CTP, Child-Turcotte-Pugh; CVP, central venous pressure; HE, hepatic encephalopathy; HPS, hepatopulmonary syndrome; HRS, hepatorenal syndrome; ICP, intracranial pressure; ICU, intensive care unit; INR, international normalized ratio; MELD, Model for End-Stage Liver Disease; PTT, partial thromboplastin time; SOFA, sequential organ failure assessment.
Acute deterioration of patients with cirrhosis manifests as multiple organ failure requiring admission to an intensive care unit. Precipitating events may be viral hepatitis, typically in Asia, and drug or alcoholic hepatitis and variceal hemorrhage in the West. Patients with cirrhosis in the intensive care unit have a high mortality, and each admission is associated with a mean charge of US $116,200. Prognosis is determined by the number of organs failing (sequential organ failure assessment [SOFA] score), the presence of infection, and the degree of liver dysfunction (Child-Turcotte-Pugh or Model for End-Stage Liver Disease scores). The most common organ failing is the kidney; sepsis is associated with further deterioration in liver function by compromise of the microcirculation. Care of these critically ill patients with impending multiple organ failure requires a team approach with expertise in both hepatology and critical care. Treatment is aimed at preventing further deterioration in liver function, reversing precipitating factors, and supporting failing organs. Liver transplantation is required in selected patients to improve survival and quality of life. Treatment is futile in some patients, but it is difficult to identify these patients a priori. Artificial and bioartificial liver support systems have thus far not demonstrated significant survival benefit in these patients. (HEPATOLOGY 2011)
Epidemiology: Patients with Cirrhosis Requiring Intensive Care
Approximately 26,000 patients with cirrhosis in the United States require intensive care each year, as identified by the need for mechanical ventilation and invasive cardiovascular monitoring. The in-hospital mortality in these patients is greater than 50%, and mean length of hospitalization is 13.8 days. The total annual charges associated with intensive care unit (ICU) admissions alone are US $3 billion, or mean charges of US $116,200 per admission (data not published). More concerning is the finding that ICU mortality rates associated with cirrhosis have remained essentially unchanged over 20 years. The optimal care of the patient with cirrhosis in the ICU is discussed in this review.
Pathophysiology of Cirrhosis and Organ Failure
Acute deterioration of cirrhosis may be associated with multiple organ failure. Of the precipitating events identified (Table 1), infection is associated with the worst prognosis.
|Infection (bacterial, fungal, or viral)*|
|Superimposed viral hepatitis (e.g., hepatitis E) or reactivation of hepatitis B (in Asia and Africa)|
Patients with cirrhosis currently admitted and who had been admitted to the hospital within the previous 6 months have a higher mortality rate compared with patients not hospitalized in the preceding 6 months (78% versus 34%). An increase in the number of systemic inflammatory response criteria and nosocomial infections are also associated with a poor prognosis. Not surprisingly, as the number of failing organ systems increase, as assessed by the sequential organ failure assessment (SOFA) score, so does the mortality. The presence of two failing organ systems increases the mortality to 55%, whereas those who develop failure of three or more organs have almost 100% mortality.1, 2 Consistent with previous studies in critical care,3 the SOFA score can be used as an adjunct to define prognosis. Prognosis can also be determined by the Child-Turcotte-Pugh (CTP) or Model for End-Stage Liver Disease (MELD) scoring systems,4, 5 but genetic and inflammatory markers may also prove useful.
The pathophysiology of the individual organs failing is described below.
Sepsis and systemic inflammation may result in acute deterioration of liver function in both those with a previously normal liver and those with underlying cirrhosis. Tumor necrosis factor-α, interleukin-6, and other markers of activation of the innate immune system play a key role in the pathogenesis of hepatocellular microcirculatory dysfunction in sepsis. Microcirculatory dysfunction results in high portal pressures and reduced hepatic blood flow, which further worsen liver function. Such abnormalities are closely related to endothelial dysfunction. The intimate relation between hepatocytes and tissue macrophages (Kupffer cells) allows for a coordinated inflammatory response in the face of infection. Thus, ongoing liver injury begets an intensified inflammatory response with further liver injury, which culminates in an inexorable downward spiral and death.
The survival of patients with cirrhosis who develop renal failure, the most common organ dysfunction, is markedly shorter than those without renal failure.6 The renal failure that develops may be categorized into four main types: hepatorenal syndrome (HRS), hypovolemia-induced, parenchymal disease, and drug-induced.7 Bacterial infection is a major risk factor for the development of any type of renal dysfunction, but especially of HRS, and may in fact be the most common precipitant of renal failure in cirrhosis. Hypovolemia-related renal failure is in most instances secondary to gastrointestinal bleeding, excessive diuretic treatment, or gastrointestinal fluid losses.
Adrenal insufficiency is reported in 51%-68% of patients with cirrhosis and severe sepsis, particularly in patients with high CTP and MELD scores and hemodynamic instability. The impaired adrenal response may reflect either or both primary and secondary adrenal insufficiency with inadequate pituitary response and low adrenocorticotropic hormone levels. Adrenal insufficiency is associated with increased mortality compared to patients without adrenal insufficiency.8
Respiratory complications in acute-on-chronic liver failure can be broadly categorized as acute respiratory failure (e.g., pneumonia and acute lung injury) and those that arise from the consequences of cirrhosis, portopulmonary hypertension, and hepatopulmonary syndrome (HPS). Portopulmonary hypertension is predominantly a hemodynamic problem, whereas HPS is predominantly a problem of intrapulmonary shunting leading to hypoxemia. The presence of an exaggerated inflammatory response, coupled with a relative immunocompromised state likely predisposes to acute lung injury. Respiratory abnormalities may also reflect decreased thoracic compliance resulting from ascites, chest wall edema, and pleural effusions (hepatic hydrothorax). Atelectasis ensues, and the resulting impairment in gas exchange (hypoxemia) is exacerbated by hepatopulmonary syndrome, perhaps out of proportion to radiographic abnormalities. Patients with cirrhosis are at increased risk of pneumonia. The risk of aspiration pneumonia is also high because of altered consciousness, swallowing dysfunction, gastric stasis, increased intra-abdominal pressure due to ascites, and ileus resulting from infection and electrolyte abnormalities.
The circulatory response typical of cirrhosis is a hyperdynamic (high cardiac output), vasodilated state. Small decreases in arterial tone dramatically decrease circulating blood volume and precipitate hypotension. Elevated cardiac output is largely a function of increased heart rate; stroke volume is maintained as a consequence of ventricular dilation. Liver failure–associated cardiomyopathy is suggested by low normal ejection fraction, lower cardiac output than expected for the degree of arterial vasodilation (decreased afterload), evidence of diastolic dysfunction, and delayed repolarization evidenced by prolonged QTc intervals (Fig. 1). Tools for assessing cardiac function are outlined in Fig. 1.
The most common manifestation is an acute confusional syndrome superimposed on varying degrees of cognitive impairment that can evolve to coma. Although usually encompassed under the term hepatic encephalopathy (HE), the pathogenic mechanisms are likely to be distinct. Precipitating factors, such as infection or electrolyte abnormalities, may enhance the disturbances attributable to liver failure or exert a direct effect on the brain. Important contributing factors are the systemic inflammatory response, circulatory dysfunction, and failure of other organs.
The activation of inflammatory mediators, such as cytokines, may enhance the effects of neurotoxins such as ammonia. Neuroinflammation increases blood–brain barrier permeability and, by generation of nitric oxide and prostanoids, causes astrocyte swelling. Other cerebrovascular abnormalities include disturbances of neurotransmission, injury to astrocytes, energy impairment, brain edema, loss of autoregulation, and brain atrophy.9 In cirrhosis, cerebral edema is an uncommon finding; however, cases of increased intracranial pressure (ICP) have been identified.10
Standard tests of coagulation are abnormal as a consequence of impaired synthesis of coagulation factors and increased consumption. Prolongation of the prothrombin time is common but spontaneous bleeding as a result of the very short half-life of factor VII is rare. A relative decrease in hepatic-derived anticoagulant factors serves to offset the decrease in procoagulant factors in the patient with cirrhosis who has compensated disease. Alternative techniques for assessing coagulation such as thromboelastography (TEG) may be helpful in identifying this balance and for guiding blood product replacement. Bleeding associated with trauma or acute variceal hemorrhage may be more dramatic as a consequence of both attendant coagulopathy and enhanced fibrinolysis.
Infection is another factor in the coagulopathy of cirrhosis. With sepsis, endogenous low-molecular-weight heparinoids are detected, which disappear with resolution of infection.11, 12 Furthermore, infection increases portal pressure, which contributes to bleeding risk, and thus, antibiotics reduce early variceal rebleeding rates.13
Vascular Disease, Thrombosis, and Ischemia.
Extrahepatic portal vein thrombosis is common in patients with cirrhosis; the main precipitating factors appear to be sluggish portal flow14 and underlying thrombophilia. Portal vein thrombosis may be of insidious onset and recognized only on hepatic imaging. However, acute portal vein thrombosis in patients with cirrhosis may result in hepatic decompensation.15 Sepsis superimposed on hypovolemia leads to hypotension and further hepatic ischemia. Contrary to widely held beliefs, even patients with a prolonged international normalized ratio (INR) can develop deep vein thrombosis and the attendant complications.16
Intensive Care of the Patient with Cirrhosis
Patients with cirrhosis in the ICU benefit from a team approach of clinicians with expertise in both hepatology and critical care. The goals of treatment are to prevent further deterioration in liver function, reverse precipitating factors, and support failing organs. Liver transplantation is required in selected patients to improve survival and quality of life.
|Critical patient||Early recognition||Preemptive admission to critical care unit|
|Airway||Decreased Glasgow coma score (GCS)||Intubation|
|Ongoing encephalopathy||Consider early tracheostomy|
|Breathing||Gases (PaO2)/ pulse oximetry||Oxygenation: increase FiO2|
|Investigate etiology of hypoxia|
|Continuous positive airway pressure (if cooperative)|
|Ventilatory support (care bundles)|
|Consider hepatopulmonary syndrome/cardiac shunt (e.g.) patent foramen ovale|
|Hypotension||Arterial line||Volume bolus initially (see monitoring figures)|
|Cardiac function||Noninvasive and/or invasive cardiac/ volume status monitoring||Pressors, (norepinephrine, (0-2 μg/kg/minute) vasopressin (1-2 U/hour)|
|Inotropes (dobutamine, adrenaline, milrinone)|
|Pulmonary hypertension||Sildenafil (oral), prostaglandins, endothelin antagonists|
|Adrenal function||Pressor dependence||ACTH test and consider hydrocortisone|
|Metabolic||Blood gases (HCO3, Cl, Na, lactate, Mg, PO4, arterial ammonia)||Treat as required|
|Consider hyperchloremic acidosis and avoidance of Cl-containing fluids if present|
|Hyponatremia: potentiates HE, role of early renal replacement therapy to gently correct, especially if patient is listed for transplant|
|HCO3: may require renal replacement therapy for acidosis, diuretics may contribute to metabolic alkalosis|
|Lactate: ensure adequate volume status|
|Renal function||Urea and creatinine, poor markers of function/ reserve Renal failure may contribute to decreased GCS (“uremic encephalopathy” and decreased ammonia clearance)||Renal replacement therapy|
|i. continuous modes (hemofiltration or hemodiafiltration or dialysis)|
|ii. slow hemodialysis|
|iii. intermittent hemodialysis|
|Decision should be based on unit expertise.|
|Anticoagulation: usually low-dose heparin, regional heparin, epoprostenol. Some data now suggesting safety of citrate but need to be aware of citrate accumulation and toxicity in cirrhosis.|
|Nutrition and glucose homeostasis||Food charts||Food supplements, early enteral feeding Patients with ileus may require parenteral nutrition; watch for cholestasis|
|Glucose monitoring||Gastric residuals: prokinetics (erythromycin) “Tight glucose control.” Levels unclear but probable benefit to maintain glucose between 140-180 mg/dL|
|Lines and sepsis||Protocols and bundles||Hand hygiene standards|
|Attention to detail||Line insertion and care standards|
|Audits||Ventilator bundles of care|
|Urinary catheter care|
|Fever or hypothermia, hemodynamic, respiratory, or metabolic deterioration||Cultures|
|“Sepsis bundle” Early use of broad-spectrum antibiotics is highly recommended|
|Screening swabs||Weekly swabs: awareness of colonization status|
|Coagulation||Full blood count Prothrombin time Fibrinogen||If no active bleeding, usually no treatment For bleeding, give platelets if <50 and coagulation support if significantly deranged.|
|Activated partial thromboplastin time Thromboelastography (TEG)||Fibrinolysis may be assessed on TEG and can be treated with aminocaproic acid or tranexamic acid.|
|Communication||With patient and relatives||Realistic prognosis and regular updates|
|Referring teams||Prognosis and treatment plans|
|Prophylaxis (e.g.) beta-blockers for portal pressure, antibiotics for prevention of spontaneous bacterial peritonitis|
|Transplant center||When to transfer for consideration of transplant assessment|
Monitoring and Hemodynamics.
Patients may be hypotensive despite presence of a hyperdynamic state and being unresponsive to volume challenge. Ventricular compliance is decreased and can be assessed by manipulation of intravascular volume. That is, the change in central venous pressure (CVP) after fluid challenge is more instructive than a single measurement of the CVP. Intra-abdominal pressure is increased as a consequence of ascites and results in reduced thoracic compliance further increasing the measured CVP without an increase in ventricular preload. Echocardiography provides a much more robust assessment of ventricular function and response to volume infusion (Fig. 3). Echocardiography is noninvasive and may be relatively inexpensive. In the patient who is not breathing spontaneously, the impact of phasic increases in intrathoracic pressure on venous return and cardiac output can be assessed by analysis of stroke volume variation from an arterial catheter. Because pulmonary hypertension is associated with cirrhosis, pulmonary artery catheterization is required to measure pulmonary artery and pulmonary artery occlusion pressures.
Elevated intra-abdominal pressure due to tense ascites may also result in the abdominal compartment syndrome which leads to renal, cardiovascular, and respiratory dysfunction.17 Bladder pressure is a measure of intra-abdominal hypertension and should be maintained below 20 mm Hg by large-volume paracentesis with concomitant albumin replacement at 6-8 g albumin per liter of ascites removed.
The optimal mean arterial pressure goal is unknown. In septic shock, in the absence of liver disease, there appears to be no advantage to inducing hypertension.18 However, HRS responds to increasing perfusion pressure by administration of terlipressin. Circulating intravascular volume should be restored recognizing the difficulties in assessing volume. Vasopressors such as norepinephrine are titrated to achieve a mean arterial pressure of 65-70 mm Hg. Vasopressin (or terlipressin) is norepinephrine-sparing in sepsis and appears to have a similar effect in patients with cirrhosis.
Airway and Pulmonary Management.
Endotracheal intubation for airway control is mandatory in patients with a Glasgow coma scale score of –8 and/or in the presence of active upper gastrointestinal bleeding. Management of respiratory failure and acute lung injury mandates the use of lung protective ventilation strategies; low tidal volume ∼6 mL/kg of predicted body weight, positive end-expiratory pressure to maintain satisfactory oxygenation, and plateau pressures <30 cm/H2O to prevent further lung injury.19, 20 Routine administration of sedatives to minimize discomfort associated with translaryngeal intubation is rarely necessary in patients with cirrhosis and deep encephalopathy. In fact, sedatives delay extubation and prolong altered consciousness. The majority of patients can be managed with intermittent narcotic administration with prompt extubation once they are able to protect their airway. Prolonged translaryngeal intubation should be avoided. Percutaneous tracheostomy can be accomplished with minimal risk even in patients with coagulopathy.21 All patients, whether ventilated or not, should undergo early mobilization and early initiation of physical therapy to prevent weakness associated with immobility and critical illness.22
Hepatic hydrothorax occasionally causes significant pulmonary and even hemodynamic compromise, and thoracentesis may be necessary. Atelectasis may persist after thoracentesis and reflect a trapped lung. Measures to control ascites with sodium restriction and diuretics will usually reduce hydrothorax. A transjugular intrahepatic portosystemic shunt is recommended in selected patients with refractory hepatic hydrothorax. Chest tube placement is to be avoided, because persistent drainage renders patients hypovolemic and at risk for hemorrhage and infection.
Nephrotoxic medications such as nonsteroidal anti-inflammatory drugs, intravascular volume depletion, and avoidance of large-volume paracentesis without albumin replacement should be avoided. Renal dysfunction is often underestimated by measurements of serum blood urea nitrogen or creatinine. Measurement of glomerular filtration by iothalamate clearance is usually not feasible in critically ill patients. The current recommendation for treatment of HRS includes volume expansion with albumin (1 g/kg maximum 100 g/day initial dose then followed by 20-40 g/day) and vasoconstrictors with the goal of treatment to decrease the serum creatinine to <1.2 mg/dL. The choice of vasoconstrictor depends on availability. Acceptable regimens include terlipressin, recommended at a dose of 0.5-1 mg given every 4-6 hours, increasing to 2 mg every 4-6 hours for up to 14 days. Alternative regimens include norepinephrine at a dose of 0.5-3 mg/hour as a continuous infusion; midodrine at a dose of 7.5-12 mg orally three times daily with octreotide at a dose of 100-200 μg subcutaneously three times daily.23 Lower baseline serum creatinine and MELD scores are associated with better outcome; in approximately 50% of patients, renal function worsens despite these measures. Renal replacement therapy is recommended to treat fluid, electrolyte, and acid–base abnormalities, but is not associated with improved outcomes in HRS.
Spontaneous bacterial peritonitis, when present, is treated with cefotaxime at a dose of 2 g given intravenously three times a day in addition to albumin boluses. In selected patients, prophylactic administration of norfloxacin to prevent spontaneous bacterial peritonitis delays the development of HRS and thus has been shown to improve survival.24 The rising incidence of multi–drug-resistant bacterial infections is recognized, along with the increased risk of mortality associated with these organisms.
Management of Neurological Problems.
The mainstay of treatment of HE is use of lactulose and nonabsorbable antibiotics.25 The optimal dose of lactulose is not well established; however, titration to two to three semiformed stools per day is recommended. Avoidance of profuse diarrhea and its associated electrolyte abnormalities is essential. When advanced encephalopathy or mechanical ventilation precludes oral administration, administration should be via enteric tube or retention enema. The nonabsorbable antibiotic rifaximin is of benefit in outpatient treatment of HE,26 but has not been tested in patients with MELD scores >24, who comprise the majority of patients in the ICU. Avoidance of sedative agents is strongly recommended.
In patients who demonstrate signs of cerebral edema or increased ICP, the administration of mannitol is mandatory, and invasive ICP monitoring may be considered.
Prevention and Control of Bleeding.
Routine correction of coagulation abnormalities in the absence of active bleeding is rarely indicated. Correction may be associated with significant complications including transfusion-associated lung injury, transfusion-associated circulatory overload, and transfusion reactions.27 When correction of bleeding abnormalities is required in the presence of active bleeding, TEG, prothrombin time, complete blood count, and activated partial thromboplastin time are used to guide therapy. Correction of coagulation abnormalities prior to placement of central venous or arterial catheters, paracentesis, thoracentesis, or bronchoscopy and endoscopy without biopsy is not required.
Isolated abnormalities in the INR (in the absence of warfarin) with a normal partial thromboplastin time (PTT) and normal reaction time on a TEG do not require correction. Vitamin K, given at 2 mg intravenously daily for 3-5 days, should be administered to eliminate vitamin K deficiency as a source of coagulopathy. Massive acute hemorrhage should be managed with transfusion of red blood cells (RBCs) and fresh frozen plasma (FFP) given in a 1:1 or 2:1 ratio with transfusion of platelets and cryoprecipitate to address consumption. Less vigorous bleeding may be treated with a 4:1 RBC-to-FFP ratio. In the presence of bleeding, we recommend transfusion of platelets to maintain a level of >50 × 109/L. Qualitative platelet dysfunction may be improved with desmopressin (DDAVP). Fibrinolysis is common and is readily assessed by TEG, although the euglobulin lysis time can be measured for confirmation. Treatment of fibrinolysis with epsilon-aminocaproic acid or tranexamic acid is indicated when bleeding persists, despite correction of thrombocytopenia and clotting factors in the absence of disseminated coagulopathy. When the PTT is excessively prolonged, use of protamine, even in the absence of heparin therapy, may be beneficial to counteract endogenous heparin-like compounds.
For patients presenting with gastrointestinal bleeding, correction of coagulation abnormalities must be accompanied by antibiotic therapy, usually intravenous ceftriaxone or oral norfloxacin and vasoactive medications for up to 5 days.28 Choice of vasoactive drug can be guided by local protocol (e.g., terlipressin at a dose of 2 mg every 4 hours, somatostatin at a dose of 250-500 μg/hour, or octreotide at a dose of 50-100 μg/hour). Early transjugular intrahepatic portosystemic shunt may be considered in patients who have CTP class C (<13 points) or B cirrhosis with active variceal bleeding.29
Patients with cirrhosis are at risk for venous thromboembolism, even in the face of abnormal elevations of the INR or PTT. In the absence of contraindications, patients with cirrhosis in the ICU should have mechanical DVT prophylaxis, but routine pharmacologic DVT prophylaxis is not recommended at this time.
Nutritional support is necessary when patients are unable to maintain adequate intake. A low-protein diet does not improve the outcome of acute HE and does not reduce its recurrence. The current recommendation is to provide a diet that contains a normal amount of protein (0.8-1.2 g/kg/day). In the critically ill patient with cirrhosis, the protein requirement may be modified up or down on the basis of degree of catabolism and presence of renal failure. In patients on dialysis or continuous renal replacement therapy, the goal of protein supplementation is preventing development of a negative nitrogen balance. Provision of adequate crystalloid and colloid is essential to maintain optimal organ function, along with nutrition, ideally delivered via the enteral route. In those patients with ileus; however, aggressive enteral feeding may worsen risk of bacterial translocation and sepsis, and consideration should be given to mixed enteral and parenteral nutrition.
A functioning liver is crucial for maintaining glucose homeostasis. In advanced liver disease, glycogen storage may become impaired predisposing the patient to hypoglycemia. Caloric requirements are increased in the presence of sepsis. Thus, nutritional support must be modified to maintain normoglycemia.
Thiamine deficiency should be considered in all patients with chronic liver disease. Classic findings associated with thiamine deficiency may be difficult to assess, but the lack of these findings should not preclude replacement.30 We recommend a dose of 100 mg thiamine given intravenously daily for 3-5 days, because absorption from the gut may be unreliable.
Trace mineral deficiencies such as zinc and selenium are well documented in cirrhosis.31 Zinc replacement at a dose of 25-50 mg elemental zinc three times daily is required.32, 33 There is insufficient evidence at present to recommend routine replacement of selenium.
A large, randomized, controlled trial in patients without cirrhosis suggests that “tight” glucose control is not desirable.34 Thus, in patients with cirrhosis, we recommend maintaining blood sugars in the range of 140-180 mg/dL.
Patients with relative adrenal insufficiency may benefit from steroid therapy with hemodynamic improvement and decreased mortality.35 However, routine use of steroids was not beneficial in a recent controlled trial.36 Therefore, in the absence of adrenal insufficiency, steroid therapy in critically ill patients with cirrhosis is not recommended.
Because overt signs of infection may be absent, a high index of suspicion is necessary for diagnosis. In patients in whom infection is suspected, early use of broad spectrum antibiotics (piperacillin–tazobactam is often used, but the choice guided by the type of organism and resistance patterns), preferably within 1 hour of admission, is highly recommended as is adherence to early goal-directed therapy guidelines.37 Strict adherence to hand hygiene and “bundles” of care (e.g., ventilator and central line) are required to prevent hospital-acquired infections.38, 39
For prolonged ICU stays, weekly swabs for resistant organisms should be obtained. Testing for Clostridium difficile infection should be routinely performed and repeated in critically ill patients with diarrhea. This serious infection may be overlooked in patients receiving lactulose therapy. For patients who have active C. difficile infections and are critically ill (e.g., shock, toxic megacolon) initiating dual therapy with oral vancomycin at a dose of 500 mg every 6 hours and intravenous metronidazole at a dose of 500 mg every 8 hours is mandatory.40
Referral and Transfer to a Liver Transplant Center.
The determination of transplant candidacy is complex and beyond the scope of this review. All patients admitted to the ICU with complications of cirrhosis deserve a consultation with a transplant center to determine candidacy for liver transplantation. Perceived contraindication to transplant should never preclude this consultation because patients with cirrhosis admitted to the ICU have a mortality rate of 50%. For example, a patient with decompensated cirrhosis and active alcohol use may benefit from the expertise, assessment, and support systems available within a transplant center. Established communication between the primary provider and the referral center will provide guidance on the optimal timing for referral and/or transfer.
Patient and Family Communication.
Communication is of paramount importance to regularly update patient and family members with regard to changes in condition and to provide a realistic prognosis. When multiple referring and consulting services are involved it is important for the critical care physician to provide a cohesive plan of care to the family to avoid confusion and to facilitate informed decision making by the patient and family. To minimize futile care, daily reassessment of the patient's response to intensive care is needed. The persistence of multisystem organ failure after several days despite therapy and in the absence of an option for liver transplantation warrants a change in focus to comfort care.
Liver Support Devices.
Liver support devices are intended to support liver function until such time as native liver function recovers, or until liver transplantation. The overall efficacy of liver support devices have, at this time, failed to reach a level sufficient to gain US Food and Drug Administration approval.
Liver support devices are categorized into two main types: artificial livers, being acellular devices such as albumin dialysis and plasma-exchange/diafiltration, and bioartificial devices that contain cells from human, animal, or transformed sources. Early studies with both types of devices demonstrated biological effects (e.g., attenuation of systemic inflammatory response and improved biochemical profiles) but have failed to show a survival benefit. For example, a trial of extracorporeal albumin dialysis designed to measure the impact on advanced HE demonstrated significant improvement in HE in patients with MELD scores >30 but only a trend toward improved transplant-free survival at 2 weeks.41 These studies demonstrate that liver support devices may improve quality of life and perhaps provide an economic benefit by reducing length of hospitalization. The determination of which patient benefits from liver support devices, or should be referred to early liver transplantation, and in which patient all treatment is futile awaits the results of future studies.
We gratefully acknowledge the following participants in the Atlanta Single Topic Conference whose time and work contributed significantly to this manuscript: Arun J. Sanyal, W. Ray Kim, Jean-Louis Vincent, Roberto De Franchis, Vijay H. Shah, Robert J. Fontana, Naga Chalasani, Dominique-Charles Valla, Pere Gines, Ram M. Subramanian, Samuel S. Lee, Juan Cordoba, Andrew Burroughs, Srinivasan Dasarathy, Sergio Zanotti-Cavazzoni, and Scott L. Nyberg.