Paracetamol Does Not Compromise Early Wound Repair in the Intestine or Abdominal Wall in the Rat

Abstract

Paracetamol is a cornerstone for perioperative pain relief. Its mechanism of action may include a local anti-inflammatory effect with inhibition of cyclooxygenase isoenzymes. The scarce literature available on its effects on wound healing consists of preclinical studies into the effect of paracetamol on healing of the musculoskeletal system. Although the drug is used abundantly for pain relief after surgery of the gastrointestinal tract, there are no published data on the influence of paracetamol on anastomotic and abdominal healing. This also holds for the crucial, early inflammatory phase of repair. The recovery of wound strength could therefore conceivably be affected by paracetamol. In 78 male Wistar rats, we constructed an anastomosis in colon and ileum. The rats received either low- or high-dose (50 or 200 mg/kg/d, divided over 2 doses) paracetamol or vehicle (controls) until they were killed on day 3 or 7 after surgery (n = 13 each). In anastomoses, the main outcome variables were 2 independent measures for wound strength, bursting pressure, and breaking strength, the latter being the primary outcome variable. In addition, collagen levels were measured and histology was performed. In fascia, breaking strength was analyzed. No significant differences were found between control and paracetamol-treated groups at any time point for any of the variables. Wound strength increased significantly from day 3 to day 7 in all groups. In the colon anastomosis, the breaking strength increased from 130 ± 9 g (mean ± SEM) at day 3 to 232 ± 17 g at day 7 in the control group, from 144 ± 10 to 224 ± 9 g in the low-dose group, and from 130 ± 12 to 263 ± 28 g in the high-dose group. The lower limit for the 95% confidence interval was -11 for the difference between control and low-dose groups at day 3 and -25 for the difference between control and high-dose groups. No differences in collagen levels were found between the high-dose and control groups. Histology did not indicate the presence of gross differences between groups. Perioperative use of paracetamol in a rat model of intestinal surgery does not significantly impede wound repair in the early postoperative period.