Simvastatin in Colorectal Surgery

Statins (HMG-CoA reductase inhibitors) are a widely used class of cholesterol-lowering drugs that have an established role in the medical management of cardiovascular disease. Their benefits have also been shown in the surgical setting with decreased cardiovascular complications and lower perioperative mortality following cardiac and vascular surgery. There is now considerable evidence showing statins have useful pleiotropic properties that extend beyond cholesterol lowering, including anti-inflammatory, anti-oxidant, immunomodulatory and fibrinolytic effects. Growing evidence suggests these effects may be useful in attenuating the proinflammatory and metabolic stress response to surgery and the benefit of statins may extend to other surgical settings such as abdominal surgery. Laboratory studies demonstrate the surgically-relevant benefits of statins and show they decrease peritoneal inflammation, reduce the severity of intestinal ischaemia-reperfusion injury, improve survival in models of abdominal sepsis, decrease the formation of postoperative intraperitoneal adhesions and improve the healing of colonic anastomoses. Retrospective clinical studies show statins improve outcomes in sepsis, reduce the postoperative systemic inflammatory response syndrome (SIRS) and are associated with decreased rates of surgical wound infections and postoperative respiratory complications following various non-cardiac general surgical procedures. However, no prospective studies have specifically evaluated the perioperative use of statins in abdominal surgery. Using colorectal surgery as a model for major abdominal surgery, the investigators will conduct a randomised controlled trial evaluating the effect of perioperative statin use on postoperative morbidity, local and systemic inflammatory response, and functional recovery after surgery.

Sex

All

Minimum age

18 Years

Maximum age

90 Years

Inclusion criteria:

* Consecutive consenting patients undergoing elective colectomy, rectal resection, and reversal of Hartmann's procedure at Middlemore Hospital, Manukau Surgery Centre, Auckland City Hospital, and North Shore Hospital.

Exclusion criteria:

* Acute presentation
* Already taking statins or other lipid-lowering medication
* Known adverse reaction to statins
* Hepatic dysfunction
* Moderate to severe renal dysfunction
* Previous history of rhabdomyolysis
* On contraindicated medication
* Pregnancy
* Breastfeeding
* Patient choice.

• DERIVEDSingh PP, Lemanu DP, Soop M, Bissett IP, Harrison J, Hill AG. Perioperative Simvastatin Therapy in Major Colorectal Surgery: A Prospective, Double-Blind Randomized Controlled Trial. J Am Coll Surg. 2016 Aug;223(2):308-320.e1. doi: 10.1016/j.jamcollsurg.2016.04.004. Epub 2016 Apr 13. PMID 27086089