Intensive Management of Hepatic Failure Mary E. Rinella, M.D.1 and Arun Sanyal, M.D.2 ABSTRACT A substantial number of patients with liver failure are admitted to the intensive care unit; thus a thorough understanding of the prevention and treatment of complications in such patients is imperative. The management of liver failure is demanding and often involves the combined efforts of many specialists. Critically ill patients with hepatic failure encompass a broad spectrum of disease, ranging from acute liver failure in a patient with no prior history of liver disease, to acute on chronic liver failure. The initial assessment and management of acute liver failure are reviewed with an emphasis on the prevention and treatment of brain edema in the pretransplant setting. The current treatment of compli- cations resulting from decompensated chronic liver disease such as portal hypertensive bleeding; infection, renal failure, and hepatic encephalopathy are then discussed. KEYWORDS: Liver failure, cerebral edema, portal hypertension, management The management of liver failure is demanding plantation. Although ALF remains one of the most acute and often involves the combined efforts of many special- serious illnesses, thoughtful intensive management can ists. Critically ill patients with hepatic failure encompass optimize the patient’s chances for spontaneous hepatic a broad spectrum of disease, ranging from acute liver regeneration or a successful liver transplant.3 When failure in a patient with no prior history of liver disease, possible, etiology-targeted therapy should be initiated to end-stage decompensated cirrhosis. Both sides of this (Table 1). The goal of management should be focused spectrum present clinical challenges that involve many on the prevention of systemic infection, multiorgan fail- organ systems. Although both sides in acute and chronic ure, hepatic encephalopathy (HE), and ultimately the liver failure can have a poor prognosis, careful and development of brain edema.4–6 At this time liver trans- comprehensive intensive care can improve outcome and plantation is the only definitive therapy for those who bridge eligible patients to liver transplantation. Because fulfill criteria for poor prognosis7–9 (Table 2). The acute and chronic liver failure are very distinct clinical challenge to the clinician is selection of patients for entities, they will be discussed separately. transplant that have low likelihood of spontaneous sur- vival but are not too ill to benefit from transplantation. The principles of management of ALF are reviewed here: ACUTE LIVER FAILURE Acute liver failure (ALF) is a rapidly progressive, often fatal syndrome characterized by jaundice, encephalop- athy, and coagulopathy leading to multiorgan failure in a INITIAL EVALUATION AND MANAGEMENT patient with no prior history of liver disease.1,2 In recent Early diagnosis and identification of the subject that is years, advancements in supportive care have improved unlikely to improve spontaneously constitute a critical survival and provided a more effective bridge to trans- first step in the management of ALF. The initial triage 1Division of Hepatology, Northwestern University, Chicago, Illinois; Non-pulmonary Critical Care: Managing Multisystem Critical Ill- 2Division of Gastroenterology, Department of Internal Medicine, ness;GuestEditor,CurtisN.Sessler,M.D. Virginia Commonwealth University, Richmond, Virginia. Semin Respir Crit Care Med 2006;27:241–261. Copyright # 2006 Address for correspondence and reprint requests: Arun Sanyal, by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, M.D., Division of Gastroenterology, Department of Internal Med- NY 10001, USA. Tel: +1(212) 584-4662. icine, Virginia Commonwealth University, MCV Box 980341, DOI 10.1055/s-2006-945528. ISSN 1069-3424. Richmond, VA 23298-0341. E-mail: [email protected]. 241 242 SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE/VOLUME 27, NUMBER 3 2006 Table 1 Etiology-Targeted Therapy and an accurate history cannot be overemphasized be- Etiology Potential Therapies cause both treatment and prognosis are significantly affected by the underlying etiology. A detailed account TOXIC of the psychiatric history, including suicidal ideation Acetaminophen N-acetyl cysteine and family support, is essential to assess suitability Amanita poisoning Penicillin and silibinin for transplantation. The timing of the psychiatric evalua- VIRAL tion is of particular importance, given the rapid deterio- Herpes simplex virus Acyclovir ration in mental status that occurs in such patients. Acute heptatitis B Antivirals? METABOLIC Wilson’s disease Transplant DISEASE-TARGETED THERAPY Autoimmune hepatitis Corticosteroids A thorough discussion of the differential diagnosis of VASCULAR ALF is beyond the scope of this review; however, Acute Budd-Chiari syndrome Directed thrombolysis, Table 1 provides a summary of common etiologies of transjugular intrahepatic ALF for which potential therapies exist. Only acetami- portosystemic shunt nophen will be discussed in more detail because it is the PREGNANCY most common etiology of liver failure in the United Acute fatty liver of Urgent delivery States and has an effective antidote. pregnancy/HELLP HELLP, hemolysis elevated liver enzymes low platelets. Acetaminophen of a patient with acute liver injury to an intensive care Idiopathic and drug-related liver injuries are the most unit (ICU) is based on the presence of altered mental common causes of ALF in the United States.10 Of the status and the degree of coagulopathy. It is imperative drug-related causes, acetaminophen overdose is the most toadmitmostsubjectswithacuteliverinjurywithan common cause of ALF in the United Kingdom and international normalized ratio (INR) > 1.5 and all United States. Overdose can be either intentional or subjects with mental status changes. Rapid deteriora- unintentional.11–13 The patient, family, and close contacts tion can occur and is often irreversible in the patient must be questioned about regular alcohol use, dieting, diet with ALF. It is therefore imperative that decisions pills, medications, or recent illness that may have resulted regarding prognosis and appropriateness for liver trans- in poor nutrition. These factors greatly affect toxicity plant be made early, and potentially suitable patients either through upregulating cytochrome p450 (alcohol should be referred to a liver transplant center early in and other drugs) promoting the formation of toxic inter- the evaluation process. mediates, or through glutathione depletion. Such details The management of patients in liver failure are important because as little as 2.6 to 4.0 g of acetami- requires a multidisciplinary approach involving hepatol- nophen can lead to liver failure in this setting.14–17 ogists, transplant surgeons, intensivists, and other sub- It is worth noting that, at the time of presenta- specialists. The importance of a thorough physical exam tion, a patient with acetaminophen-induced liver failure may have undetectable blood levels of acetaminophen. Table 2 King’s College Criteria for Acute Liver Failure This is particularly true when the toxicity manifests itself Acetaminophen induced several days after ingestion of acetaminophen for ther- apeutic purposes in a susceptible subject. However, in Arterial blood pH < 7.3 (regardless of degree of the majority of cases, detectable acetaminophen levels encephalopathy) are present at the time of presentation. When acetami- If no acidosis then all three of the below criteria: nophen overdose is confirmed, N-acetylcysteine (NAC) Prothrombin time > 100 seconds must be initiated in a timely manner, ideally within Serum Creatinine > 2.5 mg/dL 16 hours of ingestion, to have a significant impact on Grade 3 or 4 encephalopathy Nonacetaminophen induced survival. NAC decreases injury through enhancement of glutathione synthesis resulting in less formation of Prothrombin time > 100 seconds acetaminophen’s hepatotoxic intermediate.18,19 Even if If prothrombin time < 100 seconds, then any of the below the patient is delayed in reaching the hospital or the criteria (regardless of degree of encephalopathy): diagnosis is not forthcoming, there is evidence that late Drug-induced, non-A, non-B, halothane hepatitis administration of NAC can be beneficial.20 NAC may Time from jaundice to encephalopathy > 7 days also improve outcome through its effects on micro- Age < 10 or > 40 years circulatory function. A large multicenter study (the Prothrombin > 50 seconds ALF study group) is currently addressing the utility of Bilirubin > 17.5 mg/dL NAC in nonacetaminophen-induced ALF. INTENSIVE MANAGEMENT OF HEPATIC FAILURE/RINELLA, SANYAL 243 Table 3 Acute Liver Failure: General Management Guidelines On Admission Daily Tid Hourly If Indicated Monitoring IV access, CVP and arterial Blood sugar Mental status Mechanical intubation, line, Foley catheter ICP monitoring Thorough history Interview family members and physical Laboratories Liver panel, renal panel, Basic laboratories, AFP, Blood gas Changes in CBC, PT, Hep A,B,C arterial ammonia ICP monitor serologies, HSV, CMV, (or more if mental EBV, ceruloplasmin, ANA, status deteriorating anti-sm Ab, SPEP, phosphate, HIV, acetaminophen factor V level level, toxicology screen, cosyntropin stimulation test, TSH, blood type, blood cultures Imaging US with Doppler Head CT for neurological changes or suspected edema Directed therapy where indicated Drugs, cooling for cerebral edema AFP, alpha feta protein; ANA, antinuclear antibody; anti-sm