REVIEW ARTICLE Year : 2022  |  Volume : 11  |  Issue : 4  |  Page : 302-309

Role of nutrition in pediatric patients with respiratory failure

Priti Arolkar1, Girija Damle2, Priyal Gala3
1 Dietitian, Department of Digestive Diseases and Clinical Nutrition, Tata Memorial Hospital, Mumbai, Maharashtra, India
2 Visiting Faculty, Department of Food Nutrition and Dietetics, Sir Vithaldas Thackersey College of Home Sciences, SNDT Women's University, Mumbai, Maharashtra, India
3 Visiting Faculty, College of Home Science, Nirmala Niketan, Mumbai, Maharashtra, India

Date of Submission07-Sep-2022Date of Decision01-Oct-2022Date of Acceptance01-Oct-2022Date of Web Publication12-Nov-2022

Correspondence Address:
Ms. Priti Arolkar
Dietitian, Department of Digestive Diseases and Clinical Nutrition, Tata Memorial Hospital, Dr. Ernest Borges Road, Parel, Mumbai - 400 012,Maharashtra
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijrc.ijrc_162_22

Respiratory failure is a consequence of malfunction of the respiratory system including neuronal and cellular aspects. The most common causes in children are pneumonitis, vasculitis, pulmonary edema, cystic fibrosis, tuberculosis, asthma, foreign-body aspiration, and respiratory infections of the upper and lower airways. Reduced immunological response due to critical illness, atrophy, and increased intestinal epithelial barrier permeability results in increased susceptibility to infections and the spread of pathogens. The search strategy included a PubMed search for articles from 2000 to 2022. Malnutrition is acquired in 50% of patients admitted to the pediatric intensive care unit, with the added burden of nutritional deficits worsening preexisting malnutrition. Nutrition forms an essential component in managing respiratory conditions, with the potential to change outcomes. Enteral nutrition (EN) can reduce inflammatory cytokine activation and release, as well as maintain gastrointestinal (GI) mucosal integrity, which lowers systemic bacterial invasion and sepsis. Therefore, EN should be the preferred mode of nutrition (when clinically indicated) to parenteral nutrition. ASPEN guidelines recommend the administration of a minimum of 1.5 g/kg/ day of protein in critically ill children. Reduction in the respiratory quotient may be achieved by lowering the carbohydrate intake in infants suffering from prolonged lung disease; however, a balance of carbohydrate and fat ratios is recommended. Immunonutrition helps in reducing inflammation and pro-inflammatory cytokine levels. During pediatric acute respiratory distress syndrome, an essential target to improve lung inflammation is the GI tract. However, no disease-specific recommendation for probiotics and immunonutrients has been established in children yet.

Keywords: Acute respiratory distress syndrome, enteral nutrition, gut lung axis, immunonutrition, malnutrition, pediatrics, respiratory failure

How to cite this article:
Arolkar P, Damle G, Gala P. Role of nutrition in pediatric patients with respiratory failure. Indian J Respir Care 2022;11:302-9
How to cite this URL:
Arolkar P, Damle G, Gala P. Role of nutrition in pediatric patients with respiratory failure. Indian J Respir Care [serial online] 2022 [cited 2022 Nov 12];11:302-9. Available from: http://www.ijrc.in/text.asp?2022/11/4/302/361049   Introduction 

The exchange of gases, acid-base balance, speech, pulmonary defense, and metabolism, and the management of bioactive chemicals are some of the functions of the respiratory system.[1] Respiratory failure (RF) is the ineffectiveness of the respiratory system to fulfill the O2 requirements, and/or effectively excrete CO2 from the body.[2]

  Methodology 

A PubMed search was performed in August 2022 with clinical queries using the key terms “nutrition in RF in paediatrics,” “nutritional assessment in critically ill paediatrics,” “prevalence of pediatric RF,” “nutrition in pediatric acute respiratory distress syndrome (PARDS),” “nutrition in cystic fibrosis (CF),” “nutrition in respiratory distress,” “immunonutrition in pediatric intensive care unit (PICU),” “immunonutrition and respiratory distress,” “respiratory quotient (RQ),” “enteral nutrition (EN) in PICU,” “gut lung axis,” “gut microbiome and dysbiosis,” and “malnutrition and pediatric RF.” Literature published between January 2000 and July 2022, which included reviews, meta-analyses, randomized controlled trials, and observational studies, was referred. To add to the review, Google, Wikipedia and UpToDate were also considered. Only literature published in the English language was referred. An effort to include more Indian studies is evident in this article.

  Epidemiology of Respiratory Failure 

Studies show that RF is more prevalent in children than adults. Prematurity-related problems and the transition to extrauterine life, result in almost half of the cases of RF in neonates.[2] Acute respiratory distress syndrome (ARDS) accounts for 1%–10% of PICU hospitalizations.[3] Lodha et al[4] stated that the occurrence of ARDS was 20.1/1000 admissions with a 75% death rate. In most cases, pneumonia was discovered to be the underlying reason.[4]

  Causes of Respiratory Failure 

RF is a consequence of malfunction of the pulmonary system, including the neuronal and cellular components, along with the respiratory system itself. Pneumonitis, CF, vasculitis, tuberculosis, pulmonary edema, asthma, foreign-body aspiration, and respiratory infections of the upper and lower airways (such as croup, bronchiolitis, and pneumonia) are the common diseases related to the lung, leading to RF.[5],[6] About 10%-70% of COVID-19-positive critically ill children, also developed ARDS.[7]

  Effect of Malnutrition on Respiratory Failure Outcomes 

Malnutrition is a prognostic factor for RF; however, it may go unnoticed. In addition, because of the cumulative protein and energy deficit brought on by catabolism, it has a likelihood to exacerbate during the PICU stay.[8],[9]

As per[10] De Souza Menezes et al., malnutrition in the pediatric population has a significant positive association with the duration of ventilatory support (of >5 days) and hospital stay. Systemic functioning changes are the root cause of the complications brought on by malnutrition in critically ill individuals. Reduced immunological response, atrophy, and increased intestinal epithelial barrier permeability are some of the modifications, which increase susceptibility to infections and the spread of pathogens.[10]

Pertaining to PARDS, muscle mass wasting and impaired diaphragmatic function may worsen the patient's RF and prolong their need for a ventilator.[11] The development of muscular fatigue and diaphragmatic dysfunction during disease progression could be a result of prolonged ventilation, systemic inflammation, malnutrition, increased protein turnover, use of neuromuscular and immunomodulatory drugs, and the range of contraction of the diaphragm during ventilator support.[12]

Lower body mass index (or weight for height for children <2 years), z score and reduced diaphragmatic potency have a direct correlation with chronic malnutrition found in patients with CF. After initiation of mechanical ventilation, the diaphragmatic function is affected by various factors such as nutritional status, acquired nutritional deficiencies, dyselectrolytemia, and individual risks.[12]

During inspiration, the external intercostals are active and during expiration, internal intercostals are active. Due to undernutrition, there is reduced diaphragmatic muscle mass, decreased respiratory muscle strength, decreased inspiratory muscle pressure, and increased chest wall resistivity adversely affecting lung parenchyma, muscle structure, function, and respiratory mechanics.[13],[14] As the abdominal fat deposition increases, shallow and rapid breathing reduces the thoracic volume and increases respiratory dead space, leading to obstruction in the trachea, partial atelectasis, and ultimately respiratory distress.[15]

  Effect of Chronic Respiratory Diseases on Respiratory Failure Outcomes 

The most significant clinical effects of dietary deficits in patients with chronic respiratory diseases are reduction in muscle mass and impaired functional status. Nutritional deficits negatively affect bone and fat tissues, muscle structure, and function, progressing to cachexia in more severe cases. Malnutrition also affects the patient's immune system, increasing the risk for infections and disease exacerbations, which in turn may further impair nutritional status.[16]

  Metabolism in Respiratory Failure 

Children and adolescents in critical conditions frequently have a systemic inflammatory response, which results in the release of inflammatory markers, metabolic dysregulation, and muscle breakdown.[17]

Catecholamines cause triglycerides to mobilize and enhance metabolic rate, O2 consumption (VO2), and CO2 generation (VCO2). An early hypermetabolic response to acute insults may stimulate the sympathetic nervous system. Impaired glucose tolerance, increased lipid breakdown, and altered protein metabolism are all indicators of catabolism and systemic inflammation. A prolonged state of catabolism further deteriorates the patient's nutritional status, and compromises wound healing which can intensify the course of RF and prolong the need for ventilatory support.[18] In neonatal and pediatric populations, preexisting nutritional status and insufficient nutrient delivery early in critical illness are well-proven risk factors for morbidity and mortality.[11]

  Effect of Respiratory Failure on Growth and Development 

In order to recuperate and assist in the synthesis of glucose, and critical illness-specific biomolecules, metabolism shifts away from growth. When resources are diverted to support recovery from a critical illness, it prevents pediatric patients' natural growth and development.[11]

  Nutritional Screening and Assessment in the Pediatric Intensive Care Unit 

According to the CF foundation,[19] in children with CF, targeting early intervention using a screening tool is a must for any respiratory disease. However, there are no particular guidelines for the specific usage of screening tools. Six pediatric malnutrition screening tools were described. Screening Tool for Risk On Nutritional Status and Growth (STRONGkids) and Pediatric Yorkhill Malnutrition Score(PYMS) tools showed promise and effectiveness for assessing nutritional risk and nutritional status.[20]

A multidisciplinary team along with a nutritionist should guide and monitor anthropometric assessment that should be individually interpreted to reduce nutrition deficits during hospitalization in the PICU with the correct diagnosis of nutritional status. If preadmission anthropometric data are unavailable, predictive formulas for the same, may be used along with biochemical parameters to assess nutrition status on PICU admission.[21] Mid-Upper Arm Circumference (MUAC) may also be used as a surrogate.[22] Grippa et al.[23] argue that physical measurements are poor indicators of nutritional status in PICU patients because of the impact of measurement quality, interpersonal variability, and critical illness-related factors like fluid shift. According to Vermilyea et al.,[24] subjective global nutritional assessment tool (SGNA) could be used in place of anthropometric measurements to recognize malnutrition in PICU patients. However, for nutritional assessment in the PICU, there is currently no established standard.[25]

  Nutritional Requirements during Pediatric Respiratory Failure 

Nutrition is important in the management of pediatric respiratory diseases, with the potential to change outcomes.[26] Feeding patients with PARDS have both direct and indirect clinical advantages. Malnutrition is acquired in 50% of patients during the course of PICU admission, with the added burden of nutritional deficits worsening preexisting malnutrition. Malnutrition is directly proportional to mortality.[11] Hence, efficient delivery of nutrients improves outcomes.[17]

  Permissive Underfeeding 

According to the PermiT trial,[27] reduced insulin needs and lower blood glucose levels were linked to permissive underfeeding. Between underfeeding (40%–60% energy requirements) and standard feeding (70%–100% energy requirements), there was no significant difference found in terms of mortality. The study also found no improvement in protein catabolism in PICU patients with higher caloric intake when assessed based on nitrogen balance and levels of prealbumin, transferrin, and urinary nitrogen excretion. In acute RF patients (mechanically ventilated), there was no difference in clinical outcomes between early trophic feeds and early full EN feeds, except for reduced events of gastrointestinal (GI) disturbances.[28],[29]

  Nutritional Support: Enteral and Parenteral Nutrition for Pediatric Respiratory Failure 

Patients with respiratory diseases may require multiple feeding modes or even complete nutritional support, depending on the severity and intensity of the illness. According to clinical studies, administration of EN within 24–48 hrs of being admitted to the PICU, along with 60%–70% of nutritional needs being met during the first 7 days of PICU stay, have shown to positively impact prognosis.[30] The PALICC statement strongly recommends preferring EN over parenteral nutrition (PN) wherever feasible.[31] EN can reduce inflammatory cytokine activation and release and maintain GI mucosal integrity, lowering the risk of bacterial translocation and sepsis. Initially, <60%–80% of the total requirements should be established, followed by a gradual increase based on tolerance. Nutritional support should be initiated as soon as possible, with special attention to children classified as stunted or wasted according to WHO criteria, using pre-admission data.[22],[31]

  Energy 

Nutritional deficiency aggravates due to underfeeding, resulting in poor growth of the child. Malnutrition leads to excessive breakdown of protein in the body to meet the metabolic requirements. Immunosuppression is a major adverse effect of this protein breakdown. As a result, the patient may be more susceptible to postponed weaning from ventilator support, acquiring infection, and delayed wound healing. However, overfeeding can lead to electrolyte imbalance, increased CO2 synthesis, etc.[32],[33],[34],[35] Consumption of 54–58 kcal/kg/d may be linked to increased protein synthesis and resultant positive balance.[36] According to ASPEN guidelines, usage of Indirect calorimetry (IC) is suggested to determine energy requirements. However, where IC is not possible, predictive equations like Schofield and WHO equations are useful for calculating resting energy expenditure (REE) in critically ill children.[36] In some studies, estimating energy expenditure based on standard equations, especially Harris-Benedict and Recommended Dietary Allowances (RDA) (aimed at healthy populations)[36] has shown to be inaccurate and can significantly underestimate or overestimate the energy requirements in critically ill children. However, the Schofield equation was found to show the lowest errors in REE estimation.[36] Finally, they recommend that energy intake be adapted to take into account disease states that may increase REE, but suggest that predictive equations be used without the routine addition of “stress factors” in critically ill children.[30]

  Protein 

According to ASPEN, a minimum protein intake of 1.5 g/kg/day is recommended in critically ill children, with requirements as high as 2.5–3 g/kg/d in those dependent on ventilator support.[26],[36] An increased protein intake supported by adequate intake of other macronutrients is known to support protein metabolism and utilization.[25]

EN can improve calorie deficit and promote protein metabolism.[37] Consensus on initiating PN in the PICU when EN is not feasible has not been established. According to ASPEN and ESPGHAN guidelines for PN,[36],[38] in premature infants initially, 1.5–3 g/kg/d of protein should be started, followed by a daily increase of 1 g, with an aim to achieve a goal of 3–4 g/kg/day.

  Carbohydrates, Lipids, and Respiratory Quotient 

A low RQ can be achieved in pediatric patients, with a diet slightly lower in carbohydrate content (36% of total energy).[39],[40] RQ for carbohydrates is higher (1.0) than for protein (0.8) and fat (0.7). A study found protein deficit and higher delivery of fat to be associated with raised levels of inflammatory cytokines. Higher serum IL-6 and TNF-a levels were linked with particularly low supply of protein. In malnutrition studies where compromised status of assumed energy and protein intake exists, increased levels of inflammatory markers are seen. Pro-inflammatory fatty acids can act directly or by activating receptors which results in signaling the inflammatory response.[41]

Fatty acids are a key fuel source in critical diseases. Thus, lipid metabolism and turnover are elevated. Excess carbohydrates are converted to lipids, but the process produces CO2, which may prolong mechanical ventilation. Lipids should account for 30%–40% of total calories. This suggests that even relatively smaller meal changes in the proportion of carbohydrates and fat may have significant effects on functional and breathing capacity in RF patients.[39]

A high-carbohydrate (50%–65% of total energy) diet would result in greater CO2 production at the same oxygen intake, but a high-fat, low-carbohydrate diet may cause a reduction in RQ and improve pulmonary function.[40] It was later observed that not the carbohydrate component but the total calorie content of food, determined the CO2 production even after the ratio of carbohydrate to fat was not altered with an increase in total calories.[11],[42] Al Dorzi[43] argues that the ratio of macronutrients is not a contributing factor in altering PaCO2 levels, especially when the total energy intake is based on the patient's requirements. Thus balanced carbohydrate and fat ratios are advisable.[44]

A ketogenic diet (KD) might favorably affect lung inflammation through the production of beta-hydroxybutyrate (BHB).[40],[42],[44] However, BHB also decreases endothelial angiotensinogen activity, leading to massive hemorrhage or interstitial and alveolar neutrophil infiltration, and increases the susceptibility to respiratory distress.[45] Therefore, studies to establish a stronger consensus on the use of KD in RF patients are required.

RQ fluctuates throughout the PICU stay, affecting substrate consumption and nutritional support. This can be due to factors related and unrelated to feeding, like disease pathophysiology, and individual differences in metabolism and response to feed composition. Two clinically relevant issues, the absence of underfeeding and the presence of (carbohydrate) overfeeding can be determined by RQ lower than 0.85 and RQ higher than 1.0, respectively.[46] In the PICU, due to patient-specific differences[46] and unique individual metabolic systems, there is limited evidence for the use of RQ to evaluate the adequacy and efficacy of nutrition therapy.[47]

  Fluid 

The Holiday-Segar method is frequently used to calculate maintenance fluids for children.[48],[49] The efficacy of mechanical transport while swallowing, depends on the hydration status of mucosal surfaces. Mucin production and ciliary activity acted as the primary regulators of airway mucus clearance. However, hydration remains the main factor influencing mucus clearance.[50]

  Immunonutrition and Micronutrients 

PICU patients are at a major risk for immunosuppression associated with increased infections, hyperinflammation, etc., Immunonutrition helps in reducing inflammation, and pro-inflammatory cytokine levels, but there are no apparent clinical outcome studies for specific requirements. Different combinations of nutritional and pharmacologic additives targeted at modifying the inflammatory and immunological response in critically sick adults have not demonstrated benefits. Many antioxidants like arginine, glutamine, omega-3 fatty acids, zinc, and selenium have all been studied.[35][Table 1] summarizes studies on immunonutrition in respiratory diseases.

Other phytochemicals such as allicin, garcinia, green tea extract, and licorice, have been vaguely studied. However, limited research exhibiting the anti-inflammatory effects of these substances has been conducted in children. Further research focusing on the role of micronutrients and antioxidants along with the requirements in RF in children needs to be studied.

  Gut-Lung Axis and Dysbiosis 

In PICU, critical illness and related respiratory pathologies may cause organ damage. Shock, vasoactive medication, and lack of oxygen make the intestines more vulnerable to damage. The mucosa in the lung and the gut are continuous, yet they have separate microbiomes. The GI tract plays a major role in modulating immunity. During PARDS, an essential target to improve lung inflammation is the GI tract. The gut barrier is not only involved in the absorption of water and nutrients but also prevents the entry of pathogens and toxins.[11] The GI cytokines reach the lungs via lymphatic circulation. Gut injury may, therefore, modulate the severity of lung injury. Prevotella, Veillonella, and Fusobacterium, nonpathogenic anaerobic bacteria, inhabit healthy, disease-free alveoli, and Bacteroidetes and Enterobacteriaceae species make up healthy gut flora. In RF, the lungs experience dysbiosis, with bacteria that normally live in the gut being discovered there.[20]

Children who are critically ill show severe gut microbiome dysbiosis. Various PICU factors, including the administration of antibiotics, morphine and gut rest, etc., are linked to dysbiosis. Dysbiosis may result in negative clinical effects that adversely affect outcomes. EN might control dysbiosis.[82] Feeding may also downregulate systemic inflammation and prevent further damage to the lungs.[11] Thus, EN should be preferred over PN wherever feasible.

  Role of Probiotics in Respiratory Failure 

Probiotics are living microorganisms, that have various health benefits for the host when administered in the correct doses.[83] These range from host gut microflora, immunity, autoimmune diseases, IBS, mental health, etc. Probiotics have a significant role in promoting health.

Lactobacillus rhamnosus, L. rhamnosus, Bifidobacterium animalis subsp. lactis BB-12, and Limosilactobacillus fermentum, or a mixture of several probiotic strains, reduced the risk of bronchitis and pneumonia and the duration of illness.[84] In a clinical study with school-going children, L. rhamnosus HN001 (6 × 109 CFU) significantly reduced wheezing and alleviated the symptoms of asthma, further improving immunological response.[85],[86]

Another study conducted on children with CF stated that a mixed probiotic can improve long-term outcomes and prevent morbidity.[87] However, no disease-specific recommendation for probiotics has been established in children.

  Long-Term Effects of Respiratory Failure 

The cause of RF in children is idiopathic. Due to its multifactorial progression (physically, pathophysiologically, and in the clinical course of the disease), it negatively affects the child's cognitive thinking, quality of life, social life, growth, and mental health. Hence, there is a need to evaluate the caregiver as well as the patient.[88]

  Conclusion 

RF is the ineffectiveness of the respiratory system in effectively balancing O2 and CO2 turnover. Lung diseases such as pneumonitis and vasculitis are most likely to cause RF in pediatric patients. Muscle mass wasting and diaphragmatic dysfunction may probably worsen the patient's respiratory dynamics. Children and adolescents in critical conditions frequently have a systemic inflammatory response, which results in cytokines and chemokines release, metabolic dysregulation, and muscle breakdown. It is recommended to prefer EN over PN wherever feasible. Due to compromised immunity in PICU patients, there is a very high risk for immunosuppression associated with increased infections, hyperinflammation, etc. However, there are no strong guidelines for immunonutrition. The gut–lung axis is an important factor when choosing the route of nutrition delivery. In pediatric patients with respiratory diseases, malnutrition is an important modulator of disease outcome, which establishes the need for timely and adequate medical nutrition therapy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 

  References 
1.Tortora GJ, Derrickson B. Principles of Anatomy and Physiology, 13th Edition. Vol. 46, Medicine & Science in Sports & Exercise. John Wiley and Sons Inc.; New Jersey USA 2014. p. 1055.  
    2.Vo P, Kharasch VS. Respiratory failure. Pediatr Rev 2014;35:476-84.  
    3.Orloff KE, Turner DA, Rehder KJ. The current state of pediatric acute respiratory distress syndrome. Pediatr Allergy Immunol Pulmonol 2019;32:35-44.  
    4.Lodha R, Kabra SK, Pandey RM. Acute respiratory distress syndrome: Experience at a tertiary care hospital. Indian pediatrics 2001;38:1154-9.  
    5.Hammer J. Acute respiratory failure in children. Paediatr Respir Rev 2013;14:64-9.  
    6.Mace SE. The pediatric patient with acute respiratory failure: clinical diagnosis and pathophysiology. Pediatr Emerg Med Rep 2001;6:21-32.  
    7.Wang H, Qi Y, Qian L. Severe pediatric COVID-19 with acute respiratory distress syndrome: A narrative review. Pediatr Med 2021;4:Published online Vol 4 (August 2021) doi: 10.21037/pm-20-111.  
    8.Grippa RB, Silva PS, Barbosa E, Bresolin NL, Mehta NM, Moreno YM. Nutritional status as a predictor of duration of mechanical ventilation in critically ill children. Nutrition 2017;33:91-5.  
    9.Hulst J, Joosten K, Zimmermann L, Hop W, van Buuren S, Büller H, et al. Malnutrition in critically ill children: From admission to 6 months after discharge. Clin Nutr 2004;23:223-32.  
    10.de Souza Menezes F, Leite HP, Koch Nogueira PC. Malnutrition as an independent predictor of clinical outcome in critically ill children. Nutrition 2012;28:267-70.  
    11.Wilson B, Typpo K. Nutrition: A primary therapy in pediatric acute respiratory distress syndrome. Front Pediatr 2016;4:108.  
    12.Khemani RG, Ross PA, Typpo K. The authors reply. Crit Care Med 2017;45:e1304-5.  
    13.Dias CM, Pássaro CP, Cagido VR, Einicker-Lamas M, Lowe J, Negri EM, et al. Effects of undernutrition on respiratory mechanics and lung parenchyma remodeling. J Appl Physiol (1985) 2004;97:1888-96.  
    14.Taylor A. The contribution of the intercostal muscles to the effort of respiration in man. J Physiol 1960;151:390-402.  
    15.Park JE, Chung JH, Lee KH, Shin KC. The effect of body composition on pulmonary function. Tuberc Respir Dis (Seoul) 2012;72:433-40.  
    16.Barreiro E, Gea J. Amino Acid and Protein Metabolism in Pulmonary Diseases and Nutritional Abnormalities: A Special Focus on Chronic Obstructive Pulmonary Disease. In The molecular nutrition of amino acids and proteins Academic Press. London United Kingdom 2016; pp. 145-59.  
    17.Delgado FA, Cicero Falcao M, Brasil Iglesias S. Nutrition in pediatric/neonatology patients submitted to mechanical ventilation. Curr Respir Med Rev 2011;8:60-7.  
    18.Gea J, Sancho-Muñoz A, Chalela R. Nutritional status and muscle dysfunction in chronic respiratory diseases: Stable phase versus acute exacerbations. J Thorac Dis 2018;10:S1332-54.  
    19.Mueller SA, Mayer C, Bojaxhiu B, Aeberhard C, Schuetz P, Stanga Z, et al. Effect of preoperative immunonutrition on complications after salvage surgery in head and neck cancer. J Otolaryngol Head Neck Surg 2019;48:25.  
    20.Hulst JM, van Goudoever JB, Zimmermann LJ, Hop WC, Albers MJ, Tibboel D, et al. The effect of cumulative energy and protein deficiency on anthropometric parameters in a pediatric ICU population. Clin Nutr 2004;23:1381-9.  
    21.Briassoulis G. Nutritional assessment in the critically Ill child. Curr Pediatr Rev 2006;2:233-43.  
    22.Zamberlan P, Delgado AF, Brunow de Carvalho W. Will the use of anthropometric measurements solely to assess nutritional status in PICU suffice? Crit Care Med 2016;44:e1152-3.  
    23.Grippa RB, Silva PS, Barbosa E, Bresolin NL, Mehta NM, Moreno YMF. Nutritional status as a predictor of duration of mechanical ventilation in critically ill children. Nutrition 2017;33:91–5.  
    24.Vermilyea S, Slicker J, El-Chammas K, Sultan M, Dasgupta M, Hoffmann RG, et al. Subjective global nutritional assessment in critically ill children. JPEN J Parenter Enteral Nutr 2013;37:659-66.  
    25.Feferbaum R, Delgado AF, Zamberlan P, Leone C. Challenges of nutritional assessment in pediatric ICU. Curr Opin Clin Nutr Metab Care 2009;12:245-50.  
    26.Iyer R, Bansal A. What do we know about optimal nutritional strategies in children with pediatric acute respiratory distress syndrome? Ann Transl Med 2019;7:510.  
    27.Arabi YM, Aldawood AS, Haddad SH, Al-Dorzi HM, Tamim HM, Jones G, et al. Permissive underfeeding or standard enteral feeding in critically Ill adults. N Engl J Med 2015;372:2398-408.  
    28.Rice TW, Mogan S, Hays MA, Bernard GR, Jensen GL, Wheeler AP. Randomized trial of initial trophic versus full-energy enteral nutrition in mechanically ventilated patients with acute respiratory failure. Crit Care Med [Internet] 2011;39:967-74.  
    29.Rice TW, Wheeler AP, Thompson BT, Steingrub J, Hite RD, Moss M, et al. Initial trophic vs full enteral feeding in patients with acute lung injury: the EDEN randomized trial. JAMA [Internet] 2012;307:795-803.  
    30.Sharma BS, Meena HM, Garg V, Sharma PS. Acute respiratory distress syndrome in children: Recent perspective. Clin Res Pulmonol 2017;5:1044.  
    31.Jouvet P, Thomas NJ, Willson DF, Erickson S, Khemani R, Smith L, et al. Pediatric acute respiratory distress syndrome: Consensus recommendations from the pediatric acute lung injury consensus conference. Pediatr Crit Care Med 2015;16:428.  
    32.American Society for Parenteral and Enteral Nutrition (ASPEN) Board of Directors. Clinical guidelines for the use of parenteral and enteral nutrition in adult and pediatric patients, 2009. JPEN J Parenter Enteral Nutr 2009;33:255-9.  
    33.Mehta NM, Bechard LJ, Cahill N, Wang M, Day A, Duggan CP, et al. Nutritional practices and their relationship to clinical outcomes in critically ill children – An international multicenter cohort study. Crit Care Med 2012;40:2204-11.  
    34.de Mello MJ, de Albuquerque Mde F, Ximenes RA, Lacerda HR, Ferraz EJ, Byington R, et al. Factors associated with time to acquisition of bloodstream infection in a pediatric intensive care unit. Infect Control Hosp Epidemiol 2010;31:249-55.  
    35.Allen K, Hoffman L. Enteral nutrition in the mechanically ventilated patient. Nutr Clin Pract 2019;34:540-57.  
    36.Mehta NM, Skillman HE, Irving SY, Coss-Bu JA, Vermilyea S, Farrington EA, et al. Guidelines for the provision and assessment of nutrition support therapy in the pediatric critically Ill patient: Society of critical care medicine and American Society for parenteral and enteral nutrition. Pediatr Crit Care Med 2017;18:675-715.  
    37.Yi DY. Enteral nutrition in pediatric patients. Pediatr Gastroenterol Hepatol Nutr 2018;21:12-9.  
    38.Van Goudoever JB, Carnielli V, Darmaun D, Sainz de Pipaon M, Braegger C, Bronsky J, et al. ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition: Amino acids. Clin Nutr. 2018 ;37(6 Pt B):2315-23.  
    39.Suteerojntrakool O, Sanguanrungsirikul S, Sritippayawan S, Jantarabenjakul W, Sirimongkol P, Chomtho S. Effect of a low-carbohydrate diet on respiratory quotient of infants with chronic lung disease. J Med Assoc Thai 2015;98 Suppl 1:S21-8.  
    40.Malmir H, Onvani S, Ardestani ME, Feizi A, Azadbakht L, Esmaillzadeh A. Adherence to low carbohydrate diet in relation to chronic obstructive pulmonary disease. Front Nutr 2021;8:690880.  
    41.Zaher S, White D, Ridout J, Valla F, Branco R, Meyer R, et al. Association between enteral macronutrient delivery and inflammatory response in critically ill children. Clin Nutr [Internet] 2019;38:2287-96.  
    42.Soares NP, Campos KK, Pena KB, Bandeira AC, Talvani A, Silva ME, et al. The effects of the combination of a refined carbohydrate diet and exposure to hyperoxia in mice. Oxid Med Cell Longev 2016;2016:1014928. doi: 10.1155/2016/1014928.  
    43.Al-Dorzi HM, Aldawood AS, Tamim H, Haddad SH, Jones G, McIntyre L, et al. Caloric intake and the fat-to-carbohydrate ratio in hypercapnic acute respiratory failure: Post-hoc analysis of the PermiT trial. Clin Nutr ESPEN 2019;29:175-82.  
    44.Youm YH, Nguyen KY, Grant RW, Goldberg EL, Bodogai M, Kim D, et al. The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Nat Med 2015;21:263-9.  
    45.McCloud LL, Parkerson JB, Freant L, Hoffman WH, Catravas JD. Beta-hydroxybutyrate induces acute pulmonary endothelial dysfunction in rabbits. Exp Lung Res 2004;30:193-206.  
    46.Hulst JM, van Goudoever JB, Zimmermann LJ, Hop WC, Büller HA, Tibboel D, et al. Adequate feeding and the usefulness of the respiratory quotient in critically ill children. Nutrition 2005;21:192-8.  
    47.Veldscholte K, Joosten K, Chaparro CJ. Energy expenditure in critically ill children. Pediatr Med 2020;3: doi: 10.21037/pm-20-62.  
    48.Arrahmani I, Ingelse SA, van Woensel JB, Bem RA, Lemson J. Current practice of fluid maintenance and replacement therapy in mechanically ventilated critically Ill children: A European survey. Front Pediatr 2022;10:828637.  
    49.Meyers RS. Pediatric fluid and electrolyte therapy. J Pediatr Pharmacol Ther 2009;14:204-11.