P. Singh1, D. Lemanu1, M. Soop1, I. Bissett1, J. Harrison2, A. Hill1 1University Of Auckland,Surgery,Auckland, -, New Zealand 2University Of Auckland,Pharmacy,Auckland, -, New Zealand
Introduction:
Statins (HMG-CoA reductase inhibitors) have been shown to have numerous benefits relevant to abdominal surgery, such as decreasing peritoneal inflammation and improving survival in abdominal sepsis. In clinical studies, their use has been associated with a reduction in the systemic inflammatory response syndrome (SIRS), wound infection and anastomotic leak following colorectal surgery. However, this clinical evidence is limited to retrospective studies. This study aimed to investigate whether perioperative statin therapy can attenuate the surgical pro-inflammatory response and reduce complications following major colorectal surgery.
Methods:
A prospective, multi-centre, double blind, parallel-group, randomised controlled trial was conducted at three public tertiary hospitals in New Zealand (Middlemore Hospital/Manukau Surgery Centre, Auckland City Hospital, and North Shore Hospital) between October 2011 and August 2013. Patients undergoing elective colorectal resection for any indication or reversal of Hartmann’s procedure were randomised to receive either 40mg oral simvastatin or an identical-appearing placebo once daily for 3-7 days before surgery till 14 days after surgery. The primary outcome was the total incidence of complications for 30-days postoperatively. Secondary outcomes included the systemic and peritoneal cytokine response (IL-1α, IL-1β, IL-6, IL-8, IL-10, and TNFα), measured in venous blood and samples of abdominal drain fluid on postoperative day 1, respectively. Concentrations of C-reactive protein (CRP) and the presence of SIRS were evaluated on postoperative days 1 to 3.
Results:
There were 132 patients included in the study, with 65 patients allocated to the simvastatin group and 67 patients to the placebo group. There were no significant differences between the two groups at baseline with regards to patient, operation and disease characteristics. There were no significant differences between the two groups in the incidence, grade and type of postoperative complications. Systemic levels of IL-6, IL-8 and TNFα, and peritoneal concentrations of IL-6 and IL-8, were significantly lower in the simvastatin group postoperatively. CRP levels were significantly lower in the simvastatin group on postoperative days 1 to 3. A lower number of patients in the simvastatin group exhibited SIRS on day 1 and 2 postoperatively, but this difference did not reach statistical significance.
Conclusion:
Perioperative simvastatin therapy in major colorectal surgery attenuates the early pro-inflammatory response to surgery but does not reduce postoperative complications.