Cardiovascular Medicine and Surgery NetWork Online Puzzler - December 2008

Diagnoses and Discussion

Diagnoses:

1. Atrial fibrillation with a complete heart block and junctional bradycardia escape rhythm.
2. Digitalis toxicity due to a reduced glomerular filtration rate (GFR) (interaction of the angiotensin enzyme converting [ACE] inhibitor with a nonsteroidal antiinflammatory drug [NSAID]) plus inhibited digitalis secretion from the verapamil interaction.

Discussion:

Excretion of digoxin is approximately 80 to 85% renal, with filtration as the predominant mechanism. The drug is also actively secreted through the renal tubules, yet this mechanism can be inhibited by other drugs, including verapamil, quinidine, and amiodarone. Most physicians are aware of the combined effect of ACE inhibitors and NSAIDs in causing azotemia, but they sometimes forget that aspirin, at analgesic/antiinflammatory doses, has similar effects; the combination dilates efferent and afferent arterioles, critically reducing transglomerular filtration pressure and the excretion of any drug normally filtered in significant amounts. Although the impact of inhibited tubular secretion of digoxin by other drugs is not clearly more common in the presence of azotemia, it often makes otherwise tolerable glomerular clearance levels inadequate, reducing one major alternative excretion pathway.

Laboratory values for the patient included a serum creatinine level of 4.0 mg/dL (estimated GFR of 25 mL/min), serum CO2 concentration of 15 mEq/L, and serum potassium concentration of 6.2 mEq/L (both from reduced GFR and from the digoxin itself, which inhibits real sodium-potassium-dependent adenosine triphosphatase [ATPase] and can raise potassium levels as a consequence of toxicity).

The patient underwent emergency hemodialysis but remained in complete heart block. Digoxin-specific Fab fragments were then administered with recovery of normal conduction. With discontinuation of the verapamil, enalapril and aspirin, the patient fully recovered in 72 h and was discharged to go home with a near baseline renal function and a ventricular rate of 80 bpm.

Puzzler and case report submitted by:
Stephen A. Geraci, MD, FCCP
Chair, Cardiovascular Medicine and Surgery NetWork
Professor and Vice Chair, Internal Medicine
University of Mississippi School of Medicine
Chief, Medical Service GV (Sonny) Montgomery VAMC
Jackson, Mississippi