Analyze Diet
Animals : an open access journal from MDPI2023; 13(22); doi: 10.3390/ani13223447

Analgesic Efficacy of Non-Steroidal Anti-Inflammatory Drug Therapy in Horses with Abdominal Pain: A Systematic Review.

Abstract: This systematic review aimed to identify the evidence concerning the analgesic efficacy of non-steroidal anti-inflammatory drugs to treat abdominal pain in horses, and to establish whether one non-steroidal anti-inflammatory drug could provide better analgesia compared to others. This systematic review was conducted following the "Systematic Review Protocol for Animal Intervention Studies". Research published between 1985 and the end of May 2023 was searched, using three databases, namely, PubMed, Embase, and Scopus, using the words equine OR horse AND colic OR abdominal pain AND non-steroidal anti-inflammatory drug AND meloxicam OR flunixin meglumine OR phenylbutazone OR firocoxib OR ketoprofen. Risk of bias was assessed with the SYRCLE risk of bias tool, and level of evidence scored according to the Oxford Centre for Evidence-based Medicine. A total of 10 studies met the inclusion criteria. From those only one study judged pain with a validated pain score, and a high risk of bias was identified due to the presence of selection, performance, and "other" types of bias. Therefore, caution is required in the interpretation of results from individual studies. To date, the evidence on analgesic efficacy to determine whether one drug is more potent than another regarding the treatment of abdominal pain in horses is sparse.
Publication Date: 2023-11-08 PubMed ID: 38003065PubMed Central: PMC10668864DOI: 10.3390/ani13223447Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Journal Article
  • Review

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research paper systematically reviews the effectiveness of non-steroidal anti-inflammatory drugs (NSAIDs) in relieving abdominal pain in horses, and also evaluates if one NSAID is more effective than others.

Methodology

  • The researchers carried out this systematic review following the rules outlined in the “Systematic Review Protocol for Animal Intervention Studies”.
  • They combed through research articles published between 1985 and May 2023. The search was carried out on three databases: PubMed, Embase, and Scopus.
  • The search terms used for this review were “equine OR horse AND colic OR abdominal pain AND non-steroidal anti-inflammatory drug AND meloxicam OR flunixin meglumine OR phenylbutazone OR firocoxib OR ketoprofen.”

Assessment of Risk and Level of Evidence

  • The researchers assessed the risk of bias in the included studies using the SYRCLE (Systematic Review Centre for Laboratory Animal Experimentation) risk of bias tool.
  • The evidence level of the included studies was scored based on the criteria set by the Oxford Centre for Evidence-based Medicine.

Findings

  • Out of many, only 10 studies met the inclusion criteria set by the researchers.
  • Among those, only one used a validated pain score to assess pain levels in horses.
  • The researchers identified a high level of bias in the studies due to issues such as selection, performance, and “other” types of biases.
  • These biases necessitate a cautious approach in interpreting the results of the individual studies.

Conclusion

  • According to the research, current evidence regarding the analgesic efficacy of one NSAID over another in treating abdominal pain in horses is limited. In other words, it’s not yet clear if one drug is definitively more potent than another for this particular use-case.

For further and broader understanding, more clinical trials with less bias and more rigorous methods of pain assessment in horses are needed. The paper highlights the importance of this area of study, as abdominal pain (also known as colic) is a common and serious issue in horses.

Cite This Article

APA
Citarella G, Heitzmann V, Ranninger E, Bettschart-Wolfensberger R. (2023). Analgesic Efficacy of Non-Steroidal Anti-Inflammatory Drug Therapy in Horses with Abdominal Pain: A Systematic Review. Animals (Basel), 13(22). https://doi.org/10.3390/ani13223447

Publication

ISSN: 2076-2615
NlmUniqueID: 101635614
Country: Switzerland
Language: English
Volume: 13
Issue: 22

Researcher Affiliations

Citarella, Gerardo
  • Section of Anaesthesiology, Department of Clinical Diagnostics and Services, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland.
Heitzmann, Vanessa
  • Section of Anaesthesiology, Department of Clinical Diagnostics and Services, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland.
Ranninger, Elisabeth
  • Section of Anaesthesiology, Department of Clinical Diagnostics and Services, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland.
Bettschart-Wolfensberger, Regula
  • Section of Anaesthesiology, Department of Clinical Diagnostics and Services, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland.

Conflict of Interest Statement

The authors declare no conflict of interest.

References

This article includes 41 references
  1. Frölich J.C.. A classification of NSAIDs according to the relative inhibition of cyclooxygenase isoenzymes.. Trends Pharmacol. Sci. 1997;18:30–34.
    doi: 10.1016/S0165-6147(96)01017-6pubmed: 9114728google scholar: lookup
  2. Vane J.R., Bakhle Y.S., Botting R.M.. Cyclooxygenases 1 and 2.. Annu. Rev. Pharmacol. Toxicol. 1998;38:97–120.
  3. Warner T.D., Mitchell J.A.. Cyclooxygenase-3 (COX-3): Filling in the gaps toward a COX continuum?. Proc. Natl. Acad. Sci. USA 2002;99:13371–13373.
    doi: 10.1073/pnas.222543099pmc: PMC129677pubmed: 12374850google scholar: lookup
  4. Tinker M.K., White N.A., Lessard P., Thatcher C.D., Pelzer K.D., Davis B., Carmel D.K.. Prospective study of equine colic incidence and mortality.. Equine Vet. J. 1997;29:448–453.
  5. Cook V.L., Blikslager A.T.. The use of nonsteroidal anti-inflammatory drugs in critically ill horses.. J. Vet. Emerg. Crit. Care. 2015;25:76–88.
    doi: 10.1111/vec.12271pubmed: 25521286google scholar: lookup
  6. Marshall J.F., Blikslager A.T.. The effect of nonsteroidal anti-inflammatory drugs on the equine intestine.. Equine Vet. J. 2011;43:140–144.
  7. Duz M., Marshall J.F., Parkin T.D.. Proportion of nonsteroidal anti-inflammatory drug prescription in equine practice.. Equine Vet. J. 2019;51:147–153.
    doi: 10.1111/evj.12997pubmed: 30048005google scholar: lookup
  8. Joubert K.E.. The use of analgesic drugs by South African veterinarians: Continuing education.. J. S. Afr. Vet. Assoc. 2001;72:57–60.
    doi: 10.4102/jsava.v72i1.613pubmed: 11563724google scholar: lookup
  9. Fogle C., Davis J., Yechuri B., Cordle K., Marshall J., Blikslager A.. Ex vivo COX-1 and COX-2 inhibition in equine blood by phenylbutazone, flunixin meglumine, meloxicam and firocoxib: Informing clinical NSAID selection.. Equine Vet. Educ. 2021;33:198–207.
    doi: 10.1111/eve.13280google scholar: lookup
  10. de Vries R.B.M., Hooijmans C.R., Langendam M.W., van Luijk J., Leenaars M., Ritskes-Hoitinga M., Wever K.E.. A protocol format for the preparation, registration and publication of systematic reviews of animal intervention studies.. Evid. Based Preclin. Med. 2015;2:e00007.
    doi: 10.1002/ebm2.7google scholar: lookup
  11. Leenaars M., Hooijmans C.R., van Veggel N., ter Riet G., Leeflang M., Hooft L., van der Wilt G.J., Tillema A., Ritskes-Hoitinga M.. A step-by-step guide to systematically identify all relevant animal studies.. Lab. Anim. 2012;46:24–31.
    doi: 10.1258/la.2011.011087pmc: PMC3265183pubmed: 22037056google scholar: lookup
  12. Howick J.. The 2011 Oxford Levels of Evidence (Introductory Document).. OCEBM (2011) Levels of Evidence Working Group. The Oxford Levels Of Evidence, 2nd. Oxford Centre for Evidence-Based Medicine, Chalmers, I. (Ed.) Oxford Centre for Evidence-Based Medicine. [(accessed on 15 May 2023)] Available online: https://www.cebm.net/index.aspx?o=5653.
  13. Hooijmans C.R., Rovers M.M., De Vries R.B.M., Leenaars M., Ritskes-Hoitinga M., Langendam M.W.. SYRCLE’s risk of bias tool for animal studies.. BMC Med. Res. Methodol. 2014;14:43.
    doi: 10.1186/1471-2288-14-43pmc: PMC4230647pubmed: 24667063google scholar: lookup
  14. Gobbi F.P., Di Filippo P.A., Mello L., Lemos G.B., Martins C.B., Albernaz A.P., Quirino C.R.. Effects of Flunixin Meglumine, Firocoxib, and Meloxicam in Equines After Castration.. J. Equine Vet. Sci. 2020;94:103229.
    doi: 10.1016/j.jevs.2020.103229pubmed: 33077071google scholar: lookup
  15. Lemonnier L.C., Thorin C., Meurice A., Dubus A., Touzot-Jourde G., Couroucé A., Leroux A.A.. Comparison of Flunixin Meglumine, Meloxicam and Ketoprofen on Mild Visceral Post-Operative Pain in Horses.. Animals 2022;12:526.
    doi: 10.3390/ani12040526pmc: PMC8868280pubmed: 35203234google scholar: lookup
  16. Olson M.E., Fierheller E., Burwash L., Ralston B., Schatz C., Matheson-Bird H.. The Efficacy of Meloxicam Oral Suspension for Controlling Pain and Inflammation After Castration in Horses.. J. Equine Vet. Sci. 2015;35:724–730.
  17. Sanz M.G., Sellon D.C., Cary J.A., Hines M.T., Farnsworth K.D.. Analgesic effects of butorphanol tartrate and phenylbutazone administered alone and in combination in young horses undergoing routine castration.. J. Am. Vet. Med. Assoc. 2009;235:1194–1203.
    doi: 10.2460/javma.235.10.1194pubmed: 19912042google scholar: lookup
  18. Naylor R.J., Taylor A.H., Knowles E.J., Wilford S., Linnenkohl W., Mair T.S., Johns I.C.. Comparison of flunixin meglumine and meloxicam for post operative management of horses with strangulating small intestinal lesions.. Equine Vet. J. 2014;46:427–434.
    doi: 10.1111/evj.12224pubmed: 24372991google scholar: lookup
  19. Ziegler A.L., Freeman C.K., Fogle C.A., Burke M.J., Davis J.L., Cook V.L., Southwood L.L., Blikslager A.T.. Multicentre, blinded, randomised clinical trial comparing the use of flunixin meglumine with firocoxib in horses with small intestinal strangulating obstruction.. Equine Vet. J. 2019;51:329–335.
    doi: 10.1111/evj.13013pmc: PMC6788450pubmed: 30156312google scholar: lookup
  20. Cook V.L., Meyer C.T., Campbell N.B., Blikslager A.T.. Effect of firocoxib or flunixin meglumine on recovery of ischemic-injured equine jejunum.. Am. J. Vet. Res. 2009;70:992–1000.
    doi: 10.2460/ajvr.70.8.992pubmed: 19645580google scholar: lookup
  21. Little D., Brown S.A., Campbell N.B., Moeser A.J., Davis J.L., Blikslager A.T.. Effects of the cyclooxygenase inhibitor meloxicam on recovery of ischemia-injured equine jejunum.. Am. J. Vet. Res. 2007;68:614–624.
    doi: 10.2460/ajvr.68.6.614pubmed: 17542694google scholar: lookup
  22. Urayama S., Tanaka A., Kusano K., Sato H., Nagashima T., Fukuda I., Fujisawa C., Matsuda H.. Oral Administration of Meloxicam Suppresses Low-Dose Endotoxin Challenge–Induced Pain in Thoroughbred Horses.. J. Equine Vet. Sci. 2019;77:139–143.
    doi: 10.1016/j.jevs.2019.03.001pubmed: 31133308google scholar: lookup
  23. Tomlinson J.E., Wilder B.O., Young K.M., Blikslager A.T.. Effects of flunixin meglumine or etodolac treatment on mucosal recovery of equine jejunum after ischemia.. Am. J. Vet. Res. 2004;65:761–769.
    doi: 10.2460/ajvr.2004.65.761pubmed: 15198216google scholar: lookup
  24. Fadel C., Giorgi M.. Synopsis of the pharmacokinetics, pharmacodynamics, applications, and safety of firocoxib in horses.. Vet. Anim. Sci. 2023;19:100286.
    doi: 10.1016/j.vas.2023.100286pmc: PMC9852958pubmed: 36684818google scholar: lookup
  25. King J.N., Gerring E.L.. Antagonism of endotoxin-induced disruption of equine bowel motility by flunixin and phenylbutazone.. Equine Vet. J. 1989;21:38–42.
  26. Graubner C., Gerber V., Doherr M., Spadavecchia C.. Clinical application and reliability of a post abdominal surgery pain assessment scale (PASPAS) in horses.. Vet. J. 2011;188:178–183.
    doi: 10.1016/j.tvjl.2010.04.029pubmed: 20627635google scholar: lookup
  27. Pritchett L.C., Ulibarri C., Roberts M.C., Schneider R.K., Sellon D.C.. Identification of potential physiological and behavioral indicators of postoperative pain in horses after exploratory celiotomy for colic.. App Anim. Behav. Sci. 2003;80:31–43.
  28. Gibbs R., Duz M., Shipman E.. A survey of non-steroidal anti-inflammatory drug use in the post-operative period following equine colic surgery.. Equine Vet. Educ. 2023;35:121–130.
    doi: 10.1111/eve.13660google scholar: lookup
  29. Button K.S., Ioannidis J.P.A., Mokrysz C., Nosek B.A., Flint J., Robinson E.S.J., Munafò M.R.. Power failure: Why small sample size undermines the reliability of neuroscience.. Nat. Rev. Neurosci. 2013;14:365–376.
    doi: 10.1038/nrn3475pubmed: 23571845google scholar: lookup
  30. Deeks J.J., Dinnes J., D’Amico R., Sowden A., Sakarovitch C., Song F., Petticrew M., Altman D.. Evaluating non-randomised intervention studies.. Health Technol. Assess. 2003;7:1–173.
    doi: 10.3310/hta7270pubmed: 14499048google scholar: lookup
  31. Hung M., Bounsanga J., Voss M.W.. Interpretation of correlations in clinical research.. Postgrad. Med. 2017;129:902–906.
  32. Toutain P.L., Cester C.C.. Pharmacokinetic-pharmacodynamic relationships and dose response to meloxicam in horses with induced arthritis in the right carpal joint.. Am. J. Vet. Res. 2004;65:1533–1541.
    doi: 10.2460/ajvr.2004.65.1533pubmed: 15566092google scholar: lookup
  33. Di Salvo A., Giorgi M., Nannarone S., Lee H.K., Corsalini J., della Rocca G.. Postoperative pharmacokinetics of meloxicam in horses after surgery for colic syndrome.. J. Vet. Pharmacol. Ther. 2018;41:369–373.
    doi: 10.1111/jvp.12461pubmed: 29057473google scholar: lookup
  34. Mercer M.A., Davis J.L., McKenzie H.C.. The Clinical Pharmacology and Therapeutic Evaluation of Non-Steroidal Anti-Inflammatory Drugs in Adult Horses.. Animals 2023;13:1597.
    doi: 10.3390/ani13101597pmc: PMC10215112pubmed: 37238029google scholar: lookup
  35. Cox S., Villarino N., Sommardahl C., Kvaternick V., Zarabadipour C., Siger L., Yarbrough J., Amicucci A., Reed K., Breeding D.. Disposition of firocoxib in equine plasma after an oral loading dose and a multiple dose regimen.. Vet. J. 2013;198:382–385.
    doi: 10.1016/j.tvjl.2013.07.035pubmed: 24076125google scholar: lookup
  36. Schaafsma M.K.. Assessment of Pain in Horses after surgical Castration Composition of a Pain Scale.. PhD Thesis. Utrecht University; Utrecht, The Netherlands: 2009.
  37. Van Loon J.P.A.M., Van Dierendonck M.C.. Objective pain assessment in horses (2014–2018). Vet. J. 2018;242:1–7.
    doi: 10.1016/j.tvjl.2018.10.001pubmed: 30503538google scholar: lookup
  38. Androutsos O., Anastasiou C., Lambrinou C.P., Mavrogianni C., Cardon G., Van Stappen V., Kivelä J., Wikström K., Moreno L.A., Iotova V.. Intra- and inter-observer reliability of anthropometric measurements and blood pressure in primary schoolchildren and adults: The Feel4Diabetes-study.. BMC Endocr. Disord. 2020;20:7.
    doi: 10.1186/s12902-020-0501-1pmc: PMC7066724pubmed: 32164691google scholar: lookup
  39. Dzikiti T.B., Hellebrekers L.J., Van Dijk P.. Effects of intravenous lidocaine on isoflurane concentration, physiological parameters, metabolic parameters and stress-related hormones in horses undergoing surgery.. J. Vet. Med. A Physiol. Pathol. Clin. Med. 2003;50:190–195.
  40. De Grauw J.C., Van Loon J.P.A.M.. Systematic pain assessment in horses.. Vet. J. 2016;209:14–22.
    doi: 10.1016/j.tvjl.2015.07.030pubmed: 26831169google scholar: lookup
  41. Gluud L.L.. Bias in clinical intervention research.. Am. J. Epidemiol. 2006;163:493–501.
    doi: 10.1093/aje/kwj069pubmed: 16443796google scholar: lookup