Effect of Preoperative Immunonutrition on Outcome in Patients Undergoing Liver Resection: A Randomised Pilot Study

Abstract

Hypothesis: A specialised immune-modulatory nutritional formula containing n-3 fatty acids, arginine and nucleotides taken preoperatively will provide benefit in terms of body composition, immune and inflammatory status and clinical outcome in patients undergoing liver resection for primary or metastatic cancer. Background and aims: Major surgery induces a stress response which involves metabolic changes and can result in immune dysregulation. Provision of specific nutrients in supra-physiological doses has been shown to provide important substrates that can modulate immune and metabolic responses and improve clinical outcome in a number of surgical studies. The current study investigates the benefit of preoperative nutritional supplementation containing n-3 fatty acids, arginine and nucleotides on postoperative outcome in term of nutritional, immune and inflammatory status as well as infectious complications and length of stay, in patients undergoing liver resection. Methods: Patients scheduled for liver resection between December 2012 and April 2014 were enrolled and randomised to receive either five days of preoperative Impact® (1020 kcal/d, IMN group), or standard care (no supplementation, STD group). Baseline nutritional status was measured at recruitment by subjective global assessment (SGA) and 24 hour diet recall. Body composition (by dual-energy X-ray absorptiometry, in vivo neutron activation analysis, whole-body counting, and bioimpedance analysis), energy expenditure (by indirect calorimetry) and functional (grip strength, fatigue and performance status) assessments were carried out on the day prior to surgery, and on postoperative days 7 and 30. Inflammatory and immune markers were measured on the day prior to surgery, and postoperatively on days 1, 3, 5, 7, 10 and 30. Postoperative complications were recorded prospectively while in hospital and followed up until postoperative day (POD) 30. Results: There were 30 patients included, 16 IMN and 14 STD. Baseline characteristics between the groups did not differ for age, gender, SGA, ASA rating or nutritional intake. Most patients (28) were well nourished (SGA A) with only two found to have malnutrition preoperatively (SGA B + C), both in the IMN group. Intraoperative characteristics also did not differ in terms of major vs. minor resection, weight of tissue resected or duration of surgery. In the IMN group preoperative supplementation resulted in a significant increase in plasma eicosapetaenoic acid (EPA) plus docosahexaenoic acid (DHA) (p<0.0001) and the (EPA+DHA)/arachidonic acid (AA) ratio (p<0.0001) which remained significantly higher than the STD group until POD5 (p=0.020) and borderline significantly higher on POD7 (p=0.051). No treatment effect was detected for weight, body composition, function, immune (white cell count and total lymphocytes) or inflammatory markers (C-reactive protein and interleukin-6). A borderline significant interaction effect (p=0.059) was seen for changes in resting energy expenditure (REE) over the study period however there was no difference between the groups in the REE changes over the first 7 study days. Infectious complications were seen in 9 patients in the IMN group and 4 patients in the STD group (p=0.159). The median length of hospital stay was 8.5 days in the IMN group and 8 days in the STD group (p=0.696). Conclusions: The current pilot study failed to demonstrate any clear advantage of routine preoperative immunonutrition in the form of Impact containing n-3 fatty acids, arginine and nucleotides, in well nourished patients undergoing elective liver resection surgery.