e1 26 Deleted in review 27 Deleted in review 28 Chan FK, Kyaw M, Tanigawa T, et al Similar efficacy of proton pump inhibitors vs H2 receptor antagonists in reducing risk of up per gastrointestinal ble[.]
e1 References Dinan TG, Cryan JF The microbiome-gut-brain axis in health and disease Gastroenterol Clin North Am 2017;46(1):77-89 Sertaridou E, Papaioannou V, Kolios G, Pneumatikos I Gut failure in critical care: old school versus new school Ann Gastroenterol 2015;28(3):309-322 Klingensmith NJ, Coopersmith CM The gut as the motor of multiple organ dysfunction in critical illness Crit Care Clin 2016;32(2):203-212 Lyons JD, Coopersmith CM Pathophysiology of the gut and the microbiome in the host response Pediatr Crit Care Med 2017; 18(3_suppl suppl 1):S46-S49 Wahbeh G, Christie D Basic aspects of digestion and absorption In: Wyllie R, Hyams J, Kay M, eds Pediatric Gastrointestinal and Liver Disease Philadelphia: Elsevier; 2016:10-21 Goulet O, Olieman J, Ksiazyk J, et al Neonatal short bowel syndrome as a model of intestinal failure: physiological background for enteral feeding Clin Nutr 2013;32(2):162-171 Deleted in review Deleted in review Chen LQ, Cheung LS, Feng L, Tanner W, Frommer WB Transport of sugars Annu Rev Biochem 2015;84:865-894 10 Wischmeyer PE, McDonald D, Knight R Role of the microbiome, probiotics, and ‘dysbiosis therapy’ in critical illness Curr Opin Crit Care 2016;22(4):347-353 11 Kekuda R, Torres-Zamorano V, Fei YJ, et al Molecular and functional characterization of intestinal Na(1)-dependent neutral amino acid transporter B0 Am J Physiol 1997;272(6 Pt 1):G1463-G1472 12 Elwyn D The role of the liver in regulation of amino acid and protein metabolism In: Munro HN, ed Mammalian Protein Metabolism New York: Academic Press; 1970 13 Wales PW, Allen N, Worthington P, et al A.S.P.E.N clinical guidelines: support of pediatric patients with intestinal failure at risk of parenteral nutrition-associated liver disease J Parenter Enteral Nutr 2014;38:538-557 14 Kulkarni DH, Newberry RD Intestinal macromolecular transport supporting adaptive immunity Cell Mol Gastroenterol Hepatol 2019;7(4):729-737 15 Hamosh M The milky way: from mammary gland to milk to newborn—Macy-Gyorgy Award presentation (1999) Adv Exp Med Biol 2002;503:17-25 16 Black DD Development and physiological regulation of intestinal lipid absorption I Development of intestinal lipid absorption: cellular events in chylomicron assembly and secretion Am J Physiol Gastrointest Liver Physiol 2007;293(3):G519-G524 17 Venkatasubramanian J, Ao M, Rao MC Ion transport in the small intestine Curr Opin Gastroenterol 2010;26(2):123-128 18 Mace OJ, Tehan B, Marshall F Pharmacology and physiology of gastrointestinal enteroendocrine cells Pharmacol Res Perspect 2015;3(4):e00155 19 Tobias A, Sadiq NM Physiology, gastrointestinal nervous control In: StatPearls Treasure Island, FL: StatPearls Publishing LLC; 2019 20 Wilcox C, Turner J, Green J Systematic review: the management of chronic diarrhoea due to bile acid malabsorption Aliment Pharmacol Ther 2014;39(9):923-939 21 Colgan SP, Curtis VF, Lanis JM, Glover LE Metabolic regulation of intestinal epithelial barrier during inflammation Tissue Barriers 2015;3(1-2):e970936 22 Mundi MS, Shah M, Hurt RT When is it appropriate to use glutamine in critical illness? Nutr Clin Pract 2016;31(4):445-450 23 Kumar L, Barker C, Emmanuel A Opioid-induced constipation: pathophysiology, clinical consequences, and management Gastroenterol Res Pract 2014;2014:141737 24 Viswanathan VK, Hodges K, Hecht G Enteric infection meets intestinal function: how bacterial pathogens cause diarrhoea Nat Rev Microbiol 2009;7(2):110-119 25 Deleted in review Deleted in review 27 Deleted in review 28 Chan FK, Kyaw M, Tanigawa T, et al Similar efficacy of protonpump inhibitors vs H2-receptor antagonists in reducing risk of upper gastrointestinal bleeding or ulcers in high-risk users of low-dose aspirin Gastroenterology 2017;152(1):105-110.e1 29 Quenot JP, Thiery N, Barbar S When should stress ulcer prophylaxis be used in the ICU? Curr Opin Crit Care 2009;15(2):139-143 30 Mourani PM, Sontag MK Ventilator-associated pneumonia in critically ill children: a new paradigm Pediatr Clin North Am 2017;64(5): 1039-1056 31 Greenwood-Van Meerveld B, Johnson AC, Grundy D Gastrointestinal physiology and function Handb Exp Pharmacol 2017;239:1-16 32 Di Nardo G, Karunaratne TB, Frediani S, De Giorgio R Chronic intestinal pseudo-obstruction: Progress in management? Neurogastroenterol Motil 2017;29(12) 33 Downes TJ, Cheruvu MS, Karunaratne TB, De Giorgio R, Farmer AD Pathophysiology, Diagnosis, and Management of Chronic Intestinal Pseudo-Obstruction J Clin Gastroenterol 2018;52(6):477-489 34 Kemp DM, Thomas MK, Habener JF Developmental aspects of the endocrine pancreas Rev Endocr Metab Disord 2003;4(1):5-17 35 Chandra R, Liddle RA Modulation of pancreatic exocrine and endocrine secretion Curr Opin Gastroenterol 2013;29(5):517-522 36 Chandra R, Liddle RA Recent advances in the regulation of pancreatic secretion Curr Opin Gastroenterol 2014;30(5):490-494 37 Boamah L, Balistreri W Manifestations of liver disease In: Kliegman R, ed Nelson Textbook of Pediatrics Philadelphia: Saunders Elsevier; 2007 38 Lane ER, Hsu EK, Murray KF Management of ascites in children Expert Rev Gastroenterol Hepatol 2015;9(10):1281-1292 39 Bass LM, Shneider BL, Henn L, et al Clinically evident portal hypertension: an operational research definition for future investigations in the pediatric population J Pediatr Gastroenterol Nutr 2019;68(6):763-767 40 Teoh N, Farrell G Liver disease caused by drugs In: Feldman M, Friedman L, Sleisenger M, eds Sleisenger and Fordtran’s Gastrointestinal and Liver Disease Philadelphia: WB Saunders; 2006:1807-1853 41 Jiao J, Friedman SL, Aloman C Hepatic fibrosis Curr Opin Gastroenterol 2009;25(3):223-229 42 Arroyo V, Navasa M Ascites and spontaneous bacterial peritonitis In: Schiff E, ed Schiff’s Diseases of the Liver Philadelphia: Lippincott Williams & Wilkins; 2007 43 Bunchorntavakul C, Reddy KR Pharmacologic management of portal hypertension Clin Liver Dis 2019;23(4):713-736 44 Vincent JL, Russell JA, Jacob M, et al Albumin administration in the acutely ill: what is new and where next? Crit Care 2014;18(4):231 45 Devakonda A, George L, Raoof S, Esan A, Saleh A, Bernstein LH Transthyretin as a marker to predict outcome in critically ill patients Clin Biochem, 2008;41(14-15):1126-1130 46 Fairbanks KD, Tavill AS Liver disease in alpha 1-antitrypsin deficiency: a review Am J Gastroenterol 2008;103(8):2136-2141; quiz 2142 47 Teckman JH, Rosenthal P, Abel R, et al Baseline analysis of a young alpha-1-antitrypsin deficiency liver disease cohort reveals frequent portal hypertension J Pediatr Gastroenterol Nutr 2015;61(1):94-101 48 Umar SB, Dibaise JK Protein-losing enteropathy: case illustrations and clinical review Am J Gastroenterol 2010;105(1):43-49; quiz 50 49 Van Winckel M, De Bruyne R, Van De Velde S, Van Biervliet S Vitamin K, an update for the paediatrician Eur J Pediatr 2009; 168(2):127-134 50 De Gasperi A, Corti A, Mazza E, Prosperi M, Amici O, Bettinelli L Acute liver failure: managing coagulopathy and the bleeding diathesis Transplant Proc 2009;41(4):1256-1259 51 Matoori S, Leroux JC Recent advances in the treatment of hyperammonemia Adv Drug Deliv Rev 2015;90:55-68 52 Zanger UM, Schwab M Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation Pharmacol Ther 2013;138(1):103-141 e2 53 Tang X, Chen S Epigenetic regulation of cytochrome P450 enzymes and clinical implication Curr Drug Metab 2015;16(2):86-96 54 Mesotten D, Wauters J, Van den Berghe G, Wouters PJ, Milants I, Wilmer A The effect of strict blood glucose control on biliary sludge and cholestasis in critically ill patients J Clin Endocrinol Metab 2009;94(7):2345-2352 55 George J, Ganesh HK, Acharya S, et al Bone mineral density and disorders of mineral metabolism in chronic liver disease World J Gastroenterol 2009;15(28):3516-3522 56 Hogler W, Baumann U, Kelly D Endocrine and bone metabolic complications in chronic liver disease and after liver transplantation in children J Pediatr Gastroenterol Nutr 2012;54(3):313-321 57 Nagpal R, Yadav H Bacterial translocation from the gut to the distant organs: an overview Ann Nutr Metab 2017;71(suppl 1):11-16 58 Hilliard KL, Allen E, Traber KE, et al The lung-liver axis: a requirement for maximal innate immunity and hepatoprotection during pneumonia Am J Respir Cell Mol Biol 2015;53(3):378-390 59 Bäckhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI Hostbacterial mutualism in the human intestine Science 2005;307(5717): 1915-1920 60 Arrieta MC, Stiemsma LT, Amenyogbe N, Brown EM, Finlay B The intestinal microbiome in early life: health and disease Front Immunol 2014;5:427 61 Alexander VN, Northrup V, Bizzarro MJ Antibiotic exposure in the newborn intensive care unit and the risk of necrotizing enterocolitis J Pediatr 2011;159(3):392-397 62 Greenwood C, Morrow AL, Lagomarcino AJ, et al Early empiric antibiotic use in preterm infants is associated with lower bacterial diversity and higher relative abundance of Enterobacter J Pediatr 2014;165(1):23-29 63 Izcue A, Coombes JL, Powrie F Regulatory lymphocytes and intestinal inflammation Annu Rev Immunol 2009;27:313-338 64 Josefowicz SZ, Lu LF, Rudensky AY Regulatory T cells: mechanisms of differentiation and function Annu Rev Immunol 2012;30: 531-564 65 Avelar Rodriguez D, Ryan PM, Toro Monjaraz EM, Ramirez Mayans JA, Quigley EM Small intestinal bacterial overgrowth in children: a state-of-the-art review Front Pediatr 2019;7:363 66 Ravi A, Halstead FD, Bamford A, et al Loss of microbial diversity and pathogen domination of the gut microbiota in critically ill patients Microb Genom 2019;5(9):e000293 67 Cebula A, Seweryn M, Rempala GA, et al Thymus-derived regulatory T cells contribute to tolerance to commensal microbiota Nature 2013;497(7448):258-262 68 Borody T, Fischer M, Mitchell S, Campbell J Fecal microbiota transplantation in gastrointestinal disease: 2015 update and the road ahead Expert Rev Gastroenterol Hepatol 2015;9(11):1379-1391 69 Weingarden AR, Vaughn BP Intestinal microbiota, fecal microbiota transplantation, and inflammatory bowel disease Gut Microbes 2017;8(3):238-252 70 Klaassen CD, Cui JY Review: mechanisms of how the intestinal microbiota alters the effects of drugs and bile acids Drug Metab Dispos 2015;43(10):1505-1521 71 Knackstedt R, Gatherwright J The role of thermal injury on intestinal bacterial translocation and the mitigating role of probiotics: a review of animal and human studies Burns 2020;46(5):1005-1012 72 Hukkinen M, Mutanen A, Pakarinen MP Small bowel dilation in children with short bowel syndrome is associated with mucosal damage, bowel-derived bloodstream infections, and hepatic injury Surgery 2017;162(3):670-679 73 Pham HP, Hsu SX, Parker-Jones S, Samstein B, Diuguid D, Schwartz J Recombinant activated factor VII in patients with acute liver failure with UNOS Status 1A: a single tertiary academic centre experience Vox Sang 2014;106(1):75-82 74 Rosen R, Vandenplas Y, Singendonk M, et al Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition J Pediatr Gastroenterol Nutr 2018;66(3):516-554 e3 Abstract: The gastrointestinal (GI) and hepatobiliary systems are vital to survival following critical illness Whether from primary GI disease, sequelae of surgery, or from complications of systemic disease, restoration of hepatic and GI function is central to successful discharge from the pediatric intensive care unit The GI tract subserves multiple functions beyond digestion that impact systemic immunology, endocrinology, and microbiology New insights into the role of gut innervation are emerging as well as into the compelling importance of the intestinal microbiome in drug metabolism and host protection The interactions between gut, liver, and lung and between liver and kidneys have led to the view that the gut plays a role as an engine of multiple organ dysfunction as well as a regulator of metabolic and immunologic homeostasis This chapter provides a comprehensive overview of basic GI and hepatobiliary function for clinicians dealing with critically ill children Key words: Gastrointestinal tract, digestion, liver, pancreas, intestine 95 Disorders and Diseases of the Gastrointestinal System LAUREN BODILLY AND SAMUEL A KOCOSHIS PEARLS • • • • • So much reliance is placed on electronic monitoring of patients that physicians are often tempted to perform only a cursory examination or go days without laying hands on the patient Regrettably, adopting such an approach deprives the clinician of an adequate perspective on the patient’s day-to-day condition and deprives the patient of optimal care When compared with a scintiscan of the lungs after administration of a radiolabeled meal or with the discovery of lipid-laden macrophages after bronchoalveolar lavage, the use of colorants to monitor for aspiration pneumonitis is notoriously inaccurate Several antireflux barriers exist in the region of the lower esophageal sphincter Beyond intrinsic myogenic tone, barriers such as the cardioesophageal angle, abdominal esophagus (which acts as a flutter valve), mucosal rosette of the sphincter (which acts as a choke valve), and diaphragmatic crura themselves act to prevent reflux of gastric contents The association between Helicobacter pylori infection and both chronic gastritis and duodenal ulcer is well established, but the role of H pylori in the pathogenesis of gastric ulceration remains somewhat speculative Intravenous administration of somatostatin or its synthetic analogue, the active octreotide moiety, has been effective in Gastrointestinal Evaluation of the Critically Ill Child Dramatic advances in pediatric critical care have improved outcomes for children admitted to pediatric intensive care units (PICUs) Indeed, the technology available today has improved management strategies for a variety of conditions So much reliance is placed on electronic monitoring of patients that physicians are often tempted to perform only a cursory examination or go days without laying hands on the patient Regrettably, adopting such an approach deprives the clinician of an adequate perspective on the patient’s day-to-day condition and deprives the patient of optimal care Daily physical examination is of paramount importance in the assessment of children with either life-threatening • • • stemming variceal hemorrhage and may work for other causes of gastrointestinal bleeding In addition to their hemodynamic effects, these agents inhibit gastric acid production Tranexamic acid may also reduce gastrointestinal bleeding Crohn disease and ulcerative colitis are chronic, relapsing disorders without known causes The transmural inflammation of Crohn disease may affect any portion of the alimentary tract in a patchy distribution, whereas the inflammation of ulcerative colitis is confined to the mucosa of the colon An abdominal plain film showing pneumatosis intestinalis, hepatic portal air, or both confirms the diagnosis of necrotizing enterocolitis Because the pathogenesis is unknown, treatment must be symptomatic In most centers, feedings are discontinued for 48 hours to weeks depending on the severity of symptoms Fluid resuscitation and broad-spectrum parenteral antibiotics are the bases of medical therapy Surgical resection is reserved for severe cases when medical management fails and gangrenous bowel develops Abdominal compartment hypertension and syndrome are two distinct entities becoming increasingly recognized in the intensive care setting Prompt recognition of clinical symptoms and signs may prevent vital organ compromise gastrointestinal disease or gastrointestinal manifestations of multisystem disease This chapter reviews the current approach to gastroenterologic diagnosis and therapy as well as the principles of gastroenterologic physical examination Abdominal Examination Astute clinicians recognize that the abdomen extends from the neck to the knees A thorough examination of the head, neck, and chest is essential when patients with abdominal symptoms are evaluated For example, pneumonia may be discovered by chest auscultation in the child who has abdominal pain The abdominal examination, which can be difficult to perform on young children without life-threatening illness, is made more 1141 1142 S E C T I O N X Pediatric Critical Care: Gastroenterology and Nutrition difficult in the ICU setting Pain and fear limit cooperation Patients who are obtunded by narcotics, sedatives, or an underlying central nervous system (CNS) disorder display inconsistent responses to abdominal palpation Neuromuscular blockade abolishes abdominal guarding Children with multisystem trauma may not localize pain These impediments notwithstanding, the observant clinician can glean a great deal of information from a carefully performed examination Simple inspection of the child’s abdomen can reveal generalized distention, abnormally prominent abdominal wall veins (which signify portal hypertension), or anterior and lateral abdominal wall ecchymoses, such as Cullen sign or Grey Turner sign (which herald acute pancreatitis) In addition, because of the child’s relatively undeveloped abdominal musculature, visceromegaly or abdominal masses may be apparent on inspection Auscultation will ascertain the frequency and quality of peristaltic sounds They normally occur every 10 to 30 seconds and are low pitched High-pitched, frequent bowel sounds suggest enteritis or obstruction In obstruction, bowel sounds characteristically reverberate and seem to originate from a deep well Bowel sounds are absent in paralytic ileus or peritonitis Ancillary findings include venous hums, which suggest portal obstruction, or bruits that may denote arteriovenous malformations In pediatric patients, palpation should generally precede percussion because it is less threatening The child should be in the supine position and, when possible, the hips and knees should be comfortably flexed to enhance abdominal wall relaxation The abdomen should be palpated through all phases of respiration in all four quadrants The examiner should lightly palpate to judge guarding and tenderness and should use gentle ballottement Deeper palpation better localizes organomegaly or masses Percussion permits estimation of visceral size and helps to diagnose obstruction, peritonitis, or ascites Excessive tympany implies that bowel loops are distended with air, whereas dullness suggests that excessive fluid or a solid mass is present Shifting dullness is relatively easy to detect in cooperative children with percussion of the abdomen, with the child in the supine, left lateral, and right lateral positions When the child with ascites is in the supine position, dullness is found primarily over the flanks The dullness moves to a new level nearer the midline when the child is moved to each lateral position It is essential to perform a digital examination of the rectum in children with gastrointestinal dysfunction Inspection of the perineum may reveal perianal or perirectal abscesses, which may be the first sign of acute leukemia, chronic granulomatous disease of childhood, or Crohn disease Similarly, deep fissures or sentinel piles suggest ulcerative colitis or Crohn disease, and hemorrhoids can be found in portal hypertension The digital examination should be performed in the alert, older child only after its purpose is explained Any material that returns on the examining finger should be evaluated for occult blood Absence of stool in the vault can corroborate Hirschsprung disease in an infant with abdominal distention and a history of obstipation Rectal masses related to pelvic abscesses or tumors may be digitally palpated Rectal tenderness signifies mural or extramural inflammation or infection Gastrointestinal Endoscopy The development of flexible fiberoptic endoscopes appropriately sized for use in infants and children has greatly expanded the value of endoscopy in diagnosing and treating a variety of gastroenterologic disorders in critically ill pediatric patients For example, pediatric endoscopes with an outside diameter of mm can now be used for diagnostic purposes in newborn infants Electrocautery, injection therapy, or variceal banding of gastrointestinal bleeding sites can also be performed with devices that now fit within the biopsy channels of a standard 9.4-mm pediatric endoscope Upper gastrointestinal endoscopy (esophagogastroduodenoscopy [EGD]) is performed most often with the child under deep sedation or general anesthesia, although some clinicians report successful unsedated upper endoscopy in very young infants Many pediatric endoscopists in North America use a combination of narcotic sedative and benzodiazepine to achieve acceptable sedation analgesia.1 Other agents commonly used for sedation are propofol and ketamine General anesthesia with endotracheal intubation is appropriate when the side effects of sedation or the endoscopy pose an undue risk of respiratory compromise (e.g., when underlying pulmonary disease, upper airway disease, or disorders of respiratory control are present) or if the patient is at risk for aspiration of gastric contents (e.g., when massive upper gastrointestinal hemorrhage is present or when an emergency foreign body extraction is performed on a child with a full stomach) In an ICU setting, patients supported by ventilators should receive additional sedation and neuromuscular blockade if the endoscopist anticipates that the procedure will be lengthy or excessively difficult Advantages of elective endotracheal intubation for EGD also include control of both the airway and ventilation during the procedure In very small patients, the relatively large endoscope may partially obstruct the glottis Distention of the gut with air may interfere with diaphragmatic movement The risk of inadvertent intubation during EGD, however, mandates careful fixation of the endotracheal tube and careful monitoring of ventilation during the procedure by a physician from the critical care team Because bacteremia may occur during both upper and lower gastrointestinal endoscopy, some endoscopists routinely use perioperative antibiotics for endoscopy in patients with a significant cardiac lesion, central venous line, ventriculoperitoneal shunt, or who are immunocompromised Therapeutic endoscopy has complemented diagnostic endoscopy Gastrointestinal tract hemorrhage from varices, peptic ulceration, and angiodysplasia may be controlled by injection therapy or photocoagulation, electrocoagulation, and thermocoagulation Band ligation of esophageal varices is also a proved therapy for variceal hemorrhage Percutaneous endoscopic gastrostomy has become a popular alternative to surgical gastrostomy to provide a reliable route for enteral nutrition for patients in the ICU who cannot take oral alimentation on a long-term basis The diagnosis and treatment of oropharyngeal dysphagia can be difficult but are improved with the use of fiberoptic endoscopic evaluation of swallowing (FEES) The endoscope can be passed transnasally to visualize both laryngeal and pharyngeal structures Both the structure and functioning of the pharyngeal phase of swallowing can be evaluated by giving the patient food and liquid boluses Sensory testing can also be conducted to elicit the laryngeal adductor reflex Some studies have suggested a good correlation between FEES and videofluoroscopy Wireless video endoscopy or video capsule endoscopy (VCE) is a noninvasive technology used to provide imaging of the small intestine, an anatomic site often difficult to visualize The images acquired are of excellent resolution—the procedure uses the principle of physiologic endoscopy via passive movement and does not inflate the bowel, thus, images of the mucosa are captured in a collapsed state Primary indications include the diagnosis of ... engine of multiple organ dysfunction as well as a regulator of metabolic and immunologic homeostasis This chapter provides a comprehensive overview of basic GI and hepatobiliary function for clinicians... organ compromise gastrointestinal disease or gastrointestinal manifestations of multisystem disease This chapter reviews the current approach to gastroenterologic diagnosis and therapy as well as... variceal banding of gastrointestinal bleeding sites can also be performed with devices that now fit within the biopsy channels of a standard 9.4-mm pediatric endoscope Upper gastrointestinal endoscopy