Elderly patients with suspected chronic digoxin toxicity: A comparison of clinical characteristics of patients receiving and not receiving digoxin‐Fab

Arbabian, Hooman; Lee, Hwee Min; Graudins, Andis

doi:10.1111/1742-6723.12873

Cited by 12 publications

(11 citation statements)

References 16 publications

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“…There are several studies reporting the effect of cardenolides in heart diseases (Campbell and Mc Donald 2003;Biteker et al 2017;Gurel et al 2017), but evaluation of these compounds to treat VL is lacking. Although cardenolides have been reported as toxic compounds (Hauptman et al 2016;Arbabian et al 2018), the low doses of either DIGI on its free form or incorporated into a micellar composition (DIGI/Mic) tested in our study did not induce any significant toxicity when used to treat the infected hosts. Conversely, infected animals receiving miltefosine did present with toxicity.…”

Section: Discussioncontrasting

confidence: 50%

Digitoxigenin presents an effective and selective antileishmanial action against Leishmania infantum and is a potential therapeutic agent for visceral leishmaniasis

et al. 2020

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Treatment for visceral leishmaniasis (VL) is hampered mainly by drug toxicity, their high cost, and parasite resistance. Drug development is a long and pricey process, and therefore, drug repositioning may be an alternative worth pursuing. Cardenolides are used to treat cardiac diseases, especially those obtained from Digitalis species. In the present study, cardenolide digitoxigenin (DIGI) obtained from a methanolic extract of Digitalis lanata leaves was tested for its antileishmanial activity against Leishmania infantum species. Results showed that 50% Leishmania and murine macrophage inhibitory concentrations (IC 50 and CC 50 , respectively) were of 6.9 ± 1.5 and 295.3 ± 14.5 μg/mL, respectively. With amphotericin B (AmpB) deoxycholate, used as a control drug, values of 0.13 ± 0.02 and 0.79 ± 0.12 μg/mL, respectively, were observed. Selectivity index (SI) values were of 42.8 and 6.1 for DIGI and AmpB, respectively. Preliminary studies suggested that the mechanism of action for DIGI is to cause alterations in the mitochondrial membrane potential, to increase the levels of reactive oxygen species and induce accumulation of lipid bodies in the parasites. DIGI was incorporated into Pluronic® F127-based polymeric micelles, and the formula (DIGI/Mic) was used to treat L. infantum– infected mice. Miltefosine was used as a control drug. Results showed that animals treated with either miltefosine, DIGI, or DIGI/Mic presented significant reductions in the parasite load in their spleens, livers, bone marrows, and draining lymph nodes, as well as the development of a specific Th1-type response, when compared with the controls. Results obtained 1 day after treatment were corroborated with data corresponding to 15 days after therapy. Importantly, treatment with DIGI/Mic induced better parasitological and immunological responses when compared with miltefosine- and DIGI-treated mice. In conclusion, DIGI/Mic has the potential to be used as a therapeutic agent to protect against L. infantum infection, and it is therefore worth of consideration in future studies addressing VL treatment.

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Section: Discussioncontrasting

confidence: 50%

Digitoxigenin presents an effective and selective antileishmanial action against Leishmania infantum and is a potential therapeutic agent for visceral leishmaniasis

et al. 2020

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“…Most patients that present with digoxin toxicity are elderly, have other cardiac and noncardiac comorbidities, and take multiple medications including those known to potentially interfere with serum digoxin concentrations (SDC) [12]. The most common presentation of digoxin toxicity is due to unintentional overdose or decreased drug clearance due to hepatic or renal dysfunction, as opposed to acute, intentional ingestions [2,6,12]. Most patients with acute toxicity present with anorexia, nausea, emesis, and fatigue.…”

Section: Discussionmentioning

confidence: 99%

“…Visual changes such as halos, scotomas, flashing lights, and xanthopsia may also be reported [2,11]. Historically, bradycardia has been associated with digoxin toxicity, but recent studies have suggested that bradycardia in the setting of digoxin toxicity is more likely multifactorial and minimally improves with treatment [6,11]. Renal failure is the most common precipitating event to digoxin toxicity causing decreased drug clearance, and is associated with worse outcomes when concurrent hyperkalemia and ventricular arrhythmias are present, as in our patient [13,14].…”

Section: Discussionmentioning

confidence: 99%

“…Digoxin use is also recommended in patients with atrial fibrillation with rapid ventricular response despite treatment with other agents, or when other treatments cannot be used [4,5]. Despite significant reduction in digoxin use, improved therapeutic monitoring, and the availability of digoxin-Fab, digoxin toxicity remains a significant cause of hospitalizations due to adverse drug events, morbidity, and mortality [6]. From 2005 to 2010, digoxin toxicity accounted for over 5,000 annual emergency department (ED) visits in the U.S., amounting to 1.0% of all ED visits for adverse drug events (ADEs), and over 75% of these visits resulted in hospitalization [7].…”

Section: Introductionmentioning

confidence: 99%

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A Case of Digoxin Toxicity Due to Acute Renal Failure

Digiovanni-Kinsley

Duke

Giovane

et al. 2021

Cureus

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“…However, it is unclear to what extent digoxin accounts for clinical features manifested by patients with an elevated digoxin concentration. Elevated digoxin concentrations are expected in patients who have multiple organ failure from any cause [7]. In a previous study, we showed that 1-2 vials of digoxin-specific Fab (digoxin-Fab) in patients with chronic digoxin poisoning rapidly led to zero free serum digoxin concentrations; but had only a modest effect on heart rate and no effect on blood pressure or other features [8,9].…”

Section: Introductionmentioning

confidence: 91%

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

Chan

Page

Isoardi

et al. 2018

Clinical Toxicology

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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 ¼ .06), systolic blood pressure of 110 mmHg (range: 65-180) vs 125 mmHg (range: 90-184) (p ¼ .009), respectively. Digoxin concentrations 4.4 nmol/L (range: 3.3-9) vs 4.2 (range: 2-11.2) (p ¼ .42) and potassium concentrations 5.4 mmol/L (range: 3-11) vs 5.1 mmol/L (range: 3.5-8.2) (p ¼ .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 À2.5%; 95% CI: À14 to 9%; p ¼ .68). The median LOS was six days in both groups. Mean changes in potassium concentration [À0.5 ± 0.1 vs. À0.4 ± 0.1 mmol/L; difference À0.1 (95% CI: À.02, 0.4), p ¼ .70] and HR within 4 h [8 ± 1 vs. 7 ± 3 bpm; difference À1.0 (95% CI: À6.7, 4.8), p ¼ 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.

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Elderly patients with suspected chronic digoxin toxicity: A comparison of clinical characteristics of patients receiving and not receiving digoxin‐Fab

Cited by 12 publications

References 16 publications

Digitoxigenin presents an effective and selective antileishmanial action against Leishmania infantum and is a potential therapeutic agent for visceral leishmaniasis

Digitoxigenin presents an effective and selective antileishmanial action against Leishmania infantum and is a potential therapeutic agent for visceral leishmaniasis

A Case of Digoxin Toxicity Due to Acute Renal Failure

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

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