Diuretic Renal Scintigraphy in Patients with Sulfonamide Allergies: Possible Alternative Use of Ethacrynic Acid

DISCUSSION

In patients with a known severe allergy to sulfonamides, radiologists and nuclear medicine physicians face the difficult choice of whether to use furosemide for diuretic renal scintigraphy. Furosemide may induce sulfonamide hypersensitivity reactions ranging from fever to life-threatening events such as hepatic necrosis and Stevens–Johnson syndrome. Sulfonamide reactions occur in 3%–6% of the general population and in up to 60% of those with HIV (1). Although the mechanism may not be a true cross-reaction, patients with hypersensitivity reactions to antibiotic sulfonamides will react to nonantibiotic sulfonamides such as furosemide with a frequency approaching 10% (2–4). When the sulfonamide-allergic patient presents for diuretic renal scintigraphy, there are 2 options: administering furosemide regardless of the known sulfamide reaction and relying on the rarity and often mildness of cross-reactions, or performing nondiuretic renal scintigraphy that cannot adequately evaluate for obstructive uropathy. A review for alternatives to furosemide revealed a sulfonamide moiety in many diuretics, including thiazides, carbonic anhydrase inhibitors, and most proximal loop diuretics, such as azosemide, bumetanide, and torsemide (5). The exception is ethacrynic acid, a rapidly acting loop diuretic available for intravenous administration (Fig. 2), making it an ideal alternative for renal scintigraphy of patients with severe sulfonamide allergies (6,7). The major risk factor to consider when using intravenous ethacrynic acid is immediate volume depletion, a relevant life-threatening reaction for one-time use, requiring blood pressure monitoring. Attention to ototoxicity is important; temporary hearing loss and even deafness can result, particularly when ethacrynic acid is paired with aminoglycoside antibiotics. Less concerning reactions with repeated use include hypokalemic metabolic alkalosis and magnesium depletion (8–10).

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FIGURE 2.

Sulfonamide drugs share common sulfur moiety (SO₂NHR) attached to benzene ring. Sulfonamide antibiotics (upper boxes) have arylamine at N4 position, which incites metabolites responsible for allergic reactions. The diuretics bumetanide, furosemide, and torsemide have molecularly similar N4 sites that can cross-react and harm an allergic patient. Ethacrynic acid (lower box) does not contain a sulfonamide group.

To confirm or rule out obstructive uropathy in patients with a known severe sulfonamide allergy, we developed a diagnostic imaging protocol for ethacrynic acid with input from our pharmacy department. Ethacrynic acid has nearly 100% bioavailability, with a steeper dose–response curve than furosemide. With intravenous injection, onset of action occurs in 5 min, with the peak diuretic effect occurring within 30 min (11). Clinically, the weight-based dose of intravenous ethacrynic acid is 0.5–1 mg/kg, not to exceed 100 mg in a single dose (12). A typical patient with pulmonary edema may receive 25–50 mg of ethacrynic acid intravenously over 20–30 min. To minimize the dose risk yet provide a brisk diuretic effect, we chose 25 mg of ethacrynic acid in 50 mL of 5% dextrose water infused intravenously over a slightly shorter period of 15 min. The postdiuretic image acquisitions were set to initiate after completion of ethacrynic acid infusion and to continue for 30 min.

Postdiuretic imaging of the 5 patients adequately answered the question of whether obstructive uropathy was present (Figs. 1 and 3). Our limited series further supports our initial short report on ethacrynic acid use for diuretic renal scintigraphy (13). The advantages of using ethacrynic acid in diuretic renal scintigraphy are its availability, relative simplicity of administration, absence of negative clinical impact for one-time use, and, most of all, ability to fully assess obstructive uropathy in patients with sulfonamide allergy. The main drawback resides in its cost of $300–$600 for a 25-mg intravenous dose. Overall, when the diagnosis of obstructive uropathy is crucial for patient care, the cost of ethacrynic acid is probably counterbalanced by its imaging benefits, avoiding recourse to any other less efficient imaging modalities or invasive urologic procedures.

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FIGURE 3.

A 25-y-old man with severe sulfa allergy and history of urinary bladder extrophy—after closure, ureteral reimplantation, and subsequent appendicovesicostomy—presenting with left hydronephrosis and recurrent urinary tract infections. Prediuretic renal scintigraphy (not shown) demonstrated prominent activity in left collecting system suggestive of obstruction. Diuretic challenge using ethacrynic acid showed satisfactory emptying of both collecting systems, with half-times of 3.8 and 4.7 min on right and left sides, respectively, ruling out obstructive uropathy.