Intestinal Neoplasm, Perioperative Care
Conditions
Keywords
Statin, Colon, Colorectal, Intestinal Neoplasms, ERAS, Perioperative Care
Brief summary
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.
Interventions
DRUGSimvastatin
40mg orally, given 3-7 days pre-op and continued till 14 days post-op
DRUGPlacebo
Placebo (Inert calcium lactate) tablets 3-7 days pre-op to 14 days post-op (as per experimental arm)
Sponsors
Counties Manukau Health
Waitemata District Health Board
Auckland District Health Board
University of Auckland, New Zealand
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total complications | Up to post-operative day 30 | Complications pre-defined and graded by the Clavien-Dindo classification |
Secondary
| Measure | Time frame |
|---|---|
| Peritoneal Cytokines | Postoperative Day 1 |
| Serum cytokines | Post-operative Day 1 |
| Change in serum C-reactive protein (CRP) | Baseline and Postoperative Day 1, 2 and 3 |
| Change in functional recovery | Baseline and Postoperative Day 1, 3, 7, 14, and 30 |
Countries
New Zealand
Outcome results
None listed