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Multicentre, blinded, randomised clinical trial comparing the use of flunixin meglumine with firocoxib in horses with small intestinal strangulating obstruction
Author(s) -
Ziegler A. L.,
Freeman C. K.,
Fogle C. A.,
Burke M. J.,
Davis J. L.,
Cook V. L.,
Southwood L. L.,
Blikslager A. T.
Publication year - 2019
Publication title -
equine veterinary journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.82
H-Index - 87
eISSN - 2042-3306
pISSN - 0425-1644
DOI - 10.1111/evj.13013
Subject(s) - medicine , prostanoid , horse , phenylbutazone , cyclooxygenase , meglumine , prostaglandin , prostaglandin e2 , anesthesia , pharmacology , gastroenterology , chemistry , biology , paleontology , biochemistry , radiology , magnetic resonance imaging , enzyme
Summary Background 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. Objectives 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. Study design 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 E 2 (PGE 2 ), thromboxane B 2 (TXB 2 ), 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 TXB 2 by firocoxib and significant inhibition by flunixin meglumine (P = 0.014). Both drugs inhibited the COX‐2 prostanoid PGE 2 . 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. Main limitations 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.