The clinical and economical impact of postoperative ileus in patients undergoing colorectal surgery.

BACKGROUND: Colorectal surgery is associated with postoperative ileus (POI). Despite its widespread manifestation, the influence of POI on recovery, quality of life (QoL), and costs is largely unknown. The aim of this study was to assess whether the inflammatory processes found in experimental studies are also evident in patients undergoing colorectal surgery. In addition, the impact of POI on short and long-term QoL and costs was investigated. METHODS: We analyzed the outcomes of the SANICS-II trial, including prospective evaluation of inflammatory parameters in blood samples, costs from a societal perspective and QoL, using validated questionnaires. Outcomes were compared between patients with and without POI, and in particular patients with POI as unique complication. KEY RESULTS: A total of 265 patients (POI, n = 66 vs non-POI, n = 199) were included and 38/66 had POI as only complication. CRP levels were significantly increased on postoperative day (POD) 1, 2, 3, and 4 in patients with POI. Furthermore, plasma levels of cytokines IL-6, Il-8 and IL-10 were significantly increased the first 2 days after resection. Patients with POI had a higher overall complication rate and a reduced QoL 3 months postoperatively, even in the only POI group. Moreover, mean societal cost per patient with POI was 38%-47% higher at 3 months postoperatively. CONCLUSIONS & INFERENCES: Supporting findings from experimental studies, inflammatory parameters were increased in patients with only POI and comparable with all patients with POI. These results demonstrate the impact and large contribution of POI in postoperative inflammation, costs and QoL in patients undergoing colorectal surgery.

An economic evaluation of perioperative enteral nutrition in patients undergoing colorectal surgery (SANICS II study).

AIMS: The objective of this (trial based) economic evaluation was to assess, from a societal perspective, the cost-effectiveness of perioperative enteral nutrition compared with standard care in patients undergoing colorectal surgery. MATERIALS AND METHODS: Alongside the SANICS II randomized controlled trial, global quality-of-life, utilities (measured by EQ-5D-5L), healthcare costs, production losses, and patient and family costs were assessed at baseline, 3 months, and 6 months. Incremental cost-effectiveness ratios (ICERs) (i.e. cost per increased global quality-of-life score or quality-adjusted life year [QALY] gained) and cost effectiveness acceptability curves were visualized. RESULTS: In total, 265 patients were included in the original trial (n = 132 in the perioperative enteral nutrition group and n = 133 in the standard care group). At 6 months, global quality-of-life (83 vs 83, p = .357) did not differ significantly between the groups. The mean total societal costs for the intervention and standard care groups were €14,673 and €11,974, respectively, but did not reach statistical significance (p = .109). The intervention resulted in an ICER of -€6,276 per point increase in the global quality of life score. The gain in QALY was marginal (0.003), with an additional cost of €2,941, and the ICUR (Incremental cost utility ratio) was estimated at €980,333. LIMITATIONS: The cost elements for all the participating centers reflect the reference prices from the Netherlands. Patient-reported questionnaires may have resulted in recall bias. Sample size was limited by exclusion of patients who did not complete questionnaires for at least at two time points. A power analysis based on costs and health-related quality-of-life (HRQoL) was not performed. The economic impact could not be analyzed at 1 month post-operatively where the effects could potentially be higher. CONCLUSIONS: This study suggests that perioperative nutrition is not beneficial for the patients in terms of quality-of-life and is not cost-effective.

Perioperative lipid-enriched enteral nutrition versus standard care in patients undergoing elective colorectal surgery (SANICS II): a multicentre, double-blind, randomised controlled trial.

BACKGROUND: Postoperative ileus and anastomotic leakage severely impair recovery after colorectal resection. We investigated the effect of perioperative lipid-enriched enteral nutrition versus standard care on the risk of postoperative ileus, anastomotic leakage, and other clinical outcomes. METHODS: We did an international, multicentre, double-blind, randomised, controlled trial of patients (≥18 years) undergoing elective colorectal surgery with primary anastomosis at six clinical centres in the Netherlands and Denmark. Patients were randomly assigned (1:1), stratified by location (colonic and rectal) and type of surgery (laparoscopic and open), via online randomisation software, with block sizes of six, to receive either continuous lipid-enriched enteral tube feeding from 3 h before until 6 h after surgery (intervention) or no perioperative nutrition (control). Surgeons, patients, and researchers were masked to treatment allocation for the entire study period. The primary outcome was postoperative ileus. Secondary outcomes included anastomotic leakage, pneumonia, preoperative gastric volumes, time to functional recovery, length of hospital stay, the need for additional interventions, intensive care unit admission, postoperative inflammatory response, and surgical complications. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02175979, and trialregister.nl, number NTR4670. FINDINGS: Between July 28, 2014, and February 20, 2017, 280 patients were randomly assigned, 15 of whom were excluded after random allocation because they fulfilled one or more exclusion criteria. 265 patients received perioperative nutrition (n=132) or standard care (n=133) and were included in the analyses. A postoperative ileus occurred in 37 (28%) patients in the intervention group versus 29 (22%) in the control group (risk ratio [RR] 1·09, 95% CI 0·95-1·25; p=0·24). Anastomotic leakage occurred in 12 (9%) patients in the intervention group versus 11 (8%) in the control group (RR 1·01, 95% CI 0·94-1·09; p=0·81). Pneumonia occurred in ten (8%) patients in the intervention group versus three (2%) in the control group (RR 1·06, 95% CI 1·00-1·12; p=0·051). All other secondary outcomes were similar between groups (all p>0·05). INTERPRETATION: Perioperative lipid-enriched enteral nutrition in patients undergoing elective colorectal surgery has no advantage over standard care in terms of postoperative complications. FUNDING: Netherlands Organisation for Health Research and Development (ZonMW), Fonds NutsOhra, and Danone Research.

Effect of Early vs Late Start of Oral Intake on Anastomotic Leakage Following Elective Lower Intestinal Surgery: A Systematic Review.

BACKGROUND: Experimental and clinical studies have demonstrated a beneficial effect of early enteral nutrition (EN) on anastomotic leakage following colorectal surgery. Early oral intake is a common form of early EN with various clinical benefits, but the effect on anastomotic leakage is unclear. This systematic review investigates the effect of early vs late start of oral intake on anastomotic leakage following lower intestinal surgery. METHODS: A systematic literature search was performed using the PubMed, Embase, Medline, and Cochrane databases. Randomized controlled trials were included that compared early (within 24 hours) vs late start of oral intake following elective surgery of the small bowel, colon, or rectum. Meta-analysis was performed for anastomotic leakage, overall complications, length of stay, and mortality. Sensitivity analysis was performed in which studies of inferior methodological quality were excluded. RESULTS: Nine studies including 879 patients met eligibility criteria. Early start of oral intake significantly reduced overall complications (odds ratio [OR], 0.65; 95% confidence interval [CI], 0.46-0.93; P = .02), length of stay (mean difference, -0.89; 95% CI, -1.22 to -0.57; P < .001), and anastomotic leakage (OR, 0.40; 95% CI, 0.17-0.95; P = .04) compared with late start of oral intake. However, in the sensitivity analysis only the overall reduction of length of stay remained significant. CONCLUSION: The effect of early oral intake on anastomotic leakage is unclear as existing studies are heterogeneous and at risk of bias. High-quality studies are needed to study the potential benefit of EN on anastomotic healing.

The effects of stimulation of the autonomic nervous system via perioperative nutrition on postoperative ileus and anastomotic leakage following colorectal surgery (SANICS II trial): a study protocol for a double-blind randomized controlled trial.

BACKGROUND: Postoperative ileus and anastomotic leakage are important complications following colorectal surgery associated with short-term morbidity and mortality. Previous experimental and preclinical studies have shown that a short intervention with enriched enteral nutrition dampens inflammation via stimulation of the autonomic nervous system and thereby reduces postoperative ileus. Furthermore, early administration of enteral nutrition reduced anastomotic leakage. This study will investigate the effect of nutritional stimulation of the autonomic nervous system just before, during and early after colorectal surgery on inflammation, postoperative ileus and anastomotic leakage. METHODS/DESIGN: This multicenter, prospective, double-blind, randomized controlled trial will include 280 patients undergoing colorectal surgery. All patients will receive a selfmigrating nasojejunal tube that will be connected to a specially designed blinded tubing system. Patients will be allocated either to the intervention group, receiving perioperative nutrition, or to the control group, receiving no nutrition. The primary endpoint is postoperative ileus. Secondary endpoints include anastomotic leakage, local and systemic inflammation, (aspiration) pneumonia, surgical complications classified according to Clavien-Dindo, quality of life, gut barrier integrity and time until functional recovery. Furthermore, a cost-effectiveness analysis will be performed. DISCUSSION: Activation of the autonomic nervous system via perioperative enteral feeding is expected to dampen the local and systemic inflammatory response. Consequently, postoperative ileus will be reduced as well as anastomotic leakage. The present study is the first to investigate the effects of enriched nutrition given shortly before, during and after surgery in a clinical setting. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02175979 - date of registration: 25 June 2014. Dutch Trial Registry: NTR4670 - date of registration: 1 August 2014.