Editorials

REFERENCES

1. Striker TW, Stool S, Downes JJ: Prolonged nasotracheal intubation in infants and children. Arch Otolaryngol 1967; 85:210–213 2. Little LA, Koenig JC Jr, Newth CJ: Factors affecting accidental extubations in neonatal and pediatric intensive care patients. Crit Care Med 1990; 18:163–165 3. Black AE, Hatch DJ, Nauth-Misir N: Complications of nasotracheal intubation in neonates, infants and children: A review of 4 years’ experience in a children’s hospital. Br J Anaesth 1990; 65:461–467 4. Popernack ML, Thomas NJ, Lucking SE: Decreasing unplanned extubations: Utilization of the Penn State Children’s Hospital Sedation Algorithm. Pediatr Crit Care Med 2004; 5:58–62 5. da Silva PS, de Aguiar VE, Neto HM, et al: Unplanned extubation in a paediatric intensive care unit: Impact of a quality improvement programme. Anaesthesia 2008; 63:1209–1216 6. Lucas da Silva PS, de Carvalho WB: Unplanned extubation in pediatric critically ill patients: A systematic review and best practice recommendations. Pediatr Crit Care Med 2010; 11:287–294 7. Kanthimathinathan H, Durward A, Murdoch IA, et al: Factors related to unplanned extubation in PICU. Pediatr Crit Care Med 2014; 15S:207

8. Klugman D, Berger JT, Spaeder MC, et al: Acute harm: Unplanned extubations and cardiopulmonary resuscitation in children and neonates. Intensive Care Med 2013; 39:1333–1334 9. Grant MJ, Balas MC, Curley MA; RESTORE Investigative Team: Defining sedation-related adverse events in the pediatric intensive care unit. Heart Lung 2013; 42:171–176 10. Roddy DJ, Spaeder MC, Pastor W, et al: Unplanned Extubations in Children: Impact on Hospital Cost and Length of Stay. Pediatr Crit Care Med 2015; 16:572–575 11. Pittet D, Tarara D, Wenzel RP: Nosocomial bloodstream infection in critically ill patients. Excess length of stay, extra costs, and attributable mortality. JAMA 1994; 272:1819–1820 12. Classen DC, Pestotnik SL, Evans RS, et al: Adverse drug events in hospitalized patients. Excess length of stay, extra costs, and attributable mortality. JAMA 1997; 277:301–306 13. Dominguez TE, Chalom R, Costarino AT Jr: The impact of adverse patient occurrences on hospital costs in the pediatric intensive care unit. Crit Care Med 2001; 29:169–174 14. Haley RW: Measuring the costs of nosocomial infections: Methods for estimating economic burden on the hospital. Am J Med 1991; 91:32S–38S

A Multidisciplinary Mobile Nutritional Assessment Model for Family-Supported Dietary Optimization in Home-Ventilated Children* George Briassoulis, MD, PhD Pediatric Intensive Care Unit University Hospital University of Crete Heraklion, Greece Rosan Meyer, RD, PhD Department of Gastroenterology Great Ormond Street Hospital London, United Kingdom

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here has been an increase in the requirement for longterm ventilatory support in children with chronic diseases. This often impacts on the bed occupation on the PICU, increasing the need for resources that places both a fiscal and work source burden on PICUs (1). As such, there has been a growing demand for children to be discharged and cared for

*See also p. e157. Key Words: diet intervention; energy expenditure; family support; home ventilation; indirect calorimetry Dr. Meyer consulted for Nestle, Mead Johnson, Nutricia, and Danone (review their academic literature) and lectured for Nestle, Mead Johnson, Nutricia, and Danone (academic lectures). She and her institution received grant support from Nutricia (study on prevalence of lactose intolerance in cow's milk protein allergy). Dr. Briassoulis has disclosed that he does not have any potential conflicts of interest. Copyright © 2015 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies DOI: 10.1097/PCC.0000000000000457

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in special in-house units, long-term care facilities, or at home with healthcare professional support. Children receiving longterm mechanical ventilation at home require the input of a multidisciplinary team to assist in maintaining growth and support for both physical and emotional developmental (2). Many have altered body composition and energy requirements related to their underlying illness (3, 4). Thereby, the availability of professional support with clinical dietitians, physiotherapists, speech therapists, nurses, and specialist teachers is essential to optimal home-based care outcome. In this issue of Pediatric Critical Care Medicine, Martinez et al (5) conducted a prospective, open-labeled interventional study in children who are tracheostomy dependent, requiring at least half a day of mechanical ventilatory support at the study participants’ homes. Initial measurements showed that 69% of participants were either underfed or overfed and that in 56% of participants, protein intake was below the lower range of age-based recommendations. Authors examined the effect of an individualized diet intervention on changes in weight, lean body mass, minute ventilation, and carbon dioxide production (Vco2). They showed that it is possible, by using a mobile multidisciplinary team model, to individualize dietary intake, irrespective of feeding route in children on long-term mechanical ventilation. On average for the entire cohort, the delivery of energy as carbohydrates and fat was significantly decreased, whereas the energy from protein was increased in the interventional diet. Such a modification was associated with a significant decrease in minute ventilation, a trend toward significant reduction in carbon dioxide production, and improved body July 2015 • Volume 16 • Number 6

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Editorials

composition (5). The authors hypothesized that this model may be applicable to other cohorts of children with chronic respiratory insufficiency. The same authors had recently reported that the nutritional and metabolic status of children on long-term ventilation via tracheostomy fall largely outside of the recommended ranges and they are vulnerable to further nutritional deterioration as the result of unintended overfeeding and underfeeding and suboptimal protein delivery (6). Using the double-labeled water method in pediatric intensive care patients receiving long-term ventilatory support, it was previously shown that total energy requirements of these patients are significantly reduced compared with healthy children, due to a reduction in lean muscle mass and increase in fat which affects basal metabolic rate (7). Acute malnutrition is highly prevalent at admission to a PICU and at discharge (8, 9). In this population, overfeeding commonly occurs with a detrimental effect on ventilatory support, blood glucose management, autophagy, or mitochondrial biogenesis (10, 11). Accordingly, malnourished patients have been shown to be candidates for indirect calorimetry (IC) per American Society for Parenteral and Enteral Nutrition guidelines (12). Due to limited access to IC (13), inaccurate rudimentary estimates of energy through prediction equations and protein requirements are usually replacing a comprehensive nutritional assessment, including body composition and IC measurement. The inaccuracy of predictive energy equation has been highlighted by many authors and as such IC remains the gold standard method (14). Although a 30-minute IC test has been used to determine the Resting Energy Expenditure as a proxy marker for the entire 24-hour period, this still does not represent total energy expenditure (TEE). Children who spend significant time off of the ventilator may expend more energy during periods of unassisted breathing. In addition, in such a cohort of chronically ill children, concurrent illnesses may also affect their energy needs, whereas expired tidal volume less than 100 mL may produce inaccurate Vco2 measurements. Furthermore, IC in this cohort of nonsedated children may not account for oxygen requirements variation, thermic effect of bolus feedings, patient’s own respiratory efforts or in physical activity, which all affect TEE. Another limitation of the study is the small sample size, obviously attributable to the logistics and resources required to test this novel home-based assessment model. Thus, although the presented results are mostly statistically significant or show a trend toward significance, the change in measured variables is very small, and its effect on the children’s clinical status is vague. In addition, with such a small sample, applying methods validated in healthy or critically ill children to a different population with unknown body consistency may make any conclusions drawn invalid. Similarly, the diversity in comorbidities probably influencing the metabolic state of individual subjects may not allow for extrapolation of any results to other cohorts of chronically ill children. However, the findings are such that they would justify a larger study, as they may have a far-reaching impact on management of home-ventilated children. Pediatric Critical Care Medicine

A novel aspect of this study is the exploration of the feasibility of a mobile nutritional assessment for children on chronic mechanical ventilation along with the alteration in nutritional regimens. The study does demonstrate feasibility at the institution/region where it was performed, but does not provide any resource and cost data that would help readers extrapolate this information into their clinical practice. In the majority of subjects, authors were able to achieve their nutritional interventions using their baseline route of nutrition and formula or foodstuff. They followed-up every 4 weeks subjects who completed the intervention, and all parents reported no issues with administration of the modified diet or noncompliance. It seems that the parents of this cohort had a baseline understanding of the importance of diet for their child’s well-being and were keen on the approach to optimize diet. Families with home-ventilated children experience a significant impact on their quality of life and carry the burden that goes with caring for such a child. This burden includes the time required for the care and the treatments necessary to maintain normal physical and emotional development. This in turn may lead to social isolation, an increased fiscal burden, and a toll on the family’s emotional well-being. Families managing the demanding care regimens of these children undergo functional changes that may severely affect “normal” lifestyle. Mothers of technology-dependent children are at high risk for various depression syndromes that may affect family cohesion (15). Future studies must evaluate the impact of this intervention on clinical outcomes, such as reduced work of breathing, decrease in the duration and degree of ventilatory support, subjective comfort, growth and development, and even immune response to acute illness. The provocative (and still unanswered) question raised by this work is whether improved nutrition in children receiving home ventilation will be associated with better long-term clinical outcomes. Logical next steps include replication of this model in other populations and settings (hospital and outpatient clinic), cost-benefit analysis, and impact on patients’ clinical outcomes and families’ psychological functioning.

REFERENCES

1. Briassoulis G, Filippou O, Natsi L, et al: Acute and chronic paediatric intensive care patients: Current trends and perspectives on resource utilization. QJM 2004; 97:507–518 2. Benneyworth BD, Gebremariam A, Clark SJ, et al: Inpatient health care utilization for children dependent on long-term mechanical ventilation. Pediatrics 2011; 127:e1533–e1541 3. Bott L, Béghin L, Hankard R, et al: Resting energy expenditure in children with neonatal chronic lung disease and obstruction of the airways. Br J Nutr 2007; 98:796–801 4. García-Contreras AA, Vásquez-Garibay EM, Romero-Velarde E, et al: Intensive nutritional support improves the nutritional status and body composition in severely malnourished children with cerebral palsy. Nutr Hosp 2014; 29:838–843 5. Martinez ΕΕ, Bechard LJ, Smallwood CD, et al: Impact of Individualized Diet Intervention on Body Composition and Respiratory Variables in Children With Respiratory Insufficiency: A Pilot Intervention Study. Pedaitr Crit Care Med 2015; 16:e157–e164 6. Martinez EE, Smallwood CD, Bechard LJ, et al: Metabolic assessment and individualized nutrition in children dependent on mechanical ventilation at home. J Pediatr 2015; 166:350–357 www.pccmjournal.org

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Editorials 7. Wells JC, Mok Q, Johnson AW, et al: Energy requirements and body composition in stable pediatric intensive care patients receiving ventilatory support. Food Nutr Bull 2002; 23:95–98 8. Joosten KF, Hulst JM: Prevalence of malnutrition in pediatric hospital patients. Curr Opin Pediatr 2008; 20:590–596 9. Briassoulis G, Zavras N, Hatzis T: Malnutrition, nutritional indices, and early enteral feeding in critically ill children. Nutrition 2001; 17:548–557 10. Briassoulis G, Briassouli E, Tavladaki T, et al: Unpredictable combination of metabolic and feeding patterns in malnourished critically ill children: The malnutrition-energy assessment question. Intensive Care Med 2014; 40:120–122 11. Mehta NM, Bechard LJ, Dolan M, et al: Energy imbalance and the risk of overfeeding in critically ill children. Pediatr Crit Care Med 2011; 12:398–405

12. Kyle UG, Arriaza A, Esposito M, et al: Is indirect calorimetry a necessity or a luxury in the pediatric intensive care unit? JPEN J Parenter Enteral Nutr 2012; 36:177–182 13. van der Kuip M, Oosterveld MJ, van Bokhorst-de van der Schueren MA, et al: Nutritional support in 111 pediatric intensive care units: A European survey. Intensive Care Med 2004; 30:1807–1813 14. Meyer R, Kulinskaya E, Briassoulis G, et al: The challenge of developing a new predictive formula to estimate energy requirements in ventilated critically ill children. Nutr Clin Pract 2012; 27: 669–676 15. Toly VB, Musil CM, Carl JC: Families with children who are technology dependent: Normalization and family functioning. West J Nurs Res 2012; 34:52–71

How We Manage Hyperferritinemic Sepsis-Related Multiple Organ Dysfunction Syndrome/Macrophage Activation Syndrome/Secondary Hemophagocytic Lymphohistiocytosis Histiocytosis* Joseph A. Carcillo, MD Dennis W. Simon, MD Bradley S. Podd, MD Department of Critical Care Medicine University of Pittsburgh School of Medicine Pittsburgh, PA

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hether it is due to changing epidemiology or increased recognition, hyperferritinemic sepsis is becoming increasingly diagnosed in critically ill children. An acute rise in ferritin is part of the normal host response to infection, and recent in vivo and in vitro studies have demonstrated the immunomodulatory effects of ferritin and its individual subunits, light-chain ferritin and heavy-chain ferritin (1–3). In Brazilian children with severe sepsis and septic shock, lack of an increased ferritin response (ferritin, < 200 ng/mL) is associated with 23% mortality, an increased ferritin response (ferritin, 200–500 ng/mL) is associated with best outcome 9% mortality, and a hyperferritinemic response (ferritin, > 500 ng/mL) is associated with 58% mortality (4). This suggests that an increased ferritin level is protective during sepsis but that too high of a response is not,

*See also p. e165. Key Words: hemophagocytic lymphohistiocytosis; hyperferritinemia; macrophage activation syndrome; sepsis Dr. Carcillo received support for article research from the National Institutes of Health (R01 GM108618). His institution received grant support. The remaining authors have disclosed that they do not have any potential conflicts of interest. Copyright © 2015 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies DOI: 10.1097/PCC.0000000000000460

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either because ferritin at higher concentrations is injurious or hyperferritinemia is a marker of injurious hyperinflammation. In a study of all children admitted to Seattle Children’s Hospital tested for serum ferritin, patients with ferritin at least 1,000 ng/mL and at least 3,000 ng/mL have a stepwise increased risk of intensive care admission and death over the next 5 years (5). Although patients with cancer, hemoglobinopathy, or autoimmune disease were more likely to have elevated serum ferritin, the increased risk of PICU admission and death was present even after controlling for these underlying diagnoses. When hyperferritinemic sepsis is associated with five of eight criteria reflective of hyperinflammation (ferritin, > 500 ng/mL, two-line cytopenia, organomegaly, hypertriglyceridemia, hypofibrinogenemia, elevated sCD25, absent natural killer (NK) cytotoxic activity, and hemophagocytosis), it might be called multiple organ dysfunction syndrome (MODS) by intensivists, macrophage activation syndrome (MAS) by rheumatologists, and hemophagocytic lymphohistiocytosis histiocytosis (HLH) by oncologists (6). Unfortunately, the distinction between these syndromes is so important that children cannot afford to have diagnoses given according to specialty practice. We therefore believe it is paramount for intensivists to understand the pathobiology and risk factors for these three clinical syndromes and guide their clinical practice accordingly. MAS has a mortality rate less than 10% (7). Hyperinflammation in this syndrome is related to heterozygous mutations or epigenetically reduced T-regulatory (Treg) cell, natural killer (NK) cell, and cytoxic T lymphocyte (CTL) cell function in rheumatologic diseases or mutations in inflammasome proteins such as in cryopyrin-associated periodic syndromes (CAPS) (8). Importantly, immune cell function is reduced, July 2015 • Volume 16 • Number 6

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