DIGITALIS GLYCOSIDE TOXICITY ED management

Emergency management of digitalis toxicity

1. DIGITALIS GLYCOSIDE TOXICITY BY: DR.AISHWARYA TD MODERATOR: DR.SHRUTHI

2. INTRODUCTION Digitalis is a plant-derived cardiac glycoside commonly used in the treatment of chronic heart failure (CHF), atrial fibrillation, and re-entrant supraventricular tachycardia . Cardiac glyosides  are found in certain flowering plants, such as oleander and lily-of-the-valley. Indigenous people in various parts of the world have used many plant extracts containing cardiac glycosides as arrow and ordeal poisons.

3. MECHANISM OF ACTION Direct and indirect effects resulting in: increased inotropy (mild effect ). increased automaticity. negative dromotropy  (slowing of AV conduction ). increased vagal tone. DIRECT: inhibition of Na/K ATPase on the cell surface. -> increased intracellular Na+ and increased extracellular K +. -> increased intracellular Ca2+ due to Na+/Ca2+ antiporter . -> calcium-mediated   inotropy and increased automaticity, as well as negative dromotropy due to decreased intracellular K +.

4. THERMOKINETICS Absorption – good oral absorption with oral bioavailability of 80% and peak levels at 6 hours. Distribution – 30% protein bound, Vd 10L/kg (higher in the elderly and obese ). Metabolism – minimal hepatic metabolism. Elimination – 60% renal, t ½ of 30-40 h, longer in renal failure.

5. CLINICAL FEATURES

6. DIAGNOSIS In patients with heart failure and normal renal function: daily Digoxin doses- 125 to 250mcg . Fatalities: acute ingestion of 10mg in adults, 4mg in children. Screening : ECG Specific: serum potassium and digoxin levels. Acute:  perform at 4 hours post-ingestion and then every 4 hours until definitive treatment or toxicity has resolved.  Chronic :  perform levels 6hours of post last dose, to monitor steady state level . levels can be misleading as levels near the therapeutic range 0.5-2.0ng/ml(1.0-2.6nmol/L) correlate poorly with severity of intoxication.

7. ECG: The most common arrhythmias in digoxin toxicity are premature ventricular contractions and bradycardic rhythms.

8. Four specific findings: Flattening or inversion of T wave. QT- interval shortening. Scooped depression of ST segment/ Salvador Dali’s moustache ” Increased U wave amplitude.

9. Additional ECG Features Mild  PR interval  prolongation, up to 240 ms (due to increased vagal tone) Prominent  U waves . Peaking of the terminal portion of the T waves. J point  depression (usually in leads with tall R waves ). NOTE: The presence of digoxin effect on the ECG is  not  a marker of  digoxin toxicity . — it merely indicates that the patient is taking digoxin .

10. MANAGEMENT Resuscitation: Attend to life-threats resulting from dysrhythmias and hyperkalaemia . Digoxin -induced cardiotoxicity is refractory to standard measures. Bradyarrhythmias : Digibind ( Digoxin specific antibody fragments) is the definitive treatment. Atropine: 0.5-1.0mg IV as temporary mearues . Adrenaline (but may aggravate cardiac irritability). Transcutaneous Pacing (rarely effective).

11. Tachyarrhythmias : Digibind is the definitive treatment. Mgso 4  as an adjunctive measure. Lignocaine (unproven). Often refractory to cardioversion . Hyperkalemia : Insulin and glucose, bicarbonate ( salbutamol may aggravate automaticity). Calcium is traditionally contra-indicated due to the risk of precipitating a ‘stone heart’ .

12. Supportive care and monitoring Cardiac monitoring must continue until reversal of toxicity. Decontamination Activated charcoal if presents <1h post-ingestion(unlikely to prevent severe toxicity in large ingestions). Gastric lavage is not recommended. Antidote Digibind is the definitive treatment.

13. DIGOXIN-SPECIFIC ANTIBODY FRAGMENTS (DIGOXIN-FAB) Digoxin-Fabs are derived from ovine antibodies to digoxin . Following IV infusion, the antibody fragments bind digoxin in the plasma and distribute widely throughout the body, removing digoxin from tissues .

14. Based on suspected amount ingested Digoxin body load (mg) = 0.8 × suspected ingested amount (mg) Digoxin body load (mg) = serum digoxin concentration ( ng / mL ) × 5.6 L/kg × weight (kg)/1000 One vial (about 40 mg) digoxin-Fab neutralizes 0.5 milligram Adigoxin ingested Based on total serum digoxin concentration Number of vials = serum concentration ( ng / mL ) × patient weight (kg)/100 Calculation of Digoxin -Specific Antibody Fragment ( Fab ) Full Neutralizing Dose

15. In an acute poisoning, each vial of digoxin-Fab reverses approximately 0.5 milligram of ingested digoxin . In hemodynamically stable patients, half the calculated total neutralizing dose is infused initially, and the other half is given if an adequate clinical response is not seen in 1 to 2 hours. Observational studies report that a total of 200 to 480mg of digoxin-Fab (5 to 12 vials) were required to effectively treat severely digoxin -toxic patients. When the ingested dose is unknown and serum level is unavailable, 10 vials are recommended as initial treatment in life-threatening situations. Digoxin-Fab is administered IV over 30 minutes, except in cardiac arrest, when the dose is given as an IV bolus.

16. In chronic toxicity, an acceptable approach in the hemodynamically stable patient without clear lifethreatening arrhythmias : administer half of the dose calculated by level. If instability develops, the remaining of the full calculated dose can be administered. One to three vials (40 to 120 milligrams) of digoxinFab are often adequate in reversing chronic toxicity.

17. DISPOSITION: Falling serial serum digoxin levels. Normal serum K. No GI symptoms. No evidence of cardiotoxicity . Or if digoxin -specific fab given: Patients normal serum K. No significant cardiac arrhythmia. Remains clinically well over the next 6h. Psychiatry assessment.