A.S.P.E.N. Clinical Guidelines: Nutrition Support of the Critically Ill Child

Abstract

The prevalence of malnutrition among critically ill patients, especially those with a protracted clinical course, has remained largely unchanged over the last 2 decades.1,2 The profound and stereotypic metabolic response to critical illness and failure to provide optimal nutrition support therapy during the intensive care unit (ICU) stay are the principal factors contributing to malnutrition in this cohort. The metabolic response to stress, injury, surgery, or inflammation cannot be accurately predicted and the metabolic alterations may change during the course of illness. Although nutrition support therapy cannot reverse or prevent this response, failure to provide optimal nutrients during this stage will result in exaggeration of existing nutrient deficiencies and in malnutrition, which may affect clinical outcomes. Both underfeeding and overfeeding are prevalent in the pediatric intensive care unit (PICU) and may result in large energy imbalances.3 Malnutrition in hospitalized children is associated with increased physiological instability and increased resource utilization, with the potential to influence outcome from critical illness.4,5 The goal of nutrition support therapies in this setting is to augment the short-term benefits of the pediatric stress response while minimizing the long-term harmful consequences. Accurate assessment of energy requirements and provision of optimal nutrition support therapy through the appropriate route is an important goal of pediatric critical care. Ultimately, an individualized determination of nutrient requirements must be made to provide appropriate amounts of both macro- and micronutrients for each patient at various times during the illness course. The delivery of these nutrients requires careful selection of the appropriate mode of feeding and monitoring the success of the feeding strategy. The use of specific nutrients, which possess a drug-like effect on the immune or inflammatory state during critical illness, continues to be an exciting area of investigation. The lack of systematic research and clinical trials on various aspects of nutrition support in the PICU is striking and makes it challenging to compile evidence based practice guidelines. There is an urgent need to conduct well-designed, multicenter trials in this area of clinical practice. The extrapolation of data from adult critical care literature is not desirable and many of the interventions proposed in adults will have to undergo systematic examination and careful study in critically ill children prior to their application in this population. In the following sections, we will discuss some of the key aspects of nutrition support therapy in the PICU; examine the literature and provide best practice guidelines based on evidence from PICU patients, where available. While some PICU popu lations include neonates, A.S.P.E.N. Clinical Guidelines for neonates will be published as a separate series. The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) is an organization comprised of healthcare professionals representing the disciplines of medicine, nursing, pharmacy, dietetics, and nutrition science. The mission of A.S.P.E.N. is to improve patient care by advancing the science and practice of nutrition support therapy. A.S.P.E.N. vigorously works to support quality patient care, education, and research in the fields of nutrition and metabolic support in all healthcare settings. These clinical guidelines were developed under the guidance of the A.S.P.E.N. Board of Directors. Promotion of safe and effective patient care by nutrition support practitioners is a critical role of the A.S.P.E.N. organization. The A.S.P.E.N. Board of Directors has been publishing clinical guidelines since 1986.6-8 Starting in 2007, A.S.P.E.N. has been revising these clinical guidelines on an ongoing basis, reviewing about 20% of the chapters each year in order to keep them as current as possible. These clinical guidelines were created in accordance with Institute of Medicine recommendations as "systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances."9 These clinical guidelines are for use by healthcare professionals who provide nutrition support services and offer clinical advice for managing adult and pediatric (including adolescent) patients in inpatient and outpatient (ambulatory, home, and specialized care) settings. The utility of the clinical guidelines is attested to by the frequent citation of this document in peer-reviewed publications, and their frequent use by A.S.P.E.N. members and other healthcare professionals in clinical practice, academia, research, and industry. They guide professional clinical activities, they are helpful as educational tools, and they influence institutional practices and resource allocation.10 These clinical guidelines are formatted to promote the ability of the end user of the document to understand the strength of the literature used to grade each recommendation. Each guideline recommendation is presented as a clinically applicable definitive statement of care and should help the reader make the best patient care decision. The best available literature was obtained and carefully reviewed. Chapter author(s) completed a thorough literature review using Medline, the Cochrane Central Registry of Controlled Trials, the Cochrane Database of Systematic Reviews and other appropriate reference sources. These results of the literature search and review formed the basis of an evidence-based approach to the clinical guidelines. Chapter editors work with the authors to ensure compliance with the author's directives regarding content and format. The initial draft is then reviewed internally to ensure consistency with the other A.S.P.E.N. Guidelines and Standards and externally reviewed (by experts in the field within our organization and/or out side of our organization) for appropriateness of content. Then the final draft is reviewed and approved by the A.S.P.E.N. Board of Directors. The system used to categorize the level of evidence for each study or article used in the rationale of the guideline statement and to grade the guideline recommendation is outlined in Table 1.11 The grade of a guideline is based on the levels of evidence of the studies used to support the guideline. A randomized controlled trial (RCT), especially one that is double blind in design, is considered to be the stron gest level of evidence to support decisions regarding a therapeutic intervention in clinical medicine.12 A level of I, the highest level, will be given to large RCTs where results are clear and the risk of alpha and beta error is low (well-powered). A level of II will be given to RCTs that include a relatively low number of patients or are at moderateto-high risk for alpha and beta error (under-powered). Systematic reviews are a specialized type of literature review that analyzes the results of several RCTs, and may receive a grade level of I or II, depending on the overall quality of the reports. Meta-analyses can be used to combine the results of studies to further clarify the overall outcome of these studies but will not be considered in the grading of the guideline. A level of III is given to cohort studies with contemporaneous controls, while cohort studies with historic controls will receive a level of IV. Case series, uncontrolled studies, and articles based on expert opinion alone will receive a level of V. Table 2 provides the entire set of guidelines recommendations for nutrition support in the critically ill child. 1A) Children admitted with critical illnesses should undergo nutrition screening to identify those with existing malnutrition or those who are nutritionally at-risk. Grade D 1B) Formal nutrition assessment with the development of a nutrition care plan should be required, especially in those children with premorbid malnutrition. Grade E The prevalence of malnutrition in hospitalized children has remained unchanged over several years and has implications on hospital length of stay (LOS), illness course and morbidity.4,5 Children admitted to the PICU are further at risk of longstanding altered nutrition status and anthropometric changes that may be associated with morbidity.13 Hulst et al observed a correlation between energy deficits and deterioration in anthropometric parameters such as mid-arm circumference and weight in a mixed population of critically ill children.13 These anthropometric abnormalities accrued during the PICU admission returned to normal by 6 months after discharge.1 Using reproducible anthropometric measures, Leite et al reported a 65% prevalence of malnutrition on admission with increased mortality in this group.5 On follow up, a significant portion of these children had further deterioration in nutrition status (Table 3). Nutrition assessment of children during the course of critical illness is desirable and can be quantitatively assessed by routine anthropometric measurements. Routine monitoring of weight is a valuable index of nutrition status in critically ill children. However, weight changes and other anthropometric measurements during the PICU admission should be interpreted in the context of fluid therapy, other causes of volume overload, and diuresis. Nutrition assessment can also be achieved by measuring the nitrogen balance and resting energy expenditure (REE). Albumin, which has a large pool and much longer half-life (14-20 days), is not indicative of the immediate nutrition status. Independently of nutrition status, serum albumin concentrations may be affected by albumin infusion, dehydration, sepsis, trauma, and liver disease. Thus, its reliability as a marker of visceral protein status is questionable. Prealbumin (also known as transthyretin or thyroxine-binding prealbumin) is a stable circulating glycoprotein synthesized in the liver. It binds with retinol binding-protein and is involved in the transport of thyroxine as well as retinol. Prealbumin, so named by its proximity to albumin on an electrophoretic strip, has a half-life of 24-48 hours. Prealbumin serum concentration is diminished in liver disease and may be falsely elevated in renal failure. Prealbumin is readily measured in most hospitals and is a good marker for the visceral protein pool.14,15 Visceral proteins such as albumin and prealbumin do not accurately reflect nutrition status and response to nutrition intervention during inflammation. In children with burn injury, serum acute-phase protein levels rise within 12–24 hours of the stress, because of hepatic reprioritization of protein synthesis in response to injury.16 The rise is proportional to the severity of injury. Many hospitals are capable of measuring C-reactive protein (CRP) as an index of the acute-phase response. When measured serially (once a day during the acute response period), serum prealbumin and CRP are inversely related (ie, serum prealbumin concentrations decrease and CRP concentrations increase with the magnitude proportional to injury severity and then return to normal as the acute injury response resolves). In infants after surgery, decreases in serum CRP values to levels< 2 mg/dL have been associated with the return of anabolic metabolism and are followed by increases in serum prealbumin levels.17 Standard anthropometric measurements may be inaccurate in critically ill children with fluid shifts, edema, and ascites. The prevalence of malnutrition in this group of patients and the dynamic effects of critical illness on nutrition status require the ability to accurately measure body composition in hospitalized children. Body composition measurement in children admitted to the PICU has been limited due to the absence of reliable bedside techniques while existing measurement techniques such as the dual energy X-ray absorptiometry (DEXA) scan are impractical in this cohort. Future research related to validation of simple, noninvasive bedside body composition measurement techniques is desirable and will allow monitoring of relevant parameters such as lean body mass, total body water, and fat mass in critically ill children. Furthermore, long-term follow up studies in survivors of critical illness will provide a better idea of the toll of a PICU course on nutrition status of children. For the purpose of such long-term follow up, qualitative markers of lean body mass integrity and function or indicators of return to baseline activity are examples of outcome variables relevant to nutrition in children surviving critical illness. 2A) Energy expenditure should be assessed throughout the course of illness to determine the energy needs of critically ill children. Estimates of energy expenditure using available standard equations are often unreliable. Grade D 2B) In a subgroup of patients with suspected metabolic alterations or malnutrition, accurate measurement of energy expenditure using indirect calorimetry (IC) is desirable. If IC is not feasible or available, initial energy provision may be based on published formulas or nomograms. Attention to imbalance between energy intake and expenditure will help to prevent overfeeding and underfeeding in this population. Grade E Acute injury markedly alters energy needs. Acute injury induces a catabolic response that is proportional to the magnitude, nature, and duration of the injury. Increased serum counter-regulatory hormone concentrations induce insulin and growth hormone resistance, resulting in the catabolism of endogenous stores of protein, carbohydrate, and fat to provide essential substrate intermediates and energy necessary to support the ongoing metabolic stress response.19 In mechanically ventilated children in the PICU, a wide range of metabolic states has been reported with an average early tendency towards hypermetabolism.20 Children with severe burn injury demonstrate extreme hypermetabolism in the early stages of injury whereby standard equations have been shown to underestimate the measured REE.21 Failure to provide adequate energy during this phase may result in loss of critical lean body mass and may worsen existing malnutrition. Stress or activity correction factors have been traditionally factored into basal energy requirement estimates to adjust for the nature of illness, its severity and the activity level of hospi talized subjects.22,23 On the other hand, critically ill children who are sedated and mechanically ventilated may have significant reduction in true energy expenditure, due to multiple factors including decreased activity, decreased insensible fluid losses and transient absence of growth during the acute illness.8 These patients may be at a risk of overfeeding when estimates of energy requirements are based on age-appropriate equations developed for healthy children and especially if stress factors are incorporated. The application of a uniform stress correction factor for broad groups of patients in the ICU is simplistic, likely to be inaccurate and may increase the risk of overfeeding. IC testing may be considered before incorporating stress factor correction to energy estimates in critically ill children. Therefore, the application of correction factors for activity, insensible fluid loss and the energy or caloric allotment for growth, which is substantial in infancy, must be reviewed. To account for dynamic alterations in energy metabolism during the critical illness course, REE values remain the only true guide for energy intake. It is likely that resource constraints and lack of available expertise restricts the regular use of IC in the PICU. Estimating energy expenditure needs based on standard equations has been shown to be inaccurate and can significantly underestimate or overestimate the REE in critically ill children (see Table 4). This exposes the critically ill child to potential underfeeding or overfeeding during the ICU stay, with significant morbidity associated with each scenario. While the problems with underfeeding have been well documented, overfeeding too has deleterious consequences.24,25 It increases ventilatory work by increasing carbon dioxide production and can potentially prolong the need for mechanical ventilation.26 Overfeeding may also impair liver function by inducing steatosis and cholestasis, and increase the risk of infection secondary to hyperglycemia. Hyperglycemia associated with caloric overfeeding has been associated with prolonged mechanical ventilator requirement and PICU LOS.27 The use of the respiratory quotient (RQ) as a measure of substrate use in individual children cannot be recommended. However, a combination of acute phase proteins (CRP) and RQ may reflect transition from the catabolic hypermetabolic to the anabolic state. There are no data in general pediatric populations for the role of hypocaloric feeding. The application of hypocaloric feeding in a select group of chronically ill children at high risk of obesity is currently sporadic. In general, the energy goals should be assessed and reviewed regularly in critically ill children. Table 4 summarizes studies examining the performance of estimated energy needs in relation to measured REE in critically ill children requiring mechanical ventilator support. In general, these small sized, prospective or retrospective cohort studies demonstrate the variability of the metabolic state and the uniform failure of estimated energy needs in accurately predicting the measured REE in critically ill children. In the absence of REE, some investigators recommend that basal energy requirements should be provided without correction factors to avoid the provision of calories and/or nutrition substrates in excess of the energy required to maintain the metabolic homeostasis of the injury response. Criteria for targeting a select group of children in the PICU for IC measurement of REE may be useful for centers with limited resources for metabolic testing. Some children in the PICU are likely to be at risk of altered metabolism or malnutrition, where estimates of energy expenditure using standard equations are likely to be inaccurate. If resources are limited, this subset of the population may benefit from targeted IC for accurate measurement of REE to guide energy administration. IC remains sporadically applied in critically ill children in the setting of mounting evidence of the inaccuracy of estimated basal metabolic rate using standard equations. This could potentially subject a subgroup of children in the PICU to the risk of underfeeding or overfeeding. In the era of resource constraints, IC may be applied or targeted for certain high-risk groups in the PICU. Selective application of IC may allow many units to balance the need for accurate REE measurement and limited resources (Appendix 1). 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 body mass index (BMI). Children at high risk for metabolic alterations who are suggested candidates for targeted measurement of REE in the PICU include the following: 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 > 7 days Neurologic trauma (traumatic, hypoxic and/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 > 7 days 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 > 4 weeks may benefit from IC to assess adequacy of nutrient intake. There are insufficient data to make evidence-based recommendations for macronutrient intake in critically ill children. After determination of energy needs for the critically ill child, the rational partitioning of the major substrates should be based upon basic understanding of protein metabolism and carbohydrate- and lipid-handling during critical illness. Grade E Critical illness and recovery from trauma or surgery are characterized by increased protein catabolism and of high protein is that a of is available for synthesis of this a of from muscle to the and other involved in the inflammatory response. This for at times of injury or illness. Although children with critical illness have increases in both protein and protein it is the that during the stress response. Thus, these patients protein and nitrogen balance characterized by muscle weight and immune The catabolism of muscle protein to and inflammatory response proteins is an short-term but it is limited because of the protein available in children and during the provision of alone is in the endogenous production in the Therefore, without of the stress for catabolism (ie, the critical illness or the of muscle mass from critical results in loss of and muscle to respiratory and to the loss of The of protein required to protein is in critically ill in healthy children. demonstrate protein after surgery and a increase in nitrogen with The provision of protein to protein and the inflammatory response, and muscle protein mass is the most important nutrition intervention in critically ill children. The of protein for critically ill neonates and children are based on limited severely such as significant burn injury, may require protein to meet metabolic protein should be as has been documented, in children with renal and hepatic Studies using high protein of have been associated with effects such as metabolic and A of the effects of high protein using formulas is desirable. Although the composition to best increase protein balance has to be stable techniques to study this protein requirements for children of various groups are as and protein needs have been safe caloric using and energy have effects on protein synthesis and overall protein balance in critically ill is the energy used by the and renal and is useful in the of stores are limited and in illness or injury, resulting in the need for In and a increase in and has been as well as an in A significant of the metabolic stress response is that the provision of not the catabolism of muscle protein to continues and to provide large intake in critically ill patients have been The has in critically ill adults based on results of a trial that decreased mortality in critically ill adults randomized to this strategy. studies examining the role of in adults have results and the of in these studies is Hyperglycemia is prevalent in critically ill children and has been associated with outcomes in retrospective The of during the stress response is the prevalence of in the pediatric intensive care no data currently the effects of in the pediatric Both and variability also are associated with increased LOS and and are in the critically ill In the absence of definitive cannot be as in the critically ill child. is by critical illness, surgery, and it has been shown that critically ill children have a rate of fat Thus, this that in the of energy in children. of the increased for use in critical illness with the limited fat stores in the pediatric critically ill children are to the of essential if a this as and increased to To avoid essential in critically ill or the allotment of and is at concentrations of and of total The provision of available fat to critically ill children the risk of essential results in protein and not significantly increase production or metabolic in critically ill children at and over a of days to with monitoring of is to a of of total this practice has not been by clinical In critically ill children with a nutrition should be the mode of nutrient if Grade A of to in the PICU. must identify and prevent to in critically ill children. Grade D There are insufficient data to recommend the appropriate for feeding in critically ill children. or may improve caloric intake when to feeding may be considered in children at high risk of or those who have a trial of feeding. Grade the determination of energy expenditure and requirement in the critically ill child, the is to select the appropriate route for delivery of In the critically ill child with a the route is to nutrition has been shown to be without the risk of infection with However, the optimal route of nutrient delivery has not been in children and is no the effects of practice in many centers the of or feeding within hours after is used to or in those patients where alone is to meet the nutrition In children with are insufficient data to make recommendations regarding the of feeding et al examined the role of small feeding in critically ill randomized to receive or The study was not to in was in a large number of in this study and caloric goals were in a small of the population This not in and between the or A of in the small group achieved their caloric goal to the et al better in critically ill children early hours after PICU after the children in their cohort who were to have to early nutrition and had decreased of