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. 2012 Dec 27:8:247.
doi: 10.1186/1746-6148-8-247.

Carprofen for perioperative analgesia causes early anastomotic leakage in the rat ileum

Affiliations

Carprofen for perioperative analgesia causes early anastomotic leakage in the rat ileum

Rozemarijn J van der Vijver et al. BMC Vet Res. .

Abstract

Background: There is increasing evidence that perioperative use of NSAIDs may compromise the integrity of intestinal anastomoses. This study aims to characterize the negative effects of carprofen on early anastomotic healing in the rat ileum.

Results: In 159 male Wistar rats an anastomosis was constructed in the ileum. In experiment 1 eighty-four rats were divided over control and experimental groups, which received daily buprenorphine or carprofen, respectively, as an analgesic and were killed on day 1, 2 or 3 after surgery. In experiment 2 three groups of 15 rats received carprofen either immediately after surgery or with a delay of 1 or 2 days. Animals were killed after 3 days of carprofen administration. In experiment 3 three groups of 10 rats received different doses (full, half or quarter) of carprofen from surgery. In significant contrast to buprenorphine, which never did so, carprofen induced frequent signs of anastomotic leakage, which were already present at day 1. If first administration was delayed for 48 hours, the leakage rate was significantly reduced (from 80 to 20%; p = 0.0028). Throughout the study, the anastomotic bursting pressure was lowest in animals who displayed signs of anastomotic leakage. Loss of anastomotic integrity did not coincide with reduced levels of hydroxyproline or increased activity of matrix metalloproteinases.

Conclusions: Carprofen interferes with wound healing in the rat ileum at a very early stage. Although the mechanisms responsible remain to be fully elucidated, one should be aware of the potential of NSAIDs to interfere with the early phase of wound repair.

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Figures

Figure 1
Figure 1
Presence of COX-1 and COX-2 during normal healing. Anastomotic segments from the buprenorphine group of experiment 1 were immunostained for COX-1 (panels on the left) and COX-2 (panels on the right). Panels represent uninjured intestine (a and e) and tissue segment with the anastomosis in the middle and the mucosal layer on top (at a magnification of approximately x100) at day 1 (b and f), 2 (c and g) and 3 (d and h) after surgery.
Figure 2
Figure 2
Anastomotic strength in experiment 1. Animals received either buprenorphine or carprofen from the day of operation and were terminated at day 1, 2 or 3 after operation. Panel A gives the individual bursting pressures (and means as horizontal bars) for all animals: black circle denotes an absence of signs of anastomotic leakage and ○ the presence of such signs. The bursting site was always in the anastomotic line. In panel B bars represent mean (+ SEM) for breaking strength.
Figure 3
Figure 3
Anastomotic hydroxyproline content in experiment 1. Bars represent mean and SEM (in μg hydroxyproline/5 mm tissue) in anastomotic segments from both the buprenorphine and the carprofen groups at the various days after operation.
Figure 4
Figure 4
Anastomotic strength in experiment 2. Animals received carprofen beginning at the day of operation or the first or second day thereafter and were terminated 3 days later. Panel A gives the individual bursting pressures (and means as horizontal bars) for all animals: black circle denotes an absence of signs of anastomotic leakage and ○ the presence of such signs, while black triangle indicates that the bursting site was outside the anastomotic line. In panel B bars represent mean (+ SEM) for breaking strength.
Figure 5
Figure 5
Anastomotic strength in experiment 3. Animals received different doses of carprofen from the day of operation and were terminated at day 3 after operation. Panel A gives the individual bursting pressures (and means as horizontal bars) for all animals: black circle denotes an absence of signs of anastomotic leakage and ○ the presence of such signs. The bursting site was always in the anastomotic line. In panel B bars represent mean (+ SEM) for breaking strength.

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References

    1. Richardson CA, Flecknell PA. Anaesthesia and post-operative analgesia following experimental surgery in laboratory rodents: are we making progress? Altern Lab Anim. 2005;33(2):119–127. - PubMed
    1. Flecknell P. Analgesia from a veterinary perspective. Br J Anaesth. 2008;101(1):121–124. doi: 10.1093/bja/aen087. - DOI - PubMed
    1. Livingston A. Pain and analgesia in domestic animals. Handb Exp Pharmacol. 2010;199:159–189. doi: 10.1007/978-3-642-10324-7_7. - DOI - PubMed
    1. Lees P, Giraudel J, Landoni MF, Toutain PL. PK-PD integration and PK-PD modelling of nonsteroidal anti-inflammatory drugs: principles and applications in veterinary pharmacology. J Vet Pharmacol Ther. 2004;27(6):491–502. doi: 10.1111/j.1365-2885.2004.00618.x. - DOI - PubMed
    1. van der Vijver RJ, van Laarhoven CJ, de Man BM, Lomme RM, Hendriks T. Perioperative Pain Relief by a COX-2 Inhibitor Affects Ileal Repair and Provides a Model for Anastomotic Leakage in the Intestine. Surg Innov. 2012. epub ahead of print. - PubMed

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