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Plant Poisoning, Glycosides - Cardiac: Treatment & Medication
Updated: Jan 27, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Prehospital Care
- Advanced life support (ALS) should transport patients who have ingested herbal cardiac glycosides or significant amounts of plants known to contain cardiac glycosides.
- Prehospital care should focus on ABCs, with special emphasis on supporting respiratory and cardiac function.
- During transport, the patient should receive supplemental oxygen and an IV line. Cardiac and pulse oximeter monitoring should be continuous.
- In patients with 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).
Emergency Department Care
Address principles of care for toxicologic emergencies, including providing general supportive care, preventing further exposure and absorption, administering antidote (eg, fragment antigen binding [Fab] fragments), and treating complications. Management is very similar to that for digoxin/digitoxin poisoning.
- General supportive care: Attention to ABCs is paramount. Treat life-threatening conditions in accordance with advanced cardiac life support (ACLS) principles, except as outlined below.
- Administer oxygen and start an IV line. Place patient on continuous cardiac monitoring and pulse oximeter.
- Treat patients with altered mental status in accordance with standard protocols based on a fingerstick glucose determination and primary survey.
- Prevent further exposure: Remove plant parts or any medications brought with patient from treatment area, particularly if patient is suicidal.
- Prevent further absorption: Oral administration of activated charcoal is recommended if no contraindications exist.
- Administer antidote: Sheep-derived digoxin antibody Fab fragments reportedly are effective for some plant cardiac glycosides. Consider use in 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
- Since onset of action of Fab fragments may take 30-60 minutes, intervening treatment of significant complications should occur.
- Bradydysrhythmias: 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 it. Transvenous pacing and use of isoproterenol have resulted in degeneration of cardiac rhythms and 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.
- Tachydysrhythmias: Phenytoin and lidocaine (which decrease automaticity without slowing 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.
- Hyperkalemia: Life-threatening hyperkalemia (>6.5 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 used to facilitate redistribution of potassium intracellularly. However, albuterol may precipitate cardiac dysrhythmias.
- Calcium should be avoided to prevent overloading myocytes with calcium, which is associated with development of a "stone heart," increased dysrhythmias, and a higher rate of death. A recent 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 at this time until more definitive studies are undertaken.5 Theoretically calcium can be used after administration of Fab fragments and reversal of cardiac-glycosides toxicity.
- Life-threatening hyperkalemia should be treated with Fab fragments.
- 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 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.
Consultations
- Poison center and toxicology: Consider consultation for any question regarding management (strongly recommended if use of Fab fragments is considered or if symptoms and signs of toxicity are severe).
- Cardiology
- Consider consultation for advice regarding treatment of cardiac manifestations of toxicity, as needed.
- Consider consultation if use of Fab fragments is contemplated and a toxicologist is unavailable.
- Psychiatry: Consultation is recommended for any patients with suspected intentional ingestions.
- Primary care physician: Consult for admission or for information regarding patient's medical histories.
- Botanist: Consultation with a botanist may facilitate plant identification.
Medication
Categories of drugs used to manage cardiac glycoside plant toxicity include drugs to minimize absorption and increase excretion, drugs that lower extracellular potassium, antidysrhythmics, and antidotes (eg, digoxin Fab fragments).
GI decontaminants
Activated charcoal is used to bind toxin within the GI tract. Due to enterohepatic/enteroenteric recirculation of cardiac glycosides, multiple doses can be given to help enhance elimination.
Activated charcoal (Liqui-Char)
Emergency treatment in poisoning caused by drugs and chemicals. Network of pores present in activated charcoal adsorbs 100-1000 mg of drug per gram of charcoal. Does not dissolve in water.
For maximum effect, administer within 30 min after ingesting poison. First dose may be given with a cathartic (eg, sorbitol); subsequent doses should be given without a cathartic, as often as q2-6h, and should not be given in presence of ileus.
Adult
Initial: 30-100 g with 240 mL diluent/30 g charcoal PO/NG (1-2 g/kg PO; not to exceed 150 g/dose)
Repeat: 20-50 g PO/NG
Pediatric
Initial, infants: 1-2 g/kg PO
Initial, children: 15-30 g PO (1-1.5 g/kg PO as a 35% solution; not to exceed 50 g/dose; repeat prn with 1/2 initial dose q4h)
May inactivate ipecac syrup if used concomitantly; effectiveness of other medications decreases with coadministration; do not mix charcoal with sherbet, milk, or ice cream (decreases adsorptive properties of activated charcoal)
Documented hypersensitivity; subsequent doses of charcoal in presence of ileus
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Not very effective in poisonings of ethanol, methanol, and iron salts; induce emesis before giving activated charcoal; after emesis with ipecac, patient may not tolerate activated charcoal for 1-2 h; can administer in early stages of gastric lavage; without sorbitol, gastric lavage returns are black; protect airway in patients with absent gag reflex
Antihyperkalemics
Hyperkalemia usually results from acute overdose and represents redistribution of potassium from intracellular to extracellular compartment; therefore, drugs of choice include agents that promote potassium redistribution from extracellular to intracellular compartments. Avoid calcium, as it may exacerbate effects of cardiac glycosides and may promote rhythm deterioration when used in this context.
Glucose (D50W) and insulin (Humulin R, Novolin R)
Redistributes potassium intracellularly; onset of action is 30 min and duration of action is 4-6h.
Used for life-threatening hyperkalemia (>6.5 mEq/L). Use cautiously with digoxin Fab as profound hypokalemia may occur.
Observe serum glucose level and administer additional D50W if needed
Adult
20 U regular insulin with 50 g glucose IV over 1 h
Pediatric
0.5-1 g glucose/kg with 1 U regular insulin/3 g glucose
Medications that may decrease hypoglycemic effects of insulin include acetazolamide, AIDS antivirals, asparaginase, phenytoin, nicotine isoniazid, diltiazem, diuretics, corticosteroids, thiazide diuretics, thyroid estrogens, ethacrynic acid, calcitonin, oral contraceptives, diazoxide, dobutamine phenothiazines, cyclophosphamide, dextrothyroxine, lithium carbonate, epinephrine, morphine sulfate, and niacin; medications that may increase hypoglycemic effects of insulin include calcium, ACE inhibitors, alcohol, tetracyclines, beta blockers, lithium carbonate, anabolic steroids, pyridoxine, salicylates, MAOIs, mebendazole, sulfonamides, phenylbutazone, chloroquine, clofibrate, fenfluramine, guanethidine, octreotide, pentamidine, and sulfinpyrazone
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Hyperthyroidism may increase renal clearance of insulin, and more insulin may be required to treat hyperkalemia; hypothyroidism may delay insulin turnover, and less insulin may be required to treat hyperkalemia; monitor glucose carefully; dose adjustments of insulin may be necessary in patients diagnosed with renal and hepatic dysfunction
Sodium bicarbonate (Neut)
Sodium counteracts potassium effects, while alkalosis created by bicarbonate leads to a redistribution of potassium intracellularly. Onset of action is 5-10 min and duration of action is 1-2 h.
Used for life-threatening hyperkalemia (>6.5 mEq/L). Use cautiously with digoxin Fab as profound hypokalemia may occur.
Adult
50-100 mEq IV over 5-10 min; may repeat in 15 min once prn
Pediatric
1-2 mEq/kg IV over 5-10 min; may repeat in 15 min once prn
Urinary alkalinization, induced by increased sodium bicarbonate concentrations, may cause decreased levels of lithium, tetracyclines, chlorpropamide, methotrexate, and salicylates; increases levels of amphetamines pseudoephedrine, flecainide, anorexiants, mecamylamine, ephedrine, quinidine, and quinine
Documented hypersensitivity; volume overload states, alkalosis, hypernatremia, and hypocalcemia
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Only to be used to treat documented metabolic acidosis and hyperkalemia-induced cardiac arrest; can cause alkalosis, decreased plasma potassium, hypocalcemia and hypernatremia; caution in electrolyte imbalances (eg, CHF, cirrhosis, edema, corticosteroid use, renal failure); when administering, avoid extravasation since it can cause tissue necrosis; can cause fluid overload in patients with low ejection fraction or renal failure
Antiarrhythmic agents
Used to treat variety of bradydysrhythmias and tachydysrhythmias occurring with cardiac glycoside toxicity.
Atropine (Atropisol)
Used for bradycardia and conduction blocks in standard ACLS doses.
Doses <0.1 mg in children or 0.5 mg in adults may lead to paradoxical bradycardia.
Adult
2 mg IV (asystole) or
0.5-1 mg IV (bradycardia); may repeat in 5 min; not to exceed 0.04 mg/kg (about 3 mg in 70-kg adult)
Pediatric
0.02 mg/kg IV; may repeat in 5 min; not to exceed 0.04 mg/kg (infants), 1 mg (children), or 2 mg (adolescents)
Coadministration with other anticholinergics have additive effects; pharmacologic effects of atenolol and digoxin may increase; antipsychotic effects of phenothiazines may decrease; tricyclic antidepressants with anticholinergic activity may increase effects of atropine
Documented hypersensitivity; thyrotoxicosis; narrow-angle glaucoma; tachycardia
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Avoid in patients with Down syndrome and/or in children with brain damage to prevent hyperreactive response; also avoid in coronary heart disease, tachycardia, cardiac dysrhythmias, and hypertension; caution in peritonitis, ulcerative colitis, hepatic disease, and hiatal hernia with reflux esophagitis; in prostatic hypertrophy, prostatism can have dysuria and may require catheterization
Phenytoin (Dilantin)
Useful for ventricular dysrhythmias, such as V-fib, V-tach, and PVCs. DOC for cardiac glycoside-induced tachydysrhythmias. Only antidysrhythmic which stabilizes myocardium and improves conduction through AV node.
Monitor serum phenytoin levels closely to assure therapeutic levels of 10-20 mcg/mL.
Adult
Initial: 15 mg/kg IV; rate not to exceed 0.5 mg/kg/min
Stop/slow down if develop hypotension
Maintenance: 2 mg/kg IV q8h prn
Pediatric
Administer as in adults
Amiodarone, benzodiazepines, chloramphenicol, cimetidine, fluconazole, isoniazid, metronidazole, miconazole, phenylbutazone, succinimide, sulfonamides, omeprazole, phenacemide, disulfiram, ethanol (acute ingestion), trimethoprim, and valproic acid may increase toxicity
Phenytoin effects may decrease when taken concurrently with barbiturates, diazoxide, ethanol (chronic ingestion), rifampin, antacids, charcoal, carbamazepine, theophylline, and sucralfate; may decrease effects of acetaminophen, corticosteroids, dicumarol, disopyramide, doxycycline, estrogens, haloperidol, amiodarone, carbamazepine, cardiac glycosides, quinidine, theophylline, methadone, metyrapone, mexiletine, oral contraceptives, valproic acid
Documented hypersensitivity; sinoatrial block, second- and third-degree AV block, sinus bradycardia, or Adams-Stokes syndrome
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Perform blood counts and urinalyses when therapy is begun and at monthly intervals for several months thereafter to monitor for blood dyscrasias; discontinue use if a rash appears and do not resume use if rash is exfoliative, bullous, or purpuric; rapid IV infusion may result in death from cardiac arrest, marked by QRS widening; caution in acute intermittent porphyria and diabetes (may elevate blood sugars); discontinue use if hepatic dysfunction occurs
Lidocaine (Xylocaine)
Class IB antiarrhythmic that increases electrical stimulation threshold of the ventricle, suppressing automaticity of conduction through the tissue.
Adult
Bolus: 1-1.5 mg/kg IV push; may repeat 1 mg/kg q5-8min; not to exceed 3 mg/kg
Maintenance: 2-4 mg/min IV
Pediatric
Bolus: 1 mg/kg IV push; may repeat q5-8min to total dose of 3 mg/kg
Maintenance: 20-50 mcg/kg/min
Coadministration with cimetidine or beta-blockers, increases toxicity; coadministration with procainamide and tocainide may result in additive cardiodepressant action; may increase effects of succinylcholine
Documented hypersensitivity; Adams-Stokes syndrome and Wolff-Parkinson-White syndrome; severe sinoatrial, AV, or intraventricular block if artificial pacemaker not in place
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Use a solution without preservatives; caution in heart failure, hepatic disease, hypoxia, hypovolemia or shock, respiratory-depression, and bradycardia; may increase risk of CNS and cardiac side-effects in elderly persons; high plasma concentrations can cause seizures, heart block, and AV conduction abnormalities; reduce maintenance infusion in CHF, cardiogenic shock, or liver failure
Magnesium sulfate
Nutritional supplement in hyperalimentation; cofactor in enzyme systems involved in neurochemical transmission and muscular excitability.
In adults, 60-180 mEq of potassium, 10-30 mEq of magnesium, and 10-40 mmol/L of phosphate per day may be necessary for optimum metabolic response.
Although serum magnesium levels may be normal, existence of intracellular hypomagnesemia has been hypothesized; therefore, magnesium may be beneficial.
Adult
2-4 g IV over 2-4 min; may be followed by 2 g/h for 4 h
Pediatric
Not established
Concurrent use with nifedipine may cause hypotension and neuromuscular blockade; may increase neuromuscular blockade seen with aminoglycosides and potentiate neuromuscular blockade produced by tubocurarine, vecuronium, and succinylcholine; may increase CNS effects and toxicity of CNS depressants, betamethasone, and cardiotoxicity of ritodrine
Documented hypersensitivity; heart block; Addison disease; myocardial damage; severe hepatitis
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
Precautions
Magnesium may alter cardiac conduction leading to heart block in digitalized patients; respiratory rate, deep tendon reflex, and renal function should be monitored when electrolyte is administered parenterally; caution when administering magnesium dose since may produce significant hypertension or asystole; in overdose, calcium gluconate, 10-20 mL IV of 10% solution, can be given as antidote for clinically significant hypermagnesemia
Antidote
Sheep-derived IgG antibodies to digoxin have been used successfully in patients with oleander toxicity. They cross-react with other cardiac glycosides and may be helpful in certain situations, including hyperkalemia not quickly responsive to standard treatments, life-threatening dysrhythmias not quickly responsive to standard treatments, and cardiac arrest.
Digoxin Fab fragments (Digibind)
Because serum digoxin/digitoxin levels do not reflect ingested amount of plant cardiac glycoside, drug levels should not be used to calculate Fab dose. Elevated levels of digoxin or digitoxin only confirm exposure. Undetectable level of serum cardiac glycosides does not rule out exposure. Elevated serum potassium would be a useful indicator when considering this agent.
Adult
10-20 vials IV initially as empiric treatment for acute poisoning
Chronic poisoning: 3-6 vials IV
Pediatric
Administer as in adults in acute poisoning
Chronic poisoning: 1-2 vials IV
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Should be used with caution in patients who have had adverse reactions to sheep proteins as well as prior history of allergy to antibiotics; skin testing may be warranted but not in acute setting
More on Plant Poisoning, Glycosides - Cardiac |
| Overview: Plant Poisoning, Glycosides - Cardiac |
| Differential Diagnoses & Workup: Plant Poisoning, Glycosides - Cardiac |
 Treatment & Medication: Plant Poisoning, Glycosides - Cardiac |
| Follow-up: Plant Poisoning, Glycosides - Cardiac |
| Multimedia: Plant Poisoning, Glycosides - Cardiac |
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References
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Eddleston M, Rajapakse S, Rajakanthan, Jayalath S, Sjostrom L, Santharaj W. Anti-digoxin Fab fragments in cardiotoxicity induced by ingestion of yellow oleander: a randomised controlled trial. Lancet. Mar 18 2000;355(9208):967-72. [Medline].
el Bahri L, Djegham M, Makhlouf M. Urginea maritima L (Squill): a poisonous plant of North Africa. Vet Hum Toxicol. Apr 2000;42(2):108-10. [Medline].
Furbee B, Wermuth M. Life-threatening plant poisoning. Crit Care Clin. Oct 1997;13(4):849-88. [Medline].
Goldfrank, Flomenbaum, Lewin, et al. Cardiac glycosides. In: Goldfrank's Toxicologic Emergencies. 7th ed. 2002:724-734.
Rich SA, Libera JM, Locke RJ. Treatment of foxglove extract poisoning with digoxin-specific Fab fragments. Ann Emerg Med. Dec 1993;22(12):1904-7. [Medline].
Plants - cardiac glycosides. In: Rumack BH, ed. Poisondex. 1997:94.
Slifman NR, Obermeyer WR, Aloi BK, Musser SM, Correll WA Jr, Cichowicz SM. Contamination of botanical dietary supplements by Digitalis lanata. N Engl J Med. Sep 17 1998;339(12):806-11. [Medline].
Van Deusen SK, Birkhahn RH, Gaeta TJ. Treatment of hyperkalemia in a patient with unrecognized digitalis toxicity. J Toxicol Clin Toxicol. 2003;41(4):373-6. [Medline].
Further Reading
Keywords
cardiac glycosides, cardiac glycoside toxicity, cardiac glycoside poisoning, treatment of glycoside poisoning, symptoms of glycoside poisoning, glycoside toxicity, glycoside poisoning, plant poisoning, glycoside, Digitalis purpurea, Digitalis lanata, foxglove, Nerium oleander, common oleander, Thevetia peruviana, yellow oleander, Convallaria majalis, lily of the valley, Urginea maritima, Urginea indica, squill, Strophanthus gratus, ouabain, herbal cardiac glycosides
