Furosemide Continuous Rate Infusion in the Horse: Evaluation of Enhanced Efficacy and Reduced Side Effects and Hypomagnesemia in the Horse- A Retrospective Study of 401 Cases

Abstract

Continuous rate infusion (CRI) of furosemide is considered a superior method of administration to intermittent administration (IA) in humans. This study examined whether furosemide CRI, compared to IA, would increase diuretic efficacy with decreased fluid and electrolyte fluctuations and activation of the renin-angiotensin-aldosterone system (RAAS) in the horse.

Five mares were used in a crossover design study. During a 24-hour period each horse received a total of 3 mg/kg furosemide by either CRI (0.12 mg/kg/h preceded by a loading dose of 0.12 mg/kg IV) or IA (1mg/kg q8h IV). Urine volume and concentrations of electrolytes, aldosterone, and furosemide in urine were recorded. Serial blood samples were obtained and analyzed for hematocrit, total solids, electrolytes, and furosemide.

Although we were not able to demonstrate a statistically significant difference in urine volume over 24 hours between methods, this study demonstrated that CRI of furosemide produces a more uniform urine flow, and decreases fluctuations in plasma volume and suppresses renal concentrating ability throughout the infusion period. Importantly, there was significantly greater urine output after CRI in the first 8 hours. More K, Ca and Cl were excreted after CRI. There was no significant difference in aldosterone excretion between methods.

The furosemide disposition data conformed to a two-compartment model with elimination half-lives of 1.35 and 0.47 hours for CRI and IA, respectively. The area under the excretion rate curve, indicating exposure of the renal tubules to furosemide, was 1,285.7 and 184.2 ml*mg/ml for CRI and IA, respectively.

The second study was initiated to identify the signalment and clinical variables potentially associated with hypomagnesemia in horses evaluated at the NCSU-CVM veterinary teaching hospital between January 1999 and May 2001. A nested case reference study (nested case-control study) was conducted to examine the potential relationship between hypomagnesemia and signalment, serum chemistry panel analyses, number of hospitalization days, discharge status, and diagnosis.1 A series of independent and multivariable logistic regression models were used to assess the potential association of each variable with low total serum magnesium values.

Of all horses included in the study, 48.7% had total serum magnesium values below the normal reference range. Hypomagnesemia was more likely to occur in horses older than one month of age. Colic, acute diarrhea, other gastrointestinal disease, infectious respiratory disease, and multi-organ system disease were associated with hypomagnesemia in adult horses, while diarrhea in foals reduced the risk of hypomagnesemia. Overall there was no relationship between hypomagnesemia and mortality, but horses with colic and hypomagnesemia were more likely to survive than horses with colic and normal or elevated total magnesium. Among horses that survived, hypomagnesemia at admission was associated with a longer hospitalization period.