Nutritional and Metabolic Therapy

Fasting in the Perioperative Period

Time elapsed from last oral intake is perhaps the most immediate and relevant issue regarding how nutrition affects the delivery of anesthesia to patients. The risk of aspiration on induction presents a severe, potentially modifiable risk to patients, such that the American Society of Anesthesiology promulgates fasting guidelines for patients undergoing elective procedures requiring anesthesia. The most recent 2017 guidelines recommend fasting times for clear liquids of 2 or more hours, 4 or more hours for breast milk, 6 or more hours for a light meal, and eight or more hours for a fatty meal, prior to undergoing general anesthesia, regional anesthesia, or sedation.

With the emergence of Enhanced Recovery After Surgery (ERAS) pathways, there has been renewed interest in nutritional optimization in the immediate perioperative period. The thought that major elective surgery is stressful and strenuous has led investigators to question whether preoperative carbohydrate loading might improve outcomes. In a recent meta-analysis, Amer et al. showed that a carbohydrate load of at least 10 g of glucose within 4 hours of surgery conferred a small, but real benefit in hospital length of stay (LOS) when compared to fasting. It appears that “carbo loading” may yield attenuation of the insulin resistance associated with the surgical insult.

If not for the risk of aspiration, might it be optimal to continue nutrition through the surgical period? While it is standard care to continue parenteral nutrition (PN) through surgery, as there is no increased risk for aspiration, best practices for enteral nutrition (EN) are still the subject of debate and research. It is clear that there are certain populations of patients who benefit from EN up to and during surgical interventions. In critically injured burn patients, it has become common practice at many centers to feed through operations with significant improvement in total calories delivered. Feeding up to and through surgery has also been reported in orthopedic procedures and has recently been extended to other surgical groups. There are also data to suggest that continuing postpyloric tube feeding in the critically ill intubated patient presenting for nonabdominal surgery does not increase the incidence of aspiration, suggesting that EN can be safely continued in the perioperative period.

Benefits of Early Enteral Feeding

Early EN in the ICU has myriad reports explaining the diverse mechanisms to support the observed benefits ( Table 33.1 ). The gastrointestinal tract comprises the largest immune organ in the body and is responsible for the production of over 80% of the immunoglobulin transported to extraintestinal sites. The ability of the gut to function appropriately as an immune organ is dependent on the maintenance of both structural and functional integrity. The integrity of the gut, in turn, is greatly dependent on continued exposure to luminal nutrient substrates. Both adaptive and innate immune defenses are active in this process. Innate mechanisms are dependent on epithelial tight junctions and secretory capabilities of the mucosa. Secretory immunoglobulin A (IgA) is an important component of the adaptive immune system, as antigens are tagged and presented to dendritic cells within Peyer patches, which are in highest concentration in the distal small bowel. Gut disuse over a period of as little as 5 days has been shown to dramatically decrease the mass of gut-associated lymphoid tissue (GALT) and the production of secretory intestinal IgA. These changes are completely reversed with reinstitution of EN therapy. Increases in intestinal permeability have been shown to correlate with the development and severity of multi-organ failure (MOF) syndrome. Using EN to modify the severity of the systemic inflammatory responses by attenuating metabolic and oxidative stress is a primary goal of nutritional therapy in the surgical or critically ill patient.

Timing of Nutrient Delivery

The optimal time to start nutrition support is influenced by a host of factors, including age, premorbid conditions, route of nutrient delivery, metabolic state, and organ perfusion and function. As previously noted, literature evaluating nutritional support for critically ill patients has analyzed heterogeneous populations. Nevertheless, these diverse studies provide a foundation to guide nutritional therapy in a wide range of ICU patient types (e.g., burn, trauma, abdominal surgery, oncologic surgery, and so on).

The reported physiologic benefits of early EN are, among others, prevention of adverse structural and functional alterations in the mucosal barrier, augmentation of visceral blood flow, and enhancement of local and systemic immune response. The clinical benefits of early EN, defined as within 24 to 48 hours of ICU admission, include reduced infectious morbidity, LOS, and, in some reports, reduced mortality, all with minimal risk of harm to the patient. Despite these acknowledged benefits, nutrition delivery remains suboptimal in a significant percentage of critically ill patients.

Acknowledging that the early initiation of nutrition support constitutes best practice, a multidisciplinary approach to determining appropriate timing in the individual patient cannot be overemphasized. Enteral feeding should not proceed until appropriate resuscitation has been undertaken ( Table 33.2 ). Early resuscitation remains a cornerstone of ICU therapy. Early and aggressive resuscitation, or “early goal-directed therapy,” involves the placement of invasive lines for monitoring, drug delivery, and volume resuscitation, with vasopressors if the patient fails to respond appropriately to volume expansion. While there is no one laboratory or hemodynamic parameter signaling the successful resuscitation of the critically ill patient, trends in hemodynamic parameters—including mean arterial pressures, central venous pressures, and pressor requirements in conjunction with urine output, arterial base deficit, serum lactate, and venous oxygen saturations—are utilized in order to determine the relative success of resuscitation.

Splanchnic circulation can increase by as much as 40% to 60% in the setting of enteral feeding. The specific actions of digestion and absorption increase the metabolic demand and oxygen utilization by the gastrointestinal tract. If supply falls short of demand, rare but devastating complications, such as nonocclusive mesenteric ischemia (NMI), can ensue ( Fig. 33.1 ). Fortunately, nonocclusive mesenteric ischemia is a very rare complication, but since its effects can be devastating, with mortality rates reported as high as 80%, enteral feeding in the hemodynamically unstable patient should be undertaken with extreme caution.

Following adequate resuscitation and assuming that no other absolute contraindication to enteral feeding exists (e.g., bowel obstruction), enteral support should be initiated as soon as possible, regardless of the status of traditional markers of bowel function (bowel sounds, flatus, passage of stool).

Numerous reports support the concept that the initiation of EN should not be delayed while waiting for evidence of bowel function, though the absence of the clinical markers of bowel function may be predictive of worse patient clinical outcomes and higher rates of EN intolerance. The approach of waiting for these signs leads to unnecessary delays in feeding. In a randomized trial, oral feeding initiated within 48 hours of gastrectomy, without waiting for traditional predictors of feeding tolerance (e.g., passing flatus) demonstrated the safety of the approach. There was no increase in morbidity, and there was a reduction in LOS. A recent meta-analysis, examining 15 studies and 1240 patients with gastrointestinal anastomoses, demonstrated reduced postoperative complications when feeding was initiated within 24 hours of operation. Other meta-analyses, specifically in ICU and trauma patients, report a significant decrease in mortality and infectious complications.

Recent approaches to maximize gut function in the postoperative and critical care settings include maintenance of visceral perfusion; glycemic control; electrolyte correction; early EN; and minimization of medications that alter gastrointestinal function, such as anticholinergic agents, opioids, and high-dose vasopressors. Gastrointestinal intolerance should be continually reassessed, as it can manifest clinically in a variety of forms, including acidosis, abdominal distension, increased gastric residual volumes or nasogastric output, abdominal pain, or diarrhea. The segmental contractility of the gastrointestinal tract should be considered, as dysmotility can be focal (affecting predominantly either the proximal or distal bowel) or diffuse. Impaired gastric and proximal gastrointestinal motility ( Fig. 33.2 ) can be overcome rather efficiently through the placement of postpyloric feeding tubes. Postpyloric tubes can be successfully placed at the bedside in greater than 80% of patients.

Prokinetic agents can be used early and are helpful in some patients. Erythromycin acts on motilin receptors, resulting in increased motility, and can be used on a short-term basis but is limited due to tachyphylaxis. Metoclopramide, a 5-hydroxytryptamine (5HT ₄ ) receptor agonist, works via cholinergic stimulation and is primarily efficacious in the proximal gut. When using metoclopramide (see Chapter 32 ), one must also consider the potential for extrapyramidal side effects, especially in patients with altered mental status from traumatic head injury or cerebral vascular events. Alvimopam (see Chapters 17 and 18 ), a peripherally acting µ-antagonist, has demonstrated some success in the setting of dysmotility associated with opioid administration in the postoperative setting. No single prokinetic agent will have uniform success in the ICU, and the factors contributing to gastrointestinal dysmotility in each patient must be considered. Caution should be taken when using prokinetic agents on patients at high risk for bowel necrosis or obstruction.

Early EN is best accomplished in the ICU and postoperative settings, using standardized protocols. Protocolizing early enteral feedings in appropriately selected patients can reduce duration of mechanical ventilation, infectious complications, hospital LOS, and mortality.

Pharmaconutrition-Immunonutrition

In 1794, John Hunter described in his book, A Treatise on Blood, Inflammation and Gunshot Wounds, A Mechanism of Inflammation , an observation that “many types of injury produce a similar inflammation.” Similarly, in 1904, Sir William Osler stated, “except on few occasions the patient appears to die from the body's response to infection rather than from it.” These two extremely insightful and prophetic comments were both made over 100 years ago. The current strategy in the ICU of using nutrition therapy to modulate inflammation and immune response in the surgical, traumatically injured, and critically ill populations is now widely accepted. This strategy of nutrition therapy, sometimes called pharmaconutrition or immunonutrition, uses specific nutrients to attenuate or control the body's metabolic response to stress and trauma rather than allowing systemic inflammatory response syndrome (SIRS) to progress to persistent inflammation, immunosuppression, and catabolism syndrome (PICS). The metabolic response to stress that can ultimately lead to PICS has been well described, which includes a hyperdynamic cardiac and pulmonary state, insulin resistance, hyperglycemia, accelerated protein catabolism from muscle, poor adaptation to starvation, and increased oxidative stress. Unabated, the metabolic response to stress can culminate in immune suppression. During this hyperdynamic phase of critical illness, surgery, or trauma, the loss of lean body mass continues, despite delivery of seemingly adequate enteral or parenteral protein and calories. In effect, administration of standard “calories and protein” to the hyperdynamic patient will not reverse the adverse effects of ongoing loss of lean body tissue. The hyperdynamic induced loss of lean body tissue is made worse by “muscle unloading” ( Fig. 33.3 ). Several reports have now shown that using specific nutrients—such as fish oils, selected amino acids (e.g., arginine, glutamine, leucine), antioxidants, and nucleic acids—in quantities greater than necessary for “normal” metabolism has resulted in multiple outcome benefits, including shortened length of ICU and hospital stays, decreased incidence of infections, and reduced mortality in some cases.

A wide range of select specific nutrients have been reported to benefit the critically ill patient when delivered at pharmacologic quantities. Many of these compounds are now considered to be therapeutic agents in the management of complex, catabolically stressed patients ( Table 33.3 ). A collaboration between the Society of Critical Care Medicine (SCCM) and the American Society of Parenteral and Enteral Nutrition (ASPEN) resulted in Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient, which has been recently updated. These guidelines summarize the available evidence, and recommend that postoperative surgical ICU patients and patients with traumatic brain injury benefit from EN with immunomodulating formulas.

Several immune and/or metabolic modulating enteral formulas are now available globally. These products contain a variable quantity of nutrients identified and reported as beneficial during critical illness. Well over 100 prospective randomized human trials have been conducted with different combinations of these immune and metabolic modulating nutrients in various ICU, surgical, and medical populations. A wide range of methodologic quality is observed in these studies from relatively small, poorly designed studies to large prospective randomized clinical trials with intention-to-treat analysis. Most of the larger studies have been extensively analyzed and methodologically scrutinized by numerous reviewers. Despite the heterogeneity of the study designs, the majority of these studies report a clear benefit of reduced intensive care and hospital LOS, decreased antibiotic use, and reduced rates of infection. In particular, evidence cited in ASPEN/SCCM Guidelines suggests clinical effects of specific pharmaconutrients. These nutrients—including glutamine, fish oils, and arginine—have been credited with a reduction in infections and LOS in surgical patients. They produce a similar favorable impact on these outcomes in other ICU populations, although less dramatic benefit is noted.

Specific Nutrients

For decades, amino acids were believed to modulate intermediary metabolism, but the clinical outcome benefits of specific amino acids have only been reported over the last 15 years. Dietary supplementation with the amino acids glutamine, arginine, and leucine has been the focus of the majority of clinical trials, but other amino acids—specifically, glycine, taurine, citrulline, and glutamate—have received interest recently. This chapter will present only a brief summary of amino acid and Omega-3 fatty acid supplementation.