Oleander and Digoxin: Interaction Details

a) Treatment of acute oleander poisoning presenting with severe cardiac arrhythmia with anti-digoxin Fab (DigiTab) 1200 milligrams (mg) resulted in rapid resolution of the arrhythmia, and correction of hyperkalemia in a randomized, double-blind, placebo-controlled study of 66 patients. The dose of DigiTab was determined in a dose-finding study involving 16 patients. All 4 patients receiving 1200 mg responded, compared with 3 of 4 receiving 800 mg or 1600 mg, and 1 of 4 receiving 400 mg. Common presenting symptoms were vomiting, diarrhea, weakness, dizziness, abdominal pain, sinus bradycardia, exit block or arrest, and/or atrioventricular conduction block. Arrhythmias completely resolved within 2 hours in 15 of 34 treated patients versus 2 of 32 controls (p less than 0.001). Within 8 hours, 24 of 33 treated patients converted to sinus rhythm with heart rates greater than 44 beats/minute versus 5 of 32 controls (p less than 0.001). Within 8 hours, mean heart rate increased from 49 beats/minute to 69 beats/minute in treated patients versus an increase from 50 beats/min to 54 beats/min in controls (p less than 0.001). Within 2 hours, serum potassium decreased from 4.9 millimoles/liter (mmol/L) to 4.1 mmol/L in treated patients and remained at 4.7 mmol/L in control patients; within 48 hours, serum potassium was 4.0 mmol/L in both groups. No patients admitted into the trial died, as most deaths occur prior to admission or soon after admission. This study was not designed to evaluate mortality ¹.

b) A 66-year-old female with no previous cardiac disease or antiarrhythmic medication use developed cardiac arrhythmia following ingestion of oleander leaves. Pulse on admission was 70 beats/minute, which decreased to 20 beats/minute with asystolic periods of 4 seconds. A serum radioimmunoassay for digoxin was 0.8 nanograms/milliliter (ng/mL), potassium was 4.8 mmol/L. She was successfully treated with 5 vials (200 mg) of digoxin-specific Fab antibody fragments (Digibind(R)). Dysrhythmias resolved, and a repeat digoxin level was 0.1 ng/mL ².

c) A 26-year-old male presented with vomiting and pulse 57 beats/minute 2 hours after ingesting 3 bowls of unprocessed oleander leaves. He had no previous cardiac disease or antiarrhythmic medication use. Bradycardia developed (30 beats/minute) with first, second, and third degree AV blocks, and asystolic periods of greater than 5 seconds. Serum digoxin level was 0.77 ng/mL, serum potassium was 5.8 mmol/L. Dysrhythmia resolved after treatment with 10 vials (400 mg) of Digibind(R). Pulse and echocardiogram were normal at discharge ².

d) A female patient developed nausea, vomiting, diarrhea, and severe weakness following ingestion of a self-prepared tea from oleander and lime blossom. Electrocardiogram (ECG) showed third-degree atrioventricular block with shortened QRS. Serum digitalis was 4.2 nanograms/deciliter (ng/dL), potassium was 8.8 milliequivalents/liter (mEq/L). Hydration treatment reversed symptoms and electrocardiographic changes ³.

e) A 24-year-old male developed nausea, vomiting, abdominal pain, and confusion within 10 hours of ingestion of a mixture of orange juice and 6 ground leaves later identified as Nerium oleander (common pink oleander). Blood pressure was 100/80 mmHg, pulse 40 beats/minute. Initial ECG showed AV block with junctional escape rate of 40/minute and diffuse ST depression; 2 hours later an ECG showed complete AV block, sinoatrial block, and diffuse ST depression persisted. A digoxin level of 0.8 ng/mL confirmed a presumed diagnosis of oleander intoxication. Potassium rose from 5.2 mmol/L to 6.5 mmol/L despite Kayexalate(R) therapy, and a solution of glucose, insulin, and bicarbonate was administered. Blood pressure deteriorated to 70/40 mmHg, potassium increased to 6.8 mmol/L and the patient became oliguric and nonresponsive to external stimuli. Eighteen hours after admission, empiric treatment with digoxin-specific Fab antibody fragments (Digiband, The Welcome Foundation Ltd, Beckenmam, England) 480 mg was administered intravenously over 30 minutes. The patient awoke 4 minutes after treatment was started, ECG showed sinus rhythm (44/min) with prolonged PR interval and persistence of a digitalis effect on the ST segment. Within 15 minutes, potassium decreased to 5.1 mmol/L, blood pressure increased to 100/60 mmHg, pulse 68 beats/min. Within 1 hour, potassium normalized to 4.5 mmol/L. Within 12 hours, the patient was asymptomatic but ST depression remained evident for 6 days ⁴.

f) In one three-year study, 170 patients were admitted to a hospital in Sri Lanka with yellow oleander (Thevetia peruviana) toxicity. The most common presenting symptoms were vomiting (68%), giddiness (36%), and diarrhea (22%), 12.9% of patients remained asymptomatic. Bradycardia was noted in 50% of the patients and palpitations were noted in 3% of the patients. Seven patients died presumably from cardiac adverse effects including sinoatrial and ventricular blocks, ST depression, and ventricular excitability with a poor response to atropine ⁵.

g) A 37-year-old male developed dry mouth, cramping abdominal pain, nausea, vomiting, dizziness, and irregular heart beat after ingestion of "a handful" of oleander leaves in a suicide attempt. Medical history included chronic depression and suicide attempts, and occasional alprazolam use. The patient denied any other acute drug ingestion, specifically digitalis. Electrocardiogram showed bradycardia with rate of 30 to 45 beats/minute with frequent sinus pauses and junctional escape. Digoxin level was 1.5 ng/mL, serum potassium was 4.3 mEq/L. Five vials (200 mg) of Digibind(R) were administered empirically, resulting in improved heart rate and conduction. Serum potassium was 3.4 mEq/L ⁶.

h) A 30-year-old female developed nausea, vomiting, and a numb tongue following ingestion of a tea prepared from oleander, which the patient believed to be eucalyptus. Paramedics reported a pulse of 30 beats/minute, blood pressure was not palpable. Lactated Ringer's solution and naloxone was administered without change, followed by atropine. Heart rate transiently increased, then returned to 30 beats/minute and blood pressure remained impalpable. Isoproterenol administration led to ventricular tachycardia, then ventricular fibrillation on arrival to the hospital. The patient was electrically defibrillated. The leaves from which the tea was made were identified as oleander. Serum potassium was 6.6 mEq/L. Regular insulin and dextrose were administered in addition to phenytoin and sodium bicarbonate. Cardiac rhythm deteriorated to asystole with no response to transthoracic pacemaker insertion. Serum digoxin level on a postmortem specimen was 6.4 ng/mL ⁷.

i) A 96-year-old female was found at home, weak, vomiting, and noncommunicative after a few minutes. The patient had been depressed with suicidal intent, she took only occasional aspirin, and had no digitalis preparations at home. A history of oleander leaf ingestion was given by the patient's son. Within 15 minutes, a generalized tonic-clonic seizure occurred, after which no pulse or respirations were detected. After continuous cardiopulmonary resuscitation efforts, pharmacologic intervention, and several attempts at electrical cardioversion, the patient was pronounced dead. Ventricular tachycardia, fibrillation, and asystole were shown on electrocardiogram throughout the course. Serum potassium was 8.6 mEq/L, serum digoxin was 5.8 ng/mL. Green vegetative material was found in the stomach at autopsy ⁸.

j) A 3-year-old female developed vomiting, abdominal pain, sweating, and pulse 40 beats/min. ECG showed complete heart block. Atropine 0.4 mg was ineffective, and cardiac arrest occurred on transport to a hospital. Resuscitation attempts with intubation, closed cardiac massage, and administration of adrenaline and bicarbonate were unsuccessful. Digoxin assays performed on a postmortem heart sample indicated presence of cardiac glycosides consistent with Thevetia (yellow oleander) poisoning ⁹.

k) In 10 dogs administered tincture of oleander intravenously, digoxin-specific Fab antibody fragments (dsFab) 60 milligrams/kilogram (mg/kg) administered intravenously effectively reversed fatal dysrhythmias, converting all dogs to normal sinus rhythm within eight minutes. After a mean time of 107 minutes, three dogs treated with dsFab reverted to hemodynamically stable dysrhythmias, indicating that oleander may contain glycosides which either are less toxic, lack affinity for dsFab, or have a prolonged distribution time, causing delayed cardiac effects. All 5 dogs treated with dsFab survived. Three of the 5 dogs which did not receive dsFab did not survive. Mean total time in normal sinus rhythm was significantly greater in dogs treated with dsFab (142 +/- 35.1 minutes) versus those untreated (15 +/- 8.2 minutes) (p equals 0.007) ¹⁰.