1180 SECTION X Pediatric Critical Care Gastroenterology and Nutrition however, and net protein catabolism continues unabated 24 A combination of dietary glucose and protein may improve protein balance[.]
1180 S E C T I O N X Pediatric Critical Care: Gastroenterology and Nutrition TABLE Metabolic Stress Versus Starvation 99.2 Metabolic Stress Starvation BMR hh 6g Oxygen consumption (Vo2) hh g Protein catabolism hhh UUN hh Weight loss Rapid Slow LBM loss Early Late Response to caloric intake Protein catabolism continues hh Protein catabolism halted g Ketones hh Gluconeogenesis h g Insulin, cortisol, and catecholamines h, Mildly increased; hh, moderately increased; hhh, markedly increased; g, decreased; 6, unchanged BMR, Basal metabolic rate; LBM, lean body mass; UUN, urinary urea nitrogen however, and net protein catabolism continues unabated.24 A combination of dietary glucose and protein may improve protein balance during critical illness, primarily by enhancing protein synthesis The stress response also stimulates lipolysis and results in increased rates of fatty acid oxidation.25 Increased fat oxidation reflects the premier role of fatty acids as an energy source during critical illness Triglycerides in adipose tissue are cleaved by hormone-sensitive lipase into fatty acids and glycerol Fatty acids are oxidized by b-oxidation in the liver generating acetylcoenzyme A for energy production in the tricarboxylic acid cycle and mitochondrial electron transport chain As seen with the other catabolic changes associated with the stress response, the provision of dietary glucose does not decrease fatty acid turnover in times of illness The increased demand for lipid use in the setting of limited lipid stores puts the metabolically stressed neonate or previously malnourished child at high risk for the development of essential fatty acid deficiency.26,27 Preterm infants are most at risk for developing essential fatty acid deficiency after a short period of a fat-free nutritional regimen.27,28 Nutritional therapy should support the metabolic changes occurring during the acute catabolic stage With resolution of a hypermetabolic stress response, an anabolic phase typically follows, with increased release of growth hormone and insulin-like growth factor-1 Supply of adequate nutrition is essential for this recovery phase In summary, the metabolic response to critical illness results in glucose and lipid intolerance and increased protein breakdown Underfeeding and Overfeeding in the Pediatric Intensive Care Unit Individual assessment of energy requirements and provision of optimal energy should be the standard of care in the PICU Both underfeeding and overfeeding are prevalent in the PICU, with resultant nutritional deficiencies or excesses that are associated with complications.4,29 True energy expenditure during acute illness may not be easily predicted; several studies have documented discrepancies in measured versus equation-estimated energy expenditure.30–32 Unless increased energy requirements during the acute stage of illnesses are accurately measured and matched by adequate intake, cumulative energy deficits will ensue with a decrease in weight, loss of critical lean body mass, and worsening of existing malnutrition A variety of barriers, both unavoidable as well as some avoidable, exist that impede optimal nutrient delivery at the bedside and contribute to the likelihood of underfeeding in the PICU.33,34 Underfeeding during acute illness with cumulative negative energy balance has been associated with poor outcomes in critically ill adults.35 In a large multicenter cohort study, delivery of a higher percentage of the prescribed energy goal was associated with significantly lower 60-day mortality.36 On average, percentage daily nutritional intake (enteral route) compared with the prescribed goals in this study was 38% for energy and 43% for protein (Fig 99.2) On the other hand, overfeeding in the PICU is prevalent but may be underrecognized and have a potential negative impact on patient outcomes Children not predictably mount the characteristic hypermetabolic stress response as is seen in adults The metabolic response to stress from injury, surgery, or illness is variable The degree of hypermetabolism is unpredictable and unlikely to be sustained during a prolonged course in the PICU.37 Critically ill children cannot be presumed to be hypermetabolic following acute illness—energy expenditure may actually be decreased in some groups of patients.38–41 Children on extracorporeal life support or after surgery have failed to show any significant hypermetabolism; measured energy expenditure is close to resting energy expenditure in these populations.42 Critically ill children who are sedated and mechanically ventilated may have a significant reduction in actual total energy expenditure due to multiple factors Stress or activity correction factored into basal energy requirement estimates in an attempt to account for the perceived hypermetabolic effects of the illness may result in overfeeding in hypometabolic patients.43,44 Overfeeding can have deleterious consequences for the critically ill child,29,45 such as net lipogenesis, hepatic steatosis, liver dysfunction, and increased carbon dioxide (CO2) production resulting in difficulty with ventilator weaning.46 Investigators have proposed hypocaloric diets in critically ill adults.47,48 Hypocaloric diets may have a protein-sparing effect and have demonstrable benefits in critically ill obese patients However, it is uncertain whether administration of energy intake lower than the measured expenditure is appropriate for the pediatric patient There is not enough evidence to recommend its general use in critically ill children In general, the energy goals in critically ill children should be individualized and based on accurate and serial assessment of energy requirement during the illness course Current recommendations for nutritional requirements of the critically ill child are derived from limited data based on studies in healthy children and on limited methodological approaches The components of total energy expenditure in children include (1) basal metabolic rate (BMR) 70%, (2) diet-induced thermogenesis (DIT) 10%, (3) energy expended during physical activity (PA) 20%, and (4) energy expended for growth The sum of these components determines the energy requirement for an individual These traditional components of energy expenditure in healthy children may not apply during critical illness (eTable 99.3) Thus, prescribing optimal energy for the critically ill child requires careful review of each component of total energy expenditure Recommendations for energy requirements were based on estimates of BMR or resting energy expenditure (REE) derived by either indirect calorimetry (IC) or standard equations.39,49 REE estimates 1180.e1 eTABLE Components of Energy Expenditure: Normal Health Versus Critical Illness 99.3 Component Normal Health Critical Illness BMR (60%–70%) • Energy needed for maintaining vital processes of the body • It is measured in a recumbent position, in a thermoneutral environment after 12 to 18 h fast, just when the individual has awakened before starting daily activities • Not practical for bedside • Sleeping energy expenditure, a component of BMR, was shown to be equal to REE 0.9 • Corresponds to lean body mass • Related to metabolic state May be increased in conditions such as inflammation, fever, acute or chronic disease (i.e., cardiac, pulmonary) • Related to lean body mass REE (50%–60%) • BMR 10% • Usually measured instead of BMR REE is measured at rest in a thermoneutral environment, after 8–12 h fast and not immediately after awakening • Measured by indirect calorimetry with steady-state conditions DIT or TEF (10%) • Reflects the amount of energy needed for food digestion, absorption, and part of synthesis • Increased energy needs following enteral feeding return to baseline approximately h of feeding Growth (variable) • Energy for growth may be higher in healthy infants ,2 yo and during catch-up growth • Probably halted? Physical activity (PA; variable) • Depends on age, activity level • Decreased in hospitalized patients • Sedation, muscle relaxants, decreased activity Stress — • Variable Probably overestimated during critical illness Total energy expenditure REE DIT PA growth • Probably close to REE in most critically ill children Addition of stress factors may be necessary where relevant BMR, Basal metabolic rate; DIT, diet-induced thermogenesis; REE, resting energy expenditure; TEF, thermic effect of food CHAPTER 99 Nutrition of the Critically Ill Child 1181 100 90 % Prescription received 80 70 60 50 40 30 20 Energy from EN alone Energy from EN+PN 10 Protein from EN alone Protein from EN+PN PICU day 10 • Fig 99.2 Daily mean cumulative energy intake (as percentage of prescribed goal) in mechanically venti- lated children admitted to the pediatric intensive care unit (PICU) EN, Enteral nutrition; PN, parenteral nutrition are unreliable with large individual variability, particularly in underweight, overweight, or critically ill children.32,50,51 Newer equations have attempted to improve the prediction of REE in children by accounting for weight-based groups or including pubertal staging, with variable success.51,52 These equations have not satisfactorily been validated in critically ill children.53 The variability of the metabolic state may be responsible for the failure of estimation equations in accurately predicting the measured REE in critically ill children As a gold standard, the guidelines recommend IC, when available, for the most accurate assessment of energy expenditure in critically ill children.54 When IC is not available, the Schofield or Food Agriculture Organization/World Health Organization/United Nations University equations may be used without the addition of stress factors to estimate energy requirement Indirect Calorimetry The volume of oxygen consumed (Vo2) and the volume of CO2 produced (Vco2) are measured by IC over a period of time.55 The Vo2 and Vco2 values are then used to calculate REE using the modified Weir equation: REE [Vo2 (3.941) Vco2 (1.11)] 1440 This technique has been validated in healthy children by using a whole-body chamber to allow 24-hour measurement For obvious reasons, the whole-body chamber cannot be used in critically ill children The application of IC in different PICU populations has shown the variability in energy expended during illness In the past, studies have demonstrated a relatively higher resting metabolic rate in critically ill children (37% higher than the resting metabolic rate of age-matched healthy controls).56 However, contrary to beliefs held for years, more recent studies have shown that the total energy expenditure is not increased in head-injured children, postoperative general surgical patients, or children after major cardiac surgery.57–59 The muted metabolic responses to major surgeries and injuries in studies may reflect advances in surgical and intensive care over the years In critically ill mechanically ventilated children, use of sedation and muscle paralysis decreases the component of energy requirement related to physical activity.46 Thus, caloric needs in the critically ill child may be lower than previously considered IC remains sporadically applied in critically ill children despite mounting evidence of the inaccuracy of estimated BMR using standard equations This could potentially subject a subgroup of children in the PICU to the risk of underfeeding or overfeeding However, IC application is not feasible in all patients due to (1) specific subject requirements, (2) device limitations, and (3) the need for expertise and resources Table 99.4 describes some of the common problems associated with IC testing in critically ill children In the era of resource constraints, IC may be applied or targeted for certain high-risk groups in the PICU.3 Selective application of IC may allow many units to balance the need for accurate REE measurement and limited resources (see eBox 99.1 for suggested criteria for targeted IC).54 In centers where IC is not available, the use of a simplified equation to determine REE based on Vco2 values alone was recently shown to be more accurate than estimating equations.55 Although IC application has illuminated our understanding of energy expended during critical illness, this is yet to be translated into improving patient outcomes Studies examining the role of simplified IC technique, its role in optimizing nutrient intake, its ability to prevent overfeeding or underfeeding in selected subjects, and the cost/benefit analyses of its application in the PICU are desirable The effect of energy intake on outcomes needs to be examined in pediatric populations, especially in those on the extremes of BMI In summary, energy expenditure must be carefully evaluated throughout the course of critical illness, using actual measurements when available In patients meeting the requirements for this test, IC provides an accurate measurement of REE IC may 1181.e1 • eBOX 99.1 Suggested Criteria for Targeted Indirect Calorimetry3,54 Children at High Risk for Metabolic Alterations Who Are Suggested Candidates for Targeted Measurement of REE in the PICU • • • • • • • • • • Underweight (BMI ,5th percentile for age), at risk of overweight (BMI 85th percentile for age) or overweight (BMI 95th percentile for age) Children with 10% weight gain or loss during ICU stay Failure to consistently meet prescribed caloric goals Failure to wean or need to escalate respiratory support Need for muscle relaxants for d Neurologic trauma (traumatic, hypoxic, or ischemic) with evidence of dysautonomia Oncologic diagnoses (including children with stem cell or bone marrow transplant) Children with thermal injury Children requiring mechanical ventilator support for d Children suspected to be severely hypermetabolic (status epilepticus, hyperthermia, systemic inflammatory response syndrome, dysautonomic storms, etc.) or hypometabolic (hypothermia, hypothyroidism, pentobarbital or midazolam coma, etc.) • Any patient with ICU LOS wk may benefit from indirect calorimetry to assess adequacy of nutrient intake BMI, Body mass index; ICU, intensive care unit; LOS, length of stay; PICU, pediatric intensive care unit; REE, resting energy expenditure 1182 S E C T I O N X Pediatric Critical Care: Gastroenterology and Nutrition TABLE 99.4 Factors Associated With Inaccurate or Unreliable Indirect Calorimetry Measurements Error in Vco2 and Vo2 Measurement Limitations or Mechanical Issues With the Device Failure to Reach Steady State Air leak 10% around endotracheal tube High inspired Fio2 (.60%) Recent interventions (suctioning, painful procedure) Air leak in the circuit Calibration issues Fever, seizures, dysautonomia Chest tube for pneumothorax Moisture or obstruction due to water in the circuit Recent change in ventilator settings Study period too short Fio2, Fraction of inspired oxygen; Vco2, volume of carbon dioxide produced 15 Theoretical curve (logistic regression) 95% confidence interval Likelihood ratio test = 9.16, P = 002 14 13 12 Probability of mortality (%) 11 10 0 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 Protein adequacy (%) • Fig 99.3 Linear relation between enteral protein intake adequacy (percentage of the protein goal delivered) as a continuous variable and 60-day mortality (From Mehta NM, et al Adequate enteral protein intake is inversely associated with 60-d mortality in critically ill children: a multicenter, prospective, cohort study Am J Clin Nutr 2015;102:199–206.) need to be targeted to specific patient groups due to the risk of metabolic instability, but it may help prevent unintended underfeeding and overfeeding in these patients In the absence of measured REE, equation5estimated REE may be used However, the uniform application of stress factors is not advisable and must be used only in individual cases after careful evaluation Once energy needs are determined, the optimal substrate required for maintenance of energy needs is then administered as mixed fuel with glucose and fat; the proportion of each varies according to the clinical situation Protein Requirements Protein turnover and catabolism are increased severalfold in critically ill children This is one of the most characteristic features of the metabolic stress response and probably represents an adaptive response that was critical to survival of prehistoric humans during periods of illness or injury prior to the agricultural age The continuous flow of amino acids from protein breakdown allows for maximal physiologic adaptability at times of injury or illness Specifically, this process involves a redistribution of amino acids from skeletal muscle to the liver, wound, and other tissues involved in the inflammatory response Although this is an excellent short-term adaptation, it is ultimately associated with morbidity because of the limited protein reserves available in children and neonates.60 Although children with critical illness also have increases in whole-body protein synthesis, it is the whole-body protein degradation that predominates during the stress response and results in a net negative protein balance.23,61 The role of protein intake in offsetting these losses by improving protein balance and eventually improving patient outcomes is being investigated In a large international cohort study of more than 1200 mechanically ventilated children, 60-day mortality was lower in children who received a higher proportion of their daily prescribed protein goal.62 Fig 99.3 depicts the linear relation between enteral protein intake adequacy (percentage of the protein goal delivered) and 60-day mortality in mechanically ventilated patients in this cohort A similar association between lower ... illness Specifically, this process involves a redistribution of amino acids from skeletal muscle to the liver, wound, and other tissues involved in the inflammatory response Although this is an excellent... children despite mounting evidence of the inaccuracy of estimated BMR using standard equations This could potentially subject a subgroup of children in the PICU to the risk of underfeeding or... Although IC application has illuminated our understanding of energy expended during critical illness, this is yet to be translated into improving patient outcomes Studies examining the role of simplified