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Equine veterinary journal2018; 51(3); 329-335; doi: 10.1111/evj.13013

Multicentre, blinded, randomised clinical trial comparing the use of flunixin meglumine with firocoxib in horses with small intestinal strangulating obstruction.

Abstract: Small intestinal strangulating obstruction (SISO) is associated with endotoxaemia which leads to an increased risk of death. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat signs of endotoxaemia by inhibiting cyclo-oxygenases (COX). COX-1 is expressed constitutively and promotes gut barrier function, whereas COX-2 is inducible and contributes to the signs of endotoxaemia. In preclinical SISO trials, intestinal barrier recovery was more complete with reductions in endotoxin permeability in horses treated with COX-2 selective NSAIDs as compared with horses treated with flunixin meglumine. Objective: We hypothesised that treatment of post-surgical SISO horses with firocoxib (COX-2 selective) would reduce the signs of endotoxaemia to a greater extent than flunixin meglumine (nonselective COX inhibitor) while continuing to provide similar levels of pain control. Methods: Blinded randomised clinical trial. Methods: In addition to clinical monitoring, preoperative and 12-, 24- and 48-h post-operative plasma samples were assessed for prostaglandin E2 (PGE2 ), thromboxane B2 (TXB2 ), TNF⍺ and soluble CD14 (sCD14). Results: In 56 recruited SISO horses, either flunixin meglumine (1.1 mg/kg, i.v., q12h) or firocoxib (0.3 mg/kg, i.v. loading dose; 0.1 mg/kg, i.v., q24h) was given in the post-operative period in three university hospitals from 2015 to 2017. COX-2 selectivity was confirmed by a relative lack of inhibition of the COX-1 prostanoid TXB2 by firocoxib and significant inhibition by flunixin meglumine (P = 0.014). Both drugs inhibited the COX-2 prostanoid PGE2 . There were no significant differences in pain scores between groups (P = 0.2). However, there was a 3.23-fold increased risk (P = 0.04) of increased plasma sCD14 in horses treated with flunixin meglumine, a validated biomarker of equine endotoxaemia. Conclusions: Horses were all treated with flunixin meglumine prior to referral. In addition, many horses were treated with lidocaine, which has been shown to mitigate the deleterious effects of flunixin meglumine. Conclusions: In SISO cases, firocoxib reduced a biomarker of endotoxaemia as compared with flunixin meglumine while continuing to provide similar levels of pain control.
© 2018 EVJ Ltd.
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Publication Date: 2018-09-21 PubMed ID: 30156312PubMed Central: PMC6788450DOI: 10.1111/evj.13013Google Scholar: Lookup
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  • Clinical Trial
  • Veterinary
  • Journal Article
  • Multicenter Study

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.

This research paper discusses how horses with small intestinal strangulating obstruction (SISO) responded when treated with two different nonsteroidal anti-inflammatory drugs (NSAIDs): firocoxib, a COX-2 selective inhibitor, and flunixin meglumine, a nonselective COX inhibitor. With a hypothesis that firocoxib might reduce signs of endotoxaemia while offering similar pain control to flunixin meglumine, 56 SISO horses were tested in a clinical trial. Results pointed to a reduction of endotoxaemia biomarkers in horses treated with firocoxib while still maintaining comparable levels of pain control.

Objective and Hypothesis

  • Small intestinal strangulating obstruction (SISO) in horses is connected with endotoxaemia, leading to an increased risk of death. NSAIDs, like firocoxib and flunixin meglumine, are used to manage endotoxaemia symptoms.
  • The objective of the study was to investigate if firocoxib would reduce endotoxaemia symptoms to a greater extent compared to flunixin meglumine, while maintaining similar levels of pain control in post-surgical SISO horses. This hypothesis was based on preclinical SISO trials, where a COX-2 selective NSAID led to better intestinal barrier recovery and lower endotoxin permeability than flunixin meglumine.

Methods and Study Design

  • This was a blinded randomized clinical trial, where SISO horses were treated with either flunixin meglumine or firocoxib.
  • In addition to the clinical observation, preoperative and multiple post-operative plasma samples were analyzed to assess levels of prostaglandin E, thromboxane B, TNF⍺ and soluble CD14 (sCD14).
  • The study was conducted in three university hospitals from 2015 to 2017.

Results

  • Flunixin meglumine and firocoxib both inhibited the COX-2 prostanoid PGE, confirming COX-2 selectivity of firocoxib and significant inhibition by flunixin meglumine.
  • There was no significant difference in the pain scores between the two groups, validating the initial hypothesis about similar pain control levels of these two drugs.
  • However, horses treated with flunixin meglumine have a 3.23-fold higher risk of increased plasma sCD14, a biomarker of endotoxaemia, compared to those treated with firocoxib.

Conclusions

  • The study concludes that in SISO horses, firocoxib reduces a biomarker of endotoxaemia compared to flunixin meglumine while delivering similar pain control. This adeptly supports the initial hypothesis of this study.
  • Before the study, all horses were treated with flunixin meglumine, and many of them with lidocaine, which can lessen the harmful effects of flunixin meglumine.

Cite This Article

APA
Ziegler AL, Freeman CK, Fogle CA, Burke MJ, Davis JL, Cook VL, Southwood LL, Blikslager AT. (2018). Multicentre, blinded, randomised clinical trial comparing the use of flunixin meglumine with firocoxib in horses with small intestinal strangulating obstruction. Equine Vet J, 51(3), 329-335. https://doi.org/10.1111/evj.13013

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 51
Issue: 3
Pages: 329-335

Researcher Affiliations

Ziegler, A L
  • Department of Clinical Sciences, North Carolina State University, Raleigh, North Carolina, USA.
Freeman, C K
  • Department of Clinical Sciences, North Carolina State University, Raleigh, North Carolina, USA.
Fogle, C A
  • Department of Clinical Sciences, North Carolina State University, Raleigh, North Carolina, USA.
Burke, M J
  • Department of Clinical Sciences, North Carolina State University, Raleigh, North Carolina, USA.
Davis, J L
  • Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, Virginia, USA.
Cook, V L
  • Department of Large Animal Clinical Sciences, Michigan State University, East Lansing, Michigan, USA.
Southwood, L L
  • Department of Clinical Studies, University of Pennsylvania, Kennett Square, Pennsylvania, USA.
Blikslager, A T
  • Department of Clinical Sciences, North Carolina State University, Raleigh, North Carolina, USA.

MeSH Terms

  • 4-Butyrolactone / administration & dosage
  • 4-Butyrolactone / analogs & derivatives
  • 4-Butyrolactone / therapeutic use
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Clonixin / administration & dosage
  • Clonixin / analogs & derivatives
  • Clonixin / therapeutic use
  • Female
  • Horse Diseases / drug therapy
  • Horses
  • Intestinal Obstruction / complications
  • Intestinal Obstruction / veterinary
  • Male
  • Pain, Postoperative / drug therapy
  • Pain, Postoperative / veterinary
  • Random Allocation
  • Sulfones / administration & dosage
  • Sulfones / therapeutic use

Grant Funding

  • T32 DK007737 / NIDDK NIH HHS
  • Grayson Jockey Club Research Foundation

Conflict of Interest Statement

Authors’ declaration of interests. No competing interests have been declared.

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