Age-Related Differences in Digoxin Toxicity and its Treatment

Abstract

Digoxin toxicity remains a common medical problem for both adults and children. In addition to a vastly improved understanding of the mechanisms for digoxin action on the heart, there are now data which clearly demonstrate that there are potentially important developmental differences in both the pharmacodynamics and pharmacokinetics of digoxin which have a direct impact on its efficacy and toxicity profile. The developmental pharmacokinetics of the drug have been extensively studied such that profiles for age-dependent differences in the apparent volume of distribution, plasma and renal clearance and elimination half-life now exist. It is these data which have also produced the current age-specific dosing guidelines for the therapeutic administration of digoxin in various paediatric subpopulations. Despite this new knowledge, both accidental and iatrogenic digoxin toxicity still occurs in paediatric patients, with potentially life-threatening arrhythmias being produced when steady-state serum digoxin concentrations exceed 5.1 nmol/L. Consequently, the clinician may be faced with the decision to use antidotal therapy with digoxin-specific Fab fragments (d-Fab). This article reviews the developmental basis for digoxin disposition and its pharmacological and toxic effects. Additionally, the treatment of acute digoxin toxicity in children is reviewed, especially as pertains to the therapeutic use of d-Fab.

Population Pharmacokinetic Investigation of Digoxin in Japanese Infants and Young Children

“…Rane and Wilson 14 show that infants (1.3–11 months) have a plasma clearance of 0.642 L/h/kg, and young children (2–5 years) have a value of 0.348 L/h/kg. Wells et al 15 show that infants (2–24 months) have total body clearance of 0.162 to 0.6 L/h/kg, and young children (2–10 years) have the value of 0.168 to 0.36 L/h/kg. Our results indicate that the CL/F of infant (8 kg of body weight, CHF = 0, elixir preparation, a target digoxin serum concentration of 1 ng/mL) was 0.43 L/h/kg.…”

Serum digoxin concentrations and clinical signs and symptoms of digoxin toxicity in the paediatric population

“…2 In children, however, symptoms may vary due to differences in age-related symptomatology, existing co-morbidities, inability to communicate symptoms, or other disease processes that mimic digoxin toxicity. 3 Causality also differs between adults and children. Digoxin toxicity in adults is commonly associated with altered digoxin distribution and elimination from renal insufficiency, polypharmacy, or other co-morbidities, whereas accidental digoxin ingestion and errors in dosing have frequently been reported as aetiologies for digoxin toxicity in children.…”

“…In adults, clinical signs and symptoms of digoxin toxicity include anorexia, nausea, vomiting, diarrhoea, abdominal pain, headache, dizziness, confusion, atrial tachycardias, and other more worrisome ventricular tachyarrhythmias 2 . In children, however, symptoms may vary due to differences in age-related symptomatology, existing co-morbidities, inability to communicate symptoms, or other disease processes that mimic digoxin toxicity 3 . Causality also differs between adults and children.…”

Digitalis Intoxication

“…The serum digoxin concentration is oflimited use in chronic cases, since some patients will require higher concentrations to achieve the intended clinical benefit. [38] However at serum digoxin concentrations >2.0 Ilg/L (2.6 nmollL) © Adis International Limited. All rights reserved.…”

“…Moreover, serum concentrations are confounded by the presence of so-called 'endogenous digitalislike substances' which crossreact with some, but not all, laboratory assays and are present in patients with hepatic or renal disease, pregnant women and neonates. [38,[40][41][42][43][44][45] Thus, the decision to use Fab is dictated by the patient's risk factors, signs of toxicity and clinical progression; within this context, the serum digoxin or digitoxin concentration can be helpful in confirming the clinician's suspicions. [46] 4.…”