Subcutaneous (SC) furosemide administration is not uncommon in the management of congestive heart failure (CHF) in dogs. The biochemical adverse effects of furosemide (eg, azotemia) are well described in companion animals, whereas nonbiochemical adverse effects are largely unreported. This report describes a dermatologic adverse effect of SC furosemide in a dog undergoing treatment of CHF.
A 10-year-old 4.4-kg neutered male dachshund was presented for tachypnea and coughing, and consequently diagnosed with CHF secondary to degenerative mitral valve disease. Initial cardiac medications included the following: furosemidea (1.42 mg/kg PO q12h), enalaprilb (0.57 mg/kg PO q12h), and pimobendanc (0.28 mg/kg PO q12h). The dog's clinical signs resolved with treatment.
Three months after the initial diagnosis and treatment, the dog was represented with a recurrence of CHF. The dose of furosemide was increased (2.27 mg/kg PO q8h). In addition, spironolactoned was administered (1.42 mg/kg PO q12h). Enalapril and pimobendan were continued as previously prescribed.
Over the next month, cardiac medications were adjusted multiple times because the dog suffered a left atrial rupture (which was treated conservatively) followed by 2 additional episodes of CHF. Enalapril was temporarily discontinued during left atrial rupture management caused by severe hypotension. When ACE inhibitor therapy could be safely reinstituted, benazeprile (0.28 mg/kg PO q24h) was substituted for enalapril. Despite high doses of oral furosemide (>10 mg/kg/d), pulmonary edema was not adequately controlled; therefore, SC furosemide administration was implemented.
The dog's evening furosemide dose (4.5 mg/kg) was changed to the SC route using an injectable formulation.f In addition, an afternoon dose of pimobendan (0.14 mg/kg PO) was added to the therapeutic regimen. Eight days later, the dog was presented again for dyspnea because of recurrent CHF. The dog was hospitalized for acute treatment of CHF for 24 hours. At the time of discharge from the hospital, the following medication adjustments were made: (1) furosemide dose and route were changed (4.5 mg/kg SC q8h); (2) hydrochlorothiazideg was administered (1.42 mg/kg PO q24h); and (3) pimobendan afternoon dose was increased (0.28 mg/kg PO).
The clinical signs resolved once more shortly after instituting these changes. Six weeks later, the client accidentally broke the glass bottle of furosemide. Because of a temporary shortage of the initial brand of furosemidef at the hospital, the client was provided with an alternate brand of injectable furosemide.h The dose and frequency of SC furosemide administration remained the same, and no other medication changes were made.
Approximately 2 weeks after the change in brand of furosemide, the dog developed multiple ulcerative dermal lesions at the sites of SC injections. All furosemide injections during that 2-week period were from a single bottle of the alternate brand of furosemide. The lesions ranged in size from 0.75 to 1.5 cm in diameter. The client also reported that the dog resented injections of the “new” brand of furosemide. The dermal lesions were suspected to be associated with the alternate formulation of injectable furosemide; therefore, this formulation was discontinued and the initial brand of furosemide substituted. During the subsequent week, no additional lesions developed and the pre-existing dermal ulcerations appeared to be resolving without specific treatment. In addition, the dog no longer resented SC furosemide injections. However, because of the recurrence of severe dyspnea associated with CHF, the dog was euthanized 1 week later. Histopathology of the dermal lesions was not performed.
Because the development of dermal lesions apparently coincided with the change in brand of furosemide, we hypothesized that differences in solution constituents, pH or osmolality were associated with the adverse dermatologic reaction in this dog. First, we contacted the distributors of both brands of furosemide. Technical support staff at Butler Schein Animal Health stated that they obtained their furosemide from Intervet Schering-Plough, and that their formulation was relabeled for distribution. Technical support staff at Intervet International GmbH stated that they prepared their furosemide at their facilities.
Next, we compared the constituents of each furosemide preparation. Several differences in the formulations became apparent: (1) the salts of furosemide differed (diethanolamine in the Intervet product versus monoethanolamine in the Butler product); and (2) pH adjustment in the Intervet product was with NaOH, and with NaOH or HCl in the Butler product. Diethanolamine salts of furosemide have a pH of 7–7.8, whereas monoethanolamine salts of furosemide have a pH of 8–9.3.
Finally, to determine if the brands differed in pH and osmolality, we measured pH and osmolality of aliquots of each furosemide formulation obtained from additional bottles of each formulation (different from those used by the client). The pH of Intervet solution was 7.20, whereas the pH of the Butler solution was 8.66 at 22°C. We repeated testing on different furosemide samples from different lots and our results were replicated; the Butler formulation of furosemide had a pH of 9.05, whereas the Intervet formulation had a pH of 7.47 at 22°C. The osmolality of the 2 brands differed slightly (244 [Intervet] and 280 [Butler]), but neither was sufficiently hyperosmolar to be of clinical importance. It is important to note that all bottles of furosemide tested were different than the bottles used for the dog in this report.
Subsequent online listserve discussions among veterinary cardiologists highlighted several similar instances of dermal ulceration, or pain/discomfort with SC administration of furosemide. However, no consistent association with formulation or brand was identified in that discussion.