Acute Respiratory Distress Syndrome: Metabolic Support

Michele Umbrello, Danilo Radrizzani, and Gaetano lapichino

Stress Response and Critically Ill Patients' Metabolic Requirements

Nutritional support to ARDS patients either shares metabolic concepts common to critically ill patients or generates particular concern due to the limitation of oxygen supply and the difficulties of carbon dioxide disposal. Metabolic response to injury and sepsis is characterized by the increased secretion of pro-inflammatory cytokines (IL-1, IL-6, and TNF) [1], catabolic hormones (cortisol, glucagon, and catecholamines) [2], as well as increased insulin resistance [3]. All these lead to glycoge- nolysis, increased gluconeogenesis and lipolysis, and enhanced muscle protein breakdown ensuring both energy and amino acids for wound repair and immune function.

Particularly, glucose is an indispensable substrate for host response in damaged tissues and immune cells. Endogenous glucose production from amino acids, lactate, and glycerol is necessary because glycogen stores are limited. Lipolysis is also necessary because of the energy required by gluconeogenesis. In fact this

M. Umbrello

Unita Operativa di Anestesia e Rianimazione, Ospedaliera San Paolo-Polo Universitario,

ASST Santi Paolo e Carlo, Milan, Italy

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D. Radrizzani

Unita Operativa di Anestesia e Rianimazione, Ospedale Nuovo di Legnano, ASST Ovest

Milanese, Legnano, Italy

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G. Iapichino (*)

Unita Operativa di Anestesia e Rianimazione, Ospedaliera San Paolo-Polo Universitario, ASST Santi Paolo e Carlo, Milan, Italy

Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Universita degli Studi di Milano, Milan, Italy

cycling of substrates costs in terms of ATP and is responsible in part of the increased energy expenditure. Amino acid from muscle protein is in part converted to glutamine and alanine and then to glucose and urea. This is mainly the fate of branched chain amino acids. Despite the increased protein synthesis of acute phase protein, the dissimilarity of different amino acids’ catabolism explains the large amount of wasted muscle tissue (500-1000 g per day) [4].

The stress response can only be reversed by resolution of the triggering event as infection control, wound healing, and so on. However, the rate of muscle tissue loss can be reduced by an adequate amount of energy and protein intake. This is important because body wasting impacts on tissue functions and hence on the recovery that can be delayed or even prevented by the loss of functional tissue.

For this reasons, metabolic support would comprise energy and protein/amino acids. Substrates can be administered either parenterally or by the enteral route. Parenteral nutrition can be given via the central or peripheral vein according to the osmolality; enteral tract can be accessed at the gastric or jejunal level either by nasal tubes or ostomies. Jejunal approach is preferred when the stomach fails to empty adequately. The relationship of gastric residual volume and diet tolerance is not completely understood; however, gastric residuals up to 500 mL can be tolerated, providing that in the end, the diet progresses to the jejunum [5]. Ostomies are indicated for long-term support.

Enteral nutrition is preferred because it maintains the absorptive function and the integrity of the intestinal barrier and leads to fewer complications, and also because it costs much less than parenteral nutrition. Enteral nutrition can be contraindicated (complete intestinal obstruction) or problematic (severe inflammation, high-output fistula) and sometimes is difficult to cover all the nutritional needs with the enteral administration. In these cases, it is necessary to substitute or integrate the enteral diet with parenteral nutrition in order to fulfill the requirements. The timing and the amount of this substitution/integration is a matter of debate [6, 7]; what is certain is that sooner or later, protein and energy deficits have negative effects on prognosis and that the negative effects are in some way proportional to the severity of the patient [8-10].

If some is good, more is not always better, and even if lack of energy and protein has negative effect, an excess of diet can be dangerous as well, both because of diet- induced thermogenesis (DIT) that furtherly increases energy expenditure and because excess substrates have to be stored or disposed giving way to waste product that can challenge organ functions of critically ill patients. For ARDS patients, energy excess can be particularly difficult to manage as will be explained ahead.

In the absence of the measurement of energy expenditure by indirect calorimetry, current guidelines suggest 20-30 kcal/kg/day [11-13]. The recommended protein/ amino acid intake has increased in the last years up to 2 g/kg/day [14]. When nutritional support is administered enterally, the diet composition is predetermined. A standard diet is characterized by a ratio of 50:30:20 that represents the proportion of carbohydrates (CHO), fats, and protein in calories. Diets may differ for concentration (hypo- or hypercaloric) or composition. Differences in composition can depend upon relative quantity (high protein or fat) with respect to standard diet or upon quality of nutrients. Proteins’ quality regards the source (casein, whey protein, soy, egg) and the degree of hydrolysis (from whole protein to single amino acid passing through oligopeptides). Lipid quality is represented by the length of chain and by the content of polyunsaturated fatty acid with double bond on carbon w3 or w6. CHO generally consist of maltodextrins, and their content varies to allow the variation of protein or lipid content.

The differences for parenteral nutrition are more or less the same; however, protein content consists of synthetic amino acids and, allowing chemical stability, can be varied in many ways. Lipid content can be really different comprising w9 polyunsaturated fatty acid. CHO are represented by glucose that as we have seen before is an indispensable substrate in critical illness.

Apart from the concentration that allows different water loads, detailed description of the indication of different diets is beyond the purpose of this chapter; however, any difference in composition of interest for ARDS patients will be discussed later.

Whichever the source of CHO, they are mainly metabolized to glucose that is the primary source of easily available energy for all tissues. However, stress hyperglycemia may have deleterious effect on outcome. For this reason, glycemic control, after many years of conflicting studies, stands yet as a significant target in critically ill patients. The key questions are the appropriate target ranges in different patients’ population and the way to obtain it; both these goals should satisfy safety and feasibility. Glucose control is obtained by standardized i.v. insulin infusion. Protocols can either consist of intuitive rules or they can be paper-based or computerized algorithms; however, they generally do not take into account factors such as the degree of patient stress, i.e., insulin sensitivity, and the amount of nutritional support. Recently, a pathophysiology-based glucose control protocol which takes into account patient CHO load intake and patient insulin resistance has been proposed [15]. Computerization allows increasing complexity of the decisional tree, while diminishing the work effort; moreover, it performs better in terms of glucose control either as time in target or preventing hypoglycemia [16]. The more complex computer programs are able to react to or to anticipate glucose changes; future development in this field will probably be a closed-loop insulin infusion sustained by continuous glucose monitoring.

Critically ill patients receiving nutritional support may develop depletion of vitamins or trace elements; in some cases they can be already depleted. Usually, an adequate intake of calorie by the enteral route ensues the needs of microelements and vitamins; in case of inadequate intake or of parenteral support, trace elements and vitamins have to be supplemented.

Pharmakonutrition (i.e., nutritional support enriched with anti-inflammatory or immunomodulating substrates) is supported by many biochemical studies. It includes w3 polyunsaturated fatty acids, glutamine, arginine, and antioxidants. Larger clinical studies have demonstrated deleterious effect particularly of the amino acids glutamine and arginine as well as of antioxidants [17, 18]. These results have to be interpreted cautiously because of excessive dosage or due to different actions in different patient population (e.g., trauma vs septic shock patients). Particular effect of pharmakonutrients on ARDS patients will be discussed ahead.