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critically ill children J Nutr Biochem 2002;13(9):560 98 Petrillo-Albarano T, Pettignano R, Asfaw M, Easley K Use of a feeding protocol to improve nutritional support through early, aggressive, enteral nutrition in the pediatric intensive care unit Pediatr Crit Care Med 2006;7(4):340-344 99 Martinez EE, Bechard LJ, Mehta NM Nutrition algorithms and bedside nutrient delivery practices in pediatric intensive care units: an international multicenter cohort study Nutr Clin Pract 2014; 29(3):360-367 100 Brown AM, Fisher E, Forbes ML Bolus vs continuous nasogastric feeds in mechanically ventilated pediatric patients: a pilot study JPEN J Parenter Enteral Nutr 2019;43(6):750-758 101 Meert KL, Daphtary KM, Metheny NA Gastric vs small-bowel feeding in critically ill children receiving mechanical ventilation: a randomized controlled trial Chest 2004;126(3):872-878 102 Fivez T, Kerklaan D, Mesotten D, et al Early versus Late Parenteral Nutrition in Critically Ill Children N Engl J Med 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Wheeler AP, Thompson BT, deBoisblanc BP, Steingrub J, Rock P Enteral omega-3 fatty acid, gamma-linolenic acid, and antioxidant supplementation in acute lung injury JAMA 2011; 306(14):1574-1581 109 Anez-Bustillos L, Dao DT, Baker MA, Fell GL, Puder M, Gura KM Intravenous fat emulsion formulations for the adult and pediatric patient: understanding the differences Nutr Clin Pract 2016; 31(5):596-609 110 Gura KM, Lee S, Valim C, et al Safety and efficacy of a fish-oil-based fat emulsion in the treatment of parenteral nutrition-associated liver disease Pediatrics 2008;121(3):e678-e686 111 Lee S, Gura KM, Kim S, Arsenault DA, Bistrian BR, Puder M Current clinical applications of omega-6 and omega-3 fatty acids Nutr Clin Pract 2006;21(4):323-341 112 Greene HL, Hambidge KM, Schanler R, Tsang RC Guidelines for the use of vitamins, trace elements, calcium, magnesium, and phosphorus in infants and children receiving total parenteral nutrition: report of the Subcommittee on Pediatric Parenteral Nutrient Requirements from the Committee on Clinical Practice Issues of the American Society for Clinical Nutrition Am J Clin Nutr 1988;48(5):1324-1342 113 Bailey MJ Reduction of catheter-associated sepsis in parenteral nutrition using low-dose intravenous heparin Br Med J 1979; 1(6179):1671-1673 114 Collier PE, Ryan JJ, Diamond DL Cardiac tamponade from central venous catheters Report of a case and review of the English literature Angiology 1984;35(9):595-600 115 Agarwal KC, Khan MA, Falla A, Amato JJ Cardiac perforation from central venous catheters: survival after cardiac tamponade in an infant Pediatrics 1984;73(3):333-338 116 Bechard LJ, Rothpletz-Puglia P, Touger-Decker R, Duggan C, Mehta NM Influence of obesity on clinical outcomes in hospitalized children: a systematic review JAMA Pediatr 2013;167(5):476-482 117 Jeevanandam M, Young DH, Schiller WR Obesity and the metabolic response to severe multiple trauma in man J Clin Invest 1991;87(1):262-269 118 McCowen KC, Friel C, Sternberg J, et al Hypocaloric total parenteral nutrition: effectiveness in prevention of hyperglycemia and infectious complications—a randomized clinical trial Crit Care Med 2000;28(11):3606-3611 119 McCarthy MC, Cottam GL, Turner Jr WW Essential fatty acid deficiency in critically ill surgical patients Am J Surg 1981; 142(6):747-751 120 Martinez EE, Ariagno K, Arriola A, Lara K, Mehta NM Challenges to nutrition therapy in the pediatric critically ill obese patient Nutr Clin Pract 2015;30(3):432-439 e4 Abstract: Critical illness increases metabolic demand on children during the stress response, during which nutrient intake is often limited Assessment and early intervention with adequate energy and protein delivery is essential to promote positive outcomes in critically ill patients The precise amount and timing of nutrient delivery must be individualized in this heterogeneous population Key words: nutrition, pediatrics, critical care, malnutrition, enteral nutrition SECTION XI Pediatric Critical Care: Immunity and Infection 100 101 102 103 104 105 106 Innate Immunity, 1190 Adaptive Immunity, 1199 Critical Illness and the Microbiome, 1208 Congenital Immunodeficiency, 1215 Acquired Immune Dysfunction, 1229 Immune Balance in Critical Illness, 1242 Pediatric Rheumatologic Disease, 1249 107 Bacterial and Fungal Infections, 1263 108 Life-Threatening Viral Diseases and Their Treatment, 1273 109 Healthcare-Associated Infections, 1284 110 Pediatric Sepsis, 1293 111 Multiple-Organ Dysfunction Syndrome, 1310 1189 100 Innate Immunity SAMIRAN RAY, RACHEL S AGBEKO, AND MARK J PETERS The immune system is a complex, sophisticated defense system that protects the body from danger Danger may be intrinsic (e.g., cancer) or extrinsic (e.g., pathogenic organisms) The immune system provides constant surveillance to detect potential danger, identifies the nature of the threat, and then mounts a nullifying response The immune system is also self-regulating—once the threat is nullified, the response needs to be called off Traditionally, a distinction has been made between adaptive and innate immune responses The adaptive immune system has been studied in greater detail and is responsible for a specific response to individual pathogens Adaptive immunity is a highly sophisticated process with many safety mechanisms to target responses at pathogens (or pathogen-infected cells) while leaving normal tissues alone This sophistication and specificity take time to develop (days to weeks) and have many effector cells and molecules to deliver a coordinated response, including T and B lymphocytes and immunoglobulins While the adaptive response is essential for health and in particular for the phenomenon of immunologic memory, it is not sufficient to address a sudden major bacteremia or widespread tissue injury—or even the thousands of minor bacterial inoculums that all individuals experience during their lifetimes (e.g., during teeth brushing) Bacterial growth is exponential under optimal conditions Neisseria meningitides counts can double in 20 minutes Given these threats, there is a need for a ready-made system that can act swiftly to neutralize external threats This is called the innate immune system Innate immunity is phylogenetically conserved and found in nearly all multicellular organisms Again, this contrasts with the adaptive immune system that is found in vertebrates only In humans, the innate immune system is largely present at birth in contrast to the years it takes to build an adaptive immune repertoire The hallmarks of the innate immune system are immediacy, promiscuousness, redundancy, and generality Given that the adaptive immune system evolved in the presence of innate immunity, these systems not operate in isolation from each other Rather, the innate immune system presents to and instructs the adaptive part of immunity 1190 • Innate immunity provides the frontline ready-made response to pathogen invasion These same pathways are activated in response to other critical insults, including trauma, hypoxic/ischemic injury, and bypass • • • PEARLS Pattern recognition molecules recognize exogenous and endogenous molecular patterns Therapeutic interventions in the intensive care unit can have consequences on the innate immune response Innate immunity is mediated through immune cells, such as tissue macrophages, neutrophils, and monocytes It is also mediated through cells that are primarily known for other functions: platelets and endothelial cells Complex networks of circulating mediators—including the complement cascade, collectins, defensins, and the coagulation cascade—are integral parts of innate immunity Recent work has highlighted apparent contributions from neurohumoral and autonomic nervous systems No critically ill child is admitted to the intensive care unit (ICU) without activation of the child’s innate immune system No intensivist can function adequately without a good working knowledge of innate immunity, as it is central to many of the clinical entities that the intensivist faces on a day-to-day basis Infection, trauma, ischemia-reperfusion, acute respiratory distress syndrome (ARDS), and cardiopulmonary bypass sequelae are all largely mediated by the innate immune system This chapter provides a framework and outline of concepts in innate immunity that will help in the understanding of some of the pathophysiologic processes central to pediatric critical care Components of Innate Immune System An ideal first-line response to danger would be pervasive, prompt, effective, and calibrated The required steps are recognition of a danger signal, dispatch of messengers to mount a response, mounting an effector response that neutralizes danger, and controlling the response to contain damage Innate Immune Stimulus: Danger Hypothesis The traditional paradigm of the immune system suggests that it is programmed, through evolution and adaptation, to differentiate between self and nonself In this view, invading pathogens such as bacteria would be recognized as nonself and trigger an immune response, while newly replicating blood cells would not trigger a response However, this does not explain how animals can host entire microbiomes on their mucosal surfaces without inducing ... neutralize external threats This is called the innate immune system Innate immunity is phylogenetically conserved and found in nearly all multicellular organisms Again, this contrasts with the adaptive... In this view, invading pathogens such as bacteria would be recognized as nonself and trigger an immune response, while newly replicating blood cells would not trigger a response However, this... critically ill patients The precise amount and timing of nutrient delivery must be individualized in this heterogeneous population Key words: nutrition, pediatrics, critical care, malnutrition, enteral