Effect of Statins on the Surgical Stress Response in Colorectal Surgery

Abstract

Major colorectal surgery leads to a significant physiological stress response that is associated with postoperative morbidity and prolonged patient recovery. Statins are a widely used class of cholesterollowering drugs with useful pleiotropic effects that are relevant to abdominal surgery. Despite considerable experimental evidence, the clinical evidence of their benefits in the setting of abdominal surgery is limited to retrospective and observational studies. The aims of this thesis was to examine the correlation of the surgical stress response to postoperative morbidity following major colorectal surgery and explore the novel concept of whether statins can attenuate this response and improve clinical outcomes after surgery. Chapter one discusses the basis of the surgical stress response, introduces the concept of statins and presents the evidence demonstrating their surgically relevant benefits. Chapter two explores the association between postoperative inflammation and morbidity after colorectal surgery by presenting a meta-analysis which shows C-reactive protein levels in the early postoperative period correlate with the development of anastomotic leakage and have a useful negative predictive value. Chapter three presents a retrospective study which demonstrates the relationship between patient-reported functional recovery and morbidity following colonic surgery using the surgical recovery score questionnaire and shows it closely correlates with postoperative complications and their severity. In chapter four, a retrospective review of patients undergoing elective colectomy is presented and shows patients on statins during the perioperative period achieved equivalent outcomes for complications and functional recovery despite significantly higher perioperative risk and had a significantly lower rate of anastomotic leak. Chapter five is a systematic review which critically appraises the available clinical studies on the use of statins in abdominal surgery and shows the various benefits demonstrated, particularly for inflammatory and infective outcomes. This leads to a placebo-controlled, randomised clinical trial presented in chapter six which shows that perioperative oral simvastatin therapy in patients undergoing major elective colorectal surgery leads to a significant reduction in inflammatory markers in the early postoperative period but no difference in complications or functional recovery. Therefore, the addition of perioperative simvastatin therapy cannot be recommended as a routine for patients undergoing major elective colorectal surgery.