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Research review outcomes will be displayed as 3 progressive layers of information:
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There is good quality evidence that the majority of racehorses have a small amount of bleeding into the lungs following exercise but only a few horses display nasal bleeding consistent with a larger amount of haemorrhage. An internal examination (using an endoscope and/or sampling of fluids) is therefore often required for diagnosis.
EIPH (bleeding into the lung following exercise) is associated with fast bouts of exercise and is seen in higher intensity equine sports including 3-day eventing, polo and show-jumping .
Some studies measure visual evidence of bleeding from the nose (epistaxis), some measure the appearance of blood in the airways and some rely on the presence of blood in fluid secretions.
Furthermore, because the amount of blood and the specific site of bleeding within the lungs can vary, some techniques for detecting and measuring EIPH severity are not precise.
As a result, different studies have found varying results. Overall however, it is clear that EIPH is very common.
–> 64 (4%) episodes of endoscopically visible tracheal bleeding.
–> 824 (51%) episodes of increased quantities of haemosiderophages in tracheal washes (cells that that contain the remains of red blood cells indicating past bleeding).
Despite differences between studies in actual percentage of horses affected, there is evidence that EIPH occurs very frequently in horses after racing.
Furthermore, EIPH in the preceding month significantly increased the risk of an EIPH episode the following month (25).
Graph 1: Incidence and severity (graded 0-4) of 744 Australian racehorses
(EIPH was detected in 412 [55%] of total study population,
but less than 1% had high grades of bleeding.
There is no treatment that is 100% effective at PREVENTING EIPH.
A number of different pharmaceutical preparations and management strategies have been attempted, some based on sound rationale, but no studies have shown a complete cessation of signs of bleeding or the severity of bleeding in all horses tested (3).
Furosemide (Lasix) reduces the signs but does not PREVENT or eliminate EIPH and has a performance enhancing effect (3).
There is high quality evidence that furosemide reduces the incidence and severity of EIPH in Thoroughbred racehorses.
Furosemide (Latex/ Salix) works as a diuretic, increasing urine production and decreasing blood volume (and body weight). During exercise, the drug causes a decrease in blood volume and lowers blood pressure in the lung, thus reducing the amount of stress on the pulmonary capillaries and reducing the severity and/ or incidence of EIPH.
Furosemide is banned from most racing jurisdictions as race-day medication (including the UK) but it is widely used in the USA and is also used as a training aid for horses prone to bleeding elsewhere, including in the UK. The long term health implications, if any, are not understood therefore more research evidence is required to answer this question.
Diuretic effect – reducing blood volume
Furosemide is a diuretic and inhibits the re-absorption of electrolytes and water in the kidneys, increasing urine volume and blood volume by around 10% (62).
Administration of furosemide causes:
–> A significant reduction in capillary and venous pressures of standing horses (160).
–> Reduced right atrial and pulmonary vascular pressures during exercise compared to without furosemide (160).
|Graph 2: Furosemide causes an increase in urine volume, reducing blood volume and cardio-vascular pressure. Source: (Soma et al, 2002) Journal of Veterinary Pharmacology Therapeutics|
|Furosemide reduces blood volume and caridovascular pressure, but not of sufficient magnitude to reduce pressures within the capillaries to a level that prevents rupture and haemorrhage completely (62).|
Although study results have varied, the most well controlled studies suggest that furosemide is effective in reducing the amount of visible blood on endoscopy.
In a 1981 study, 30 of 56 furosemide-treated horses which were examined had evidence of pulmonary haemorrhage (45).
A 1990 study concluded furosemide failed to prevent the development of EIPH and may have even exacerbated its development:
–>32 (61.5%) of 52 EIPH-positive horses which were given furosemide before a race remained EIPH-positive after that race (89).
–>62 (25.3%) of 235 EIPH-negative horses became EIPH-positive after racing with furosemide (89).
A 2002 study suggested that there was no difference in the incidence or severity of EIPH between horses with or without pre-race furosemide administration (57).
However, to contradict the above, in 2014 a systematic review of 17 individual studies involving 5,653 horses found:
high quality evidence that furosemide reduces the incidence and severity of EIPH in Thoroughbred racehorses (5).
a reduction of at least one severity grade after furosemide in 68% of horses which had previously been diagnosed with EIPH (5).
Grade 2 Grade 3 Grade 4
|Images: The amount of blood detected in the lower airway by endoscopy depicts the severity of EIPH (graded 1-4) (Photos: provided by the University of Edinburgh)|
Details of studies involved in a 2014 Review of Research on EIPH (5):-
Eight studies used furosemide at a dosage of 0.5 mg/kg bwt, and 3 studies used 1 mg/kg bwt. Six studies detailed a range of doses, or did not detail a specific dose but stated that furosemide was administered as per racing regulatory guidelines.
Furosmide was generally given by intravenous injection 4 hours prior to exercise.
Trials assessing visible bleeding in the airways (i.e. using a tracheobronchoscope) to determine the presence and severity of EIPH were considered higher quality evidence than those measuring red blood cells in lung washes. The tracheobronchoscopic severity score is the only method of assessing EIPH severity that has been associated with racing performance. Although measuring red blood cells in the lung washes is arguably a more sensitive measure of EIPH severity and has the benefit of being objectively quantified, researchers have not determined what constitutes a clinically significant degree of haemorrhage, nor have studies detected associations between amount of red cells in these washes and racing performance.
The review investigated study design and bias and found that trials which used randomisation, allocation concealment or a placebo detected a significant effect of furosemide to reduce or prevent EIPH, whereas studies that did not use these methods found no effect of furosemide.
The effect of furosemide was greater in the studies conducted in simulated or actual racing conditions when compared to exercise on a treadmill.
The overall quality of the evidence for furosemide decreasing incidence and severity of EIPH was high:-
This review suggests that 93 fewer horses per 1000 horses examined will develop endoscopically visible EIPH after treatment with furosemide.
When evidence from high-quality randomised controlled trials only is considered, 243 fewer horses per 1000 examined will develop endoscopically visible EIPH.
Additionally, 68% of horses that develop endoscopically visible EIPH experience a reduction in EIPH severity by at least one severity grade after administration of furosemide.
Despite earlier studies that did not find an association between EIPH and furosemide, there is now high quality evidence that furosemide reduces the incidence and severity of EIPH in Thoroughbred racehorses.
There is good quality evidence that furosemide significantly decreases race time, and the effect of furosemide may be influenced by age and sex.
In 1990, a study of 79 Thoroughbred horses without exercise-induced pulmonary haemorrhage (EIPH) and 52 horses with EIPH reported females, colts and geldings had faster race times following pre-race furosemide however, only the race times of geldings were significantly faster (89).
In 2009, 167 Thoroughbred racehorses were studied to investigate the efficacy of furosemide for prevention of EIPH under typical racing conditions. Severity of EIPH was scored on a scale from 0 to 4 after each race by means of tracheobronchoscopy (scope) (16).
–> Horses were substantially more likely to develop EIPH (of grade 1 or higher) or develop moderate to severe EIPH (grade 2 or higher) following the administration of saline solution when compared to furosemide.
–> In addition, 81 of the 120 horses (67.5%) that had EIPH after administration of saline solution had a reduction in EIPH severity score of at least 1 when treated with furosemide.
A study in 2000 which investigated 788 Standardbred pacers competing in 8,378 races at one racetrack (Pocono Downs racetrack, Pennsylvania) reported horses administered with pre-race furosemide ran an average of 0.67 seconds faster than untreated pacers (Graph 3 & 4)
–> providing good quality evidence that furosemide significantly decreases race time (61).
|Graph 3: 10 sequential races, 5 before pacers were given pre-race frusemide and 5 following the pre-race administration of frusemide. There was a significant difference when comparing race 1 with 5 (#) (nonfrusemide). In races 6 through to 10 (frusemide) racing times were significantly decreased when compared to race 5 (*)||Graph 4: Race times for pacers with and without the pre-race administration of furosemide at finishing positions 1 to 8. There was significant difference in racing times at each position when comparing horses with and without the prerace administration of furosemide.
Furthermore, the same study reported that age and sex influenced race time.
The younger horses showed the greatest response to furosemide in the groups aged 3, 4 and 5 years, with a decrease in response as their times improved and no improvement in the older horses.
However, this data could have been skewed as there were fewer older horses in the study (Graph 5) (61).
Horses, geldings and females ran a mean of (0.46 seconds faster), geldings (0.31 seconds) and females (0.74 seconds), respectively (61).
There is good quality evidence that furosemide has a performance enhancing effect resulting in quicker race times, and the magnitude of this effect may be associated with sex and age.
Graph 5: Racing times of horses administered with pre-race furosemide
plotted against age and gender. Furosemide progressively shortened
race time until the age of 6 and increased thereafter.
Studies have evaluated a number of different pharmaceutical medications purported to reduce the severity of EIPH.
Effect of clenbuterol on EIPH incidence
–> Clenbuterol administration at rest – when administered alone, or when combined with furosemide, clenbuterol caused an increased heart rate but no significant changes in heart or lung blood vessel pressures.
–> Clenbuterol effects on exercise – heart rate increased and blood pressure within the heart and lungs increased progressively with increasing work intensity. However, these values were not significantly different compared to exercise without clenbuterol; the incidence of EIPH was unaffected by using clenbuterol.
–> Furosemide & Clenbuterol, combined effects on exercise – heart rate, and heart and lung pressures increased significantly but were not significantly different from that of the furosemide only experiments, suggesting that the effects were due to furosemide alone and not clenbuterol. All horses experienced EIPH.
Thus both of these studies concluded that clenbuterol (a bronchodilator) is ineffective in modifying the blood pressures within the lungs in standing or exercising horses and is unlikely to offer any benefit to healthy horses experiencing EIPH.
It must be noted that the drug’s eﬀect on EIPH severity was not assessed.
Effect of Atropine and ipratropium on EIPH incidence
–> but this study was low quality, with very low numbers of horses and the examiners were not blinded to the treatments used.
To date, there is low quality evidence that bronchodilators affect EIPH.
Effect of Aminocaproic acid administration on EIPH incidence or severity
–> Pulmonary inflammation decreased but ACA was not effective in reducing the incidence or severity of EIPH.
–> Aminocaproic acid administration had no effect on any measurements and thus ACA was deemed ineffective in preventing or reducing the severity of EIPH (68).
There is very low quality evidence that aminocaproic acid affects EIPH severity.
Effect of corticosteroids on EIPH incidence
–> Dexamethasone failed to significantly improve gas exchange and all horses in the study, whether treated or not, developed EIPH as demonstrated by bleeding in the airways. The severity of EIPH was not graded (238).
There is very low quality evidence that corticosteroids affect EIPH incidence.
–> Addition of flunixin had no effect on the effects of furosemide
–> The effects of flunixin on its own were not tested
–> A similar study in 1998 showed that phenylbutazone also had no influence on the effects of furosemide (241).
–> Phenylbutazone did not reduce lung blood vessel pressures; the authors’ suggested therefore that phenylbutazone is unlikely to alter the prevalence or severity of EIPH.
There is very low quality evidence that nonsteroidal anti-inflammatory drug treatment (NSAIDs) affect EIPH.
–> Pentoxifylline administration at rest – caused anxiety, increased heart rate, muscle tremors and mild sweating, but no statistically significant changes in heart or lung blood vessel pressures.
–> Pentoxifylline effects on exercise – neither heart rate nor heart and lung blood pressures were significantly different from those in the control study; the incidence of EIPH remained unchanged.
–> Pentoxifylline had no eﬀect exercising Thoroughbred horses.
–> Pentoxyfylline was ineffective on lung blood pressures when used alone or in combination with furosemide.
There is very low quality evidence that pentoxifylline affects EIPH.
–> this dose resulted in no significant differences in heart and lung blood pressures, heart rate, arterial oxygen content or arterial carbon dioxide content compared to controls
–> the authors’ concluded therefore that this dose does not protect the lung blood vessels from exercise-induced high pressures and is unlikely therefore to prevent EIPH (167).
–> there was a small but consistent and significant reduction in blood pressure within the heart/lungs
–> EIPH severity was significantly greater in the treated horses.
This study suggested that nitric oxide treatment may actually exacerbate the severity of EIPH.
It is proposed that externally applied nasal strips open up the upper airway which in turn, alleviates lung pressures and reduces the risk of EIPH.
In 2001 there were several small studies that investigated the effectiveness of nasal strips and furosemide whilst galloping horses at near maximal effort on a treadmill:-
A study of 5 Thoroughbreds (80) (Graph 6) and another of 8 Thoroughbreds (79) reported that the external nasal strip alone, furosemide alone and simultaneous use of furosemide and nasal strips reduced EIPH severity but did not eradicate it.
Furthermore, there was no further gain of simultaneously using both furosemide and nasal strips (80).
A further study of 7 horses evaluated respiratory gases (Oxygen and Carbon Dioxide) in the blood which fluctuate in accordance with exercise and reported that the application of an external nasal dilator strip had no significant effect on this process (81).
Although there is some evidence that nasal strips reduce severity of EIPH, it must be noted that these two studies (79) and (80) involved only a small number of horses and were part funded by the company that produces this product.
Further research is needed to verify these findings in a larger population.
It must also be noted that nasal strips are banned by horseracing authorities in some countries e.g. UK.
Graph 6: Nasal strips and furosemide reduced EIPH but did not eradicate it and this study was part funded by the company that produces the product
Further research is needed to answer whether the observed improvement of race times following pre-race administration of furosemide is due to a reduction in bleeding or to other actions of the drug (62).
The majority of horses are rested (varying durations) and/or receive anti-inflammatory medication. In some racing jurisdictions there is an enforced period of rest from racing.
Although these and other similar suggestions such as paddock turnout are sensible, there is currently no research evidence to validate these suggestions.
The authors are not aware of studies that evaluate the value of different rest periods for mitigating against the repercussions of EIPH.
Suggestions such as paddock turnout are sensible however, there is currently no research evidence that validates this.
Effect of clenbuterol and corticosteroids on removal of blood from the airways
A 2006 study investigated the effect of autologous blood (i.e. blood drawn from the horse itself) instilled into the lungs (128) and the effect of the following medications:-
–> Inhaled Beclomethasone diproprionate – administered via a metered dose inhaler using the Aeromask 8 inhalation device.
–> Oral Prednisolone – administered orally mixed with feed.
This technique reliably caused inflammation and others have also used this model to make assumptions about the inflammatory effects of bleeding into the airways.
This study showed that clenbuterol and inhaled or oral glucocorticoids altered some of the inflammatory cell populations within lung washes but the results were variable and of unknown clinical significance.
Further work is required to evaluate such therapies
It has been proposed avoiding hard surfaces and preventing exposure to airborne particles such as mouldy feed may reduce the risk of developing EIPH and epistaxis (nasal bleeding). Although, these suggestions are sensible there is currently no research evidence to validate these suggestions.
One of the theories proposed for causing or exacerbating the development of EIPH is limb-surface induced trauma due to the mechanical forces occurred whilst galloping.
In response to this theory, one study has proposed that track watering to reduce surface forces may reduce the risk of EIPH and epistaxis (nasal bleeding) (21).
No significant differences were noted in the incidence of EIPH with horses stabled on paper bedding compared to straw (44).
This is a dated study and further research evidence is needed.
BRITISH HORSERACING AUTHORITY: Rules of Racing – Point 8. Use of Nasal Strips is not permitted in Britain
The development of a telemetric overground endoscope – HBLB funded project
Straight Talking – Enhancing performance – Mark Johnston Racing 20.01.16
There are several articles available within online Trainer Magazines and they have kindly provided full access to these magazines below:-
The Sid Fernando Column – The Lasix anomaly – page 88 – North American Trainer Magazine 26.07.14
The 50 shades of gray in the EIPH and Salix debate – page 88 – North American Trainer Magazine 20.07.12
Training the untrainable – how to improve the respiratory system – Trainer Magazine website 17.09.08
Increasing Oxygen Concentration in the Blood of the Racehorse – Trainer Magazine website 14.02.08
Nasal Strips – increasing performance, reducing EIPH – Trainer Magazine website 01.07.07
Inhalation therapy – treating airway problems in the racehorse – Trainer Magazine 30.06.06