1148 SECTION X Pediatric Critical Care Gastroenterology and Nutrition Small Intestine and Colon Malrotation In embryonic life, the cecum and ascending colon are located on the left side of the abdomen[.]
1148 S E C T I O N X Pediatric Critical Care: Gastroenterology and Nutrition Small Intestine and Colon Malrotation In embryonic life, the cecum and ascending colon are located on the left side of the abdomen and the small bowel is on the right During gestation, the midgut transiently protrudes into the umbilicus and rotates 270 degrees; the cecum is moved to the right lower quadrant and the duodenojejunal junction to the left upper quadrant Incomplete rotation is of little consequence unless midgut volvulus, which can be a catastrophic event, occurs Some patients with malrotation experience partial duodenal obstruction because of extrinsic compression by mesenteric bands Chronic diarrhea and protein-losing enteropathy may be seen, among other conditions, without complete obstruction Clinical features of obstructing volvulus include severe abdominal pain, bilious vomiting, and abdominal distention Surgical treatment requires a Ladd procedure, in which mesenteric bands are divided and the bowel is returned to its fetal position Failure to promptly relieve the volvulus leads to ischemic necrosis of all the gut supplied by the superior mesenteric artery (proximal jejunum to midtransverse colon) Short gut syndrome results from resection of the affected intestine Necrotizing Enterocolitis Necrotizing enterocolitis (NEC) is primarily a disorder of premature infants, affecting 2.5% of neonatal patients in the ICU but only 0.2% of all infants The most common areas involved are the ileum and proximal colon, but any part of the intestinal tract may be affected Its pathogenesis is unknown, but bowel ischemia, feeding of hyperosmolar formula, rapid advancement of feeding,52 reduced immune surveillance, and population of the bowel by excessive quantities of enterotoxin-producing bacteria53 may all play a role The classic clinical features are abdominal distention, bilious vomiting, and bloody stools, but symptoms are more subtle in some infants If left unrecognized, NEC may become fulminant, leading to shock, disseminated intravascular coagulation, and apnea An abdominal plain film showing pneumatosis intestinalis, hepatic portal air, or both may confirm the diagnosis of NEC 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 basis of medical therapy Surgical resection is reserved for severe cases when medical management fails and gangrenous bowel develops Data have emerged suggesting that changes in the neonatal fecal microbiome or production of excessive quantities of volatile organic acids are early markers of NEC; however, the ability to detect these entities is not yet practical for the clinician at the bedside.54,55 Perforation may sometimes be managed successfully in infants with very low birth weight, with simple peritoneal drainage performed with the infant under local anesthesia.47 Low Cardiac Output Syndrome Advancements in surgical techniques have led to significant improvement in morbidity and mortality after pediatric cardiothoracic surgery However, patients remain at risk for decreased cardiac output and impaired systemic oxygen delivery, especially in the early postoperative period The drop in cardiac output after cardiac surgery is characterized as low cardiac output syndrome (LCOS) LCOS is defined as an inability of the heart to provide adequate oxygen delivery to meet the body’s metabolic demand It is primarily due to transient myocardial dysfunction compounded by acute changes in myocardial loading Cardiopulmonary bypass, along with residual cardiac abnormalities, may further aggravate the underlying low cardiac output state.56,57 Although there are several manifestations of this clinical constellation beyond the scope of this chapter, it is important to recognize its clinical signs and symptoms (see Chapter 36) Systemic venous congestion may be observed in the gastrointestinal tract Manifestations include hepatomegaly, ascites, and peripheral edema Hypoperfusion to the liver can result in hepatic insufficiency and may lead to coagulopathy if severe enough Furthermore, intolerance to enteral feeding may be evident in these patients with LCOS and central venous hypertension Feeding difficulties may be further compounded by high-dose inotropes and narcotic infusions These patients often require parenteral nutrition Complications such as mesenteric ischemia or NEC may be observed in rare cases and are often fatal.58,59 Food Allergy Food allergy can be defined as a reproducible, immunologically mediated reaction to an ingested food protein Pathogenic events can be classified according to the schema of Gell and Coombs as type I (reaginic, immediate hypersensitivity reaction), type II (cytotoxic reaction), type III (immune-complex reaction), or type IV (delayed hypersensitivity reaction) Manifestations may be systemic60 or confined to the gastrointestinal tract.61 Life-threatening systemic manifestations include acute urticaria and anaphylaxis.62 Gastrointestinal reactions, which are sometimes severe, include allergic enteritis, allergic colitis, and celiac crisis Acute urticaria is usually easily recognized by the classic wheal and flare cutaneous lesions often accompanied by laryngeal edema and angioedema Anaphylaxis is an antigen-triggered immune reaction that leads to vascular collapse and bronchospasm (see also Chapter 106) Food protein–induced enteropathy is characteristically a disorder of the infant and toddler The small bowel develops patchy villous atrophy Symptoms and signs range from those of malabsorption and enteric protein loss to those of profound diarrhea and shock Colitis caused by food protein sensitivity is seen most commonly among infants younger than months.61 Bloody, mucoid diarrhea develops several days or weeks after their first oral antigen challenge Even though this colitis usually takes a benign course, it may be severe enough to mimic NEC Although some not categorize gluten enteropathy as true food allergy, it shares enough features with allergy to justify inclusion with this category of disorders.61 Celiac crisis is a rare, lifethreatening complication that may occur among untreated patients with a large gluten load or in treated patients as a result of dietary indiscretion Massive fluid and electrolyte loss leads to shock The cornerstone of long-term therapy is elimination of the offending food, but emergency measures are also required Immediate administration of epinephrine and corticosteroids is essential in the treatment of anaphylaxis Urticaria may require the administration of antihistamines, corticosteroids, and epinephrine Corticosteroid administration also seems to benefit patients in celiac crisis Rapid administration of crystalloid or colloid is crucial in the management of any of these reactions CHAPTER 95 Disorders and Diseases of the Gastrointestinal System Hemolytic Uremic Syndrome Hemolytic uremic syndrome (HUS) may occur in epidemic or sporadic forms (see Chapter 74) It is frequently preceded by enteric infection with bacterial63 or viral pathogens Infection with Shiga toxin–producing Escherichia coli precedes a high number of cases.64,65 Instigating factors, such as bacterial verotoxin, cause endothelial damage in the kidney, liver, heart, brain, adrenal glands, and gastrointestinal tract Clinical features include a prodrome of abdominal pain, vomiting, and diarrhea, which may be bloody Patients may have endoscopic, radiographic, or histologic evidence of ischemic bowel disease As gastrointestinal symptoms improve, hemolytic anemia and thrombocytopenia rapidly appear with associated symptoms of petechiae, epistaxis, gingival bleeding, and pallor Subsequently, patients become oliguric, hypertensive, and azotemic Pancreatitis may further complicate the clinical course Seizures and altered mental status may occur The intensivist caring for children with acute, hemorrhagic colitis must pay exceptional attention to fluid balance, hemogram, and renal function studies Any sudden change in hemoglobin, platelet count, blood urea nitrogen, or urine output should be considered a potential sign of HUS In the absence of hypovolemic shock, fluid intake should be curtailed if HUS is documented In the event of severe renal insufficiency, dialysis is necessary Atypical hemolytic uremic syndrome (aHUS) presents similarly to HUS, with hemolytic anemia, thrombocytopenia, and renal dysfunction, but is usually not associated with a prior bacterial infection or diarrhea In aHUS, dysregulation of the complement cascade leads to uncontrolled complement activation Patients were previously treated with plasma exchange; however, the morbidity and mortality rates remained high Eculizumab, a monoclonal antibody that targets C5 to block the complement cascade and prevent formation of the terminal complement complex, has been used in children with aHUS with better results than plasma exchange.66 Inflammatory Bowel Disease rohn disease and ulcerative colitis are chronic, relapsing disorders C 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 The latter always involves distal colon, and its contiguous inflammation extends for varying distances from the rectum The two entities are different enough to usually permit accurate categorization, but there is sufficient overlap in symptoms and distribution that the diagnosis is indeterminate in 15% of cases Table 95.1 summarizes the clinical, radiographic, endoscopic, and histologic differences between the two The cause of these disorders remains speculative Clearly, genetic factors predispose patients to one or the other, but environmental factors also appear to play a role.67 Etiologic factors considered important over the years have included psychogenic predisposition, food allergies, infectious processes, immunologic deficiency, and immunologic hyperreactivity Presenting signs and symptoms include abdominal pain; bloody or nonbloody diarrhea; anorexia; abdominal mass; and extraintestinal manifestations, such as weight loss, fever, arthritis, or erythema nodosum Patients are often anemic and hypoproteinemic, and they may show hematologic or biochemical signs of acute-phase response The radiographic and histologic features are typical (see Table 95.1) The cornerstone of achievement of remission has long been corticosteroids Enteral feedings are emerging as an important 1149 TABLE Differential Diagnosis Between Ulcerative 95.1 Colitis and Crohn Disease Feature Ulcerative Colitis Crohn Disease Relative Incidence of Symptoms Rectal bleeding (gross) Common Rare Diarrhea Often severe Moderate or even absent Pain Less frequent Almost always Anorexia Mild or moderate Can be severe Weight loss Moderate Severe Growth retardation Usually mild Often pronounced Extraintestinal manifestations Common Common Extensive — 10% Lower ileum 5%–10% 90% Colon 100% 75% Rectum 95% 50% Anus 5% 85% Distribution of lesions Continuous Segmental Radiologic features Superficial ulcers, loss of haustration, no skip areas, shortening Serpiginous ulcers, thumbprinting, skip areas, string sign Pathologic changes Diffuse mucosal disease Focal transmural disease, granulomas Involvement Small bowel involvement Response to Treatment Steroids and sulfasalazine 75% 25%–75% Parenteral nutrition and elemental diets Poor Very good for small bowel Azathioprine and 6-mercaptopurine Good in selected cases Good in selected cases Surgery Excellent Fair or poor Remissions Common Common Relapse after surgery Rare 5%–100% Cancer risk High in pancolitis Slight Course Modified from Silverman A, Roy CC, eds Pediatric Clinical Gastroenterology 3rd ed St Louis: Mosby; 1983:354 component of achieving remission.68 5-Aminosalicylic acid (5-ASA) is effective for maintenance therapy for mild ulcerative colitis and Crohn colitis Evidence is less compelling that 5-ASA is effective in small intestinal Crohn disease Immunosuppressants, such as 6-mercaptopurine (6-MP) and methotrexate, have been used for 1150 S E C T I O N X Pediatric Critical Care: Gastroenterology and Nutrition Crohn disease, and 6-MP also seems effective in the treatment of ulcerative colitis Biological agents have revolutionized the therapy of Crohn disease.69 Infliximab, a monoclonal antibody against tumor necrosis factor (TNF), has shown dramatic efficacy against Crohn disease in up to 75% of patients A second antiTNF agent, adalimumab, can be given subcutaneously New biological agents such as vedolizumab and natalizumab bind to integrin alpha beta (LPAM-1), target a different pathway and are being used when first-line biologicals fail Janus kinus (JAK) inhibitors—for example, tofacitinib—are also being developed for the management of Crohn disease and ulcerative colitis Severe complications may also be directly attributed to therapy Pancreatitis is associated with 5-ASA and 6-MP In addition, bone marrow suppression as well as hepatitis have been observed with 6-MP Infliximab is associated with lymphoid malignancies, and the concomitant use of 6-MP with infliximab may synergistically heighten the risk of lymphoma Patients who take infliximab should also be observed for possible anaphylaxis Patients with Crohn disease are at increased risk of secondary hemophagocytic lymphohistiocytosis (HLH); there is an increased risk associated with 6-MP use as well as primary Epstein-Barr virus infection.70 Patients with HLH often come to the attention of intensivists because of their high risk of infection as well as pulmonary, hematologic, and hepatic complications (see also Chapter 106) Hepatosplenic T-cell lymphoma and other nongastrointestinal malignancies have been associated with the combined use of anti–TNF-a agents and 6-MP, with males being at higher risk.71 Integrin-binding agent natalizumab has been associated with development of progressive multifocal leukoencephalopathy (PML); however, this has not been demonstrated in clinical trials for vedolizumab PML is not associated with JAK inhibitors in any trials to date Complications most likely to require an intensivist’s attention are perforation, toxic dilation of the colon, and fulminant colitis A patient whose bowel has perforated exhibits decreased bowel sounds and abdominal rigidity Point and rebound tenderness may be present Abdominal x-ray films may reveal free intraperitoneal air Most perforations in Crohn disease produce intraabdominal abscesses, but peritonitis does not Some abscesses, however, can contaminate the peritoneum Free colonic perforation tends to occur among patients with ulcerative colitis Toxic dilation and fulminant colitis are also more common with ulcerative colitis but may occasionally occur in Crohn colitis Because management of severe inflammatory bowel disease frequently includes immunosuppression with high-dose corticosteroids, cyclosporine, or azathioprine, some of the signs and symptoms of perforation may be masked in the population most likely to have such complications Factors such as patient immobility, antiperistaltic drugs, rigorous cathartic use, and electrolyte imbalance are frequently associated with toxic dilation of the colon Patients initially exhibit massive abdominal distention and pain X-ray films reveal an increased transverse colonic diameter The patient’s status is observed through careful monitoring of vital signs, physical examination, and repeated abdominal radiographs Management includes giving nothing by mouth during nasogastric tube suction and inserting a rectal tube for decompression Frequent position changes may aid in redistributing air distally Fluid and electrolyte balance is aggressively maintained, and broadspectrum parenteral antibiotics are given Efforts at medical management should not exceed a few hours because of the extreme risk of perforation Clinical decompensation or perforation is an indication for urgent surgical resection of the colon Fulminant colitis is characterized by fever, shock, severe abdominal pain, 10 or more bloody stools per day, and abdominal tenderness Broad-spectrum antibiotics, intravenous corticosteroids, immunosuppressants such as cyclosporine,72 red blood cell transfusion, and fluid replacement are the mainstays of treatment for fulminant colitis Small, uncontrolled series have also suggested that infliximab may be beneficial for fulminant colitis.73 Failure to respond within a few days, however, warrants colectomy Distal Intestinal Obstruction Syndrome Distal intestinal obstruction syndrome (DIOS) is unique to the cystic fibrosis (CF) population Affected patients present with signs of bowel obstruction, including abdominal pain, abdominal distention, and emesis DIOS is characterized by a fecal mass in the ileocecum The obstruction can be either partial or complete and the onset chronic, subacute, or acute The CF bowel is more prone to obstruction due to impaired mobility as well as abnormal composition of the intraluminal contents Patients at increased risk of DIOS include those with previous abdominal surgeries, a history of meconium ileus, pancreatic insufficiency, and having undergone lung transplant Patients with incomplete obstruction can be managed with osmotic agents such as polyethylene glycol 3350 Gastrografin can be administered orally or as an enema; however, its administration is not without risk of hypovolemic shock (due to fluid shifts) and intestinal perforation.74 Exploratory laparotomy with or without bowel resection is limited to the most severe cases; in one case series, the rate of surgical intervention was approximately 12.5%.75 Hirschsprung Disease Hirschsprung disease occurs in in 5000 live births It may be the result of incomplete craniocaudal migration of neural crest elements, but some investigators believe that ganglion cells degenerate after migration Aganglionosis may involve as little as a few centimeters or the entire colon and small bowel (in rare cases) Total colonic Hirschsprung disease occurs in clusters in some families, with the risk being 21% in those families.76 The inheritance of familial Hirschsprung disease appears to be polygenic; mutations in several loci of the rearranged during transfection (RET) protooncogene are associated with autosomal dominant Hirschsprung disease that is most commonly the short-segment type Mutations of the endothelin receptor type B gene are more likely to be observed in long-segment, autosomal recessively transmitted Hirschsprung disease Other gene mutations may also modify the expression of the disease.76 The most common feature of Hirschsprung disease is the failure to pass meconium in a timely fashion after birth; 94% of infants with Hirschsprung disease pass their first stool beyond 24 hours of life Most patients with Hirschsprung disease are constipated but cannot pass flatus If their condition is undiagnosed during the first months of life, they may fail to thrive Physical findings include abdominal distention and an empty rectum on digital examination Barium enema often reveals a narrow-caliber aganglionic distal colon; a transition zone; and a dilated, ganglionic proximal colon It is essential that the barium enema be performed without prior enema preparation to preserve the transition zone Absence of the anal-inhibitory reflex on anorectal manometry is suggestive The diagnosis is confirmed histologically by rectal biopsy of the distal rectal mucosa where hypertrophic nerve trunks but no ganglion cells are found Acetylcholinesterase staining of the specimen improves the diagnostic yield by enhancement of the abnormal nerve trunks CHAPTER 95 Disorders and Diseases of the Gastrointestinal System In some children, the course of Hirschsprung disease is punctuated by episodic, severe enterocolitis, which leads to copious, bloody diarrhea, fever, and shock The intensive care of patients with enterocolitis should emphasize reconstitution of circulating blood volume with crystalloid, colloid, and red blood cells Broad-spectrum parenteral antibiotics are advisable After the patient’s condition is stabilized, urgent decompressive enterostomy is indicated Pull-through operations are usually performed after several months Enterocolitis in the remaining ganglionated intestine may occur even in some patients who have undergone a pull-through operation.77 Acute Colonic Pseudo-obstruction First described by Ogilivie et al.,77a acute colonic pseudo-obstruction is occasionally observed among critically ill adults and children who are immobilized in an ICU setting It is characterized by massive cecal dilation of to 10 cm on abdominal plain film The mechanism is uncertain, but it appears to occur among patients given neuromuscular blockade and antimotility drugs, such as narcotics If left untreated, it may result in colonic perforation at the cecal level Therapy should involve decompression of the gastrointestinal tract by nasogastric and rectal intubation and suction Placing the patient in the prone position also seems to be effective initial therapy None of these measures, though, seems to be as effective as parenteral administration of neostigmine.78 Adverse effects of neostigmine, such as excessive salivation or abdominal cramping, are self-limiting, but bradycardia that occasionally occurs must be managed with atropine The critical care physician must be mindful of starting an early and aggressive bowel regimen for patients receiving narcotics, whether as intermittent doses in the awake patient or as continuous infusions in the sedated patient Use of nonnarcotic analgesics, such as intravenous acetaminophen or ketorolac (when appropriate), can help to reduce the incidence of opioid-induced constipation Furthermore, methylnaltrexone and naloxegol (both opioid antagonists) have now been developed for the treatment of opioid-induced constipation and have been used in the pediatric population, although neither has yet been US Food and Drug Administration approved in children.79,80 Abdominal Compartment Syndrome Abdominal compartment syndrome (ACS) is defined as organ dysfunction caused by intraabdominal hypertension The organ dysfunction observed with abdominal compartment syndrome may go underrecognized because it affects patients who are critically ill and their organ dysfunction may erroneously be ascribed to their underlying illness If untreated, ACS can lead to progressive organ failure and death; timely recognition and intervention can be lifesaving The standard method for measuring intraabdominal pressure is through the assessment of urinary bladder pressure A three-way stopcock is placed between the catheter and pressure tubing The bladder is emptied Sterile isotonic saline is injected in the distal stopcock and into the bladder to allow for a continuous fluid column There is some variability in the amount of fluid administered based on tubing and patient size The pressure transducer is zeroed at the level of the midaxillary line, and the pressure is measured at end expiration while the patient is completely supine For the most accurate measurement, the patient should also be muscle-relaxed if the clinical scenario allows Intraabdominal hypertension (IAH) and ACS are distinct clinical entities Intraabdominal pressure is a steady pressure 1151 within the abdominal cavity The normal range is variable based on individual patient differences Much of the variability is due to the body habitus of the patient In children, IAH is defined as a sustained pressure of 10 mm Hg or greater.81 ACS is defined as sustained pressure greater than 10 mm Hg associated with organ dysfunction Although recording of pressure is important for research purposes, the clinical presentation is the most important component in defining ACS ACS can be classified as primary or secondary Primary ACS is due to injury or disease in the abdominal region, such as trauma or organ transplantation, and often requires early surgical decompression Secondary ACS is due to conditions requiring extensive fluid resuscitation, such as sepsis, burns, or other capillary leak syndromes IAH can impair practically every organ system and result in ACS It can impair cardiac function by reducing venous return as well as impairing cardiac function directly via diaphragmatic pressure In mechanically ventilated patients, peak inspiratory and mean airway pressures will be significantly increased, resulting in pulmonary barotrauma In addition, chest wall compliance is markedly reduced Renal impairment may be attributed to several mechanisms in patients with ACS Venous drainage can be impaired by renal vein compression The subsequent cardiac output fall can lead to renal artery vasoconstriction via the reninangiotensin systems The urine sodium and chloride concentrations will typically be decreased, whereas the renin, aldosterone, and antidiuretic hormone may be markedly increased.82,83 The organ most sensitive to changes in intraabdominal pressure is the gut Both human and animal studies have shown decreased intestinal mucosal perfusion at intraabdominal pressures of 20 mm Hg Impaired mesenteric venous drainage results in intestinal edema, which can increase intraabdominal pressure and result in progressive hypoperfusion and possible bowel ischemia.84 Finally, intracranial pressure can be elevated, leading to a decrease in cerebral perfusion.85 The management of IAH and ACS requires both supportive care and, in some instances, surgical decompression In general, surgical decompression is indicated for ACS There is increasing evidence that surgical decompression prior to the development of ACS may be beneficial.86 Following decompression, the abdomen is left open and may be covered with a negative pressure dressing or prosthetic mesh.87 Early recognition and timing of decompression of ACS may be crucial in the preservation of organ function Acute and Chronic Pancreatitis Even though gallstone pancreatitis and ethanolic pancreatitis are uncommon in children, numerous structural, toxic metabolic, and infectious diseases are associated with acute childhood pancreatitis Appropriate radiographic or biochemical evaluation for pancreatitis should be performed on all children admitted to the ICU with acute abdomen Acute pancreatitis is preceded by intrapancreatic activation of proteases The triggering mechanism remains obscure, but once protease inhibitors are overcome and trypsinogen is converted to trypsin, a cascade of steps produces active proteases, lipase, and amylase The enzymes induce local and distant organ damage, which includes edema, increased vascular permeability, cytolysis, and fat necrosis The clinical hallmark of acute pancreatitis is severe, boring epigastric or left upper quadrant pain that radiates through to the back Serum amylase and lipase levels are greatly elevated, and radiographic imaging studies reveal pancreatic enlargement, 1152 S E C T I O N X Pediatric Critical Care: Gastroenterology and Nutrition sonolucency, or irregularity of the margin Ultrasonography is a satisfactory screening technique, but CT scanning should be used when the course is severe If CT scanning is performed with a dynamic, contrast-enhanced technique, interstitial pancreatitis can be differentiated from the more ominous necrotic pancreatitis, which often requires surgical debridement Because serum lipase is almost exclusively pancreatic in origin and amylase derives from a number of organs, the serum lipase concentration may be a better indicator of pancreatitis Use of both measures to follow the course of pancreatitis is preferable to using either one alone Several nonspecific laboratory derangements—such as anemia, hypoglycemia, hypocalcemia, and hypoproteinemia—may occur Intensive support may be required for severe acute attacks Severe hemorrhagic necrosis of the pancreas carries a poor prognosis Extraordinarily large third-space fluid and electrolyte losses must be replaced If significant hyperglycemia occurs, insulin must be given Calcium infusions may also be necessary Physicians should be able to minimize pancreatic stimulation by giving the patient nothing by mouth and using nasogastric suction, although the efficacy of suction has been questioned for patients without ileus Use of protease inhibitors, H2 antagonists, somatostatin, 5-fluorouracil, and glucagon has not found much support in the literature Antibiotics are not indicated unless an abscess is suspected Several complications may be catastrophic Rupture of a pancreatic duct or leakage of a pseudocyst must be suspected if ascites develops Gastrointestinal hemorrhage during pancreatitis may originate from a variety of sources Discovery of gastric varices suggests splenic vein thrombosis Gastritis may also appear Pseudoaneurysms of the hepatic or splenic artery may bleed into the pancreas Small bowel or colonic ischemia caused by fat necrosis may produce gastrointestinal hemorrhage Infected pancreatic necrosis is uniformly fatal unless the patient undergoes an emergency operation to debride the necrotic tissue Time to recovery from pancreatitis is variable and may be prolonged (weeks to months) Early enteral feeding is the preferred route of nutrition for patients with pancreatitis.88 Protease inhibitors, free-radical scavengers, and other antiinflammatory agents have all been employed in the treatment of acute pancreatitis, with disappointing results.89 Acute recurrent and chronic pancreatitis in children are frequently secondary to genetic conditions Similar to acute pancreatitis, acute recurrent and chronic pancreatitis can be complicated by pseudocyst, splenic vein thrombosis, pseudoaneurysm, and obstruction Treatment to relieve obstruction includes endoscopic retrograde cholangiopancreatography or pancreatic drainage procedures If chronic pain and pancreatic endocrine and exocrine dysfunction persist, total pancreatectomy with islet cell autotransplantation can be an effective therapeutic intervention for selected patients These patients are managed postoperatively in the ICU with insulin infusions to maintain glycemic control.90 Acute and Chronic Liver Failure Acute liver failure is considered in detail in Chapter 97 The term liver failure refers to the constellation of symptoms, signs, and biochemical aberrations that appear when hepatic synthetic capacity is severely compromised Liver failure is categorized as fulminant when encephalopathy appears within the first months of the illness, as late onset when it appears within months, and as chronic when it appears beyond the sixth month of liver dysfunction Infectious, metabolic, and toxic liver diseases, elevated right-sided cardiac pressures following a Fontan procedure, and biliary obstruction may all lead to liver failure (eTable 95.2) Obviously, it is advisable to establish a cause of liver disease before the onset of liver failure It is beyond the scope of this chapter to outline a diagnostic approach to childhood liver disease, but several reviews are available (see also Chapter 97).91,92 Elucidating the cause of fulminant hepatic failure is often made more difficult by the rapid development of coagulopathy and ascites, which preclude percutaneous liver biopsy Laparotomy with surgical wedge biopsy may be necessary Transjugular liver biopsy is also an option A core of liver tissue is obtained by passing the biopsy forceps retrograde through the superior vena cava and hepatic vein after introduction via the jugular vein The biopsy site then bleeds directly into the liver parenchyma, minimizing extravasation Hepatic encephalopathy is more difficult to diagnose in young children than in adults, as an infant may first present with simply increased fussiness Progressive hepatic encephalopathy culminates in coma When patients have entered coma, CNS resuscitation becomes necessary Patients should undergo elective endotracheal intubation; administration of benzodiazepines should be avoided Beyond CNS metabolic derangements, cytotoxic cerebral edema often complicates hepatic failure Placement of an intracranial monitoring device should be contemplated; the risk of instrumentation in patients with coagulopathy should be weighed against the benefit of continuous CNS pressure monitoring.93 The non-CNS manifestations of liver failure are protean Hepatosplenomegaly is common in the early stages of fulminant failure, but the liver may shrink rapidly In end-stage liver disease caused by cirrhosis, the liver is shrunken, firm, and nodular Most patients with liver failure have jaundice Spider angiomas, palmar erythema, ascites, and peripheral edema are common features of chronic liver disease Fetor hepaticus (mercaptan breath) may be present The biochemical features of liver failure are variable depending on its cause, duration, and severity Hypoglycemia should be corrected when present Serum bilirubin levels may be elevated or normal Liver aminotransferase concentrations are increased in acute liver disease but decrease as hepatocytes are lost Therefore, they may be only mildly elevated or normal in cirrhosis and in the terminal stages of failure Decreasing aminotransferase levels and albumin in the face of rising bilirubin, prothrombin time, and partial thromboplastin time denote a failing liver Serum globulin and ammonia levels are usually elevated The serum aminogram reveals an elevated aromatic/branched-chain amino acid ratio Renal insufficiency may appear because of perennial azotemia, acute tubular necrosis, or hepatorenal syndrome (HRS).94 Patients with both acute and chronic liver failure frequently develop renal failure HRS is the most common cause of acute renal failure in this population From 40% to 80% of patients with hepatic failure develop HRS The onset often occurs following an acute change in intravascular volume The development of HRS is precipitated commonly by hemorrhage, excessive diuresis, or sepsis HRS is a diagnosis of exclusion once other causes of renal failure and absent diuretic response are further explored Although certain clinical characteristics may or may not exist in the description of HRS, almost all patients have hyponatremia prior to the development of renal insufficiency.95 The treatment is nonspecific but includes volume administration and maintenance of adequate systemic perfusion This is achieved by overcoming the splanchnic vasodilation and increasing renal perfusion and filtration.96 Patients with late-onset or chronic liver failure are likely to have portal hypertension Ascites may develop as plasma oncotic ... failure is categorized as fulminant when encephalopathy appears within the first months of the illness, as late onset when it appears within months, and as chronic when it appears beyond the sixth... been associated with development of progressive multifocal leukoencephalopathy (PML); however, this has not been demonstrated in clinical trials for vedolizumab PML is not associated with JAK... disease frequently includes immunosuppression with high-dose corticosteroids, cyclosporine, or azathioprine, some of the signs and symptoms of perforation may be masked in the population most likely