Furosemide facts and fiction

When it comes to the use of furosemide for treating EIPH, here's what we can all agree on.
Mar 01, 2013

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"There is terror in numbers," writes Darrell Huff in his mathematical primer How to Lie with Statistics. Published in 1954, this best-selling book rapidly changed the way people viewed numbers and data in research and how that data could be used to influence ideas and opinions. More than 50 years later, Huff's hypothesis still holds true: Data can be interpreted, slanted and presented to support virtually any agenda. He went on to explain that "the secret language of statistics, so appealing in a fast-minded culture, is employed to sensationalize, inflate, confuse and oversimplify."

The current debate in the horse racing world over the use or abuse of the diuretic furosemide contains many of these elements—sensationalism by the press and various animal welfare groups, inflated claims by both sides and oversimplification of the science involved. Furosemide proponents think that the drug helps treat an important condition found in almost all athletic horses and that its use is both ethical and humane. Critics maintain that it is an unnecessary performance-enhancing drug that's rarely used in the racing world outside of North America and that its continued use is ultimately weakening racehorse genetics.

Both camps can cite scholarly studies, field research projects and statistics to bolster their arguments, but all this science has not produced much common ground. There are, however, some indisputable facts regarding furosemide and exercise-induced pulmonary hemorrhage (EIPH), the disease that furosemide is used to treat in racehorses. Any attempts to clarify this contentious debate should start there.

Agreeing on etiology

While it is often linked with racehorses, EIPH is a condition that can affect all categories of performance horses, including three-day eventers, polo ponies and draft horses. EIPH results from rupture of pulmonary capillaries and subsequent leakage of blood into the airway. The site of initial bleeding is in the dorsocaudal lung. The reason for this is not fully understood.

The most commonly accepted theory to explain the occurrence of EIPH relates to the dramatic increase in blood pressure that normally occurs in the lungs of a maximally exercising horse. Increased blood pressure is caused by an increase in cardiac output. As a horse exercises, there is an increased oxygen demand by the body, and the normal equine heart is capable of tremendous increases in output to meet this demand. The huge difference between high blood pressure inside the capillaries and low pressure outside the vessels in the lungs causes capillaries to burst.

"To some extent, EIPH is an inevitable consequence (some might say physiological consequence) of the extremely high cardiac output required by racehorses," says Cate Steel, BVSc, FACVS, in Racing Victoria magazine.

Some theories suggest that there are other contributing factors, including any problems that restrict airflow (upper airway obstruction "roaring" and allergic, bacterial or viral airway disease), changes in blood viscosity, mechanical concussion and shear forces in the chest associated with running and bronchial artery angiogenesis. With each bleeding bout, the horse experiences inflammation of the airways and subsequent fibrosis. This pattern of inflammation and less than functional repair is repeated with each bleeding episode, leading to repetitive damage.

Pinning down prevalence

The true prevalence of EIPH stirs debate. Horses with EIPH are called "bleeders" because the classic clinical sign of this condition is poor performance and bleeding from the nostrils after exercise. Most bleeders (about 95 percent), however, do not show blood at their nostrils, even when they are bleeding deep in their lungs.1

The best and most accurate method of diagnosing a bleeder is with a tracheobronchial examination via fiberoptic scope. Although EIPH has been described in horses for hundreds of years, the horses that were known to suffer from this condition were those that bled, sometimes copiously and dramatically, from the nose. Horses that showed no external bleeding were considered free from EIPH and to be normal.

The development of the fiberoptic endoscope and the small flexible versions that followed in the 1970s helped us understand where the blood was coming from and exactly how many horses were affected. However, many countries did not and still do not have ready access to such equipment. Some trainers and owners forego these exams even when appropriate equipment is available, so the actual incidence of EIPH varies depending on how studies have been conducted. Some countries and breeders report a low incidence of EIPH, but these claims are rarely substantiated with well-controlled studies using endoscopic examination.

Much EIPH research, even some done very recently, suffers because of a lack of uniform agreement as to what constitutes a bleeder. Is it only a horse that visibly bleeds? Is it a horse that is assigned one of the four grades of abnormal bleeding in the trachea as seen with a scope? How and when should these individuals be examined? Within an hour after racing or sooner? After one race or after several? The decision about how and when to examine possible bleeders plays a large role in the statistical outcome. The results of any investigation cannot be relied on if the methodology is inconsistent.

However, it has been shown conclusively in the United States that between 43 and 75 percent of racehorses exhibit signs of EIPH based on a single endoscopic examination.2 In 1990, veterinary researchers at the University of Pennsylvania's New Bolton Center at the School of Veterinary Medicine showed that the prevalence of EIPH increases with the frequency of examination.3 More than 80 percent of horses showed evidence of EIPH on at least one occasion when examined after three consecutive races. Ken Hinchcliff, BVSc, MSc, PhD, repeated this work in 2005 in Australia and reported that 55 percent of horses examined showed some evidence of EIPH and that if horses were scoped after three successive strenuous workouts, nearly 100 percent would show some bleeding by the third endoscopic exam.4

Prevalence statistics reported from other countries by the International Federation of Horseracing Authorities all show relatively similar rates for the incidence of epistaxis in horses after racing, with Japan reporting 1.5 cases per 1,000 starts, the U.K. showing 0.83 per 1,000 starts, South Africa reporting 1.65 per 1,000 starts and Korea reporting a high of 4.4 per 1,000 starts.

Opponents of the use of furosemide to pretreat racehorses point out that this drug is used for this purpose only in the United States and Canada and that the rest of the world does not race on it. Furosemide is not needed, goes the argument, because EIPH is not seen in as high prevalence in other countries. Science does not support this view, and since many other countries only identify bleeders visually, the number of endoscopic-confirmed EIPH cases would likely be much greater. The simple scientific fact is that EIPH occurs with similar frequency in racehorses and equine athletes in almost all parts of the world.5