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Evidence for perioperative treatments used in colic patients
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There are a number of controversial aspects of perioperative treatment of colic patients, including which treatments are optimal for reducing inflammation, and whether motility-modifying drugs are indicated and efficacious. The evidence for use of perioperative drugs is limited, but there has been an increase in the number of evidence-based studies in recent years. This presentation will focus on the non-steroidal anti-inflammatory drugs and lidocaine, some of the most widely used perioperative colic treatments.
Non-Steroidal Anti-Inflammatory Drugs
Non-steroidal anti-inflammatory drugs (NSAIDs) form the cornerstone therapy for inflammation and clinical signs of endotoxemia in horses with colic. NSAIDs have been shown to reduce signs of endotoxemia in horses as a result of inhibiting production of prostanoids by cyclooxygenases (COX). This has in turn has been linked to increased survival in colic patients, although this remains to be proven in clinical trials. Nonetheless, there is good evidence that NSAIDs reduce pain in patients suffering from colic. However, recent studies indicate that complete blockade of COX (including COX-1 and COX-2) with flunixin meglumine (1.1mg/kg, IV, q12h) inhibits repair of ischemic lesions in the small intestine. The most notable effect of inhibited repair is increased gut leakage of lipopolysaccharide (LPS), which is counter-intuitive to the ‘anti-endotoxic’ claim that has been made for flunixin. Interestingly, flunixin meglumine does not reduce mucosal repair in the colon, according to pre-clinical trials on horses with experimental large colon strangulation, suggesting different repair mechanisms in ischemic colon. As an alternative to non-selective COX inhibitors like flunixin, there are now two medications available in the EU: meloxicam (0.06mg/ kg, q24h) and firocoxib (0.1mg/kg, q24h). In pre-clinical trials, horses with experimental strangulation of the jejunum had delayed recovery of mucosal integrity when treated with flunixin meglumine as compared to horses treated with meloxicam or firocoxib. However, these findings have been followed up by a recent clinical trial in the UK in which flunixin was compared with meloxicam in horses with naturally occurring small intestinal strangulation, and there were no significant differences in critical factors such as LPS levels. Some important pitfalls of the study were acknowledged, including the double dosing of meloxicam (administered twice daily, instead of the labeled once-daily dosing) and the lack of statistical power (too few cases). The double-dosing may have effectively made meloxicam a non- selective COX inhibitor, but additional work will be needed to determine if that is the case. The lack of difference between the drugs suggests a similar efficacy of meloxicam for managing postoperative pain, which is reinforced by pre-clinical trials confirming its ability to reduce behavioral signs of pain. Firocoxib has yet to undergo clinical trials on colic patients. However, as of this writing, a randomized blinded multi-institutional clinical trial comparing flunixin with firocoxib in patients recovering from surgery for small intestinal strangulating obstruction is being performed in the US, with results expected by 2017. [...]
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