Possible dose dependent effect of perioperative dexamethasone and laparoscopic surgery on the postoperative systemic inflammatory response and complications following surgery for colon cancer

Abstract

Background

Perioperative dexamethasone is associated with attenuation of the postoperative systemic inflammatory response and fewer postoperative complications following elective surgery for colorectal cancer.

This study examined the impact of different doses of dexamethasone, given to reduce postoperative nausea and vomiting (PONV) after elective colonic resection for cancer, on the postoperative Glasgow Prognostic Score (poGPS) and morbidity.

Methods

Patients from a single centre were included if they underwent potentially curative resection of colonic cancer from 2008 to 2017 (n = 480). Patients received no dexamethasone (209, 44%), or either 4 mg (166, 35%), or 8 mg (105, 21%), intravenously during anaesthesia, at the discretion of the anaesthetist. The postoperative Glasgow Prognostic Score (poGPS) on day 3 and 4, and complication rate at discharge were recorded.

Results

When patients were grouped by surgical approach (open or laparoscopic) and dexamethasone dose (0 mg, 4 mg or 8 mg), there was a statistically significant linear trend toward a lower postoperative systemic inflammatory response (day 3 poGPS) with the use of minimally invasive surgery and higher doses of dexamethasone (p < 0.001). Furthermore, this combination of laparoscopic surgery and higher doses of dexamethasone was significantly associated with a lower proportion of postoperative complications (p < 0.001).

At multivariate Cox regression, dexamethasone was not significantly associated with either improved or poorer cancer specific or overall survival.

Conclusions

Higher doses of perioperative dexamethasone are associated with greater reduction in postoperative systemic inflammation and complications following surgery for colonic cancer without negative impact on survival.

Introduction

Long term survival following surgery for colorectal cancer is primarily related to disease stage, however postoperative morbidity is also a negative prognostic factor [1]. These complications have a high price in terms of both health care costs, and impact on wider society, due to prolonged hospital stay and delay in return to function.

Postoperative complications have been reported to be associated with an exaggerated systemic inflammatory response following surgery for colorectal cancer [2]. The acute phase marker C-reactive protein (CRP) is increasingly recognised to be a reliable measure of this postoperative systemic inflammatory response (SIR) [3]. Postoperative CRP concentrations are now considered to be a useful, early surrogate marker for developing postoperative complications [4]. In addition, increasing evidence suggests that the postoperative SIR may have a causal influence on postoperative complications, and a negative impact on oncologic outcomes following surgery for colorectal cancer [5].

Corticosteroids are commonly administered at the induction of anaesthesia in colorectal surgery for the prevention of postoperative nausea and vomiting (PONV) [6]. A recent meta-analysis has reported that pre-operative administration of corticosteroids is associated with a reduction in the post-operative systemic inflammatory response, measured by CRP, and complications following surgery for gastrointestinal cancers [7]. A further recent randomised controlled trial (RCT) of perioperative corticosteroids in pancreatic cancer surgery reported a reduction in postoperative complications in patients given preoperative steroids [8]. In colorectal cancer surgery a recent observational study reported a significant association between dexamethasone, administered to reduce risk of PONV, and a reduction in both postoperative CRP concentrations and complications [9].

Despite this, no study has sought to detect whether a dose response relationship exists between perioperative steroids and either the postoperative systemic inflammatory response or complications. Furthermore, some concerns have been raised regarding the possibility of increased rates of disease recurrence in patients given perioperative steroids [10]. Therefore, the aims of the present study were to examine the impact of varying doses of dexamethasone given in the perioperative period to prevent PONV, on the postoperative systemic inflammatory response, complications, and survival following elective surgery for colon cancer.