Introduction

Nutrition support for critically ill and injured patients has undergone significant advances in recent decades—the direct result of scientific progress and our increased knowledge of the biology and biochemistry of key nutrient changes induced by injury, sepsis, and other critical illnesses, both in adults and in children. The science of nutrition support (or, more accurately, of nutrition therapy) has become more disease-based. Also called “specialized” or “artificial” nutrition support, nutrition therapy refers to the provision of either enteral nutrition (EN) via tube feeding or total parenteral nutrition (TPN). In contrast, “standard therapy” refers to a patient’s own volitional intake, without the provision of nutrition therapy [1].

Depending on the individual patient’s metabolic needs, nutrition therapy helps ensure that key nutrient substrates are replenished, or added in larger amounts, to supplement specific deficiencies or to simply prevent further deterioration and clinical consequences [2]. The benefit of early institution of either EN or TPN in the overall care of critically ill and injured patients has now been well established. After a critical illness or injury, the patient’s energy and overall metabolic requirements greatly increase, in order to sustain increased metabolism and the process of wound repair. Given current evidence derived from randomized controlled trials (RCTs), early provision of nutrition for critically ill and injured patients is now a level I recommendation [2].

The mainstay of nutrition delivery in intensive care units (ICUs), EN has benefits for the patient’s gastrointestinal (GI) tract and associated immune system. The methods of delivering nutrition therapy, however, continue to be debated. Some clinicians mistakenly hoped that EN could be used in all patients and at all times. No doubt, the GI tract should be used when possible, but TPN continues to be a great modality for many critically ill and injured patients. However, the risks and pitfalls of interruptions in EN, as well as mechanical problems associated with its delivery, are now better appreciated. Improvements in TPN formulations have also undercut the notion that EN can be given to every patient. Thus, TPN remains an important technique in patients with GI feed intolerance or EN failure [3].

Pathophysiology of nutrition imbalance

No patient is more difficult to feed than one with multiple injuries and/or multiple organ failure. As levels of catecholamines, cytokines, and insulin rise in response to such traumatic insults, energy expenditure and protein turnover increase. It is difficult to develop guidelines applicable to all critically and injured patients, given the heterogeneity of this patient population. There is a profound need for clinical judgment [4]. Critical illness and tissue injury initiate a complex series of rapid homeostatic events in an attempt to prevent ongoing tissue damage and to activate the repair process. Classically, inflammation has been recognized as the hallmark of the homeostatic response. But, more recently, attention has focused on defining the response at the metabolic, cellular, and molecular levels [5].

Three response phases

The response to stress and injury has been described as involving three phases: the ebb phase, the catabolic flow phase, and the anabolic flow phase [6, 7]. Each of these phases has distinct changes that require specific interventions in order to eliminate or minimize the consequences of illness and/or injury. First, the ebb phase is dominated by circulatory changes that require resuscitation (with fluid, blood, and blood products) over a period of 8–24 h. Second, the catabolic flow phase, dominated by catabolism, typically lasts 3–10 days, but may last longer; this phase is driven by cytokine mediators released from lymphocytes and macrophages in the cellular immune reaction, dominated by interleukin-6 (IL-6) [7]. The release of these mediators is proportional to the intensity of the injury, but the release of cytokines themselves is upregulated by hormonal and humoral events [7]. Third, the anabolic flow phase emerges as the patient’s metabolism shifts to synthetic activities and reparative processes [7].

Protein and nitrogen metabolism

The metabolic response to injury is associated with a striking increase in protein catabolism, a negative nitrogen balance, and a marked increase in urinary loss of nitrogen, phosphorus, sulfur, potassium, magnesium, and creatinine. This process peaks several days after injury and gradually returns to normal over several weeks [5, 8]. Measurement of the excretion of 3-methylhistidine serves as an index of muscle protein catabolism [9]. Amino acid requirements increase by 2–3 times as a result of hypercatabolism and the inefficient reuse of endogenous nitrogen [10]. Furthermore, amino acids are redistributed from peripheral tissues to splanchnic organs in order to maintain protein synthesis in the gut mucosa and immune system [11].

Acute phase response and proteins

The acute phase response (APR) is an early and nonspecific response to systemic tissue injury. Responsible for the reprioritization (depending on the magnitude and severity of the injury) of protein synthesis in the liver, the APR is characterized by an exponential increase in positive acute phase proteins and by a decrease in negative acute phase proteins [12–14]. A variety of cytokines, released at the site of injury or infection, have been implicated in the production of acute phase proteins from the liver, including IL-1 and IL-6, as well as tumor necrosis factor-alpha (TNF-alpha) [15].

The acute phase proteins reach a maximum concentration within a few days after the onset of tissue damage and return to their normal concentrations within a week [15]. First, the serum concentration decreases for most of these proteins, both for positive reactants and for negative reactants. Later, the hepatic synthesis of negative acute phase proteins decreases, and the concentration of serum albumin remains depressed for days to weeks after the injury. Albumin reaches a nadir by the fifth post-injury day [16]. Whether or not nutrition therapy in the immediate post-injury period can alter or blunt the APR has not been adequately investigated. In one study, nutrition therapy increased the concentration of prealbumin within the first week after the injury, although the concentration lagged behind the increased protein–calorie intake and nitrogen balance; serum albumin levels slowly declined within the first week and still decreased 18 days after the injury [13]. C-reactive protein (CRP) is the earliest acute phase reactant to respond; its serum concentration peaks at 48 h [15]. The serum protein concentration of positive acute phase proteins after minor injuries returns to normal by the end of the first week.

Continued and prolonged production of acute phase proteins in critically ill patients may be an indicator of ongoing sepsis and tissue damage, however, and is associated with higher mortality rates [17]. Perhaps some of the changes at this stage are responsible for what is defined as compensatory anti-inflammatory response syndrome (CARS). CARS, which follows systemic inflammatory response syndrome (SIRS), is characterized by cutaneous anergy, a reduction in the number of lymphocytes because of apoptosis, a decrease in the cytokine response of monocytes to stimulation, downregulation of human leukocyte antigen (HLA) receptors, and the production of transforming growth factor-beta and prostaglandin-E2 [18].

Positive acute phase proteins seem to be a protective response to tissue injury. They have diverse functions as antioxidants, proteolytic inhibitors, and mediators of coagulation. Negative acute phase proteins are albumin, prealbumin, retinol-binding protein, and transferrin. Their serum concentrations fall immediately after an injury, in proportion to its severity. They are used to monitor the nutritional status of acutely ill patients [5].

Preadmission nutritional status

The preadmission nutritional status of patients is a critical factor. If patients are malnourished or have a limited nutritional reserve, their outcome is poorer [19]. Having a low body mass index (BMI) is an independent predictor of increased mortality and of multiple organ failure [20].

Thermal injuries, severe central nervous system (CNS) insult, sepsis, and certain comorbidities, such as cancer, chronic obstructive pulmonary disease (COPD), alcoholism, and heart disease, produce added metabolic challenges and complications. Such conditions exacerbate energy expenditure and protein catabolism brought on by severe injury and critical illness, thereby, evoking variation even among patients with the same disease process [21]. It is imperative to evaluate the nutritional status of patients upon admission.

The safety and practicality of nutritional support

In most critically ill patients, EN is practical and safe. The beneficial effects of EN over TPN have been well documented in numerous RCTs involving a variety of critically ill patient populations (including those with trauma, burns, head injuries, and acute pancreatitis, as well as those who have undergone major surgery) [22–24]. Nonetheless, a number of patients cannot be fed either orally or enterally, and will require TPN. About 10–20 % of ICU patients have either a contraindication to EN (such as bowel obstruction, short bowel syndrome, abdominal compartment syndrome, or mesenteric ischemia) or a very limited tolerance to EN. Problems with tolerance to EN are frequently limited to about 3–5 days, so are a relative indication for TPN. But in some patients, intolerance to EN lasts much longer and, thus, is an absolute indication for TPN [25]. TPN is efficacious in patients who are malnourished and unable to receive adequate oral or enteral nutrients (in particular, those with short gut syndrome, severe gut dysfunction, mesenteric vascular insufficiency, prolonged bowel obstruction, high-volume fistulas, and sepsis with hemodynamic instability) [26].

To prevent undernutrition and related adverse effects, all ICU patients who are not expected to be on a full oral diet within 3 days should receive EN. Accordingly, EN is recommended as the first choice for nutrition therapy in ICU patients; however, in critically ill patients on nutrition therapy, there is a large discrepancy in the frequency of EN [27–32]. The American Society for Parenteral and Enteral Nutrition (ASPEN) Board of Directors and the American College of Critical Care Medicine Guidelines Committee expressed concern that continuing to provide standard therapy (that is, no nutrition therapy) beyond 7 days would lead to deterioration of the patient’s nutritional status and would have an adverse effect on clinical outcome [1].

If EN cannot be provided and if the patient has evidence of protein–calorie malnutrition (usually defined by recent weight loss of >10–15 % or by an actual body weight <90 % of the ideal body weight), then the use of TPN is mandatory [33]. The use of TPN (vs. standard therapy) in malnourished ICU patients was associated with a significantly lower rate of overall complications [34].

The best timing for the initiation of TPN in ICU patients has not been demonstrated. On the other hand, the European Society of Parenteral and Enteral Nutrition (ESPEN) [35] and the Canadian Society for Nutritional Sciences (CSCN) [36] both recommend early EN initiation after ICU admission (within 24 h, per ESPEN; within 24–48 h, per CSCN). It seems reasonable to assume that all patients who are not expected to be on normal nutrition within 2–3 days after ICU admission should receive TPN, if EN is contraindicated or not tolerated. No significant differences in clinical outcome have been shown between EN versus TPN in ICU patients [37].

Nutritional assessment

The best assessment of a patient’s prior nutritional state comes from a detailed history of prior illness, but obtaining such a history is not possible in some critically ill and injured patients. Calculating a patient’s nutritional intake, combined with a clinical examination of fat and muscle distribution, would also be ideal, but again, not necessarily doable. The BMI (weight in kg/height in m2) is useful, but obtaining an accurate weight can be difficult as well; moreover, it may be distorted by resuscitative fluid administration [3]. The challenges of alcohol intoxication, coma, ventilator support, and frequent use of anesthetics can also add to the inherent difficulty. If a patient’s history is obtainable, it should note any alcoholic tendencies (which are associated with malnutrition) and history of diabetes, chronic pulmonary disease, renal failure, weight gain, and weight loss (all of which are associated with increased morbidity) [38]. One of the most common methods for estimating caloric needs or basal energy expenditure (BEE) is the Harris–Benedict equation (HBE), calculated as follows:

$$ {\text{Males: BEE}} = 66.5 + 13.8 \, \left( {\text{weight in kg}} \right) + 5 \, \left( {\text{height in cm}} \right) - 6.8 \, \left( {\text{age}} \right) $$
$$ {\text{Females: BEE}} = 65. \, 5 + 9.6 \, \left( {\text{weight in kg}} \right) + 1.7 \, \left( {\text{height in cm}} \right) - 4.7 \, \left( {\text{age}} \right) $$

The HBE yields a calculation of basic energy requirements that are frequently multiplied by various activity factors and/or stress factors, thereby, generating an individual patient’s estimated resting energy expenditure (REE). For example, for stress factors, minor surgery is assigned a multiplier of 1.2; trauma, 1.35; sepsis, 1.6; and major burns, 2.1. Thus, REE = BEE × stress factors. The patient’s current actual body weight may change after a period of aggressive volume resuscitation, which could result in the overestimation of caloric requirements. Ideally, an admission weight before initial resuscitation should be obtained [39–41]. An accurate measurement of body weight is an arduous task in critically ill and injured patients, who often have bulky dressings, catheters, monitoring wires, tubes, and drains. Under such circumstances, the ideal body weight (IBW) may prove useful, calculated as follows:

$$ {\text{Males: IBW}} = 50 + \left( {2.3 \times {\text{height }}\left[ {\text{in inches}} \right] - 60} \right) $$
$$ {\text{Females: IBW}} = 45.5 + \left( {2.3 \times {\text{height }}\left[ {\text{in inches}} \right] - 60} \right) $$

Obesity poses another scenario where overfeeding may result if the patient’s actual body weight is used. It is defined as an actual body weight more than 120 % above the patient’s IBW or as a BMI >30. For all of the above reasons, the adjusted body weight (ABW) is commonly used for calculating energy requirements:

$$ {\text{ABW}} = 0.25 \, \times \, \left( {{\text{actual weight}}-{\text{IBW}}} \right) + {\text{IBW}} $$

A more specific method that may be used to determine caloric needs in patients who are on mechanical ventilators is indirect calorimetry (IC), which is considered to be the gold standard for caloric assessment. A computerized “metabolic cart” is used to collect the patient’s expired gases to determine CO2 production and O2 consumption, which are then used to calculate the REE using the Weir equation [39–41]:

$$ {\text{REE}} = \left[ {3.9 \, \left( {{\text{VO}}2} \right) + 1.1 \, \left( {{\text{VCO}}2} \right)} \right] \, 1.44 $$

Energy requirements

Current recommendations for most surgical patients and for patients during the acute and initial phase of critical illness are to provide about 20–25 kcal/kg/day through the administration of carbohydrates (70 %) and lipids (<30 %). During the anabolic recovery phase and in patients with severe undernutrition, the aim should be to provide 25–30 total kcal/kg/day (ESPEN guidelines, level III). Protein should not be included in these energy calculations: the intent is for the protein to be incorporated into new muscle, rather than metabolized into energy.

Assessment of immune competence

Immunity is suppressed by malnutrition. Cell-mediated immunity is affected more than humoral immunity [42]. The two most frequently used tests are the total lymphocyte count (TLC) and the delayed hypersensitivity skin test (DHST). A TLC under 3,000/mm3 reflects immunodeficiency, but it is not a useful test in critically ill patients, in whom sepsis, trauma, and disseminated intravascular coagulopathy also depress immune function. DHST results and morbidity have been strongly associated; in addition, mortality rates are higher in patients with negative (vs. normal) DHST results [43].

Choice of nutritional formulations and key nutrients

In critically ill and injured patients, immune-modulating or immune-enhancing enteral formulations that are supplemented with agents such as arginine, glutamine, nucleic acid, omega-three fatty acids, and antioxidants should be used, depending on their clinical condition. Patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) should be on an enteral formulation characterized by an anti-inflammatory lipid profile (that is, omega-3 fish oil, borage oil) and antioxidants [44]. Furthermore, nutritional therapy must be tailored to the individual patient’s disease or disorder and unique metabolic changes. The seemingly logical strategy would be to replace deficiencies of key nutrients (such as amino acids, proteins, vitamins, minerals, and trace elements) in the doses required, within the appropriate time, and in the manner (early oral feeding, enteral, and/or parenteral) most conducive to helping prevent cellular injury and clinical consequences. But, given so many complicating factors, many immune-enhancing and immune-modulating formulas have been developed for use in critically ill and injured patients [5].

Although it is difficult to demonstrate the precise impact of nutrition therapy, and in particular the individual effects of certain nutrients, enteral formulas fortified with immune-enhancing substrates have been associated with a significant reduction in the risk of infectious complications and a reduction in overall hospital stay [38–41, 45–49]. Certain nutrients can modulate inflammatory, metabolic, and immune processes. Amino acids such as arginine and glutamine improve body defenses and tumor cell metabolism, increase wound healing, and reduce nitrogen loss. RNA and omega-3 fatty acids also modulate immune function [50–58]. We will review a few key nutrients as part of immune-enhancing or immune-modulating formulation (Table 1).

Table 1 Immune-enhancing nutrients
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Glutamine

A nonessential amino acid, glutamine serves as the primary fuel for enterocytes and for other rapidly proliferating cells, such as cells in wounds [59]. It is involved in many immune functions, including the production of heat shock proteins [60].

Immune-enhancing enteral diet containing glutamine reduced septic complications in patients with severe trauma [51] and significantly reduced the morbidity of, and shortened the time on, mechanical ventilation [54]. Another study found that the use of glutamine was associated with a significant reduction in the incidence of bacteremia, of septic episodes, and of pneumonia [55].

Glutamine seems to protect against Gram-negative bacteria in the most critically ill patients, but the mechanism is not entirely clear [5]. Supplementation with glutamine may lead to a decrease in nosocomial infections in patients with systemic inflammatory response [61], a decrease in blood infections in burn patients [62], and a decrease in pneumonia, sepsis, and bacteremia in trauma patients [54]. Parenterally administered glutamine has been associated with a decrease in Gram-negative bacteremia [52]. Thus, the addition of glutamine to enteral nutrition has been recommended for burn, trauma, and other ICU patients in the 2009 Society of Critical Care Medicine (SCCM)/ASPEN nutritional guidelines [33]. Glutamine should be added to the standard enteral formula in burn patients and trauma patients (ESPEN guidelines, level I).

Arginine

A nonessential or conditionally essential amino acid, arginine seems to be necessary for normal T-lymphocyte function; the levels of arginine are closely regulated by some specialized immune cells called myeloid suppressor cells [33]. Arginine may also stimulate the release of hormones such as growth hormone, prolactin, and insulin [63]. Arginine appears to have trophic effects on the immune system in humans, resulting in weight gain, increased nitrogen retention, and improved wound healing [64, 65]. A systematic review of 22 RCTs showed that, in a priori subgroup analysis, patients fed commercial formulations with high arginine levels experienced a significant reduction in infectious complications. The current recommendations are that immune-modulating formulations containing arginine are safe to use in patients with mild to moderate sepsis, but that caution should be employed in patients with more severe sepsis [33].

Nucleotides

Nucleotides have a role in the synthesis of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) and in adenosine triphosphate (ATP) metabolism; they are a part of many coenzymes involved in carbohydrate, protein, and lipid synthesis [66].

In the clinical setting, immune-modulating formulas containing nucleotides have been shown to significantly reduce infections, ventilator days, and length of hospital stay, in both critically ill and postsurgical patients [67, 68].

Antioxidants and trace minerals

Vitamins with antioxidant properties include vitamins E and C (ascorbic acid); trace minerals include selenium, zinc, and copper. A meta-analysis of 11 clinical trials showed that the overall use of antioxidants was associated with a significant reduction in mortality, but had no effect on infectious complications [69]. Among the antioxidants, selenium may be the most effective [70, 71]. The current recommendation is to provide a combination of antioxidant vitamins (especially selenium) and trace minerals to all critically ill patients receiving specialized nutrition therapy [33].

Omega-3 fatty acids

Omega-3 fatty acids can be given through the administration of fish oil. Omega-3 fatty acids from an individual’s diet are rapidly incorporated into the cell membranes, influencing membrane stability, membrane fluidity, cell mobility, and cell signaling pathways. They are able to mitigate the potency of the inflammatory response and have, thus, been implicated in a reduction in cardiovascular disease. Their role in modulating the immune system in conditions such as ARDS is well described [72].

Branched-chain amino acids

After injury and sepsis, an energy deficit may develop in skeletal muscle, but it is met by increased oxidation of branched-chain amino acids (BCAAs) [35]. A study by García-de-Lorenzo et al. [73] demonstrated that critically ill patients who were unable to be fed enterally—but who were on TPN fortified with BCAAs at a high concentration (at either 23 or 45 %)—had significantly lower morbidity and mortality rates as compared with patients on standard TPN (1.5 g/kg/day of protein). Their decreased mortality rate correlated with higher doses of BCAAs (0.5 g/kg/day or higher) [73].

Initiation for enteral nutrition

Enteral feeding should be started early, within the first 24–48 h after admission if possible. Then, over the next 48–72 h, the feedings should be advanced toward the nutrition goal for the individual patient. In the ICU patient population, the initiation of enteral feeding does not require either the presence or the absence of bowel sounds, nor does it require any evidence of passage of flatus and stool [1]. In the setting of hemodynamic compromise (that is, when significant hemodynamic support is required to maintain cellular perfusion, including high-dose catecholamine agents, alone or in combination with large-volume fluid or blood product resuscitation), EN should be withheld until the patient is fully resuscitated and/or stable [1]. Other contraindications to EN are listed on Table 2. Either gastric or small-bowel feedings are acceptable in ICU patients. If critically ill patients are at high risk for aspiration or if they are intolerant to gastric feeding, they should be fed via an enteral access tube placed in the small bowel. The need to withhold enteral feedings because of repeated high gastric residual volumes may be a sufficient reason to switch to small-bowel feedings [1].

Energy requirements

Energy requirements may be calculated by predictive equations or measured by indirect calorimetry. During the first week of hospitalization, every effort should be made to provide >50–65 % of the individual EN patient’s target goal calories. After 7–10 days of EN, if the patient’s full energy requirements (that is, 100 % of the target goal calories) are not met via the enteral route alone, then supplemental TPN should be considered. The use of additional modular protein supplements is common, because standard enteral formulations tend to have a high nonprotein calorie to nitrogen ratio. In trauma patients with a BMI <30, protein requirements should be ≥2.0 g/kg of actual body weight per day [1]. In all obese patients with a BMI ≥30, the goal of EN should not exceed 60–70 % of the target energy requirements or 11–14 kcal/kg of actual body weight/day (or 22–25 kcal/kg of ideal body weight/day). Protein requirements should be ≥2.0 g/kg of ideal body weight/day for class I and class II patients (BMI 30–40), but ≥2.5 g/kg of ideal body weight/day for class III patients (BMI ≥40) [1].

Monitoring

To initiate EN in the ICU, evidence of bowel motility (resolution of clinical ileus) is not required, but patients should be monitored for EN intolerance (determined by any complaints of abdominal pain and/or distention, physical examination, passage of flatus and stool, and/or abdominal radiographs). In the absence of other signs of intolerance, EN should not be withheld in patients with gastric residual volumes <500 mL.

Prescribing nil per os (NPO, nothing by mouth) while the patient is undergoing diagnostic tests or procedures should be minimized, in order to prevent inadequate delivery of nutrients and prolonged periods of ileus, which may be propagated by the NPO status [1]. In addition, measures to reduce aspiration risk—such as elevation of the bed and use of prokinetic drugs (metoclopramide and erythromycin) or narcotic antagonists (naloxone and alvimopan)—should be initiated where clinically feasible [1]. Diarrhea in critically ill patients on EN can be complex and should be carefully monitored.

Initiation for TPN

Early nutrition therapy via TPN has the potential to reduce disease severity, diminish complications, and decrease the ICU length of stay, when EN is not possible, by providing ongoing requirements for calories, protein, electrolytes, vitamins, minerals, trace elements, and fluids [26]. The major indication for TPN is failure of the GI tract. In general, TPN should be started when the GI tract cannot be used for more than 5 days in patients in a catabolic state (with or without evidence of malnutrition), or when patients cannot be fed for 3 days after major surgery. The underlying clinical conditions include short gut syndrome, severe gut dysfunction, mesenteric vascular insufficiency, bowel obstruction, GI bleeding, severe diarrhea, large-volume fistulas, sepsis, severe burns, and trauma associated with continuous hemodynamic instability and with severe fulminant acute and chronic pancreatitis. In many of these patient subgroups, TPN is life-saving [26].

TPN has numerous specific advantages over EN. Providing adequate intravenous (IV) nutrition, for as long as necessary, when use of the GI tract is impractical, inadequate, ill-advised, or impossible, and reduction of the urgency for surgical intervention in patients who might eventually require such intervention, but in whom prolonged, progressive malnutrition will greatly increase the operative risk and the risk of postoperative complications, are two main benefits of TPN.

Furthermore, nutrient bioavailability is better, and many nutrient effects can be obtained in shorter times [74, 75]. The major advantage is that TPN does not require a functioning GI tract or gut access. In patients with complications associated with EN (such as aspiration, gut ischemia, or diarrhea), TPN is the technique of choice. Nutrients can be easily administered, and the quantity given or delivered is not affected by abdominal distention, fistula drainage, ischemia, or nausea/vomiting [26]. Some relative contraindications to TPN include evidence that it is unlikely to be required for more than 5–7 days, intolerance of the IV fluid load required, severe hyperglycemia, severe electrolyte abnormalities, and adequate GI tract function with access for EN [76].

Table 2 Contraindications to enteral nutrition
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Monitoring

Although life-saving, TPN has its own inherent complications. The complications of TPN fall into two main categories: catheter-related and metabolic (Table 3). Most of these complications can be prevented or are easily treatable with proper and detailed attention. Glycemic control is the most crucial of all metabolic components: even moderate degrees of hyperglycemia can result in an increased incidence of infection and adverse outcomes [36, 76]. Inadequate glycemic control should be seen as a marker of overfeeding and of excessive carbohydrate administration. Lipid monitoring and the lipid response to TPN are also vital. Evidence suggests that critically ill and injured patients should not be given lipid emulsions. The latest ASPEN guidelines call for no fat during the first week in the ICU [77]. Levels of urea, creatinine, and electrolytes must be determined at least daily. In addition, attention should be paid to any abnormalities of calcium, magnesium, and, in particular, phosphate. Perhaps the most decisive parameter to watch is the clinical well-being of the patient. Appreciation that a patient is subtly deteriorating may be the first clue of a TPN-related complication, rather than an abnormal value of a specific metabolic test [35]. The general rule is that nothing should be added to TPN solutions. They should never be co-administered via the same port with any other medication; a dedicated line is imperative. Unfortunately, precipitation in TPN solutions may be obscured by their lipid component; precipitation of calcium and phosphate has been reported, even when nothing was added to TPN solutions [74].

Table 3 Complications of parenteral nutrition therapy
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Conclusion

A multidisciplinary approach to nutrition therapy for all injured and critically ill patients is required and should be based on the anatomy and biology of disease, and should be individualized for each patient and based on current published evidence and guidelines (Table 4). A close partnership and good communication among physicians, clinical dietitians, nurses, pharmacists, and other critical care practitioners is invaluable to the overall care of critically ill and injured patients, and the ultimate success of nutrition therapy.

Table 4 Recommendations for nutrition therapy, per current evidence
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