Digoxin Toxicity

Case

65 year old male PMH IDDM, hypertension, hyperlipidemia, hypothyroidism, CAD s/p CABG and CHF presents to the ED with complaint of weakness, altered mental status and vision changes. On further questioning, patient has been noticing blue color vision changes and wife notes patient “has not been himself” for the last 2-3 days. Of note patient has been afebrile and denies any trauma, headaches, chest pain, cough/cob, abdominal pain, GI or GU complaints. Physical examination is largely unremarkable and patient is hemodynamically stable: HR 80s, 134/85, 18, 97% RA, Glu 134. Soon after EKG tech hands you this:

 

You recognize the EKG changes and ask the patient if they are on any digoxin. Wife states patient is on 0.125 mg PO of digoxin every MWF but since patient has been in rehab for the last 13 days, has been receiving digoxin every day. You immediately become excited as this may represent digoxin toxicity!

Background

The foxglove plant, Digitalis purpurea, has been in use as one of the treatment modalities of heart failure since 1785 when Sir William Withering first described its use. In recent times, the use of digitalis has decreased but the number of toxic cases have remained stable. In 2011 alone where were 2513 cases reported to US poison control centers.

Kinetics

Digoxin reversibly inhibits the Na-K-ATPase pump, causing increase in intracellular Na and a decrease in intracellular K. Subsequently the increase in Na leads to the inhibition of the Na-Ca antiporter from excreting Ca from the cell and results in increase intracellular Ca. This net increase in Ca supplements inotropy while also causing potential premature contractions and arrhythmias by decreasing the refractory period. Digoxin also exhibits increases in vagal tone which can decrease conduction through the SA and AV nodes.

Clinical Features

Cardiac symptoms are the most concerning regarding digoxin toxicity as any type of arrhythmia can occur. The most commonly seen EKG arrhythmia will be PVCs but AF/A.flutter, AV block, Ectopic, Junctional, VT/Bidirectional VT and VF to name a few can occur. Patients may also exhibit GI symptoms such anorexia, nausea, vomiting, and abdominal pain. Neurologic complaints may be altered mental status, weakness/fatigue, and visual changes including alteration in color perception.

Workup

• Serial EKG
• Digoxin Level – no clinical correlation with toxicity; used more for dosing purposes of Digibind
• Basic Labs  – assessing for hypo/hyperkalemia, BUN/Cr for renal function, Glucose for potential cause of AMS
• Other – Acetaminophen/Salicylate/EtOH levels in setting of intentional ingestion, pregnancy test for childbearing age women, lactic acid for additional signs of hypoperfusion

In acute digoxin toxicity, the degree of hyperkalemia correlates with mortality. In contrast, hypokalemia is of greater concern in chronic toxicity as digoxin normally competes with potassium for binding sites at the Na-K-ATPase pump. Hence, potassium should be repleted as hypokalemia will exacerbate digoxin toxicity.

Also keep in mind that digoxin levels become unreliable following Digibind as it does not differentiate between free and bound drug levels. Thus digoxin levels should not be obtained following administration of Fab fragments.

Management

The management of digoxin toxicity starts with ABCs. Concomitantly, the patient should be placed on continuous cardiac/pulse ox monitors, and IV access. Depending on the patient’s mental status and hemodynamic stability, additional resuscitative measures such as airway protection and placement of pacer/defibrillator pads will be needed.

Ultimately, in a patient with digoxin toxicity, the treatment will be digoxin specific antibody (Fab) fragments. If unavailable, symptomatic bradycardia can be treated with atropine/pacing, hypotension with fluid boluses/pressors, and life threatening arrhythmias according to ACLS.

Indications for Digibind are:

• Hemodynamically unstable arrhythmia
• Hyperkalemia >5.0-5.5
• End-organ dysfunction (AMS, AKI)

Some advocate giving Fab fragments for serum concentrations greater than 10 in acute ingestions or greater than 4 in chronic, or when an adult ingests more than 10 mg or child more than 4 mg acutely.

Treatment

• Empiric treatment consists of 10 vials in adults and 5 vials in children
• 1 vial bind approximately 0.5 mg of digoxin
• If amount of digoxin is known but serum concentration is not:
  • calculate total body load (TBL)
    • TBL = Dose (in mg) x 0.8 (reflects bio-availability of digoxin)
    • # of vials = TBL/0.5
    • round up to the nearest number for total number of vials to be given
• if serum concentration is known:
  • # of vials = [(serum digoxin concentration) x (pt weight in kg)] / 100
  • again round up to the nearest whole number for total number of vials to be given

But wait what about hyperkalemia?

Hyperkalemia resulting from acute ingestion of digoxin should be treated at the discretion of the EM physician with this caveat in mind: hyperkalemia will rapidly correct once Fab fragments are given as the Na-K-ATPase pump is regenerated leading to potential hypokalemia. In addition, if treatment for hyperkalemia is initiated, calcium should be given without the fear for the theoretical risk of “stone heart”.

Back to our patient

Patient was given Digibind based on clinical presentation of altered mental status, vision changes and lab workup revealing creatine increase of 1.7 (baseline Cr 0.9). Serum digoxin level was therapeutic at 1.2 in setting of likely chronic toxicity. Patient had no EKG changes and continued to be hemodynamically stable. Patient was admitted to IMC.

References

• Uptodate.com
• Levine M, et al. The effects of intravenous calcium in patients with digoxin toxicity. J Emerg Med. 2011 Jan;40(1):41-6
• Ma G, et al. Electrocardiographic manifestations: digitalis toxicity. J Emerg Med. 2001; 20(2):145
• Eichhorn EJ et al. Digoxin. Prog Cardiovasc Dis. 2002; 44(4):251