Critical illness is characterised by a cascade of endocrine and metabolic reactions, affecting all major organs (Fig. 5.1). The reaction of the body to physiological stress changes over time. The acute phase response can be divided into the ebb phase and flow phase. The ebb phase is characterised by the body’s attempt to maintain normal perfusion and mobilisation of stress hormones; the flow phase is the dynamic state of acute injury and affects substrate (protein, carbohydrate and fat) metabolism. The final phase, the anabolic phase, is characterised by the slow re-accumulation of protein and body fat after the metabolic response to injury subsides [10–12].

During critical illness immune cells, e.g. macrophages, lymphocytes and neutrophils, regulate the inflammatory response through the release of cytokines [in particular interleukins (IL) such as IL-1, IL-6, IL-8, IL-10 and tumour necrosis factor α (TNFα)] and chemokines such as heat shock protein 70. All are important mediators of the stress response (Table 5.2). Cytokines signal through receptors on the surface of target cells and organs mediating the following responses:

• upregulation or downregulation of gene expression influencing wound healing and immunocompetence
  
• release of counter-regulatory hormones
  
• cell to cell signalling orchestrating the inflammatory response which affects substrate metabolism [13–15].

IL, interleukin; TNF, tumour necrosis factor.

Energy metabolism

There has been significant debate over the last 10 years about the impact of acute illness on energy metabolism in children, which differs from that seen in adults. Some older studies have suggested a hypermetabolic state during the acute phase of illness [16]; however, new evidence points towards more children being hypometabolic when it comes to energy expenditure. A recent study by Briassoulis et al. [17] found that on the first day of admission 48.6% of children were hypometabolic (<90% of predicted basal metabolic rate, BMR), 40.5% were normometabolic (90%–110% of predicted BMR) and 10.8% were hypermetabolic (>110% of predicted BMR). A hypermetabolic pattern only emerged after 2 weeks of admission in 60% of children. This unique pattern of metabolism may be explained by a multitude of factors, including the physiological response to stress, improved medical treatment as well as the unique nature of fuel utilisation in critically ill children (Tables 5.2 and 5.3) [11, 12, 18, 19].

NSAIS, non-steroidal anti-inflammatories.

In addition to the factors listed in Table 5.3 authors have speculated that during the acute phase growth does not take place and this energy is diverted into the recovery processes [19, 20]. This hypothesis is supported by the data from Hulst et al. [21] who found that insulin-like growth factor 1 (an anabolic hormone) remained low until day 4 of PICU admission and T3 levels remained below normal at days 4 and 6 in 88% and 89% of the older children, respectively. Although more research needs to take place before specific guidelines on energy expenditure can be published, it is clear that substrate metabolism varies greatly during admission and that during the early phase of illness hypometabolism is usual, whereas in the later phase of illness hypermetabolism predominates. This needs to be taken into account when calculating energy requirements and choosing feeds for these patients, which may require changes being made to prescribed energy intake during the course of a PICU stay.

Substrate utilisation

Several studies have focused on the relation between CIC’s metabolic state, their nutritional intake, substrate utilisation and nitrogen balance. In a similar way to critically ill adults the stress response and the severity of disease are characterised by protein catabolism. In contrast to adults, fat is the preferred fuel in children and is readily oxidised. Conversely carbohydrates are poorly utilised during critical illness. Gluconeogenesis is also a characteristic of paediatric critical illness and muscle mass is rapidly depleted of amino acids, such as glutamine, which are utilised in de novo glucose production [22, 23]. Maximal glucose oxidation occurs at a glucose intake of 5 mg/kg/min. If intake exceeds 8 mg/kg/min lipogenesis takes place, leading to an increase in triglyceride levels, fat deposition in the liver and an increase in fat instead of lean body mass [18]. It is therefore important to ensure that carbohydrate intake in CIC is monitored, especially if parenteral nutrition (PN) is used.

Mechanism for muscle wasting

Sepsis associated muscle wasting is well described in the adult intensive care unit (ICU), although the prevalence is not known in children. Causative factors include sepsis, muscle disuse, fasting, cancer, cardiac failure and renal dysfunction. In ICU there is often prolonged bed rest or immobilisation, use of sedatives and neuromuscular blockades, acute or chronic organ dysfunction, medication using steroids [24] and increased levels of cytokines, e.g. IL-6, IL-10, TNFα (which are associated with muscle degradation), amongst other factors [15, 24] (Fig. 5.2).

There is often an imbalance between anabolism and catabolism with protein turnover outstripping protein synthesis leading to a net loss of muscle mass which occurs as a result of de novo gluconeogenesis [22, 24]. Muscle wasting and ICU induced myopathy has not been described in children and it may be that the pathophysiology of paediatric critical illness does not result in this phenomenon. However, as a significant number of children admitted to PICU develop malnutrition it is likely that muscle wasting also occurs in children.