Strategies to optimize enteral feeding and nutrition in the critically ill child: a narrative review

Introduction

Enteral nutrition (EN) is the preferred method of providing nutrition therapy in critically ill children with a functional gastrointestinal (GI) tract. EN has been shown to be safe, well-tolerated and associated with improved outcomes. Literature has associated decreased hospital acquired infections, increased ventilator-free days, decreased length of stay, and decreased mortality with EN during critical illness (1-4). Despite this evidence, challenges related to optimal provision of nutrition therapy in this population remain. Current guidelines recommend early enteral nutrition (EEN) as a core component of best practices for care delivery (1,5-8). While these recommendations emphasize the benefit(s) of EN in critically ill children, questions persist regarding timing, route, and rate of enteral feeding as well as determining acceptable targets for feed volume, energy and protein intake.

The goal of nutrition therapy during critical illness is to meet the patient’s basal metabolic needs, support the body in response to stress and illness, and prevent the ongoing loss of lean body mass (4,9,10). The aim of this review is to discuss the metabolic derangements that occur during critical illness, the benefits of EEN and the practical strategies to optimize nutrition in critically ill children.

Methods

Collaboratively, the authors reviewed literature pertinent to the topic of interest and combined this with their collective expert opinion on nutrition therapy in pediatric critical illness to develop this summation in a narrative review format. A structured appraisal using scoping, systematic, or meta-analysis review methodology was not employed to construct this review.

Determining nutritional needs in critically ill children

Nutrition therapy during critical illness is expected to offset the burden of the metabolic stress response and prevent loss of lean mass to improve clinical outcomes. This includes prudent prescription of nutrients individualized to the patient and the phase of illness, and provide nutrients in an efficient and safe manner (Figure 1). There have been several key advances to improve understanding of energy and protein requirements. However, the amount that is most associated with improved clinical outcomes is not yet determined. Hence, there remains significant uncertainty in the best approach to prescribing energy and protein, especially during the early phase of pediatric critical illness.

Figure 1 Goals of nutrition therapy. Meeting metabolic needs, will offset the stress response and avert loss of lean mass and fat, improving outcomes from critical illness. Legend: EN, enteral nutrition; PN, parenteral nutrition.

Energy requirement in critical illness

Significant improvements in surgical, anesthetic and intensive care therapies may be responsible for a more subdued metabolic state in critically ill patients (11,12). This includes enhanced sedation and analgesic therapies, improved patient respiratory ventilator synchrony, and advancements in bedside care. Studies that examine resting energy expenditure (REE) demonstrate an unpredictable energy requirement in the heterogeneous pediatric intensive care unit (PICU) population (13). Energy requirements evolve and may vary widely over the course of critical illness.

Recommended as a precise measure of REE in critically ill children, indirect calorimetry (IC) should be used whenever possible to guide energy prescription (14). However, IC is not available at all centers, it requires significant resources and expertise, and may not be feasible in some patients during the acute phase of critical illness (14,15). In the absence of measured REE by IC, standard prediction equations such as the Schofield (16) and World Health Organization (WHO) (17) are recommended to estimate REE (1,6). Developed from measurements in healthy children these equations should be used with caution owing to the unpredictable nature of critical illness and the metabolic alterations that occur.

Driven by a complex neuroendocrine cascade, the stress response incited during critical illness imposes a varied energy burden characterized by alterations in carbohydrate, lipid, and protein metabolism (11). Predictive equations cannot account for the dynamic nature of these alterations and therefore risk under or overpredicting energy requirements in critically ill children (12,18). Attempts to develop a predictive equation specifically for use with mechanically ventilated children have met with inaccuracies and are not recommened (18). Additionally, the practice of adding disease, condition or activity-based stress factors to REE (estimated or measured) is also not recommended when estimating energy needs in critically ill children (1,6). Overall, it is prudent to be mindful of the risk of unintended over or underestimation of energy requirements due to reliance on inaccurate equations to estimate REE in the PICU population.

The optimal amount of energy necessary to improve clinical outcomes is unknown (15,16). No current trials demonstrate the benefits of matching energy intake to REE measured by IC. Importantly, a study of 500 critically ill, mechanically ventilated children, demonstrated that a higher percentage of goal energy intake was delivered via the enteral route and was significantly associated with lower 60-day mortality [odds ratio (OR) for increasing energy intake from 33.3% to 66.6%, 0.27 (0.11, 0.67), P=0.002] (2). Comparatively, the same study demonstrated higher mortality in patients who received parenteral nutrition (PN) [OR 2.61 (1.3, 5.3), P=0.008] (2). Based on such observational data showing associations between energy intake and outcomes when using predictive equations, current guidelines for nutrition delivery in critically ill children recommend targeting two-thirds (2/3rds) of the estimated REE during the first week of illness (1,2).

Protein requirement in critical illness

Children with burns have similar clinical outcomes as critically ill children who experience a depletion of lean muscle mass. Thermal or burn injury is illustrative of the burden and significance of protein catabolism, a key characteristic of the metabolic stress response during critical illness (19). Postoperative measurement of protein turnover using the ¹⁵N-glycine based urinary end-product enrichment technique in children following thoracic surgery, demonstrates elevation of both protein synthesis and breakdown (19,20). However synthetic rates of protein intake are unable to offset the degree of breakdown resulting in a net negative protein balance, and loss of muscle mass (20). The critical depletion in lean mass from a prolonged stress response may be further exacerbated by lack of intake of protein/amino acid substrate to support protein synthesis (21,22). Using measurements of isokinetic dynamometry (measures force and torque), the impact of this loss of lean mass in pediatric burn patients resulted in a decrease in functional muscle assessments (19).

Practical aspects of protein intake during critical illness

Protein delivery remains low in the acute phase of critical illness (22-24). Findings from a study of more than 1,200 children mechanically ventilated for greater than 48 hours, with median protein prescription of 1.9 g/kg/day, and delivery of 0.66 g/kg/day (38% of prescribed) showed protein intake (as a percentage of the prescribed goal) was indirectly associated with increased 60-day mortality (22,25).

Optimal protein delivery and intake is elusive and the ideal dose that results in improved clinical outcomes unknown. Several small randomized trials compare high versus low protein dose and its impact on protein balance in pediatric critical illness (1). These trials are inconclusive due to being conducted in heterogeneous populations, protein dose variation, route of delivery and inability to provide significant, consistent outcomes relationships. Despite this, based on large observational studies and small trials, a minimum protein intake of 1.5 g/kg/day is recommended to maintain positive nitrogen balance and prevent loss of lean mass in critically ill children (1,6). A dose outcome relationship has only been established with enteral protein intake. While it is currently more feasible to consistently deliver increased doses of protein parenterally, the benefit of increased parenteral protein delivery has not been adequately demonstrated and recent data suggests harm with PN protein delivery during the initial 24 hours of PICU admission (24,26).

Strategies for energy and protein delivery

Once energy and protein needs are determined, enteral feeds should be initiated as soon as possible with feed advancement in a stepwise manner using feeding algorithms to attain target energy and protein intake (25-28). In vulnerable patients where the oral or enteral route EN is insufficient or not feasible, PN must be considered by the end of the first PICU week (29). However, such a pragmatic approach, where it is initiated neither too early nor too late, has not been tested in a well-designed trial. A strategy of using an approach of EEN combined with pragmatic PN aimed at delivering individualized macronutrient targets may be the most reasonable approach in certain patient populations.

Early initiation of EN in critically ill children

Unlike adults, nutrition therapy in critically ill children must also account for differences in maintenance of nutritional status, safeguarding growth, and variances in metabolism as a function of age, size and state of illness (1,6). Adult and pediatric guidelines for nutrition therapy in critical illness recommend early initiation of enteral feeds to improve clinical outcomes (1,6,30,31). Enteral feeds promote and maintain GI mucosal integrity and function (31,32). Studies suggest benefits include fewer infections and better healing, with overall improved short-term and long-term clinical outcomes (33-36).

Pediatric data for the efficacy of EEN are largely derived from observational and retrospective studies, and do not have the same evidence from randomized controlled trials (RCTs) as adult studies (37-42). Globally, surveys of clinical practice demonstrate wide variation in approach to nutrition therapy in critically ill children (8,43-45). Smaller studies in this population have demonstrated beneficial changes in nutritional biomarkers, nitrogen balance, inflammatory cytokines and immune mechanisms from provision of EEN (38-42,46,47).

Defining EEN varies widely, from as early as six hours to as late as 72 hours following onset of critical illness and PICU admission (48-51). Studies of EEN in critically ill children vary and include the general PICU population as well as children with disease specific states (48-56). Table 1 summarizes key studies of EEN in critically ill children.

EEN in general PICU population

In general studies of EEN in PICU populations have reported a trend of fewer infections, a reduction in measures of ICU dependency, less organ dysfunction and decreased mortality (28,48,49). In addition, there may be an association between an increased proportion of EEN relative to goal energy prescription and decreased mortality, supporting a dose-response relationship (2,28,31,56,57).

EEN in children with critical illness specific disease states

In specific disease states as with a general PICU population, studies suggest EEN to be safe and beneficial even with heterogeneity of diagnosis, presentation at time of illness and interventions in the PICU setting. Retrospectives studies where EEN was initiated in critically ill children with acute respiratory failure from acute lung injury and/or acute respiratory distress demonstrated decreased length of stay, lower severity of respiratory failure, reduced use of vasoactive agents and decreased mortality (3,50,58).

Evidence for EEN is lacking in children with septic shock or other sepsis-associated illness and organ dysfunction. In the absence of such evidence and without contraindications to provision of EN, there is a clinical preference to commence EEN within 48 hours of admission in children with septic shock or sepsis-associated organ dysfunction. Recent pediatric sepsis guidelines, support initiation of EEN when appropriate, based on the child’s clinical status (7).

Initiation of EEN in children with traumatic brain injury (TBI) is associated with better clinical and functional outcomes (51,52). Recent studies favored EEN initiated in within 72 hours and demonstrated that delayed initiation of EN (greater than 48 hours) in children with TBI was an independent risk factor for worse functional status at PICU discharge (51,52,59).

In studies of critically ill children supported with extracorporeal membrane oxygenation (ECMO) findings suggest improved survival with use of EEN (53,54). Despite its suggested benefit and evidence in other PICU populations, use of EEN in children who require ECMO is variable and without clear guidelines (53-55).

Evidence to support EEN initiation in children with congenital heart disease undergoing cardiac surgery with cardiopulmonary bypass is limited but growing. This group constitutes an important cohort of critically ill children (56,57). Studies suggest use of EN is associated with decreased duration of mechanical ventilation, PICU length of stay and overall improved nutritional outcomes (56,57,60).

Strategies for nutrition delivery in PICU populations

Strategies related to initiation of enteral feeding in critically ill children must consider the severity of illness, the child’s nutritional status, and presence of clear criteria for monitoring feeding tolerance.

Use of a feeding protocol is a strategy that has demonstrated positive utility in EN provision for critically ill children (25-27), and current feeding guidelines recommended their use (1,6). Additionally, feeding protocol use is aligned with early feed initiation, minimization of avoidable interruptions and achievement of targeted fluid, energy and protein goals (25-27). Common avoidable interruptions for delivery of EN in critically ill children include real or perceived feeding intolerance, emesis, diarrhea, feeding device occlusion or malfunction, and unplanned procedures (23,58,59,61). Collaboration with a critical care trained registered dietitian and a focus on accurate assessment, determination of energy requirements and clear, timely and accurate prescription are additional strategies to successful EN initiation and advancement in critically ill children (1,6,29,30,32,62-66).

Nutrition considerations in pediatric surgical critical care

Preparation for surgery begins months in advance with a detailed history, nutrition assessment, and review of growth parameters to identify and correct derangements and optimize the child’s health prior to surgical intervention (60,67,68). Malnutrition is an associated independent variable in surgical outcomes, putting these children at increased risk for adverse postsurgical reactions (63,64,69). The risk increases for children who require PICU admission, up to 30% present with malnutrition (2,43,65,70). Multidisciplinary coordination with a systematic plan of care is necessary to ensure nutrition therapy continues throughout the perioperative period with close follow-up after discharge.

Integral to the success of the surgical encounter are the Enhanced Recovery after Surgery (ERAS) guidelines (63). First introduced in adults, these guidelines have gained momentum in pediatric surgery. ERAS is a multidisciplinary, multimodal approach to longitudinal pediatric surgical care, with overarching principles designed to limit the amount of time without nutritional intake, reduce perioperative stress and adjust treatment and therapies that will potentially contribute to long term caloric and protein deficits (63,66). ERAS guidelines are to limit variability across the numerous services who care for pediatric surgical patients during the hospitalization.

At the core of the ERAS guidelines are a focus on nutrition and metabolism, while limiting surgical stress and minimizing barriers to restoring normal digestion, absorption and utilization of energy (63). Studies evaluating use of ERAS are limited, yet findings report a reduction in hospital length of stay, decreased time to resume oral or enteral intake and reduced time to return of bowel function (66,71,72). Children are more sensitive to operative stress, to alterations in thermoregulation and glucose control. They have unique considerations that differ from adults, therefore use of the ERAS bundle guidelines may be a useful strategy to enhance postoperative care and improve surgical outcomes (73).

Preoperative considerations

A major aspect to consider in the immediate preoperative period are fasting times. Limited glycogen stores make children and infants more sensitive to fasting than adults (74,75). The purpose of enteral fasting is to achieve gastric emptying prior to induction of anesthesia to minimize the risk of aspiration and subsequent complications (76). Current perioperative guidelines no longer instruct families to fast children for prolonged periods prior to surgery (77). Instead, preoperative guidelines now recommend an allowance for clear liquids up to two hours prior to surgery, with breast milk and solids permissible until four and six hours, respectively (74,78). Despite this, fasting times remain widely variable with reported preoperative median times ranging from four to 10.5 hours (74,78-80). In the critically ill patient, pre-operative fasting guidelines require individualized modification due to gastric dysmotility induced by the illness.

Aligned with the updated preoperative fasting guidelines, administration of a carbohydrate drink has been used in pediatric ERAS protocols. In adults, this approach has been found to maintain glycogen reserves, decrease insulin resistance and minimize protein breakdown (75,81). Data suggests carbohydrate drinks may improve comfort and reduce anxiety and further implies that these drinks do not increase the risk of aspiration, and may facilitate gastric emptying (81). There is growing evidence suggesting that hyperosmotic preoperative bowel prep is not necessary, it can potentially increase the risk of surgical site infection, wound dehiscence and cause bowel edema leading to gastric dysmotility and enteral feeding intolerance (75). Planned preoperative nutritional strategies may help maintain metabolic homeostasis and achieve a euvolemic state. Studies to better understand the impact of these interventions and their effect on surgical recovery in children are needed.

Operative considerations

In response to surgical stress the body releases catecholamines, cortisol, glucagon and cytokines (82). The surgical and anesthesia teams each have a role in limiting this stress. An anesthetic plan with limited use of opiates will reduce the incidence of postoperative intestinal ileus and promote early reintroduction of oral or enteral feeds. Regional anesthesia is used to decrease the amount and frequency of postoperative sedatives and anxiolytics and has been shown to reduce the inflammatory and metabolic responses while increasing gut motility (83). Intraoperatively, the goal of fluid administration is euvolemia. Fluid overload potentially has several adverse effects including increase in mechanical ventilation days, bowel edema leading to an ileus with intolerance of nutrients into the GI tract, and prolonged time to mobilization and rehabilitation. Lastly, avoidance of prolonged use of unnecessary enteral tubes and drains (nasogastric tube, or gastric decompression catheters) and promotes early mobilization and return of gastric motility.

Postoperative considerations

Following surgery, the major nutritional goal is the restoration of normal GI function allowing nutrient intake. If mechanically ventilated, clear metrics of criteria for extubation should be set. Once extubated, a postoperative nausea and vomiting regimen may be needed to support the re-introduction of oral or EN (84). Some pediatric postoperative feeding protocols recommend starting clear fluids within two hours following surgery in low-risk patients with the goal of starting EN within 24 hours. Progressing the patient to full oral or enteral intake will facilitate the provision of nutrient delivery to mitigate the catabolism that occurs with surgical stress and enhance wound healing.

Suboptimal nutritional intake during the postoperative period, put children at risk for nutritional deterioration causing slow restoration of endogenous protein and delaying recovery (85). Potential postoperative complications such as infection, inflammation, protein loss and prolonged catabolism may extend surgical stress if appropriate interventions such as nutrition therapy are not implemented (77). Feeding interruption with prolonged duration is a known causative factor of decreased EN intake in the postoperative patient (85,86). Real or perceived feeding intolerance, feeding device mechanical issues, and preprocedural fasting are commonly identified reasons for feeding cessation (85).

The multidisciplinary focus on nutrition and metabolism throughout the entire perioperative period may positively impact surgical outcomes.

EN for critically ill children on vasoactive medications

Provision of EN to critically ill children who require use of vasoactive medication infusions is variable (86,87). In addition to overall clinical status, factors to consider are vasoactive medication infusion dose, known or suspected GI dysfunction, and evidence of tissue hypoxia with subsequent multiple organ dysfunction syndrome. Gut dysfunction with disruption of the intestinal barrier can occur due to an alteration in splanchnic circulation owing to the severity of illness, the resuscitation efforts, and the current treatments and therapies the child requires (87-90). Data in both adult and pediatric critically ill patients demonstrate safe, well-tolerated administration of EN while receiving vasoactive medications (4,88,91,92). Recent guidelines for nutrition therapy in critically ill adults acknowledge that patients may benefit from EN while receiving vasoactive medications (30,31).

The use of vasoactive medications for hemodynamic support is often thought to be a contraindication to EN due to hypoperfusion to the gut that can result in mesenteric ischemia. Uncertainty in adequacy of splanchnic circulation and GI perfusion often causes reluctance to feed a gut that may be compromised (86,93). Alterations in splanchnic perfusion can decrease normal function of the GI tract, causing an increase in oxygen demand, reduced absorption, and a decrease in peristalsis. This can increase the risk for bowel obstruction or perforation which is associated with increased mortality (87,91). In fact, EN may have a protective role in preserving gut integrity, by stimulating blood flow to the GI tract, enhancing gastric emptying and lowering the risk of bacterial translocation (94). Studies suggest use of the functioning GI tract in patients who require vasoactive medications is well tolerated and the benefits may outweigh the risks.

The American and European Guidelines for nutrition therapy in critically ill children recommend EN when safe and appropriate, including those children who require vasoactive medication support (1,6). Retrospective studies in children on vasoactive medication infusions of dobutamine, dopamine, epinephrine, milrinone, norepinephrine, phenylephrine and vasopressin who were enterally fed suggest the provision of EN is safe and use of vasoactive medications is not exclusively contraindicated and may overall be beneficial (84,92).

A systematic approach including use of a feeding protocol, close monitoring with clear definitions of feeding intolerance is a strategy to employ in critically ill children requiring vasoactive medications to optimize nutrient delivery, support GI function and decrease risks that may ensue due to the patient’s changing clinical status. The lack of RCTs and limited evidence in this area of pediatric critical care should not be an absolute contraindication to enterally feeding patients who require vasoactive medication infusions, instead an understanding of the risks and benefits of EN in these patients is warranted.

Conclusions

Optimizing EN in the pediatric critically ill patient can be extremely challenging. The heterogeneity of children by disease entity and the response to stress, age, nutrition status and differences in body size require special attention to nutrition therapy. All children admitted to the PICU are at increased risk for suboptimal nutrition therapy owing to competing priorities of care. However, there is ever-increasing data favoring EN therapy. This combined with demonstrated improved clinical outcomes, heightened understanding of the benefits of nutrition therapy, particularly EN, and the availability of evidence-based guidelines to support provision of nutrition for critically ill children, enable pediatric critical care providers collectively to appropriately modify care based on each patient’s demonstrated need. Further research is necessary to better understand how to improve nutrition therapy in various populations of critically ill children.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the Guest Editors (Lyvonne Tume, Frederic Valla and Sascha Verbruggen) for the series “Nutrition in the Critically Ill Child” published in Pediatric Medicine. The article has undergone external peer review.

Conflicts of Interest: The authors have completed the ICMJE uniform disclosure form (available at https://pm.amegroups.com/article/view/10.21037/pm-21-6/coif). The series “Nutrition in the Critically Ill Child” was commissioned by the editorial office without any funding or sponsorship. Dr. Srinivasan serves as an unpaid editorial board member of Pediatric Medicine from Jan 2021 to Dec 2022. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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