EIPH and Furosemide Use in Racehorses Explained

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Originally published on TheHorse.com

One of the most controversial topics in Thoroughbred racing today is the race-day use of furosemide (commonly called Salix or Lasix). The drug is used to lessen the effects of a respiratory condition called exercise-induced pulmonary hemorrhage (EIPH), characterized by bleeding into the lungs or out the nose during exercise. In the midst of rumor and fact regarding the drug and the disease it treats, one professor offered an explanation.

During the well-attended Oct. 2 Veterinary Science Seminar "Furosemide and EIPH: Efficacy and Controversy: The American Horsemen's Story," held in Lexington, Ky., Thomas Tobin, MVB, MSc, PhD, MRCVS, Dipl. ABT, professor of pharmacology and experimental therapeutics at the University of Kentucky Gluck Equine Research Center, reviewed the relationship between EIPH, furosemide, and the racehorse.

EIPH and its Effects

Tobin relayed that the phenomenon now known as EIPH was first recorded in the literature in the late 1700s when it was identified as epitaxis (bleeding from the nostrils) after intense exercise, and a decrease in performance. But it wasn't until the fiber-optic endoscope was invented in the 1970s that veterinarians found that up to 80% of racehorses had evidence of blood in their tracheas after a race.Later, veterinarians learned a bronchoalveolar lavage will show evidence of bleeding at the alveolar capillary level. The latter condition is now known as occult or internal EIPH.

In 2005, Tobin said, Kenneth W. Hinchcliff, BVSc, PhD, Dipl. ACVIM, a professor at the Faculty of Veterinary Science at the University of Melbourne, Australia, described an EIPH scoring system that is currently used:

• Grade 0: No blood detected in the pharynx, larynx, trachea, or mainstem bronchi.
• Grade 1: One or more flecks of blood, or two or fewer short (less than one quarter the length of the trachea) and narrow (less than 10% of the tracheal surface area) streams of blood in the trachea or mainstem bronchi present.
• Grade 2: One long stream of blood (more than one-half the length of the trachea) or more than two short streams of blood occupying less than one-third of the tracheal circumference.
• Grade 3: Multiple, distinct streams of blood, covering more than one-third of the tracheal circumference, with no blood pooling at the thoracic inlet.
• Grade 4: Multiple, coalescing streams of blood covering more than 90% of the tracheal surface with blood pooling at the thoracic inlet.

"If you want to quantify the amount (or severity) of bleeding, you can do it visually," Tobin confirmed.

Horses with chronic EIPH develop long-standing lesions in their lungs with long term effects, Tobin said. These lesions are generally bilateral and often occur in the dorsocaudal (upper, rear) lobes, an unusual location, he added. Later research would support the conclusion that the unusual location of the lesions was based upon the ailment's pathogenesis.

Three theories exist surrounding EIPH's pathogenesis, Tobin said:

• Poor collateral ventilation;
• Stress failure of pulmonary capillaries (Tobin said that the horse's normally low blood pressure rises during exercise, possibly causing his pulmonary capillaries to fail); and
• Stride driven shockwaves (Tobin noted that in treadmill studies, horses tended to preferentially bleed on the lead forelimb side, supporting the theory that a stiride-related shock waves are transmitted through the lung and reflected back to the dorsocaudal lobe; this would also explain the unusual lesion locations, he noted).

Finally, Tobin reviewed the different EIPH presentations identified in the literature:

• Bleeding in alveoli;
• Bleeding in alveolar space;
• Occult bleeder;
• Bloody nose; and
• Acute sudden death.

EIPH and Sudden Death

Although it's a less common presentation, sudden death is a real and dangerous outcome of EIPH. Tobin recalled a 1996 case he worked on in which a racehorse collapsed shortly after leaving the starting gate. While two fractured cervical vertebrae were found on necropsy, the real cause of death was identified when the horses lungs were discovered filled with blood, Tobin said.

A 1988 study by Gunson et al. evaluated nine cases of sudden death attributable EIPH during the early 1980s; all of the horses in this particular study, he said, ran on furosemide.

Tobin also brought up the fact that although EIPH is dangerous for horse health, it also presents a risk for the jockeys and exercise riders that mount affected animals each day. In one Quarter Horse race, for example, he relayed that a horse collapsed and died due to EIPH just after the finish line. Because there were no horses behind the animal at the time, the jockey sustained only minor injuries in the spill. Conversely, Tobin described one EIPH-related death at a Thoroughbred track in which the jockey of the affected horse sustained career-ending injuries when two horses trampled and/or jumped the downed animal and rider.

The points to remember about EIPH, its effects, and associated sudden death, Tobin said, are:

• All horses bleed into their lungs during races;
• EIPH and the associated side effects cause poor racing performance;
• EIPH cumulatively damages lungs and as damage accumulates, the incidence and severity of bleeding increases; and
• Untreated EIPH--and even treated, at times--places both horses and their jockeys at risk of injury or death.

Furosemide Use in Racehorses

Finally, Tobin turned to the use of furosemide--a diuretic that's been used since the early 1970s in an attempt to prevent or diminish EIPH severity--in racehorses.

"It's being used, it has been used, and it's been approved based on the inclination it is effective," Tobin said.

Theoretically, if horses are given furosemide, the drug draws the water away from the lungs and keeps the blood pressure from getting too high, thus preventing the gaps in the vessels and the blood from getting into the lungs.

Most horses are administered 350 to 500 milligrams of furosemide via an intravenous injection four hours before post-time, Tobin said. The effects of the drug are relatively short lived, he added, because it is an organic acid that is rapidly cleared from the blood into the urine.

He also noted that in the past--specifically with the introduction of the Corrupt Horse Racing Practice Act of 1980--opponents have tried to eliminate furosemide from horse racing on the grounds that it flushes additional drugs out of the body and/or acts as mask hindering a drug detection in horses' blood and urine. Tobin was instrumental in disproving both claims.

Moving forward, Tobin discussed some relevant research surrounding EIPH and furosemide administration in racehorses.

In 2005 Sanchez et al. confirmed that EIPH significantly interferes with horses' blood oxygenation, Tobin relayed. Also in 2005, Hinchcliff , in a study including more than 770 horses, found that racehorses with Grade 1 EIPH or less were four times more likely to win a race, and horses with EIPH graded 2 or higher finished significantly father behind the winner than did horses without EIPH.

Researchers also examined whether or not furosemide is effective in controlling EIPH in racehorses.

In 2009, in a 156-horse study, Hinchcliff et al. found that furosemide was effective in reducing Grades 2, 3, and 4 EIPH scores in a study of 156 South African Thoroughbred racehorses; "It basically wiped out the more severe bleeding," Tobin said.

And, although not a classic scientific study, Tobin relayed that New York racing regulator data presented in Bill Heller's 2002 book Run, Baby, Run showed a more than 400% decrease in epitaxis in racehorses in that state after furosemide was approved for use in 1995. "Data presented in book from the 1990s clearly establish the efficacy of Lasix in preventing epitaxis," he said.

Switching gears, Tobin relayed that early work by Soma suggested a positive effect on performance with furosemide administration, and a 1999 study by Hinchcliff supported the early reports. Tobin relayed that Hinchcliff et al. reviewed race records of more than 22,500 horses and found that, after the data was normalized, horses that raced on furosemide ad a three to five-and-a-half-length advantage over nonmedicated horses when raced at six furlongs; the study also showed that furosemide's performance enhancing effects were most evident in shorter races and appeared to diminish in longer races.

"These studies, however, were performed long before the 2005 Hinchcliff study showing that EIPH inhibits racing performance, and neither of these studies were able to factor in what we now know to be one explanation for positive performances by horses running with Lasix--namely that EIPH causes horses to run slower and Lasix acts to prevent and lessens EIPH," Tobin explained.

Take-Home Message

"All racing horses suffer (from EIPH) at some level," Tobin said in closing. A conservative, science-based interpretation is that furosemide acts to protects the welfare of racing horses and also their riders, he added.

And, in a salute to American horsemen and to the community at large, he noted that American horsemen had "correctly determined the benefits of furosemide 40 or so years ago, while it has taken science more than 30 years to confirm that the horsemen were on the right track, so to speak, all along with furosemide."

Disclaimer: Seek the advice of a qualified veterinarian before proceeding with any diagnosis, treatment, or therapy.

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