e3 94 Gines P, Guevara M, Arroyo V, Rodes J Hepatorenal syndrome Lancet 2003;362 1819 1827 95 Meltzer J, Brentjens TE Renal failure in patients with cirrhosis hepatorenal syndrome and renal support st[.]
e3 94 Gines P, Guevara M, Arroyo V, Rodes J Hepatorenal syndrome Lancet 2003;362:1819-1827 95 Meltzer J, Brentjens TE Renal failure in patients with cirrhosis: hepatorenal syndrome and renal support strategies Curr Opin Anaesthesiol 2010;23:139-144 96 Arroyo V, Bernardi M, Epstein M, et al Pathophysiology of ascites and functional renal failure in cirrhosis J Hepatol 1988;6:239-257 97 Moller S, Henrickson JH Cardiovascular complications of cirrhosis Gut 2008;57:268-278 98 Thanlheimer U, Triantos CK, Samonakis DN, Patch D, Burroughs AK Infection, coagulation, and variceal bleeding in cirrhosis Gut 2005;54:556-563 99 Singer AL, Olthoff KM, Kim H Role of plasmapheresis in the management of acute hepatic failure in children Ann Surg 2001;234:418-424 100 Brown JB, Emerick KM, Brown DL Recombinant factor VIIa improves coagulopathy caused by liver failure J Pediatr Gastroenterol Nutr 2003;37:268-272 101 Northrup P, Reutemamn B Management of coagulation and anticoagulation in liver transplantation candidates Liver Transpl 2018;24;1119-1132 102 Hall RJ, Lilly JR, Stiegmann GV Endoscopic esophageal varix ligation: technique and preliminary results in children J Pediatr Surg 1988;23:1222-1223 103 Gordon JD, Colapinto RF, Abecassis M, et al Transjugular intrahepatic portosystemic shunt: a nonoperative approach to lifethreatening variceal bleeding Can J Surg 1987;30:45-49 104 Schaefer B, Schmitt CP The role of molecular adsorbent recirculating system dialysis for extracorporeal liver support in children Pediatr Nephrol 2013;28:1763-1769 105 Kim JJ, Marks SD Long-term outcomes of children after solid organ transplantation Clinics (Sao Paulo) 2014;69(suppl 1): 28-38 e4 Abstract: It is important for any clinician functioning in the critical care environment to exercise appropriate diagnostic skills when faced with a critically ill patient with gastrointestinal symptoms Those skills include employing careful physical diagnostic techniques as well as capably choosing the most useful radiographic, endoscopic, hematologic, and biochemical tests When a gastroenterologic diagnosis is established, it is also important to understand basic principles of physiology and pathophysiology of luminal, hepatic, and pancreatic disease This chapter is an overview of luminal disorders involving all portions of the gastrointestinal tract, from esophagus to anus as well as disorders of the pancreas and liver While the chapter does not describe gastrointestinal disorders in great depth, it does provide a schema for diagnosis and treatment of those disorders Key Words: Central line–associated bloodstream infections, drool procedure, low cardiac output syndrome, abdominal compartment syndrome, chronic pancreatitis, hepatopulmonary syndrome, portopulmonary hypertension, cirrhotic cardiomyopathy 96 Acute Liver Failure HE NGQI (BETTY) ZHENG, MIHAELA A DAMIAN, AND SIMON HORSLEN PEARLS • • • Pediatric acute liver failure represents a large number of heterogenous etiologies Effective diagnosis requires a systemic approach; however, despite thorough workup, in a large proportion of cases, cause cannot be determined at present Prognostication is remarkably difficult in that spontaneous recovery has occurred even in patients with advanced hepatic necrosis, deep coma, and severe coagulopathy Prognostic tools Pediatric acute liver failure (PALF) is a life-threatening condition in which previously healthy children lose hepatic function rapidly, requiring immediate medical attention.1 It is a rare entity in pediatric intensive care unit (PICU) settings, but expertise is crucial to achieving optimal outcomes Management consists of supportive measures, with a focus on anticipation, prevention, and treatment of complications along with early consideration for liver transplantation.2–6 Timely intervention to treat the metabolic derangements associated with acute liver failure (ALF) is pivotal and can help mitigate the morbidity associated with this condition.7–12 This chapter focuses on acute liver injury; it does not detail the management of end-stage and life-threatening complications of chronic liver disease Acute Liver Failure Background, Definitions, Etiology, Outcomes Liver failure is defined as the loss of normal liver function that includes synthesis of serum proteins, including clotting factors and albumin; metabolism and storage of glucose and fatty acids; and detoxification and excretion of exogenous and endogenous molecules, such as drugs and products of protein metabolism, most notably ammonia Evidence of liver failure is reflected in elevations of prothrombin time, bilirubin, and ammonia In the United States, the incidence of PALF has been estimated at 17 cases per 100,000 per year.13 Diagnosis of hepatic encephalopathy (HE) in children is challenging, as it might be present only in very late stages of the disease This makes the definition of adult acute or fulminant liver failure, which includes the onset of HE within weeks of the first signs of liver disease, to be difficult to apply to infants and • • have been designed, but all have been found to be fallible and clinical experience is invaluable Orthotopic liver transplantation is lifesaving, and early transfer to an experienced liver transplant center is advisable for all children with coagulopathy secondary to acute liver disease Oversedation is to be avoided because it increases the risk of complications and prolongs stay in the intensive care unit and total length of hospital stay after liver transplantation children Subacute liver failure has been defined as the development of HE after weeks and before 24 weeks from the onset of liver disease in the absence of preexisting chronic liver disorders Etiologies PALF is a heterogeneous condition, with a broad range of etiologies It is age dependent, including infections, toxin- and drugrelated injuries; metabolic disorders; and immunologic, ischemic, and irradiation damage Despite the many known causes of PALF, a specific etiology is not determined in up to 50% of cases,1,14–17 accounting for 40% of PALF among patients younger than age years and 60% in those age years and older.18 The large number of indeterminate causes is due to several factors, including hepatic improvement prior to finishing clinical workup, lack of current available testing for all etiologies, or lack of a thorough workup The term indeterminate etiology should prompt further investigation Liver biopsy is indicated, as it can further help with diagnosis and treatment Liver biopsy can be performed safely via transjugular or percutaneous approach,19 but the risk of bleeding should be evaluated case by case Of the known etiologies, severe viral hepatitis—especially due to enteroviruses, adenovirus, and herpesvirus—may occur in the neonatal population Infantile causes of ALF also include gestational autoimmune liver disease (GALD), inborn errors of metabolism, and hemophagocytic lymphohistiocytosis (HLH) HLH is a challenging diagnosis, as it can present at any age with PALF, and correct diagnosis is very important due to specific treatment (see also Chapter 106) Acute hepatitis A and B infections are rare causes of PALF in North America but are a common cause of PALF in school-aged children in developing countries.20 Drug-induced liver disease is more common in older children, 1155 1156 S E C T I O N X Pediatric Critical Care: Gastroenterology and Nutrition • BOX 96.1 Intensive Care Unit Management No Sedation Except for Procedures Lines and Tubes • • • • • Multilumen central venous catheter Arterial tube Nasogastric tube Urinary Foley catheter Bed scale Monitor • • • • • • • • • Heart and respiratory rate Arterial BP, CVP Core/toe temperature Neurologic function Gastric pH (.5) Blood glucose (.4 mmol/L) Acid-base Electrolytes PT, PTT Fluid Balance • 75%–95% maintenance • Dextrose 10%–25% • Sodium (2–3 mEq/kg/day) Maintain Circulating Volume With Colloid/FFP Coagulation Support Only if Required Drugs • • • • • • • Vitamin K H2 antagonist Antacids Lactulose N-acetylcysteine for acetaminophen toxicity Broad-spectrum antibiotics Antifungals Nutrition • Enteral feeding (1–2 g protein/kg/day) • PN if ventilated BP, Blood pressure; CVP, central venous pressure; FFP, fresh frozen plasma; PN, parenteral nutrition; PT, prothrombin time; PTT, partial thromboplastin time especially secondary to intentional acetaminophen overdose18 (Box 96.1) To determine outcomes, investigate prognostic factors, and further decipher etiologies, the Pediatric Acute Liver Failure Study Group (PALF-SG)—involving 24 pediatric liver centers in the United States, Canada, and the United Kingdom—formed in 1999 The study’s entry criteria include evidence of hepatic injury without known chronic liver disease manifesting as an international normalized ratio (INR) of 1.5 and encephalopathy or INR of 2.0 with or without encephalopathy.18 The group has reported data on 348 subjects over a 6-year period and concluded that survival and the need for liver transplantation depend on age and diagnosis.18 For established PALF etiologies, liver transplantation is necessary in 20% to 33%18 of cases versus 46% in indeterminate cases,18 whereas spontaneous recovery ranged from 46% to 60% depending on diagnosis and age categories.18 Prognostic Assessment Several attempts to produce prognostic tools based on a snapshot of clinically available data either at presentation or at peak values have been attempted, but all have been found wanting Three of the more often quoted include the King’s College Hospital Criteria (KCHC), the liver injury unit (LIU) score, and the Clichy criteria The Clichy criteria are primarily derived from adult patients with acute hepatitis B infection; thus, its utility in the pediatric population has always been in doubt.21 The KCHC applied to the PALF-SG cohort fails to reliably identify those patients at risk of death.18 The LIU score predicted those who eventually underwent transplantation but was not a reliable predictor of death.22 This is not particularly surprising, as the LIU calculation is based on levels of bilirubin, ammonia, and prothrombin time (PT), all of which are used clinically to determine who might benefit from transplantation and, as such, were self-fulfilling predictors.22 All of these tools suffer from the fact that no account is taken for the dynamic nature of PALF Further work would benefit from examining the trends over time rather than data at a single time point.23,24 Diagnosis and Workup The care team should obtain a full history, including information about infectious illnesses, behavior changes, the time course of the development of jaundice, and foreign travel It is important to establish what medications the child has taken, including overthe-counter preparations, acne medications, folk remedies, and herbal supplements, as well as determining what other medications might be in the household.25 In adolescents, inquiries should be made about the use of illicit drugs, potential for selfharm, and sexual contact Acute hepatic dysfunction often first manifests as jaundice and general malaise Hepatomegaly may be present, but the liver edge is frequently soft and difficult to palpate Splenomegaly is unusual, and its presence may point to a metabolic or hematologic diagnosis Petechiae or ecchymoses can be associated with coagulopathy The patient’s level of consciousness and degree of HE (Box 96.2) should be established using a reliable scale,15,26,27 and a complete central nervous system examination should be performed, including examination of reflexes and mental status Parental help in the assessment of mental status is perhaps one of the best indicators of deviation from baseline neurologic status Serial neurologic examinations should be conducted once the baseline is established to identify any progression of encephalopathy as there is significant risk for increased intracranial pressure (ICP) and herniation due to cerebral edema or intracranial bleeding The presence of moderate to severe impaired central nervous system function or rapid neurologic deterioration in the setting of acute liver disease should be an indication for admission to the PICU Work of breathing should be assessed and assisted with positive pressure or mechanical ventilation if needed to ensure adequate ventilation and oxygenation Monitoring of and, if necessary, intervention for glycemic control, acid–base balance, and adequate tissue perfusion should be included in the care plan Antibiotics and antiviral medications should be started if an infectious cause is suspected Once in the PICU, a central venous catheter should be placed for administration of medication and intravenous fluids, including parenteral nutrition and high glucose infusion rate, as well as for hemodynamic monitoring and frequent blood draws An arterial line should be considered for patients with clinical deterioration or with HE.13 Urinary catheter placement can also be considered to ensure accurate fluid balance estimation and assessment of kidney function (Table 96.1) CHAPTER 96 Acute Liver Failure A basic workup for PALF with investigations reflecting agedependent etiologies is suggested in Box 96.3 Initial monitoring of blood work should include complete blood count, blood gases, lactate levels, glucose, electrolytes, aminotransferases, PT/INR, creatinine, bilirubin, and ammonia Monitoring blood work should be repeated every to 12 hours until the clinical course is determined If the patient may require liver transplantation, a • BOX 96.2 Causes of Pediatric Acute Liver Failure Viral Immune Hepatitis A cytomegalovirus Hepatitis B paramyxovirus Hepatitis D adenovirus Hepatitis E enterovirus Herpes simplex virus Parvovirus B19 Varicella zoster virus Severe acute respiratory syndrome Epstein-Barr virus Hemorrhagic fever virus Autoimmune hepatitis Hemophagocytic lymphohistiocytosis Neonatal hemochromatosis Autoimmune hemolytic anemia with giant cell hepatitis Bacterial Budd-Chiari postcardiac surgery Venoocclusive disease Liver trauma Ischemic hepatitis/shock liver Septicemia Bartonella Leptospirosis Rocky Mountain spotted fever Salmonella typhi/paratyphi Metabolic Hereditary fructose intolerance Carnitine defects Urea cycle disorders Wilson disease Organic acidemias Tyrosinemia type Fatty acid oxidation defects Niemann-Pick type C Mitochondrial disorders Acute fatty liver of pregnancy Toxic Drugs/toxins/herbal Amanita phalloides Vascular Neoplastic Leukemia Lymphoma Hepatocellular carcinoma Other Reye syndrome Massive liver resection Hypothermia Sickle cell anemia Heat stroke 1157 referral to a pediatric liver transplant center should be initiated in a timely manner, prior to clinical decompensation Families of children with PALF sometimes require a considerable amount of psychologic support and counseling The best approach to management of PALF is as a team, with collaboration among specialists in hepatology, critical care medicine, transplant surgery, and early consultation by other specialties, such as biochemical genetics, neurology, neurosurgery, and nephrology as appropriate Specific Treatments for Particular Causes of Pediatric Acute Liver Failure Acetaminophen Toxicity Acute acetaminophen overdose was noted in 14% of all children from the PALF-SG as the most common identifiable cause of PALF in children age years and older.18 Two clinical presentations were identified: acute intentional ingestion and a therapeutic misadventure, which refers to the ingestion of multiple doses exceeding daily total recommended dosing taken over a period of time to treat clinical symptoms.1 The potential severity of hepatic damage can be assessed using the Rumack-Matthew nomogram and serum acetaminophen concentration Administration of intravenous N-acetylcysteine (NAC) should not be delayed if there is reason to suspect significant hepatic injury from the ingestion (see also Chapter 126) Supportive medical treatment is necessary and the majority of patients will recover over time, with few of the adults and teenagers progressing to ALF needing liver transplantation.18 Amanita Poisoning Amatoxin is a hepatotoxin found in wild mushrooms, particularly the Amanita and Galerina species, although the majority of significant poisonings are due to the ingestion of Amanita phalloides, the death cap mushroom Once ingested, amatoxin binds to deoxyribonucleic acid (DNA)–dependent ribonucleic acid polymerase type II and decreases intracellular protein synthesis, leading to hepatocyte apoptosis.28,29 Prompt gastrointestinal decontamination with activated charcoal and supportive management with fluids should be initiated, ideally within 24 hours of ingestion High-dose penicillin G can disrupt hepatocellular uptake of TABLE Clinical Stages of Hepatic Encephalopathy 96.1 Stage Asterixis EEG Changes Clinical Manifestations None None Normal I (prodrome) Slight Infant/child: Difficult or impossible to test adequately Adult: Normal or diffuse slowing to theta rhythm, triphasic waves Infant/child: Inconsolable crying, child not acting like self to parents Adult: Mild intellectual impairment, disturbed sleep-wake cycle II (impending) Easily elicited Infant/child: Difficult or impossible to test adequately Adult: Generalized slowing, triphasic waves Infant/child: Inconsolable crying, child Adult: Drowsiness, confusion, coma/inappropriate behavior, disorientation, mood swings III (stupor) Present if patient cooperative Infant/child: Difficult or impossible to test adequately Adult: Grossly abnormal slowing of rhythm, triphasic waves Infant/child/adult: Drowsy, unresponsive to verbal commands, markedly confused, stupor, combative, hyperreflexia, positive Babinski sign IV (coma) Usually absent Infant/child/adult: Appearance of delta waves, decreased amplitudes Infant/child/adult: Unconscious, decerebrate, or decorticate response to pain present (stage IVA) or absent (stage IVB) EEG, Electroencephalography ... acute liver failure (ALF) is pivotal and can help mitigate the morbidity associated with this condition.7–12 This chapter focuses on acute liver injury; it does not detail the management of end-stage... present only in very late stages of the disease This makes the definition of adult acute or fulminant liver failure, which includes the onset of HE within weeks of the first signs of liver disease,... basic principles of physiology and pathophysiology of luminal, hepatic, and pancreatic disease This chapter is an overview of luminal disorders involving all portions of the gastrointestinal