROSPERO (CRD42022325321).
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Fibrilación Atrial , Insuficiencia Cardíaca , Humanos , Digoxina/efectos adversos , Fibrilación Atrial/complicaciones , Antiarrítmicos/efectos adversos , Revisiones Sistemáticas como Asunto , Insuficiencia Cardíaca/tratamiento farmacológicoRESUMEN
Background Digoxin acutely increases cardiac output in patients with pulmonary arterial hypertension (PAH) and right ventricular failure; however, the effects of chronic digoxin use in PAH are unclear. Methods and Results Data from the Minnesota Pulmonary Hypertension Repository were used. The primary analysis used likelihood of digoxin prescription. The primary end point was a composite of all-cause mortality or heart failure (HF) hospitalization. Secondary end points included all-cause mortality, HF hospitalization, and transplant-free survival. Multivariable Cox proportional hazards analyses determined the hazard ratios (HR) and 95% CIs for the primary and secondary end points. Among 205 patients with PAH in the repository, 32.7% (n=67) were on digoxin. Digoxin was more often prescribed to patients with severe PAH and right ventricular failure. After propensity score-matching, 49 patients were digoxin users, and 70 patients were nonusers; of these 31 (63.3%) in the digoxin group and 41 (58.6%) in nondigoxin group met the primary end point during a median follow-up time of 2.1 (0.6-5.0) years. Digoxin users had a higher combined all-cause mortality or HF hospitalization (HR, 1.82 [95% CI, 1.11-2.99]), all-cause mortality (HR, 1.92 [95% CI, 1.06-3.49]), HF hospitalization (HR, 1.89 [95% CI, 1.07-3.35]), and worse transplant-free survival (HR, 2.00 [95% CI, 1.12-3.58]) even after adjusting for patient characteristics and severity of PAH and right ventricular failure. Conclusions In this retrospective, nonrandomized cohort, digoxin treatment was associated with greater all-cause mortality and HF hospitalization, even after multivariate correction. Future randomized controlled trials should assess the safety and efficacy of chronic digoxin use in PAH.
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Insuficiencia Cardíaca , Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Humanos , Digoxina/efectos adversos , Hipertensión Arterial Pulmonar/diagnóstico , Hipertensión Arterial Pulmonar/tratamiento farmacológico , Estudios Retrospectivos , Hospitalización , Hipertensión Pulmonar Primaria Familiar , Hipertensión Pulmonar/tratamiento farmacológico , Resultado del TratamientoRESUMEN
BACKGROUND: Intravenous digoxin loading dose recommendations differ between clinical guidelines and Food and Drug Administration packaging for acute rate control. OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION AND RELEVANCE: 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.