Digoxin Poisoning Management Jimmy February 3, 2023 0 Comments Download PDF Introduction Digoxin is a cardioactive glycoside indicated for atrial flutter, atrial fibrillation, and heart failure Acts as a sodium/potassium pump inhibitor for cardiac myocytes → toxicity arises with too much intracellular Na+ inhibiting the sodium/calcium pump from working properly (increasing intracellular calcium) Increased inotropy within the cardiac myocytes → dysrhythmias EKG abnormalities: premature ventricular contractions, biphasic T wave, shortened QT interval, AV block Digoxin therapeutic levels range from 0.8-2.0 ng/ml (toxicity can begin >2 ng/ml) Pharmacology Digoxin Immune Fab (DigiFab or DigiBind) Dose 1 vial = 40mg (binds to 0.5mg of digoxin) Unknown toxicity level: Initial 10vials Vials = Total body load (mg) x 2 For chronic ingestion of unknown amount 3-6 vials can be given for adults 1-2 vials can be given for children Administration IV infusion over 30 minutes If cardiac arrest is imminent a bolus injection can be given PK/PD Onset: 20-90 minutesDuration of action: 15 – 20 hrs Adverse Effects Orthostatic hypotension, ventricular tachycardia, hypokalemia Mechanism of Action Immune antigen-binding fragments that rapidly bind with digoxin to decrease free digoxin levels within the body Compatibility 0.9% NS Only Comments Monitor K+ closely as it shifts intracellularly potentially causing hypokalemia.Total concentration of digoxin may be falsely elevated after administration due to in free drug & bounded drug.Free digoxin concentrations are more clinically useful Overview of Evidence Author, year Design/ sample size Intervention & Comparison Outcome Wei et al., 2021 Case reports (n=121) DigiBind vs DigiFab adverse events reported to FAERS from 1986-2019 87.2% of DigiBind reports were serious AEs vs. 62.8% of DigiFabHypotension, cardiac arrest, and death were among the most serious AEs Ward et al, 2000 Observational (n=16) DigiBind vs DigiFab in healthy volunteers Both Fab products reduced free digoxin serum concentrations to below assay detection Total digoxin serum concentrations increased approximately 10-fold (indicated fab product binding digoxin) Renard et al., 1997 Observational (n=16) Influence of age & renal dysfunction on digoxin-specific Fab pharmacokinetics •Doses 80-800mg infused over 0.25-2hr •Patients aged 35-90 with CrCl 10.6-122.1 ml/min Linear decrease of total body clearance is linked to renal function and age, but not VdPlasma half-lives ranged from 11-34.5hrsAll patients recovered and no adverse effects were reported Antman et al., 1990 Open-label trial (n=150) Digoxin-specific Fab fragment dosed based on total ingested amount (mg) or digoxin serum concentration (ng/ml) 90% of patient toxicity resolved or improved with 10% showing no response Median dose ~ 200mg (5 vials)Highest dose ~ 1600mg (40 vials) Conclusions Digoxin toxicity is a serious & life-threatening condition if not appropriately reversed by an available antidote For unknown amount of ingestion, administer 10 vials of digoxin Immune Fab to treat digoxin toxicity Age and renal function are proven not to be factors prohibiting digoxin toxicity treatment References Bismuth C, Gaultier M, Conso F, Efthymiou ML. 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