Clinical Evidence for Pharmaconutrition in Major Elective Surgery

Editor(s): Conference Proceedings & Specific Issues Vol.37 / 1,  2013

Summary

recent years, standard nutrition preparations have been modified by adding specific nutrients, such as arginine, ω-3 fatty acids, glutamine, and others, which have been shown to upregulate host immune response, modulate inflammatory response, and improve protein synthesis after surgery. Most randomized trials and several meta-analyses have shown that perioperative administration of enteral arginine, ω-3 fatty acids, and nucleotides (immunonutrition) reduced infection rate and length of hospital stay in patients with upper and lower gastrointestinal (GI) cancer. The most pronounced benefits of immunonutrition were found in subgroups of high-risk and malnourished patients. Promising but not conclusive results have been found in non-GI surgery, especially in head and neck surgery and in cardiac surgery, but larger trials are required before recommending immunonutrition as a routine practice. Conflicting results on the real benefit of parenteral glutamine supplementation in patients undergoing elective major surgery have been published. In conclusion, enteral diets supplemented with specific nutrients significantly improved short-term outcome in patients with cancer undergoing elective GI surgery. Future research should investigate a molecular signaling pathway and identify specific mechanisms of action of immuneenhancing substrates.

Perioperative immunonutrition significantly reduced both the postoperative infection rate and the length of hospital stay in patients undergoing elective major GI surgery. Promising results have been obtained also in non-GI surgery, especially in head and neck surgery and in cardiac surgery, but larger trials are required before recommending immunonutrition as a routine practice. According to literature data, the appropriate candidates for immunonutrition are all patients undergoing elective major surgery with a high risk of postoperative infectious complications, regardless of their baseline nutrition status. The most pronounced benefits of immunonutrition were found in subgroups of high-risk and malnourished patients. Malnutrition and its metabolic consequences are recognized as important risk factors for the development of postoperative infections. Yet, well-nourished patients may also experience severe postoperative infections, possibly because their pathophysiology is multifactorial. Postoperative infection risk is continuously changing according to new advances in perioperative care and surgery techniques. In the past years, mini-invasive surgery and enhanced recovery after surgery (ERAS) multimodal protocols (no postoperative fasting, early mobilization after surgery, and restrictive IV infusion policy) are gaining popularity among surgeons, and both have been associated with a lower postoperative infection rate and shorter hospital stay after colorectal surgery. Since the vast majority of trials showing the effectiveness of immunonutrition have been carried out in patients who underwent open surgery with traditional perioperative care, it could be interesting to investigate if mini-invasive surgery and the ERAS pathway could change nutrition and pharmaconutrition policies.

Future research should investigate the molecular signalling pathway and identify specific mechanisms of action of immune-enhancing substrates. Moreover, dose-response studies should better clarify which is the optimal dose of substrates to maximize benefits in surgical patients. New trials should be performed to confirm the effectiveness of immunonutrition in patients undergoing major mini invasive surgery with the application of ERAS protocols. Another interesting field of research could be testing the efficacy of immune-enhancing diets in cancer patients receiving neoadjuvant therapy. Glutamine supplementation should be tested in malnourished patients who represent cohorts with high glutamine demand and/or potential baseline deficits. Moreover, both the length of preoperative treatment and the amount of glutamine should be increased to obtain adequate tissue and plasma levels at the time of surgery.