Department of Surgery
Malnutrition in patients facing major surgery is frequently observed and is a major risk factor in postoperative morbidity and mortality. Thus, adequate nutritional support is strongly recommended by international guidelines. Enteral nutrition (EN) appears superior to parenteral in reduction of postoperative complications and costs. The supplementation of enteral formulas with specific nutrients having immunomodulatory properties allows control of surgery-induced immunosuppression and hyperinflammation. Perioperative use of these new formulas significantly reduces the rate of morbidity and further saves healthcare resources.
Undernutrition as a disease
Patients with cancer suffer alteration of the metabolic state, reduced food intake, cachexia and subsequent nutritional depletion. The systemic consequences of undernutrition and catabolism are well described.(1) Briefly, acute and chronic malnutrition and catabolism deeply affect immune mechanisms, wound healing, hormone and cytokine synthesis, intestinal flora ecology, and tissue/organ function and structure. As a consequence, undernutrition should in itself be considered a disease, and prolonged starvation a major cause of worsening of any ongoing illness. It should be reminded that many types of cancer may be treated successfully by surgery, but major operation, per se, is an additional factor in altered metabolism and is often associated with variable periods of starvation. Moreover, surgical trauma affects many different aspects of the body’s defences by multifactorial mechanisms.(2)
Undernutrition and immunonutrition
In undernourished surgical cancer patients, the administration of calories and proteins has been strongly recommended to correct the above alterations with the final endpoint of improving postoperative outcome.(3) Yet, only a small proportion of hospitalised patients receive an accurate nutritional screening and nutritional support.
If there is a functioning gut, EN should be preferred to total parenteral nutrition (TPN) because the enteral route has been proven to be feasible and safe, less expensive, cost-effective and more physiological. A large body of experimental evidence shows that the lack of nutrients in the intestinal lumen occurring during TPN is a cause of mucosal atrophy, impaired gut function, and local and systemic immune suppression. Physical contact, stimulation of trophic gastrointestinal hormones, enhanced local blood flow and improved intestinal cell turnover are among the underlying mechanisms in the protective effect of intraluminal infusion of nutrients. Enteral feeding also stimulates the synthesis of local immunoglobulins, motility of the gut and production of mucus, and reduces bacterial mucosal adherence and the number of pathogen bacteria. All these factors are essential for proper gut barrier function, loss of which might predispose the patient to systemic infections due to bacterial translocation. In a large multicentre randomised clinical trial, severely malnourished patients with cancer of the gastrointestinal tract received either EN or TPN after surgery. The results showed that the overall rate of postoperative complications was 34% amongst patients fed enterally, versus 49% in the patients fed parenterally, and the mean length of hospital stay (LOS) was 13.4 days in the EN group and 15.0 days in the TPN group.(4)
To improve the composition of the standard feeds, extensive research is ongoing. New substrates with immunomodulatory, anti-inflammatory, anabolic and tissue-protective activity were tested in experimental and clinical settings. These nutrients are generically named “immunonutrients” or “pharmaconutrients”, because their mechanisms of action and functions resemble more a drug than a classic nutrient. Among the most investigated are arginine and omega-3 fatty acids.
Several immunonutritional formulas supplemented with one substrate or various combinations of key nutrients are now available for practical use. The introduction of new substrates part-revolutionised the primary aim for which artificial nutrition is prescribed. In fact, these new formulas should be given not simply to provide calories and proteins, but mainly to counteract and modulate the alteration of the host homeostasis induced by surgery and undernutrition.
Several meta-analyses, encompassing more than 1,500 patients, consistently showed that patients receiving the new formulas immediately after operation had a substantial (about 40%) reduction of postoperative infections and length of hospitalisation. Even better results were obtained when these specific enteral products were given for at least five days before surgery.(5–7)
A major drawback for the routine and wide use of these new products may be the additional costs. Therefore, cost-effectiveness studies on immunonutrition were carried out to determine whether this could be a dominant economic strategy. Three trials clearly showed that, despite the cost of immunonutrition being higher than that of standard enteral diets (€347 and €104 per patient respectively), the reduction in complications and length of stay obtained in the patients treated with the new diets largely more than compensated for the product cost with a significant reduction of healthcare resources consumed to treat postoperative problems.(5,8,9)
The evidence for the advantages of the clinical use of immunonutrition are so robust that, recently, European guidelines gave the maximum grade of recommendation (grade A) for its routine use in care. In some European countries, such as France and Spain, the Ministry of Health authorised total reimbursement for this nutritional therapy, basing the decision on the strong scientific evidence showing improved patient outcome and reduced healthcare costs. It is desirable that other European countries, scientific societies and single institutions realise the importance of this new nutritional strategy and promote its routine use.
In the future, we will see results from other trials investigating new products and formulas containing different combinations of supernormal doses of vitamins, selenium, zinc, antioxidants substrates, probiotic bacteria and glutamine. Given the strong impact that these new key nutrients might have on healthcare and policy, it is essential that their potential clinical efficacy is tested through the rigorous methodology of evidence-based medicine, as with any other drug.
The importance of nutritional status and nutritional therapy in surgical patients is often underestimated and neglected by physicians, healthcare providers and political institutions. The efficacy of artificial nutrition has been largely proven and certified by the process of evidence-based medicine and cost-effectiveness analysis, as for any other drug therapy. A more scrupulous and accurate policy on artificial nutritional support may deeply affect patient outcome and significantly reduce healthcare costs. This may be obtained by simple implementation and application of the recommendation given by European and international guidelines.
- Mora RJF. Malnutrition: organ and functional consequences. World J Surg 1999;23:530-5.
- Napolitano LM, et al. Immune dysfunction in trauma. Surg Clin North Am 1999;79:1385-1416.
- Weimann A, et al. ESPEN guidelines on enteral nutrition: surgery including organ transplantation. Clin Nutr 2006;25:224-44.
- Bozzetti F, et al. Postoperative enteral versus parenteral nutrition in malnourished patients with gastrointestinal cancer: a randomised multicentre trial. Lancet 2001;358:1487-92.
- Senkal M, et al. Outcome and cost-effectiveness of perioperative enteral immunonutrition in patients undergoing elective upper gastrointestinal tract surgery: a prospective randomized study. Arch Surg 1999;134: 1309-16.
- Gianotti L, et al. A randomized controlled trial on pre-operative oral supplementation with a specialized diet in patients with gastrointestinal cancer. Gastroenterology 2002; 122:1763-70.
- Braga M, et al. Nutritional approach in malnourished surgical patients: a prospective randomized trial. Arch Surg 2002;137:174-80.
- Gianotti L, et al. Health care resources consumed to treat postoperative infections: cost saving by perioperative immunonutrition. Shock 2000;14:325-33.
- Braga M, et al. Health care resources consumed for surgical morbidity. Effect of preoperative arginine and omega-3 fatty acids supplementation on costs. Nutrition 2005; 21:1078-86.