Unlike stress-induced metabolic alterations, the metabolic response to fasting consists in a reduction of energy expenditure (metabolic rate is reduced to 20–25 kcal/kg/day). During the first hours, the glucose stored in the liver as glycogen is depleted; after that, 90% of energy is produced by lipolysis, while proteins are used as a substrate for gluconeogenesis to synthetize glucose. This would result in a decreased protein biosynthesis, if it were not for the protein–sparing response which minimises the loss of muscle mass. Starvation induces adaptive responses that, in time, can result in malnutrition.

In hyperdynamic circulation, the most common changes in haemodynamic parameters are increase of cardiac index and systolic volume index, possibility of hypertension or hypotension (depending on the level of vasoplegia) and reduction of systemic vascular resistance, central venous pressure and wedge pressure (changes in haemodynamic parameters in different types of shock are shown in Fig. 12.2).

We cannot address hypermetabolism and sepsis without mentioning lactate metabolism. Hyperlactatemia, due to hypoxia and hypoperfusion, is present in every low cardiac output condition, such as shock. Understanding lactatemia levels in septic shock has been shown to be a much more complex task though. In the early phase of septic shock, the clinical presentation is similar to that of cardiogenic and haemorrhagic shock. The administration of sympathomimetic drugs (adrenaline, noradrenaline, dopamine and dobutamine) causes an increase in lactatemia per se. A peculiar metabolic condition called “accelerated aerobic glycolysis” occurs in septic patients, and its main features are increased synthesis of glucose transporters across the cell membrane, augmented glycolysis (induced by endogenous and exogenous catecholamines) and inflammation. The rate of glycolysis exceeds the oxidative capacity of mitochondria: this imbalance, together with protein hypercatabolism, causes an increase in pyruvate concentration, especially in muscle cells. Pyruvate is then converted to lactate by fermentation. The increased lactate production acts as an adaptive mechanism in order to keep the carbohydrate metabolism from stopping when oxygen delivery is reduced. Lactate can be used both as an alternative fuel to glucose and a source of glucose itself. Cells keep it for producing energy and this protects from acidosis. Lactate is transported out of the cell by diffusional cotransport with protons (H⁺ ions), thus regulating intracellular pH. In septic shock, lactate produced in myocytes is used as a substrate in the Cori cycle (illustrated in Fig. 12.3), an effective but highly energy-consuming pathway. Lactate is transported to the liver, where it is used for gluconeogenesis: it is first converted to pyruvate and then to glucose. In this way, lactate serves to deliver additional glucose that can be used by the organism. It is also important to point out that, when the patient undergoes stress, the heart and the brain are able to use lactate as main fuel: these organs can oxidise lactate instead of glucose during anaerobic conditions, leaving glucose for other cells.

Septic patients are extremely frail, both during the early and the late phase of illness. SIRS is a pro-inflammatory syndrome: its aim is to remove the organism responsible for the infection by increasing the activity of the immune system. When this response goes out of control or is overly prolonged, it damages the patient. Studies on septic patients have shown the existence of an anti-inflammatory response, usually occurring after SIRS, called CARS (compensatory anti-inflammatory response syndrome). CARS consists in a suppression of the immune system in order to restore homoeostasis after a severe inflammatory state. SIRS and CARS are the two sides of the same coin: each one is characterised by a particular set of cytokines, and, although they are separate responses, most of the times one follows the other (even though often they take place simultaneously with different relevance). Like SIRS, CARS can be dangerous too if it is not regulated or it fails to restore homoeostasis, making the patient vulnerable to infections. Some of the clinical features of CARS are cutaneous anergy, leucopenia, hypothermia, susceptibility to infections and failure to clear infections.

Patients undergoing surgery are an ideal model for the study of hypermetabolism caused by stress response. Surgery is in fact a clear example of a stressful event: even though anaesthesia reduces afferent neural transmission to pain centres, the organism interprets surgery as a threat. The activation of different hormonal axis causes the release of stress hormones such as cortisol, catecholamines, glucagon and growth hormone. These hormones are responsible for the condition of hypermetabolism, whose biochemical aspects have been previously discussed. This mechanism takes place in elective operations, but even more in emergency surgery, major surgery and when postoperative complications occur. The stress response purpose is the survival of the critically ill patient, by using the energy reserves and retaining water. The response becomes a harmful condition when prolonged in time. Regional and local anaesthesia has been shown to be an important factor in both reducing the stress response to surgery and influencing the postoperative outcome by bringing beneficial effects on organ function.

In trauma patients, the systemic inflammatory reaction is similar to the one previously described. The splanchnic region appears to be the main source of hypermetabolic response. The increased energy expenditure is not adequately matched by an implementation in blood flow, especially right after the trauma, when the patient is often hypovolaemic due to loss of blood. Hypovolaemia causes splanchnic vasoconstriction which is an important risk factor for inadequate perfusion of splanchnic region.

Once the complex condition of the critical patient in hypermetabolic state has been analysed and understood, it is essential to think about the correct way to manage the administration of nutrients. That is important to satisfy needs and prevent negative consequences of catabolism and malnutrition. First of all, it is crucial to accurately determine energy expenditure (EE).

Historically we know two different ways to solve this problem: the use of predictive equations and the calorimetry procedure (whether direct or indirect).

Secondly, even when resorting to these formulas, we have to choose which one, from the large number available, is the most suitable for our patient. There are indeed differences that may reach 20–30% of the estimated value when choosing one rather than another (Table 12.1). It has been proven that the use of these equations can frequently lead to underfeeding (in formulas that underestimate the EE) or to overfeeding (in equations that overestimate the EE) the patient concerned. This can, obviously, compromise the patient’s prognosis. Considering the extreme variations of energy expenditure in the different conditions of stress that can occur in a critical patient, it is obvious how only the correct measurement of how much energy (EE) the patient actually consumes, and not the estimate of how much the patient should theoretically consume, can represent the baseline for the institution of a correct caloric supply.