HealthforHeart: April 2018

Yellow oleander (T. peruviana) contains cardiac glycosides, and its consumption has effects similar to digitalis poisoning. The primary pharmacological effect of these glycosides is to inhibit the Na+/K+ ATPase channel that extrudes sodium and imports potassium into cardiomyocytes. Inhibition causes buildup of sodium, which increases intracellular calcium, which in turn induces further calcium release from the sarcoplasmic reticulum. The myocardium becomes irritable and arrhythmogenic. In addition, increased vagal tone causes bradycardia. Ventricular tachycardia and fibrillation seen in cardiac glycoside toxicity are usually resistant to defibrillation.

Patients may develop arrhythmias and become hypotensive. Hypotension interferes with intracellular production of ATP through glycolysis, as lactate (produced due to anaerobic metabolism) inhibits the rate-limiting enzyme phosphofructokinase. This in turn will further reduce the activity of Na+/K+ ATPase resulting in a vicious cycle.

Conduction blocks occur in the sinus and atrioventricular (AV) nodes. Interference with sinus node conduction manifests as sinus bradycardia, sinus arrest, or sinoatrial block. Significant depression of AV nodal conduction presents as second- and third-degree AV block. Second-degree block usually manifests as a Wenckebach's phenomenon. Mobitz type II AV block though uncommon in digoxin toxicity has been reported in yellow oleander toxicity. Early toxicity may present with PR interval prolongation, decreased QT interval, scooping of ST segments, and T-wave flattening or inversion. Atrial tachycardia with heart block is caused by both disturbances in conduction and enhanced impulse formation. Certain tachyarrhythmias are characteristic of digoxin intoxication such as atrial tachycardia with variable AV block, accelerated junctional rhythms, and fascicular tachycardia.

Hyperkalemia exacerbates cardiac glycoside-induced cardiac arrhythmias and is a marker of a poor outcome in cardiac glycoside poisoning. Serum cardiac glycoside concentration was seen to correlate with the severity of yellow oleander toxicity.

Management starts with assessment of severity of toxicity, continuous hemodynamic and cardiac monitoring, and measurement of serum creatinine; electrolytes such as sodium, potassium, calcium, magnesium, and serum cardiac glycoside levels. Digoxin-specific Fab fragments are an effective treatment of acute intoxication. Treatment of hyperkalemia is controversial, largely due to limited data. Atropine antagonizes cardiac glycoside-induced vagal activation, increasing the heart rate. Doses of 0.6–1 mg are used first line. Isoprenaline (isoproterenol) infusions are not recommended for the treatment of bradycardia due to its potency to precipitate ventricular ectopy.Cardiac pacing can be used in the presence of severe bradycardia, thus ensuring adequate cardiac output. Pacing is usually indicated if heart rate <40/min, any form of sick sinus syndrome, or heart block. Tachyarrhythmias have a poor prognosis because they are more difficult to treat. Use of antiarrhythmic drugs in yellow oleander poisoning has not been studied. Lidocaine is the preferred antiarrhythmic agent. Electrical cardioversion may also result in ventricular fibrillation or asystole. Hence, it may be used only in resistant cases; using low energy levels.

Anti-digoxin Fab fragments reverse toxicity by binding digoxin in extracellular fluid, causing a decrease in the effective free extracellular drug concentration. The concentration promotes release of digoxin from receptor sites. They are now considered as first-line therapy for severe digoxin poisoning in patients with life-threatening arrhythmias, cardiogenic shock, and hyperkalemia.