Undernutrition is common at hospital admission and tends to worsen during hospitalization. In Europe and North America, 40%-50% of hospitalized patients are at risk of malnutrition (3,4,5). Several studies performed in Brazil and in other countries demonstrated that malnutrition can affect 50% of children and adolescents during hospitalization, although the classical kwashiorkor presentation is rare in critically ill infants, children, and adolescents with chronic diseases such as those in ICUs (9).

In hospital, undernutrition constitutes an important risk factor for increased morbidity, mortality, length of hospital stay, and medical costs (4). Specific associations have been reported between poor nutritional status, decreased respiratory function, impaired wound healing, and immune and gastrointestinal dysfunctions (6,7,11). Hence, proper enteral or parenteral nutritional support should be provided in ill children who are unable to feed normally and who are at risk of undernutrition. To prevent undernutrition-related complications, patients should be assessed for nutritional state and risk of becoming malnourished at the time of hospital admission, and optimal nutrition must be guaranteed in ill children who are unable to feed orally. A nutritional therapeutic plan on admission is essential to ensure adequate nutritional support during the course of illness (12).

Critically ill, undernourished children are less able to handle substrate, liquid, and solute overload. The most common absorptive disturbances involve carbohydrates (particularly lactose) and fats. Reductions in cardiac output, glomerular filtration rate, renal blood flow, or renal solute excretion capacity may arise from undernutrition. Intracellular potassium and sodium pump activity is lowered. In view of these limitations, caution is urged in initial phases of treatment as excessive volume intake of water and nutrients may cause complications or death (7). Well-nourished children who are likely to return to normal feeding within 4-5 days do not generally require artificial nutritional support, whereas undernourished patients with hypermetabolism or hypercatabolism should receive treatment as swiftly as possible (8).

Fasting (a reduction or absence of the intake of nutrition) becomes starvation when suffering or the process of perishing occurs. The physiologic changes that occur with severe malnutrition and starvation may be a result of inadequate intake of energy and basic nutrients (simple starvation) or it can be a result of increased energy expenditure (EE) unmatched by adequate intake (stress starvation). Stress starvation can develop more quickly than simple starvation (7,9,13) (Table 97.1).

For didactic purposes, the starvation response may be divided into three phases, although the biochemical events overlap and depend on baseline nutritional status, comorbidities, and the extent of the nutrient restriction (complete or partial). During phase I, glucose remains the primary source of energy and is produced by the breakdown of absorbed carbohydrate and glycogen stored in muscle and liver. Phase I begins after the consumed meal has been digested and the body has entered the postabsorptive phase. Glycogen stores are usually exhausted within 24 hours in young children.

During phase II, fats become the primary source of energy after glycogen stores have been depleted. Lipolysis mobilizes fat stores to release free fatty acids, which are oxidized to ketone bodies (aceto-acetate and β-hydroxybutyrate). These ketone bodies serve as an alternative source of energy for the brain in the face of limited glucose supply. Laboratory analysis reveals mild ketoacidosis at this stage. Proteolysis liberates amino acids from muscle to support gluconeogenesis and mitigate the risk of hypoglycemia. Hormonal changes including falling insulin levels and rising glucagon (and other counterregulatory hormone) levels contribute to maintenance of serum glucose levels.

If starvation continues, the fat stores become exhausted and the body enters phase III of starvation. During this phase proteins become the major source of energy. This phase is characterized by further breakdown of muscle (including cardiac muscle) in order to support gluconeogenesis, a process known as “protein wasting.”

Adaption to starvation involves reducing EE by suppressing metabolic rate, body temperature, and delaying growth/ reproduction (10,13). During stress starvation, the normal adaptative responses of simple starvation, which conserve body protein, are overridden by the neuroendocrine and cytokine
effects of injury. Metabolic rate rises rather than falls, ketosis is minimal, protein catabolism accelerates to meet the demands for tissue repair and for gluconeogenesis, and there is hyperglycemia and glucose intolerance. Salt and water retention is exacerbated, and this may result in a kwashiorkor-like state with hypoalbuminaemia and edema.

Refeeding syndrome (nutritional recovery syndrome) is a potentially lethal condition that can occur usually within 1-3 days after reinstitution of nutrition following 5-10 days of fasting. Patients at risk include those with severe undernutrition and anorexia nervosa. The major manifestations of refeeding syndrome include the following:

The pathophysiology of refeeding syndrome begins with a contraction of intracellular spaces and depletion of major intracellular ions (phosphorus, potassium, and magnesium) during starvation, yet normal serum levels are maintained (14). Refeeding of carbohydrates increases glucose levels, stimulates insulin release and induces protein, glycogen, and fat synthesis. Elevated insulin levels shift phosphorus, potassium, magnesium, and thiamine to the intracellular space. Hence serum levels of these ions may fall rapidly.

Cardiovascular manifestations of refeeding syndrome include heart failure and dysrhythmias. Preexisting cardiac atrophy from starvation exacerbated by thiamine and phosphate deficiency make the patient vulnerable to heart failure and fluid overload. Because most severely undernourished patients are bradycardic, the restoration of a “normal” heart rate may be a sign of impending heart failure.

Pulmonary complications of refeeding syndrome involve respiratory muscle weakness. A weak cough reflex leads to retained airway secretions, atelectasis, and pneumonia. Hypophosphatemia may lead to ventilatory failure.

Neurologic complications may entail seizures, delirium, and frank encephalopathy from thiamine deficiency (Wernicke’s encephalopathy).

Prevention is the key to management of refeeding syndrome. Electrolytes abnormalities should be anticipated and corrected when discovered in the severely undernourished child. Nutritional supplementation (especially caloric intake from carbohydrates) should be advanced gradually. Excess fluid and sodium administration are avoided. Observation for cardiac arrhythmias is particularly important, as this is the major cause of fatalities. Vitamin supplementation (especially thiamine) should also be implemented with refeeding and continued for at least 10 days.

A hypercatabolic state occurs in response to many clinical conditions (sepsis, trauma, burns, etc.) and is characterized by an increase in circulating catabolic hormones and inflammatory cytokines as well as insulin resistance. Hyperglycemia, glucose intolerance, and insulin resistance are common features of critically ill patients, especially in patients with sepsis or septic shock.

Nutrition in children with severe infection, trauma, or following major surgery is hampered by the hormonal and metabolic changes associated with the systemic inflammatory response (8,15,16). The systemic inflammatory response activates the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis. These responses are characterized by changes in glucose and lipid metabolism, along with increased protein turnover and breakdown, which results in increased EE, a negative nitrogen balance, and muscle protein loss. Deamination of branched-chain amino acids supplies amino acids for the protein synthesis required for wound healing and the immunologic response (production of immunoglobulins and acute-phase reactants) (15,16). Peripheral resistance to insulin action ensures continued glucose production with hyperglycemia, reduced glucose oxidation, and storage as hepatic glycogen. Increased lipolysis provides free fatty acids for energy and glycerol for gluconeogenesis (16,17,18). Levels of catecholamines, cortisol, glucagon, growth hormone, aldosterone, and antidiuretic hormone are increased, and insulin is generally elevated but not sufficiently to impede hyperglycemia. Insulin secretion is initially suppressed by the α-adrenergic mechanism and later increased together with glucagon levels. Peripheral resistance to growth hormone action occurs, with a reduction in insulinlike growth factor (IGF)-1 secretion, while hyperglycemia and lipolytic effects remain. Increased counterregulating hormone concentrations induce insulin- and growth hormone-resistant states (a characteristic sign of stress), which results in protein catabolism and the utilization of carbohydrate and fat stores to meet the increased basal metabolic rate. All of these mechanisms constitute the interaction between the nervous, endocrine, and immunologic systems in an effort to mediate stress (19,20,21).

An additional pathophysiologic process is the synthesis and release of inflammatory and metabolic response mediators by monocytes (primarily Kupffer cells and alveolar macrophages). These mediators include cytokines, products of arachidonic acid metabolism, and platelet activation factors. (Interleukin 6 is an important cytokine that causes an inflammatory response and increases nutritional risk.) Acting locally or distally, they promote changes in cell function and metabolism. Such mediators also act directly on hypothalamic activity, influencing the release of classic stress hormones (9,17). Continued hypermetabolism results from complicating factors, such as hypotension or infection, leading to accelerated malnutrition and lowering of immunologic function (15,17,22).

Childhood obesity is a public health crisis of epidemic proportions throughout the world, with an estimated prevalence of 10%-25% (23). Severe childhood obesity is defined as a body mass index (BMI) >35 kg/m². Pseudotumor cerebri, slipped capital femoral epiphysis, steatohepatitis, cholelithiasis, and sleep apnea represent some of the major comorbidities associated with severe obesity (1,24). Obese adults with severe respiratory failure have higher mortality rates (24,25). Recent data also suggest that obesity may be associated with increased mortality in critically ill children (26). Special problems for morbidly obese patients in the PICU include the following:

Insulin resistance is associated with obesity and may be secondary to the presence of adipocytokines. As a result, morbidly obese patients exhibit variable glucose homeostasis
including glucose intolerance, overt type II diabetes, or metabolic syndrome. Clinical clues to the presence of insulin resistance include abdominal obesity, acanthosis nigricans, hirsutism, muscle cramps, hypertension, and hypertriglyceridemia, among others.

Nutritional management of the morbidly obese patient takes into account comorbidities, special ICU problems, and insulin resistance. Excess carbohydrate administration may lead to increased CO₂ production and delayed weaning from mechanical ventilation. Insulin resistance may produce hyperglycemia, which has been associated with poor ICU outcomes. Therefore some adult studies have suggested the use of hypocaloric—high protein diets in adults with obesity (27). The goal is to avoid the complications of CO₂ retention, hyperglycemia, and fatty liver, while achieving positive nitrogen balance, which may promote wound healing. There are no randomized controlled trials on this approach in children.

An effective nutritional plan requires understanding of the individual components to be provided via the enteral or parenteral route.