Toxicology Case Files from the Utah Poison Control Center
Teaching Points
- Intentional ingestion of large quantities of oleander may cause toxicity similar to digoxin
- Serum digoxin concentration may be used in a qualitative, but not quantitative, manner
- Treatment with digoxin-specific antibody fragments (Digifab) may be helpful in management using typical indications
Case Presentation
A 32 y/o F presented to the ED about 30 minutes after ingestion of a large quantity of oleander leaves in a suicide attempt.
She was pale and vomited. Her initial vitals were normal. Activated charcoal was administered.
EKG and telemetry monitoring showed a Mobitz I AV block and premature atrial contractions. Initial labs showed a potassium of 3.8 and negative digoxin concentration.
However, about 30 minutes later the patient became bradycardic to the 40s. Four vials of Digifab were administered and the patient’s heart rate improved. She was admitted to the hospital and where she remained stable and did not require further Digifab. Unfortunately, additional digoxin concentrations were not measured.
Oleander Toxicity
There are numerous natural sources of cardioactive steroids, or cardiac glycosides, in addition to the well-known foxglove (Digitalis purpurea) and the pharmaceutical derivative digoxin. Other examples include red squill, lily of the valley, oleander (Nerium oleander), yellow oleander (Cascabela thevetia), dogbane, pong pong tree, milkweed, and sea mango. Ingestion of yellow oleander seeds is a common method of suicide in southeast Asia.1
Oleander (Figure 1) grows across the southern United States (Figure 2). The toxic cardenolide oleandrin is found in all parts of the plants with the greatest concentrations in the leaves. Toxicity has occurred with ingestion of multiple leaves or decoction of oleander. Toxicity is unlikely from small pediatric exposures.
Toxicity is similar to digoxin: nausea, vomiting, and cardiac abnormalities including bradycardia, various AV blocks, and ventricular dysrhythmias .2 Oleandrin is similar to digoxin and inhibits Na+/K+ ATPase leading to increased intracellular Na+ concentrations. This leads to diminished function of the Na+/Ca2+ antiporter causing increased intracellular Ca2+.
Digoxin immunoassays often cross-react with other structurally similar cardiac glycosides. However, the resulting concentrations should only be interpreted as “positive” and cannot be used to specifically guide treatment or quantify the amount of toxin present.
Instead, management will be based on clinical factors such as bradycardia, hypotension, and serum potassium. Serum potassium reflects the amount of inhibition of Na+/K+ ATPase. In a series of acute digoxin overdoses, no patient died with a potassium < 5.3 Conversely, no patient survived with a potassium >5.5. Thus a potassium of 5-5.5 is often used as a threshold for treatment Digifab.
Dosing of Digifab is empiric. Patients with mild bradycardia and/or hypotension could be given 2-4 vials of Digifab. Unstable patients or those in cardiac arrest likely warrant higher doses but there is no data to guide therapy.
As Digifab is specific to digoxin, it may not completely reverse the effects of other cardiac glycosides. Other standard resuscitative measures for treatment of bradycardia, hypotension, and dysrhythmias may be used as well.
Digoxin is known to undergo enterohepatic recirculation. Thus, multidose activated charcoal may be useful in removing other cardiac glycosides if Digifab is unavailable or ineffective. There is no role for hemodialysis.
References:
- Bandara V, Weinstein SA, White J, Eddleston M. A review of the natural history, toxinology, diagnosis and clinical management of Nerium oleander (common oleander) and Thevetia peruviana (yellow oleander) poisoning. Toxicon. 2010 Sep 1;56(3):273-81.
- Anselm Wong & Shaun L Greene (2018) Successful treatment of Nerium oleander toxicity with titrated Digoxin Fab antibody dosing, Clinical Toxicology, 56:7, 678-680.
- C. Bismuth, M. Gaultier, F. Conso & M. L. Efthymiou (1973) Hyperkalemia in Acute Digitalis Poisoning: Prognostic Significance and Therapeutic implications, Clinical Toxicology, 6:2, 153-162.