Perioperative Nutrition and Immunonutrition In the Era of ERAS and PSH: A Review

Roy Soto, MD

Professor Department of Anesthesiology
Oakland University
William Beaumont School of Medicine
Royal Oak, Michigan

To many, “nutrition” is a vague word that conjures visions of food pyramids, healthy salads (with dressing on the side), and daily vitamins. Patients and physicians alike inherently accept that poor nutrition in the perioperative period is probably a bad thing, yet when tasked with describing good or poor nutrition in more detail, most struggle. The goal of this article is to review what “nutrition” means, how nutrients affect the immune system, and how nutrients can affect recovery from surgery.

Enhanced recovery after surgery (ERAS) programs and the perioperative surgical home (PSH) model both strive to reduce the variability in care by incorporating standardized evidence-based protocols. Management of fluids, analgesics, antiemetics, and anesthetics has been protocolized, published, and accepted; however, perioperative nutrition has been largely ignored, partly due to its complexity and because of our poor understanding of its value. Yet the body of literature supporting the role of nutrition in wound healing is extensive, and probably contains more evidence than many of the other accepted best practices in protocols around the country.

Why We Need to Eat

Nutritional education is frequently compulsory, yet nearly always superficial. We learned about the food pyramid in elementary school (now known as MyPlate); we may have had a class or two on fats, carbohydrates, and protein in high school; and then had that knowledge reinforced taking biochemistry in college and medical school. If we were lucky, we then received another hour or two of information about healthy eating during our medical education, and then graduated to care for our patients, feeling comfortable telling them to eat healthily.

I now will act like an elementary schoolteacher and summarize the reasons we need to eat. In order to ensure that we all have the proper building blocks for the discussion to come, the Table lists components of what we eat and why we need them.

The lay sports literature is replete with reports covering which ratios of these components are best for muscle building and recovery, yet similar attention has not been given to medical recovery. The perioperative period is somewhat similar to a sporting event: Building muscle and storing energy would seemingly make patients more robust for surgery, and having energy stores should aid in recovery, when patients are expected to ambulate, participate in rehabilitation, and heal.

Healing from surgery, however, is very different than recovering from a race. The perioperative stress response profoundly affects the immune system, and this can affect bone remodeling, anastomotic healing, flap survival, and wound revascularization.¹

How the Immune System Aids in Healing

Surgical stress initiates a series of changes in the hypothalamic-pituitary-adrenal axis, the severity of which is dependent on the magnitude of induced trauma. The net effect of these hormonal changes is catabolism, resulting in breakdown of tissue and impaired healing. Healing involves a cascade of events, resulting in repair of damaged tissues and a return to normal function—the classic progression from inflammation to proliferation to remodeling.²

Table. The Components of Food Carbohydrates Provide short- and long-term energy Fats Ensure vitamin absorption, and aid with immune development Proteins Provide building blocks for muscle/tissue development/growth Vitamins/minerals Aid with immune development, and are necessary for proper growth/development

Platelets predominate in the coagulation phase, giving way to macrophages and neutrophils, and then fibroblasts and lymphocytes through proliferation. Each cell line is affected by a host of immune mediators, including vitamins, minerals, and simple and complex proteins.

How Food/Nutrition Affects The Immune System

The interactions between food and immunity are complex, and it is difficult to summarize all interactions in one brief article. Carbohydrates and fatty acids provide energy substrates, and amino acids/protein provide building blocks for tissue remodeling/regrowth. Vitamins are necessary for immune cell development and function, and nutrients directly affect cytokine and hormone formation/function.

A growing body of evidence also has demonstrated that the intestinal microbiome is a primary modulator of immune function, and that diet contributes to the composition of intestinal flora.³ Vitamin deficiencies can increase the risk for infection, and protein and calorie deficiencies can depress cellular immunity and inhibit the function of phagocytes. In short, deficiencies in certain nutrients can worsen immune function, and optimization of these components can improve it.

Immunonutrition

Standard nutritional supplements are easily digested liquids that include carbohydrates, proteins, fats, vitamins, and minerals (eg, Boost [Nestlé] and Ensure [Abbott]). Studies that have examined the role of immunonutrition have compared these standard formulations with those that include arginine, nucleotides, and omega-3 fatty acids—substances that have been shown to enhance immune function. Arginine improves T-cell function and enhances nitric oxide and collagen formation, theoretically improving wound oxygenation and healing.⁴ Nucleotides, as building blocks for RNA and DNA, are necessary for immune cell activation and cell growth.⁵ Omega-3 fatty acids enhance lymphocyte function and modulate inflammation.⁶

Evidence supports the theory that immunonutrition improves outcomes in patients who are malnourished.⁷ Similar studies in well-nourished patients revealed similar results: reduced infection rates and hospital length of stay (LOS) in patients with head and neck cancers; decreased infection in cardiac patients; and improved infection, hospital LOS, and anastomotic leak rate in patients with colorectal cancer.^8-10

Meta-analyses for preoperative immunonutrition have been described in JAMA and major surgical journals,^11,12 and guidelines for both the American and European societies of parenteral and enteral nutrition consider preoperative immunonutrition to be a standard of care for patients undergoing major surgery.13,14 Despite the weight of the evidence and strength of consensus, routine preoperative immunonutrition is frequently ignored.

Immunonutrition And ERAS/PSH

Patients undergoing surgical procedures in an ERAS/PSH care model should receive preoperative optimization. Note that preoperative nutrition is sometimes confused with carbohydrate loading. Carbohydrate loading also is an important aspect of preoperative optimization, and consists of carbohydrate-rich clear liquids consumed the morning of surgery to reduce the risk for dehydration, improve subjective satisfaction, reduce fasting/catabolism-induced insulin resistance, and potentially avoid hyperglycemia.

Preoperative optimization suggests that what is good for one patient is good for all patients. Although this may not be true (one size does not fit all), many ERAS administrators have found that it is important to keep variability to a minimum. That is, different patient types with different comorbidities should not receive different interventions based on clinician judgment, when that judgment is not evidence-based and may only lead to confusion and protocol deviation.

A simple example of this is a protocol that precludes patients older than 70 years of age from receiving preoperative anxiolysis. We all can imagine elderly patients who might benefit from benzodiazepines, but do they truly need them, or will allowing this protocol point to be vague lead to avoidable postoperative delirium/confusion?

As outlined above, immunonutrition improves outcomes for both healthy and malnourished surgical patients undergoing specific operations. It seems logical, therefore, to recommend a brief course of preoperative immunonutrition to patients—for instance, in a colorectal ERAS protocol.

The challenge, unfortunately, lies in the economics of the intervention. A typical 5-day course of immunonutrition, as outlined in the literature, costs somewhere between $30 and $60, and that cost must be borne by someone. Although some patients would be willing to pay, some certainly would not, adding variability to this important piece of the optimization puzzle.

Surgeons could pay, but chances are that they would not benefit the most from the shortened hospital LOS or reduced complication rate that the intervention might provide. In hospitals with multiple surgeon groups providing care for a specific service line, this would again add variability to the protocol.

Hospitals ultimately reap the most benefit from improved satisfaction, reduced complication rates, and shortened hospital LOS. It therefore makes the most sense for a hospital that has committed to an ERAS/PSH model to also make a small investment in the fixed costs for the program. ERAS/PSH team managers should partner with dietitians to make appropriate recommendations, and administrators should understand that this simple intervention can improve care, empower patients, and reduce cost.

Dr. Soto reported no relevant financial disclosures.

References

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