Cardiac Glycoside Plant Poisoning Treatment & Management

Management of plant cardiac glycoside poisoning is very similar to that for digoxin/digitoxin poisoning and follows the principles of care for toxicologic emergencies, which include the following:

• Provide general supportive care

• Prevent further exposure and absorption

• Administer antidote (ie, fragment antigen binding [Fab] fragments)

• Treat complications

For general supportive care, attention to airway, breathing, and circulation (ABCs) is paramount. Treat life-threatening conditions in accordance with advanced cardiac life support (ACLS) principles, except as outlined below. To prevent further exposure, remove plant parts brought with the patient from treatment area, particularly if the patient is suicidal. To prevent further absorption, oral administration of activated charcoal is recommended if no contraindications exist.

Advanced life support (ALS) personnel should transport patients who have ingested herbal cardiac glycosides or significant amounts of plants known to contain cardiac glycosides. Prehospital care should focus on the ABCs, with special emphasis on supporting respiratory and cardiac function. Cardiac and pulse oximeter monitoring should be continuous.

Administer oxygen and start an intravenous (IV) line. Place the patient on continuous cardiac monitoring and pulse oximetry. Treat patients with altered mental status in accordance with standard protocols based on a fingerstick glucose determination and primary survey.

In patients with a protected airway and normal mental status, activated charcoal can be administered. Atropine should be given to patients with clinically significant bradycardia (eg, hypotension, change of mental status). Digoxin Fab fragment treatment should be given if indicated.

Sheep-derived digoxin antibody Fab fragments reportedly are effective for some plant cardiac glycosides. Consider using this agent in patients with life-threatening complications, such as ventricular dysrhythmias, hyperkalemia, high-degree heart block, and cardiac arrest that do not respond rapidly to conventional treatment.

Indications for digoxin antibody Fab fragments are the same for both pharmaceutical as well as nonpharmaceutical cardiac glycoside toxicity and include the following:

• Hyperkalemia (>5.0 mEq/L) in acute toxicity

• Life-threatening supraventricular and ventricular dysrhythmias

• Hemodynamically significant bradycardia unresponsive to atropine

• Chronic digoxin toxicity with dysrhythmias, significant GI symptoms, acute altered mental status, or renal insufficiency

• Serum digoxin level >15 ng/mL at any time

• Ingestion of 10 mg in an adult or 4 mg in a child

• Poisoning by nondigoxin cardiac glycoside

• To aid in treatment of suspected cardiac glycoside poisoning without a confirmatory level

Digoxin levels are not meaningful after administration of digoxin-specific Fab fragments. The levels may not change or may be falsely elevated if a free digoxin assay is not used. Because onset of action of Fab fragments may take 30-60 minutes, intervening treatment of significant complications should occur.

Complications of plant cardiac glycoside poisoning may include the following:

• Bradydysrhythmia

• Tachydysrhythmia

• Hyperkalemia

• Cardiac arrest

Bradydysrhythmia

Atropine and cardiac pacing may be tried. If atropine is not rapidly successful, consider administration of Fab fragments. Patients requiring transcutaneous cardiac pacing should receive Fab fragments prior to its initiation. Transvenous pacing and use of isoproterenol have resulted in degeneration of cardiac rhythms, so both of these should be avoided. Do not delay administration of Fab fragments because of pacemaker placement. Do not use overdrive pacing for the control of ventricular dysrhythmias.

Phenytoin and lidocaine may be used as antidysrhythmics if Fab fragments are not immediately available. However, it should be remembered that Fab fragments are the definitive antidote to cardiac glycoside poisoning.

Tachydysrhythmia

Phenytoin and lidocaine (which decrease automaticity without slowing atriovenous [AV] nodal conduction and increase fibrillation threshold) may be used to treat ventricular dysrhythmias.

Magnesium has been reported to reverse digoxin-induced dysrhythmias and may be useful as long as anuric renal failure is not present.

Use cardioversion only as a last resort, since it may induce intractable ventricular fibrillation. Fab fragments should be given with cardioversion. If time permits, cardioversion should be attempted after a loading dose of phenytoin and at a significantly reduced initial power setting of 5-10 J.

Quinidine and procainamide may enhance cardiac glycoside toxicity by slowing conduction across AV node; both should be avoided. Beta-blockers and calcium channel blockers have questionable value.

Life-threatening hyperkalemia (>5.5 mEq/L) may be seen with acute toxicity and results from a redistribution phenomenon rather than increased body stores. Glucose, insulin, sodium bicarbonate, and albuterol may be administered to facilitate redistribution of potassium intracellularly. However, albuterol may precipitate cardiac dysrhythmias. Life-threatening hyperkalemia should be treated with Fab fragments.

Calcium should be avoided. Overloading of myocytes with calcium is associated with development of a "stone heart," increased dysrhythmias, and a higher rate of death.

A pilot study in a porcine model shows that, in contrast to earlier studies, IV calcium administration to treat hyperkalemia secondary to cardiac glycoside toxicity resulted in no benefit or harm. However, the authors do not recommend its use in the clinical setting until more definitive studies are undertaken. ^[6] Theoretically, calcium can be used after administration of Fab fragments and reversal of cardiac glycoside toxicity.

Forced diuresis, hemoperfusion, and hemodialysis are ineffective in enhancing the elimination of digoxin because of its large volume of distribution. Hemodialysis will efficiently remove potassium from extracellular fluid.

Cardiac arrest

Give 10-20 vials of Fab fragments and continue to treat with standard ACLS protocols. Prolonged efforts at resuscitation may be warranted until Fab fragments begin to work. Phenytoin and lidocaine are antidysrhythmics of choice in patients poisoned with cardiac glycosides.

A Cochrane review on antidotes for acute cardiac glycoside poisoning that specifically looked at yellow oleander suggests that some evidence supports multiple-dose activated charcoal (MDAC) and antidigoxin Fab fragments, but notes that these may not be effective in toxicity caused by other plant cardiac glycosides. ^[7] The authors conclude that considering the cost limits in developing countries, where most poisonings take place, research to develop less expensive antidotes is needed.

Admit patients who show any signs of cardiac glycoside toxicity to a monitored setting for observation and further care. Intensive or cardiac care unit admission is indicated for patients with severe signs of toxicity, or in whom Fab fragments were used without resolution of symptoms.

Patients treated with Fab fragments and with complete resolution of symptoms may be admitted to a monitored setting. Clinicians should be aware of possibility of delayed toxicity if GI decontamination was not completed (especially for plant leaves in the GI tract).

Arrange transfer to another facility with sufficient resources and expertise to care for patient under the following circumstances:

• Lack of Fab fragments or lack of expertise in their use (in the latter case, however, with the assistance of local poison control center, medical toxicologist, or cardiologist, administration of Fab fragments should be performed prior to the transfer of a symptomatic patient)

• Lack of personnel experienced in management of cardiac glycoside toxicity

• Lack of facilities or equipment to manage severe glycoside poisoning

Transfer is usually to a tertiary care center with a medical toxicologist.

The following consultations may be appropriate:

• Poison control center and medical toxicology - For any question regarding management (strongly recommended if use of Fab fragments is considered or if symptoms and signs of toxicity are severe)

• Cardiology - For advice regarding treatment of cardiac manifestations of toxicity, as needed; also consider if use of Fab fragments is contemplated and a medical toxicologist is unavailable

• Psychiatry - Recommended for any patients with suspected intentional ingestions

• Primary care physician - For admission or for information regarding the patient's medical history

• Botanist - May facilitate plant identification

Patients meeting the following criteria (measured serially over time) may be discharged:

• Asymptomatic throughout the course of an emergency department observation period (12 h postingestion)

• Normal vital signs

• Baseline mental status

• Baseline cardiac rate and rhythm; unchanged electrocardiogram

• Electrolytes within reference range

• Negative cardiac glycoside assay for any patient not regularly taking a digoxin preparation

• Unintentional ingestion or clearance by psychiatry in a case of intentional ingestion

Follow-up with primary care provider should be arranged within 1-2 days following unintentional ingestions of cardiac glycosides. Close follow-up is mandatory if psychiatry recommends discharge of a patient after intentional ingestion of cardiac glycosides or for any patient with underlying cardiac disease.