Summary

It is important to note that systemic Nsaids can be used very successfully, to the point where some horses with chronic lameness receive bute for extended periods of time, typically at a dose such as 1 gram once daily. However, even in these horses, it is worth considering giving horses time off from treatment, such as treating only before and after strenuous exercise on a limited number of days per week, or taking the horse off bute periodically to allow organ systems such as the gastrointestinal tract and kidneys to recover”

(End quote from research paper.)

This paper clearly states the concern that surrounds the use of Nsaids in horses. If we look at human medicine statistics in “Toxic and deathly Nsaids” (Ref. 12) there are many arguments supporting the need for more investigation into the long-term effects of Nsaids on animals in general and horses in particular. Another study points out that a conclusion reached by the Food and Drug Administration (PDA) does not coincide with published data.

Ref. 14: (Human)“PDA Reviews contain a substantial amount of unpublished data regarding NSAID-related dyspepsia that is of comparable quality to the published data. The conclusion reached by the PDA Review data is that use of Nsaids is not associated with dyspepsia, while that reached by published data is that use of Nsaids is associated with dyspepsia”

Dr. Blikslager (Ref. 13) referred to reduced bone and intestinal healing caused by Nsaids. Bandolier (Ref. 15), in a newsletter dated March 2004, also mentions several studies in animals indicating that Nsaids have a deleterious effect on bone healing. Although there is contradictory evidence, they suggest that dose and duration related issues have not been solved. An article (Ref. 16) on Nsaids and ligament injuries states:

“Since there is evidence that cell proliferation and division is associated with certain prostaglandins it may even be harmful to continue Nsaids for a long period of time.”

In this article, the potential benefits of NSAID medication for ligament injuries is seen as being less important than good management. Harder & An (Ref. 21) refer in their article to the mounting evidence indicating that Nsaids interfere with normal bone healing. These observations are in line with recent thoughts that inflammation is necessary for efficient healing.

Anti-inflammatory treatment in contemporary medicine.

The use of Nsaids is often described as ‘supportive’ (Ref. 1) for the treatment of lameness in horses. The term ‘supportive’ is open to anyone’s interpretation and cannot be described as scientific.

From reading the above mentioned papers, it becomes clear that there is no conclusive scientific evidence to support the use of Nsaids for the purpose of healing. Also, their use is mostly based on clinical impressions and not on controlled experiments

As a consequence, the only remaining reason for the use of Nsaids is in the hope of reducing pain. Pain is very much associated with suffering. We humans feel we suffer when we experience pain. When we can take away pain, it seems obvious that we take away suffering. As a consequence, painkillers are consumed in large quantities in our modern society, through over-the-counter sales and by prescription. The use of painkillers has become a trivial matter for many and borders on an epidemic. We persuade ourselves that we feel better when we take these medicines and therefore argue that  they must be good for us. There is a widespread use of painkillers for sports injuries.  Their apparent efficacy in this field has contributed to their image as useful medicines and made their automatic use for other indications more easily accepted and popular.

We extrapolate what we want and how we feel to the animals under our care. When we see an animal in pain, we reach for painkillers. As the main reason for the use of painkillers is the relief of suffering, we argue that the reason itself justifies their use. As it is not unusual to see an animal regaining liveliness, at least during the initial use of painkillers, such observations reinforce our belief that painkillers are beneficial. We should ask ourselves whether the results bear out the intention.

There is also considerable pressure on veterinarians from their clients and society in general to reduce the suffering of animals. The veterinary profession recognizes its duty to reduce suffering and promote the welfare of animals. The use of painkillers fulfils this duty because it is seen to prevent suffering.

The convenience of using painkillers, their apparent efficacy and a common short-term view of medicine has encouraged and endorsed their use by both the public and the medical professions, regardless of an increasing understanding that they carry a significant degree of toxicity.(Ref. 12)

Little consideration has been given to the long-term effects and consequences of analgesic treatment. Retired horses end up in a field or a ‘rescue’ home and do not benefit from any meta-analysis of the treatments they received during their working life. People tend to remember the horses that have done well for months and years on daily doses of phenylbutazone. They forget the others that did not do so well and fail to consider a possible relationship with the Nsaid treatment they received. Only acute illnesses (intoxications) are recorded. Insidious consequences of long-term treatment with Nsaids are difficult to establish. 

Is the absence of proof of long-term side effects sufficient evidence that there is no risk? No! Absence of evidence is not evidence of absence. We should question why so many publications warn about the long-term use of anti-inflammatory treatments.

For potential long-term consequences of analgesic treatment in veterinary medicine we have to look to what information is available from human medicine. Although we cannot extrapolate the information on humans to horses without considering species differences, the overall negative view on long-term use of Nsaids in man is so overwhelming that we should be more cautious with long-term use of Nsaids in horses.

Pain relief, welfare and choice of therapy.

I will now restrict my attention to the use of Nsaids in laminitis.

There are sufficient doubts raised about the efficacy of Nsaids in reducing the inflammatory response of laminitis to justify concluding they have no benefit for this aspect of the condition. Also, questions are raised about the inappropriateness of interfering with the inflammatory process when tissues need repairing.

The only possible remaining benefit, therefore, is in the hope of reducing pain. Some say that Phenylbutazone is clinically very effective in achieving this (Ref. 9). Others assign it only very modest analgesic effects (Ref. 7). One study concludes that the dose rate does not correlate with different levels of pain relief for chronic lameness in horses. (Ref. 6). In a web site of the University of Minnesota (Ref. 22) it says:

‘Traditional drugs such as Banamine® or Phenylbutazone may not be sufficient for pain control in horses that are very ill.’

again suggesting some insufficiencies in pain relief of Nsaids.

The plethora of approaches to pain management in horses, mentioned in the following summary of a research paper, shows the complexity of the subject of pain.

(Ref. 24) “This preliminary study investigated the attitudes, and evaluated the current practice of a sample of the veterinary profession in the UK in relation to the management of pain in horses. In June 2001, a questionnaire was posted to 260 veterinarians in specialised equine practice, and 140 veterinarians in general practice with a significant equine caseload. There was a 25 per cent response rate to the questionnaire, which recorded information about the availability and prescription of analgesic drugs, the factors influencing the selection of analgesics and their administration, and estimates of the severity of pain associated with selected clinical conditions. There were considerable variations in the practices applied to manage pain in horses, implying that there are similar attitudinal barriers to the optimal management of pain in horses as have been identified in other domestic species.”

Pain relief for laminitis is usually given for long periods. The apparent need for such a strategy itself raises questions about the efficacy of the analgesic effect. The perceived need for long-term medication should also ring an alarm bell with regard to the risk of toxic side-effects. In the absence of good scientific support for the use of Nsaids, the presence of continuous warnings about their use from researchers, and the generally unsatisfactory results from the currently orthodox management of laminitis, it seems sensible to reconsider our whole approach to this devastating disease.

When conventionally, Nsaids are used, we know they do not offer complete pain relief for horses with chronic laminitis. They reduce the pain, ‘awaiting’ the moment the pain disappears. They also interfere with the inflammation process necessary for good healing and therefore usually prolong suffering because healing is slower or only partial.

Choices should be made without yielding to emotions but based on evidence and knowledge, and by looking beyond first impressions. The UFAW (Ref. 23) Chief Executive James K. Kirkwood writes the following:

“UFAW continues to play a leading role in advancing animal welfare by (I) promoting the science aimed at providing better understanding of the animal’s needs, physical and mental, (II) promoting high standards of animal care through disseminating information and facilitating discussion, and (III) making sure that in all our interactions with them, animal’s welfare interests are properly considered and addressed.”

We should also bear the definition of health by the WHO in mind:

“Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity.”

Researchers are investigating the possible negative effects on healing of long-term painkiller use (Ref. 13, 15 ). During her work, aimed at returning the deformed hooves of chronically lame horses to a physiological shape, Dr. H. Strasser (Ref. 18) has recognised the negative effect of NSAID painkillers on this healing process and strongly discourages their use.  Others (Ref. 19) have also discovered that good healing is possible only by stopping NSAID treatment. In his paper, (Ref. 20) S. Ralston suggests that:

“Alternative and adjunct therapy to traditional NSAID therapy should be explored, since the analgesic use of Nsaids, being prolonged, carries the risk of causing gastric ulceration.”

There is a general lack of interest and even hostility by the profession to the exploration of alternatives to conventional practice. Reasons for this are historical and human. Reasons given are lack of proof of efficacy. Discussions are fuelled by emotions and inflexible views. Considerations for the patient (horse) may come second to intellectual interests.

‘Primo non noncere’ is the oath we take before becoming a veterinary surgeon. Not harming means not using treatments that worsen the disease. First impressions are not the best parameters to judge whether an animal becomes worse. Decisions should be based on sound knowledge. Too often emotionally charged sensibilities come into play to decide what can be a valid treatment.

Conclusion:

The conclusion must be that the use of Nsaids are defended on the basis of clinical impressions and habit only. There is no scientific data available to justify their use, especially in long-term problems. There is also a worrying lack of good data on their long term effects while questions are raised on their suspected long term side effects.

Emotionally charged arguments hamper the development of new alternative techniques. Economical factors determine which techniques will be researched or those which will be put to one side.

Treatment of laminitis is not making much progress regardless of large amounts of research.

Pain is often the sole parameter taken into account in deciding on animal welfare.

Alternative holistic views do not comply with the very technical and specialist dissecting approach of scientific medicine.

In such an environment it seems unlikely that various parties will come to agree on what constitutes best practice. Choices are made based on individual research, experience and convictions.

Credit:

I like to thank W.R. Cook, FRCVS, PhD, professor of surgery Emeritus of Tufts University, Massachusetts, for his help in the realization of this report.

References:

1) Caron J. P., DVM, MVSc., Department of Large Animal Clinical Sciences, Michigan State  University. USA.   ‘Non-Steroidal Anti-inflammatory Drugs.’ AAEP proceedings vol 46 200 p243.

2) Pollit, Dr. Chris., BVSc, PhD.,  Associate Professor in Equine Medicine, School of Veterinary Medicine, The University of Queensland, Australia.  ‘Equine Laminitis.’    Rural Industries Research& Development Corporation PO box 4776 Kingston ACT 2604, Australia,  November 2001.

3) Van der Windt, Van der Heijden, Scholten, Koes and Bouter.,  Institute for Research in Extramural Medicine, Vrije Universiteit, Amsterdam, The Netherlands.   ‘The efficacy of non-steroidal anti-inflammatory drugs for shoulder complaints. A blinded review.’ : Journal of Clinical Epidemiology 1995 May;48(5):691-704.

4) Van Tulder, Scholten, Koes and Deyo.,   Vrije Universiteit, Amsterdam, The Netherlands.   ‘Non-steroidal anti-inflammatory drugs for low-back pain.’ The Cochrane Database of Systematic Reviews 2005 Issue 4, The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

5) The Merck Veterinary Manual 2003

6) Hu, Dr. Helen H., 2005  ‘Evaluation of the analgesic effects of phenylbutazone administered at a high or low dosage in horses with chronic lameness’ DVM Journal of the American Veterinary Association. 226   

7) Information sheet prepared by the USP (USA) Veterinary Advisory Panel.

‘Non-steroidal Anti-inflammatory Drugs.’

8) Mcllwraith, C.W., Colorado State University. ‘Licensed Medications, ‘Generic’ Medications, Compounding and Nutraceuticals- What has been scientifically validated, where do we encounter scientific mistruth and where are we legally?’ 50th annual convention of the AAEP, 2004, Ithaca, New York.

9) Stashak, T. S., ‘Adam’s lameness in Horses’, 5th edition.

10) Cohen, N. D., Carter, G. K., Mealey, R. H., Taylor, TS.,  College of Veterinary Medicine, Texas A&M University. ‘Medical management of right dorsal colitis in 5 horses: a retrospective study (1987-1993).’

11) Directory of Veterinary Medicine 2005.

12) Bystrianyk, R., ‘Toxic and Deathly Nsaids. An investigative report.’ (www.healthsentinel.com) 

13) Blikslager, Dr. A., and Jones, Dr. S.,  Associate Professors, College of Veterinary Medicine, North Carolina State University.

‘Health News Release,  19 November 2004.’

14) Maclean, Morton, Straus, Ofrnan, Roth, Shekelle.,  for the RAND health Program UCLA.  ‘Unpublished data from the USA Food and Drug Administration New Drug Application reviews. How do they compare to published data when assessing non steroidal anti-inflammatory drugs associated dyspepsia?’

15) Bandolier. Evidence-based Healthcare.  Produced by a group of scientists from Oxford University, UK.  ‘Newsletter March 2004.’

16) Almerkinders, L., Sports Medicine Section, University of North Carolina.‘Non-steroidal anti-inflammatory drugs and ligament injuries.’

17) Belknap, Blikslager, Jennings., College of Veterinary Medicine, State University of North Carolina.  ‘Laminar COX-1 and COX-2 protein expression in the developmental stage of laminitis: a case for use of COX-2 selective inhibitors?’ 50th Annual Convention of AAEP. 2004 Denver. Ithaca, New York.

18) Strasser, Dr. Hiltrud., Kells S., Tuebingen, Germany. ‘The hoofcare specialist’s handbook.’

19) Harman, J,. and Ward, M.,   ‘Laminitis treatment: A natural medicine perspective.’  Journal of Equine Hoof Science  73.

20) Ralston, R.,  Department of Animal Sciences. State University of New Jersey.    ‘Care for the older horse: Diet and health.’ November 2001

21) Harder, A. T., An, Y. H.,   ’The mechanisms of the inhibitory effects of non-steroidal anti-inflammatory drugs on bone healing: a concise review.’ Journal of Clinical Pharmacology, 2003 43 :807.

22) University of Minnesota:  November 2005.

http://www.cvm.umn.edu/umec/Research/Breakthroughs.html

‘Research Breakthroughs.’

23) The Universities Federation for Animal Welfare, Wheathampstead, Hertfordshire UK.  ‘Annual report 2004-2005.’

24) Price. J.,  Marques, J. M., Welsh, E. M., Waran, N. K.,  2002
 ‘Pilot epidemiological study of attitudes towards pain in horses.’

The Veterinary Record, 151, 19, 570-575

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