Características de las intoxicaciones por digoxina atendidas en diversos servicios de urgencias españoles en función del tipo de intoxicación y de la administración de anticuerpos antidigoxina: estudio DIGITOX / Characteristics of digoxin toxicity attended in Spanish emergency departments according to type of poisoning and administration of digoxin antibodies: the DIGITOX study

Introducción. Las intoxicaciones por digoxina representan un pequeño porcentaje de las intoxicaciones atendidas en urgencias. El objetivo de este estudio fue describir las diferencias entre intoxicaciones agudas y crónicas y evaluar la administración de su antídoto específico: los anticuerpos antidigoxina (AcAD). Método. Estudio retrospectivo, observacional y multicéntrico en 15 servicios de urgencias hospitalarios de 8 comunidades autónomas durante 7 años. Se recogieron datos de filiación, clínica, tratamiento y destino al alta. Los pacientes se dividieron según la intoxicación era aguda o crónica y según recibían o no AcAD. Resultados. Se recogieron 27 intoxicaciones agudas y 631 crónicas. La edad media fue de 83,9 (7,9) años, y el 76,9% eran mujeres. Los pacientes con intoxicación aguda tenían menor edad media (80,0 (12) vs 84,1 (7,7) años; p < 0,038), y porcentaje de causa accidental (85,2% vs 100%; p < 0,001) y mayor gravedad en la escala Poison Severity Score (29,6% vs 12,5%; p < 0,001). Treinta y cuatro pacientes recibieron AcAD (5,4%) y constituyen un grupo de menor edad [78,7 (11,5) vs 84,2 (7,6); p < 0,001], con mayor porcentaje de intoxicaciones agudas (20,6% vs 3,2%), intencionalidad suicida (8,8% vs 0,2%) y gravedad (50% vs 11,2%, p < 0,001 en todas las comparaciones). El 76,1% precisó ingreso. La mortalidad fue del 11,4%. Conclusiones. Las intoxicaciones por digoxina suelen ser crónicas y predominan en mujeres. Las intoxicaciones agudas son de mayor gravedad. Los pacientes que precisaron administración de AcAD tenían intoxicaciones más graves y mayor porcentaje de intoxicaciones agudas y con intencionalidad suicida. (AU)

Background and objective. Digoxin toxicity accounts for a small percentage of poisonings attended by emergency departments. This study aimed to describe differences between acute and chronic digoxin toxicity and assess the use of digoxin-specific antibody fragments (digoxin-Fab) as an antidote. Methods. Retrospective, observational, multicenter study in 15 hospital emergency departments in 8 Spanish autonomous communities in 7 years. We collected patient, clinical and treatment variables, and discharge destination.Patients were classified according to whether toxicity was acute or chronic and whether digoxin-Fab was administered or not. Results. Twenty-seven acute and 631 chronic digoxin poisonings were attended. The mean (SD) patient age was 83.9 (7.9) years, and 76.9% were women. Patients with acute toxicity were younger (80.0 [12] years) than those with chronic toxicity (84.1 [7.7] years) (P < .038), and accidental poisoning was less common (in 85.2% vs 100% in chronic toxicity; P < .001). Cases of acute toxicity were also more serious (Poison Severity Score (29.6% vs 12.5% in chronic toxicity; P < .001). Thirty-four patients were treated with digoxin-Fab (5.4%). These patients were younger (78.7 [11.5] years vs 84.2 (7.6) years), their toxicity was more often acute (in 20.6% vs 3.2% in chronic toxicity), more had attempted suicide (8.8% vs 0.2% with chronic toxicity), and more had severe symptoms (50% vs 11.2%) (P < .001, all comparisons). Hospital admission was required for 76.1%. Overall, mortality was 11.4%. Conclusions. Chronic toxicity accounts for most digoxin poisoning cases, and most patients are women. Acute toxicity is more serious. Patients who required digoxin-Fab have more severe poisoning. Such patients usually have acute toxicity, and attempted suicide is more often the reason for the emergency. (AU)

[Multidisciplinary management of voluntary pink oleander poisoning: How to estimate the quantities ingested?] / Prise en charge multidisciplinaire d'une intoxication volontaire au laurier rose : comment estimer les quantités ingérées ?

This is a case of voluntary ingestion of Nerium oleander leaves in an adolescent requiring the use of atropine and emergency chartering of antidigoxin antibodies (Digifab®) due to the difficulty of assessing oleandrin level and associated toxicity. Upon hospital admission, a digoxinemia was performed (0.44µg/mL) and the presence of oleandrine was detected. Oleandrin levels at toxic levels may be suspected by a measure of blood digoxin and explain the patient's clinical signs, which could adapt the therapeutic management.

Predictive Factors for Recurrence of Serious Arrhythmias in Patients with Acute Digoxin Poisoning.

Although digoxin poisoning has declined in the past decades, it still has deleterious outcomes. The hallmark of serious life-threatening arrhythmias remains challenging due to its non-specific initial presentation. Therefore, this study aimed to evaluate the initial predictive factors for recurrent serious arrhythmias and the need for temporary pacing in acute digoxin-poisoned patients. This retrospective cohort study included all patients with acute digoxin poisoning admitted to Tanta University Poison Control Center from 2017 to 2020. Demographic and toxicological data, poisoning severity score (PSS), laboratory investigations, and serial ECG monitoring data were documented. Patients were divided according to their age into a childhood group and adolescence & adulthood group. Each age group was divided into two subgroups according to the presence of recurrent serious arrhythmias. Patient outcomes, including intensive care unit admission, temporary pacing, and in-hospital mortality were recorded. A percentage of 37.34% (n = 31) of the included patients had recurrent serious arrhythmias in both groups. Recurrent serious arrhythmias groups had significantly low heart rate, prolonged PR interval, high PSS, Mobitz II dysrhythmias, elevated serum digoxin, serum potassium and serum creatinine, and increased adverse outcomes compared to other groups. Logistic regression analysis showed that only serum digoxin and potassium levels were significant independent predictors of recurrent serious arrhythmias and temporary pacing. Serum digoxin level had an excellent discriminatory power with the best sensitivity and specificity, followed by serum potassium level in both groups. Thus, monitoring serum digoxin and potassium levels is essential in all patients with acute digoxin poisoning, especially with limited Fab availability.

Calcium channel blocker and beta blocker overdose, and digoxin toxicity management.

While relatively uncommon, an overdose of calcium channel blockers, beta blockers, or digoxin can result in significant morbidity and mortality, and management can be complex. An acute overdose will require different management strategies than chronic toxicity while on therapeutic dosing. Toxicity from these agents must be considered in bradycardic and hypotensive patients. This supplement provides an evidence-based overview of emergency department management of calcium channel blocker overdose, beta blocker overdose, and digoxin toxicity, and focuses on the caveats of treatment for each.

Calculated decisions: DigiFab® (Digibind®) Dosing for Digoxin Poisoning.

A review of the evidence behind the DigiFab® dosing calculator, which provides dosing for digoxin immune Fab in patients with confirmed digoxin poisoning or overdose.

Intoxicación letal por piedras chinas con ideación suicida / Poisoning by Chinese rocks: fatal outcome of a suicide attempt

No disponible

Digoxin-specific Fab and therapeutic plasma exchange for digitalis intoxication and renal failure.

Treatment of chronic digitalis intoxication includes suspension of drug intake, which may be sufficient in case of mild manifestations, and supportive measures. Severe bradycardia requires the administration of atropine or isoproterenol; placement of a temporary pacemaker may be required in case of absent response to pharmacological therapy. Severe and life-threatening manifestations should be treated with digoxin-specific fragment antigen binding antibodies (Fab). Therapeutic plasma exchange has been suggested, in addition to Fab therapy, to maximize the clearance of Fab-digoxin complexes in patients with renal failure. To date, few case reports have described the use of such a therapeutic approach; currently, extracorporeal methods are not recommended as part of the treatment of digitalis intoxication, and stronger evidence is required to establish their benefit.

Mortalidad inmediata y a los 30 días en las intoxicaciones digitálicas atendidas en servicios de urgencias de Cataluña / Immediate and 30 days mortality in digoxin poisoning cases attended in the Hospital Emergency Services of Catalonia, Spain

Introducción: La intoxicación digitálica es un motivo frecuente de consulta en los servicios de urgencias hospitalarios (SUH). El objetivo de este estudio es conocer la mortalidad asociada a dicha intoxicación. Método: Estudio descriptivo y observacional de las intoxicaciones digitálicas atendidas en los SUH de 4 hospitales de Cataluña durante los años 2013-15. Se recogieron datos relativos a la intoxicación, la mortalidad inmediata y a los 30 días. Se analizó la existencia de posibles factores asociados a la mortalidad. Resultados: Se registraron 171 intoxicaciones digitálicas. Siete eran agudas (4,1%) y 164 (95,9%) crónicas. La mortalidad inmediata fue del 6,4% y a los 30 días fue del 13,4%. El análisis binario no identificó ningún factor relacionado con la mortalidad inmediata. En cuanto a la mortalidad a 30 días, los pacientes que fallecieron tenían con mayor frecuencia una intoxicación aguda (13% vs 2,7%; p= 0,05), había más intoxicaciones con intencionalidad suicida (8,7% vs 0,7%; p= 0,048), más afectación renal (21,7% vs 9,5%; p= 0,037), menos sintomatología neurológica (4,3% vs 17,8%; p= 0,005), mayor digoxinemia (4,7 mg/dl vs 3,7 mg/dl; p= 0,027) y menor puntuación en el índice de Barthel (IB) (49,1 (33,4) vs 70,3 (28,5); p= 0,006). El análisis de regresión logística identificó la digoxinemia como un factor independiente de mortalidad inmediata y la puntuación en el IB en la mortalidad a 30 días. Conclusiones: La digoxinemia se relaciona con la mortalidad inmediata y el IB se relaciona con la mortalidad a 30 días

Background and objective: Digoxin poisoning is a frequent reason for seeking emergency care. This study aimed to assess mortality related to digoxin poisoning. Methods: Descriptive observational study of digoxin poisonings attended in the emergency departments of 4 hospitals in Catalonia from 2013 through 2015. We gathered data relevant to the poisonings and recorded immediate and 30-day mortality. Factors possibly related to mortality were explored. Results: A total of 171 digoxin poisonings were attended. Seven (4.1%) were acute and 164 (95.9%) were chronic. The immediate and 30-day mortality rates were 6.4% and 13.4%, respectively. Bivariate analysis did not identify factors related to immediate mortality. However, the variables more often associated with 30-day mortality in this analysis were acute poisoning (after which 13% died vs 2.7% of those with chronic poisoning, P=.05), suicide attempts (8.7% of whom died vs 0.7%, P=.048), more compromised renal function (21.7% vs 9.5%, P=.037), fewer neurologic symptoms (4.3% vs 17.8% with more symptoms, P=.005), higher mean digoxin concentrations (4.7 mg/dL in those who died vs 3.7 mg/dL, P=.027), and a lower Barthel index (mean [SD] 49.1 [33.4] in those who died vs 70.3 [28.5]; P=.006). Logistic regression analysis identified serum digoxin concentration to be independently associated with immediate mortality. A lower Barthel index was associated with 30-day mortality. Conclusions: Immediate mortality is related to a high digoxin concentration in serum, and 30-day mortality to a low Barthel index

Immediate and 30 days mortality in digoxin poisoning cases attended in the Hospital Emergency Services of Catalonia, Spain. / Mortalidad inmediata y a los 30 días en las intoxicaciones digitálicas atendidas en servicios de urgencias de Cataluña.

OBJECTIVES: Digoxin poisoning is a frequent reason for seeking emergency care. This study aimed to assess mortality related to digoxin poisoning. MATERIAL AND METHODS: Descriptive observational study of digoxin poisonings attended in the emergency departments of 4 hospitals in Catalonia from 2013 through 2015. We gathered data relevant to the poisonings and recorded immediate and 30-day mortality. Factors possibly related to mortality were explored. RESULTS: A total of 171 digoxin poisonings were attended. Seven (4.1%) were acute and 164 (95.9%) were chronic. The immediate and 30-day mortality rates were 6.4% and 13.4%, respectively. Bivariate analysis did not identify factors related to immediate mortality. However, the variables more often associated with 30-day mortality in this analysis were acute poisoning (after which 13% died vs 2.7% of those with chronic poisoning, P=.05), suicide attempts (8.7% of whom died vs 0.7%, P=.048), more compromised renal function (21.7% vs 9.5%, P=.037), fewer neurologic symptoms (4.3% vs 17.8% with more symptoms, P=.005), higher mean digoxin concentrations (4.7 mg/dL in those who died vs 3.7 mg/dL, P=.027), and a lower Barthel index (mean [SD] 49.1 [33.4] in those who died vs 70.3 [28.5]; P=.006). Logistic regression analysis identified serum digoxin concentration to be independently associated with immediate mortality. A lower Barthel index was associated with 30-day mortality. CONCLUSION: Immediate mortality is related to a high digoxin concentration in serum, and 30-day mortality to a low Barthel index.

OBJETIVO: La intoxicación digitálica es un motivo frecuente de consulta en los servicios de urgencias hospitalarios (SUH). El objetivo de este estudio es conocer la mortalidad asociada a dicha intoxicación. METODO: Estudio descriptivo y observacional de las intoxicaciones digitálicas atendidas en los SUH de 4 hospitales de Cataluña durante los años 2013-15. Se recogieron datos relativos a la intoxicación, la mortalidad inmediata y a los 30 días. Se analizó la existencia de posibles factores asociados a la mortalidad. RESULTADOS: Se registraron 171 intoxicaciones digitálicas. Siete eran agudas (4,1%) y 164 (95,9%) crónicas. La mortalidad inmediata fue del 6,4% y a los 30 días fue del 13,4%. El análisis binario no identificó ningún factor relacionado con la mortalidad inmediata. En cuanto a la mortalidad a 30 días, los pacientes que fallecieron tenían con mayor frecuencia una intoxicación aguda (13% vs 2,7%; p = 0,05), había más intoxicaciones con intencionalidad suicida (8,7% vs 0,7%; p = 0,048), más afectación renal (21,7% vs 9,5%; p = 0,037), menos sintomatología neurológica (4,3% vs 17,8%; p = 0,005), mayor digoxinemia (4,7 mg/dl vs 3,7 mg/dl; p = 0,027) y menor puntuación en el índice de Barthel (IB) (49,1 (33,4) vs 70,3 (28,5); p = 0,006). El análisis de regresión logística identificó la digoxinemia como un factor independiente de mortalidad inmediata y la puntuación en el IB en la mortalidad a 30 días. CONCLUSIONES: La digoxinemia se relaciona con la mortalidad inmediata y el IB se relaciona con la mortalidad a 30 días.

Clinical outcomes from early use of digoxin-specific antibodies versus observation in chronic digoxin poisoning (ATOM-4).

Introduction: In our previous study on chronic digoxin poisoning, there was a minor improvement after treatment with digoxin-specific antibody (digoxin-Fab). We hypothesised patients with elevated digoxin concentrations may derive little benefit from digoxin-Fab because their presenting complaint was more closely related to their multiple co-morbidities. We aimed to compare the outcome of patients who were initially treated with digoxin-Fab with those that received supportive care. Method: Patients were prospectively recruited to the study if they had an elevated digoxin concentration, signs or symptoms of toxicity thought to be from digoxin. Patients who were initially managed with digoxin-Fab were compared with those not initially receiving digoxin-Fab (observation group). Patients presented with ventricular arrhythmias before initial assessment were excluded from the analysis. Primary outcome was mortality. Secondary outcomes were length of stay (LOS), change in heart rate (HR) and potassium concentration. Results: From September 2013 to January 2018, 128 patients were recruited of which 78 (61%) received initial digoxin-Fab. Digoxin-Fab and supportive care groups had an initial median heart rate of 46 (range: 20-120) vs 52 bpm (range: 29-91) (p = .06), systolic blood pressure of 110 mmHg (range: 65-180) vs 125 mmHg (range: 90-184) (p = .009), respectively. Digoxin concentrations 4.4 nmol/L (range: 3.3-9) vs 4.2 (range: 2-11.2) (p = .42) and potassium concentrations 5.4 mmol/L (range: 3-11) vs 5.1 mmol/L (range: 3.5-8.2) (p = .33) were similar. Median dose of digoxin-Fab used was 1.5 vials (IQR: 1-2). There were 9 (12%) deaths in the Fab group compared to 7 (14%) in those treated with supportive care (risk difference -2.5%; 95% CI: -14 to 9%; p = .68). The median LOS was six days in both groups. Mean changes in potassium concentration [-0.5 ± 0.1 vs. -0.4 ± 0.1 mmol/L; difference -0.1 (95% CI: -.02, 0.4), p = .70] and HR within 4 h [8 ± 1 vs. 7 ± 3 bpm; difference -1.0 (95% CI: -6.7, 4.8), p = 0.74] were similar in the two groups. Conclusions: This study did not appear to show any benefit from the routine use of digoxin-Fab in patients thought to have chronic digoxin poisoning. These patients have multiple co-morbidities that may be contributing to their clinical features, other treatments are often equally effective.

Extracorporeal treatments in poisonings from four non-traditionally dialysed toxins (acetaminophen, digoxin, opioids and tricyclic antidepressants): A combined single-centre and national study.

The use of extracorporeal treatments (ECTRs) for poisonings with four non-traditionally dialysed toxins (NTDTs) is increasing in the United States. This study evaluated whether ECTRs are prescribed for toxin removal or the treatment of other medical illnesses or complications. We performed a 2-Phase retrospective analysis evaluating the main indication for ECTRs in patients with poisoning from a NTDT (defined for this study as acetaminophen, opioids, tricyclic antidepressants (TCAs) or digoxin) and ECTR. The first phase assessed all cases from a single site (New York City Poison Control Center) between the years 2000 and 2016, and the second phase surveyed all United States Poison Control Centers (PCCs). In Phase 1, demographics, toxin ingested and main indication for ECTR were extracted. In Phase 2, a query to the National Poison Data System using the a pragmatic subset of inclusion criteria from Phase 1 restricted to single toxin ingestions over a narrower time frame (2014-2016) provided the cases for study. A structured online questionnaire was sent to all United States PCCs to request their database review regarding the indication for ECTR for their cases. In Phase 1, 92 cases met inclusion criteria. In Phase 2, 519 cases were screened and 425 met inclusion criteria. In Phase 1 91/92 (98.9%) and Phase 2 411/425 (96.7%), of extracorporeal treatments were used to treat underlying medical conditions or poisoning-related complications rather than accelerate toxin removal. The increasing number of ECTRs reported in patients who ingested one of the four NTDTs thus appears to be for medical indications rather than attempts at toxin removal, a distinction that is important.

Enzalutamide and analytical interferences in digoxin assays.

Objective: We report two cases of elevated digoxin plasma levels in patients receiving enzalutamide. Cases reported: The first patient, an 84-year-old male treated with enzalutamide, was hospitalized due to deterioration in his general state. Atrial fibrillation was discovered and treatment with digoxin was initiated. Supratherapeutic digoxin concentrations (4 µg/L and 3.5 µg/L 3 days later) led to treatment being stopped despite the lack of clinical or biological signs of overdose. The second patient, an 84-year-old male treated with digoxin and enzalutamide, was hospitalized for the same reasons. Digoxin concentration upon admission was 2.8 µg/L. Despite stopping treatment, digoxin blood levels were observed to have increased on D3 and D7 following admission (3 and 3.6 µg/L, respectively). However, no clinical or biological findings indicated an overdose. Blood samples were sent to the Pharmacology and Toxicology Laboratory for analysis. Methods: The second patient's digoxin plasma level was determined using the chemiluminescent microparticle immunoassay (CMIA®, Abbott, Illinois) method. Enzalutamide levels were determined using HPLC-UV/DAD method. An interference study was performed using different assay methods by adding enzalutamide to control plasma at various concentrations from a Xtandi® (40mg) capsule. Results: Plasma concentration of digoxin at D7 for patient 2 was identical in both laboratories (3.5 vs. 3.6 µg/L). Enzalutamide was found in the patient's plasma (12,5 mg/L). Adding 4, 10, 20, and 40 mg/L of enzalutamide to the untreated plasma showed that the plasma concentration of digoxin was positive (from 0.35 to 3.69 µg/L) using the CMIA method. Conclusions: Our results highlight the analytical interferences of enzalutamide with digoxin assays using the CMIA method.