© Springer Science+Business Media New York 2015
Alan David Kaye, Adam M. Kaye and Richard D. Urman (eds.)Essentials of Pharmacology for Anesthesia, Pain Medicine, and Critical Care10.1007/978-1-4614-8948-1_4040. Enteral and Parenteral Nutrition
(1)
Nutrition and Food Services, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA
(2)
Department of Anesthesiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
Introduction
Critically ill patients have a multitude of stressors that cause disruption in homeostasis. Besides pathophysiologic changes resulting from critical illness, there are environmental, psychosocial, and nutritional stressors. These can lead to altered energy consumption and nutrient losses, resulting in faster depletion of body stores. Nutrition support is therefore an integral part of care of a critically ill patient. Lack of enteral nutrition (EN) can lead to a proinflammatory state resulting in increased oxidative stress, multiorgan failure, and a prolonged length of stay [1–3]. On the other hand, early and appropriate EN can decrease gut bacterial translocation, maintain gut-associated lymphoid tissue (GALT), and preserve upper respiratory tract immunity [1, 4, 5]. This translates to improved clinical outcomes and a decrease in costs, while reducing complication rates and length of stay [6]. Moreover, certain nutrients such as glutamine, arginine, and omega-3 (ω-3) fatty acids have been shown to have favorable clinical effects in critically ill patients [1, 7]. The dynamic interplay of pathophysiology and metabolism in critical illness suggests that we consider nutrition as a specific pharmacotherapeutic intervention by which an astute clinician can alter the disease process to achieve a favorable outcome.
In this chapter, we will provide an overview of nutrition support focusing on the critically ill patient. We will also discuss specific pharmaconutrients and their proposed mechanisms of action, along with a broad discussion of the interactions of nutrition with GI function, modulation of inflammation and immunity, and condition and disease-related indications for specialized nutrition support. We will also cover important drug-nutrient interactions as well as potential adverse effects associated with nutrition support.
Drug Class and Mechanism of Action
Enteral and Parenteral Nutrition
Artificial nutrition may be provided in the form of either EN or parenteral nutrition (PN). EN is defined by the American Society for Parenteral and Enteral Nutrition (ASPEN) as “nutrition provided through the gastrointestinal tract via a tube, catheter, or stoma that delivers nutrients distal to the oral cavity” [8]. EN is preferred over PN due to reduced cost and complications [8]. PN is defined as “nutrients provided intravenously” [9]. PN consists of a dextrose-amino acid solution including vitamins and minerals and an intravenous fat emulsion (IVFE) [9].
Pharmaconutrients
Specialized EN formulas containing pharmaconutrients may be beneficial for modulation of immune and inflammatory responses [1, 7, 10]. Researchers typically use commercial formulas in investigations; therefore, they have studied combinations rather than individual immune-modulating nutrients. This makes it difficult to determine precise individual dosing recommendations or to determine whether it is an individual nutrient or the synergistic effect of many pharmaconutrients that provide clinical benefit [7].
Arginine and glutamine are conditionally essential amino acids during acute periods of stress [7, 10]. Arginine is involved in many metabolic pathways, including conversion of ammonia to urea, protein and collagen synthesis, and release of anabolic hormones [10]. Arginine is required for the synthesis of polyamines which promote cell division and growth and may decrease production of proinflammatory cytokines and T cells [10]. Arginine is also involved in the production of nitric oxide [10]. Glutamine is a key substrate for gluconeogenesis and is an important fuel for rapid turnover cells, such as the small intestine epithelium and immune cells, including lymphocytes and macrophages [7, 10]. Additionally, it is involved in the regulation of T-cell proliferation, interleukin-2 production, and B-cell differentiation, as well as having a role in phagocytosis and superoxide production [10]. Parenteral supplementation has been shown to promote positive nitrogen balance and healing in postoperative patients and appears to support gut integrity in spite of its intravenous (IV) rather than enteral administration [1, 10].
Essential polyunsaturated ω-3 and omega-6 (ω-6) fatty acids are involved in cell membrane formation and production of prostaglandins and leukotrienes [10]. The less inflammatory derivatives of ω-3 fatty acids (such as 3-series prostaglandins and 5-series leukotrienes and D-series resolvins and protectins) compete with highly inflammatory ω-6 fatty acid derivatives (including 2-series prostaglandins and 4-series leukotrienes); therefore, a diet higher in ω-3 and lower in ω-6 fatty acids helps to modulate the inflammation and improve immune function [7, 10, 11].
Immune-modulating formulas may also contain increased amounts of nucleotides and antioxidants. Similar to arginine and glutamine, the need for dietary nucleotides is increased during periods of acute stress, since they are needed for synthesis of DNA and RNA and are vital for energy transfer and hormone function [7]. Nucleotide deficiency may worsen immune function and increase the risk of sepsis [12]. Antioxidant supplementation may be beneficial in critically ill (including septic) patients, those with acute respiratory distress, and those undergoing major surgery [1, 10, 13].
Indications and Clinical Pearls
The functions of artificial nutrition exceed provision of energy and nutrients in order to prevent or reverse malnutrition. Artificial nutrition can prevent loss of gut integrity and gut-associated immunity, modulate whole-body immune function and the inflammatory response, and improve clinical outcomes in many patient populations, including surgical, trauma, burn, and other critically ill patients.
Maintenance of Gut Integrity
The healthy gut acts as a physical barrier to antigens and contains specialized tissue that can trigger an immune response [4, 5]. During periods of acute stress such as critical illness, splanchnic hypoperfusion may cause injury to gut tissue within hours of injury [4, 5]. GALT, part of the mucosal-associated lymphoid tissue, is comprised of Peyer’s patches, the appendix, epithelial cells, and a layer of the lamina propria [4]. Normally, antigens are detected and absorbed in small bowel Peyer’s patches, where T and B cells are sensitized [4]. When nutrition support is held or provided with PN rather than EN or oral diet, levels of naïve T and B lymphocytes in Peyer’s patches are significantly reduced [4]. Loss of GALT mass and function has been shown to reduce overall bodily immune function in both human and animal experiments [4, 5]. Provision of EN helps to maintain gut integrity by preventing loss of tight junction proteins, by maintaining GALT mass and function, and by improving blood flow to the bowel [1].
Modulation of the Inflammatory Response
Modification of essential fatty acid balance towards more ω-3 and fewer ω-6 fatty acids may improve clinical outcomes. High doses of oral ω-3-rich fish oil (1–7 g/day) have been shown to be beneficial for the treatment of rheumatoid arthritis and cardiovascular disease and possibly (though less conclusively) inflammatory bowel disease and asthma [11]. While animal models looking at the effects of fish oil supplementation have been promising, clinical research is less conclusive [11]. One area where the use of fish oil has clear clinical benefits is when proinflammatory IVFE is replaced with a fish oil IVFE [9, 11]. Unfortunately, the only IVFE available in the United States is made of soybean oil, which contains a relatively higher proportion of ω-6 fatty acids as compared to alternative formulations available in other countries, which contain other lipid sources, including medium chain triglycerides, olive oil, and/or fish oil [13].
Perioperative Nutrition Support
Provision of immunonutrition is beneficial when provided preoperatively, postoperatively, or perioperatively; however, positive effects, specifically decreased time of mechanical ventilation, decreased infectious morbidity, and decreased length of stay, are more prominent in patients who receive immunonutrition perioperatively [8]. ASPEN strongly recommends the use of immune-modulating formulas in patients undergoing major elective surgery with especially strong evidence for use in those undergoing major GI surgery [8, 14]. Further studies and meta-analyses after publication of ASPEN’s recommendations continue to support the use of immune-modulating EN in surgical patients [15–17].
Respiratory Failure
Historically, formulas designed for use in those with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) were low in carbohydrate (CHO) and high in fat in order to decrease CO2 production [18]. It was later discovered that excess energy is more detrimental than excess CHO provision [18]. Formulas designed to modulate inflammation and cellular oxidation associated with ALI/ARDS were developed more recently [17]. Current pulmonary formulas contain ω-3 fatty acids, borage oil (gamma-linolenic acid), and antioxidants with standard amounts of CHO and fat [17]. ASPEN’s guidelines recommend these formulas for ALI/ARDS based on studies showing a reduction in mortality, ventilator days, length of stay, and organ failure [1]. The three studies this recommendation is based on, however, compared modern formulas to out-of-favor high-fat pulmonary formulas [19–21]. Since control formulas were high in total fat, they contained high levels of proinflammatory ω-6 fatty acids, which is a significant methodological flaw. When modern pulmonary formulas are compared to standard EN formulas, significant benefits are not observed [19]. Given the high cost of specialized formulas, clinicians should consider this recent evidence before using specialized pulmonary EN formulas.
Severe Acute Pancreatitis
Often the goal of therapy for acute pancreatitis is gut rest in order to minimize pancreatic stimulation. Unfortunately, this quickly leads to loss of gut integrity and bacterial overgrowth [22]. Consequently, there is increased inflammation and a blunted immune response due to downregulation of GALT, which can lead to or exacerbate existing systemic inflammation and worsen overall prognosis [22]. This can be prevented with early initiation of EN, ideally within 24–48 h, in patients with severe acute pancreatitis [26]. A polymeric formula is acceptable, although a semi-elemental formula may be considered if the standard formula is not tolerated [22]. Though feeding the small bowel past the ligament of Treitz has been recommended to minimize pancreatic stimulation, more recent studies have shown that gastric feeds may also be well tolerated [22, 23].
Other Critical Illness
Immunonutrition may also be beneficial in other critically ill patients, such as those with sepsis, trauma, burns, and traumatic brain injury [1, 10, 24–30]. The benefits for these patients, however, are less clear than for surgical patients, due to fewer available research studies [1, 10]. There is evidence that supports early EN (within 24–48 h of injury) in patients with severe burns [24–29] and traumatic brain injury [27]. Burn patients have extremely high protein-energy requirements and benefit from increased provisions of antioxidants, selenium, zinc, and copper for wound healing and prevention of cellular oxidation [28]. While there is evidence that immunonutrition may be beneficial in burn patients, more research is needed to confirm these benefits [26]. There is less available evidence regarding the use of immunonutrition in brain injury; however, animal studies have shown that glutamine supplementation may help maintain gut integrity and modulate inflammation in this patient population [29, 30].
Other Organ Failure
Patients with acute kidney injury should receive standard EN formulas unless electrolyte abnormalities occur. For these patients, specialized renal formulas should be considered [1]. Protein provision must be individualized based on other acute conditions, severity of renal failure, and blood urea nitrogen levels, keeping in mind that acute kidney injury is a hypermetabolic condition and that renal replacement therapy further increases protein needs [1, 31]. Otherwise healthy patients with chronic renal failure may require a renal, low-protein formula for preservation of renal function if not receiving dialysis. A renal, higher protein formula is indicated when receiving dialysis treatment [31].
Though specialized hepatic formulas high in branch-chained amino acids are available, these should be reserved for patients with refractory encephalopathy and should not be used routinely in those with hepatic failure [1]. As with most patient populations, EN is also the preferable form of artificial nutrition in those with hepatic dysfunction. However, PN is acceptable for those who cannot tolerate EN for more than 7 days, in spite of the potential hepatic side effects associated with PN therapy [32, 33]. In all cases of organ failure, nutrition assessment and determination of appropriate nutrition support must be highly individualized, and clinicians should not rely on specialized formulas when choosing nutrition therapy.
Dosing Options
Estimating Protein-Energy Needs
Though indirect calorimetry is the gold standard for determination of estimated energy requirement (EER), it is often not available; therefore, predictive equations must be used [18, 34]. For healthy, normal-weight individuals, EER is around 25 kcal/kg of the actual body weight (ABW) [35]. Clinicians may also use the Mifflin St. Jeor equation using ABW, especially for overweight or obese individuals [34].
There are also a number of formulas for estimation of energy needs in the critically ill. The Academy of Nutrition and Dietetics recommends using the Penn State University 2003b equation [36] or the Penn State University 2010 equation for obese patients over the age of 65 [37].
While one may surmise that a critically ill patient has increased EER due to the severity of illness, EER in this population is actually around 23 kcal/kg [35]. Intake over 25 kcal/kg is associated with liver damage, especially when provided by PN [35]. Critically ill patients may, in fact, benefit from permissive underfeeding to 50–60 % of their EER during the first week after injury, especially if the patient is obese [1]. After 1 week, efforts should be made to avoid underfeeding, as it could result in decreased respiratory muscle strength, immunosuppression, worsened wound healing, and increased risk of infection [18]. Prevention of both underfeeding and overfeeding requires close monitoring and frequent adjustments to protein-energy provision in the critically ill population.
Protein intake may be of higher importance than energy provision in critically ill patients [35]. While normal protein requirements are around 0.8 g/kg ABW [38], critically ill patients require 1.2–2 g/kg ABW when their BMI is less than 30 or 2–2.5 g/kg ideal body weight or higher if the patient is obese [1]. Protein provision may need to be further modified in the setting of renal dysfunction [31].
Initiation and Advancement of Nutrition Support
In critically ill patients for whom an oral diet is not feasible, EN should be initiated within 24–48 h of injury to maximize benefits, including a decrease in infections, length of stay, and mortality [1]. Though ASPEN guidelines recommend a starting rate of 10–40 mL/h and advancing to goal rate by 10–20 mL/h every 8–12 h as tolerated [8], it should be noted that there is a lack of research regarding appropriate and safe initiation and advancement of EN support. For short-term nutrition support, a naso- or orogastric tube is preferred due to ease of placement [1]. Naso-jejunal tubes may be preferable in patients with a known risk of aspiration or those with a history of intolerance to gastric feeds [1, 8, 39]. If EN support will be required long term (more than 4 weeks, per ASPEN), placement of a long-term feeding device such as a gastrostomy or jejunostomy tube should be considered [8].
If a patient does not tolerate EN, it is preferable to withhold nutrition support for 7 days rather than to initiate early PN [1, 40]. For malnourished patients, however, PN should be considered earlier [7]. If EN is not achievable or sufficient for longer than 7 days, PN should be considered [1]. Due to the potentially proinflammatory effects of soy-based IVFE, ASPEN recommends withholding lipids for the first week of PN therapy [1]. In noncritically ill patients, there are no clear recommendations regarding when exactly EN or PN should be initiated. Clinicians need to consider many factors, including presence of malnutrition, inflammation, and expected duration of suboptimal oral intake.
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