ICU Management of Acute Liver Failure

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Survival of patients presenting with acute liver failure (ALF) has improved because of earlier disease recognition, better understanding of pathophysiology of various insults leading to ALF, and advances in supportive measures including a team approach, better ICU care, and liver transplantation. This article focuses on patient management and evaluation that takes place in the ICU for patients who have acute liver injury. An organized team approach to decision making about critical care delivered during this period of time is important for achieving a good patient outcome.

Section snippets

Pathogenesis of acute liver failure

The specific pathogenesis of the liver injury is dependent to a large degree on the etiology. There are features of injury common to most etiologies of ALF, however. Injury to hepatocytes causes cell damage or cell death by necrosis or apoptosis; however, these processes may coexist.2 Triggering of the mitochondrial permeability transition by injury typically is associated with apoptosis if ATP stores are preserved, and necrosis if there is ATP depletion.2 Examples of mitochondrial injury

Etiologies of acute liver failure and specific therapies

The specific etiology of ALF is the most important determinant of outcome.8 The frequency of specific types of liver injury varies in different geographic locations.8, 9 The following section focuses on specific etiologies and therapies for ALF.

Evaluation of the patient with acute liver failure

The most critical element to patient survival with ALF is its early recognition. This permits rapid identification of the etiology of the liver failure, initiation of etiology-specific treatments when appropriate, and importantly the proper mobilization of personnel involved in various aspects of patient care.

The first phase of the evaluation includes obtaining a detailed history from the patient if possible or from others who may know the patient's medical history. Physical examination should

Assessing the patient for liver transplantation

Although liver transplantation is not required for many patients who have ALF, in appropriate candidates, liver transplant will be lifesaving. The decision as to whether a patient will recover with conservative management or require transplantation has been the subject of many different reports and case series; however, the Kings College Criteria remain the current standard for clinicians.43 These criteria are used to predict death in patients presenting with ALF in the setting of acetaminophen

ICU-based interventions

Advances in critical care medicine and in management strategies have reduced mortality for ALF to approximately 33% according to the USALF Study Group Registry.8 This mortality is attributed to three complications in particular: cerebral edema, multiorgan dysfunction syndrome (MODS), and sepsis. The following section will review ICU-based management strategies and interventions that have evolved to address the various organ dysfunctions associated with ALF.

Neurologic failure: cerebral edema and intracranial hypertension

Management of intracranial hypertension (ICH) remains challenging. Left untreated, mortality can exceed 90%, and some estimate that up to a third of patients succumb to brainstem herniation while awaiting an organ. Clinically recognizable risk factors associated with cerebral edema include: high-grade encephalopathy (grades 3 to 4), elevated serum ammonia (greater than 150 to 200 μm),48, 49 rapid/hyperacute progression of liver injury to hepatic encephalopathy, infection or systemic

Intracranial pressure monitoring: general considerations

In clinical practice, ICP monitoring for patients who have ALF remains controversial, in part because randomized controlled trials are lacking to guide clinicians through nuanced scenarios in which invasive monitoring may or may not be helpful. The lack of an accepted consensus protocol for managing cerebral edema hampers attempts at rigorous multicenter research studies. To fuel the controversy further, in nonrandomized studies, such devices have not been shown to improve survival.52 Despite

Intracranial pressure monitoring: practical considerations

Even after a decision is made to proceed with invasive ICP monitoring, the ideal location of placement remains unclear. In general, intraventricular placement carries the highest risk of bleeding (although with the added therapeutic potential), and epidural placement the lowest risk. The latter approach however, suffers from less accuracy in ICP measurement. The subdural position is the most commonly used location in the United States, according to a recent survey.52 Ultimately, until

Intracranial hypertension: general management principles

In general, patients should be kept in a quiet room with minimal stimulus, including infrequent endotracheal suctioning. The head of the bed should be elevated to 30° (to improve CSF drainage), and neck rotation or flexion should be limited (to avoid compromise of jugular venous drainage). Fevers should be controlled by cooling, because acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDS) should be avoided, and rigoring or shivering also avoided, as these may exacerbate ICP.54 When

Keeping it cool: therapeutic hypothermia

Moderate hypothermia (32°C to 33°C) so far appears to be a formidable tool for managing refractory ICP elevations.57, 58 Therapeutic hypothermia simultaneously alters multiple pathways important in the pathogenesis of cerebral edema and ICH and leads to:

  • Reductions in brain energy metabolism (both metabolic and electrophysiologic components)

  • Possible suppression of subclinical seizure activity

  • Normalization of cerebral blood flow and autoregulation

  • Reduced delivery of ammonia to the brain

Neurologic manifestations: seizures

Seizures can aggravate cerebral edema and ICH, but they also can be a manifestation of ICP surges. There is at least one study that has shown a benefit of phenytoin infusion in preventing subclinical seizure activity,61 although a recent clinical trial noted no benefit.62 Hypothermia reduces seizure activity in experimental models of epilepsy, and may be an additional important mechanism of action of hypothermia in ALF.63, 64 Presently the authors do not recommend prophylaxis for seizures, but

Respiratory failure: mechanical ventilation

The ideal timing for endotracheal intubation is not always clear. When considering interhospital patient transfer to a liver transplant center, one of the discussions commonly includes whether the patient should be intubated before transfer, as neurologic deterioration can be very rapid. Intubation should be considered strongly once advanced encephalopathy becomes evident at grade 3 or more. In addition to preventing gross aspiration events, mechanical ventilation and judicious sedation may

Sedation and analgesia

Because agitation (including excessive coughing and straining) and pain can exacerbate ICP elevations, adequate analgesia and judicious sedation are required, particularly before and after placement of invasive devices such as endotracheal tubes and ICP monitors.

In reality, there are not enough data to suggest a standard agent or dosing regimen in this scenario. In general, short-acting agents are preferred, although it is important to note that all sedative drugs are subject to delayed

Hemodynamic failure: shock management

Hypotension is common in patients who have ALF and is marked by a state of high cardiac output and reduced systemic vascular resistance. This hemodynamic picture closely mimics septic shock, and differentiating between the two can be challenging. Concurrent infectious workup is mandatory. Relative adrenal insufficiency occurs frequently, but treatment with moderate-dose corticosteroids is reserved for those unresponsive to pressors. In one series, 62% of patients who had ALF were found to have

Venous access devices

Catheter-related infections are a major source of avoidable complications in patients who have ALF.71, 72 As such, when placing venous access devices, meticulous attention to catheter care is paramount. Routine placement of multiple catheters is unnecessary, and placement of venous access devices probably should occur only as the need arises.

Importance of cardiac dysfunction

Recent data suggest myocardial injury may occur in ALF. Although classically felt to spare the heart, nearly 75% of patients in the US Acute Liver Failure Study Group cohort demonstrated an elevation of troponin 1 of 0.1 ng/mL or more. Importantly, patients who had elevated troponins experienced arrhythmias and higher coma grades (stage 3 or 4) at a rate two and four times respectively compared with those patients who had normal troponins.73 Mortality rates (before and after transplant) were

Hematologic failure: dealing with coagulopathy

Despite severe derangements in coagulation profile, clinically significant spontaneous bleeding remains relatively uncommon. Because subclinical vitamin K deficiency contributes to coagulopathy in up to 25% of patients, empiric administration of vitamin K 10 mg intravenously given as a single dose is recommended.74 Prophylactic transfusions to normalize coagulation profile in all patients who have ALF is unnecessary, as it has not been shown to alter the risk of significant bleeding or future

Renal failure management

Renal insufficiency that progresses to renal failure may accompany liver failure. The causes may be multifactorial, including ischemia from hypotension that may cause acute tubular necrosis, hepatorenal syndrome, and other direct toxic injuries such as copper induced tubular injury in Wilson disease,27 and contrast-induced nephropathy if contrast studies were recently performed. Urine sodium may be low in hypovolemic states, hepatorenal syndrome, and with contrast nephropathy. It is important

Infectious disease considerations

Infections are the most common cause of death and morbidity in patients who have ALF. With severe injury to the liver, Kuppfer cell function is impaired, and clearance of normal gut bacteria that translocate is less efficient. This increases the risk of patients who have ALF to infection. The most common site of bacterial infection is the lung, then urinary tract and blood.71, 72, 75, 76, 77 The most frequently identified organisms are Staphylococcus, Streptococcus and enteric gram- negative

Nutrition for the patient with acute liver failure

Patients are prone to hypoglycemia in acute liver injury because of loss of glycogen stores, impairment of gluconeogenesis, and increased circulating insulin. Intravenous supplementation with glucose solutions is recommended if the patient is not being fed. Marked hyperglycemia should be avoided, because this may impair control of intracranial pressure;78 however the benefits of attempting tight control must be weighed against the risk of hypoglycemia.

There is a need for nutritional

Liver support devices

Liver support devices may benefit patients who have liver failure by being used as a bridge to liver transplantation or liver recovery; however their utility only has been tested in nonrandomized studies to date.81 The results of ongoing multicenter trials are awaited. There are two main types of liver support devices that have been developed:

  • Artificial (cell-free systems) such as those based on plasma filtration and removal of substances by use of dialysis or charcoal or other ion exchange

Liver transplantation

Patients who have ALF not recovering despite medical/supportive treatment are candidates for liver transplantation. It is the authors' policy to list patients who have ALF meeting the minimal listing criteria as UNOS status 1A immediately after completing medical and UNOS-required evaluations. When a suitable liver offer becomes available, transplantation will be performed. The availability of deceased donor liver allograft is unpredictable, however, because of a shortage of organ donors and

Outcomes of patients with acute liver failure

Survival of patients who have ALF depends on the etiology of ALF, with spontaneous or nontransplant recovery being the best in patients with acetaminophen-induced injury who receive timely treatment with NAC. For those patients who undergo emergent liver transplantation, the outcomes are good for long-term survival but below those for patients who have chronic liver diseases or liver cancer. The 1-, 3-, and 5-year graft survivals following transplant in a published series from a single center

References (85)

  • J.R. Barton et al.

    Care of the pregnancy complicated by HELLP syndrome

    Gastroenterol Clin North Am

    (1992)
  • A. Ochs et al.

    Transjugular intrahepatic portosystemic stent–shunt (TIPS) in the treatment of Budd-Chiari syndrome

    J Hepatol

    (1993)
  • R.K. Patel et al.

    Prevalence of the activating JAK2 tyrosine kinase mutation V617F in the Budd-Chiari syndrome

    Gastroenterology

    (2006)
  • E.C. Ebert

    Hypoxic liver injury

    Mayo Clin Proc

    (2006)
  • J.G. O'Grady et al.

    Early indicators of prognosis in fulminant hepatic failure

    Gastroenterology

    (1989)
  • V.M. Shami et al.

    Recombinant activated factor VII for coagulopathy in fulminant hepatic failure compared to conventional therapy

    Liver Transpl

    (2003)
  • J. Vaquero et al.

    Keeping cool in acute liver failure: rationale for the use of mild hypothermia

    J Hepatol

    (2005)
  • R.J. Winney et al.

    Changes in brain water with haemodialysis

    Lancet

    (1986)
  • R. Jalan et al.

    Moderate hypothermia for uncontrolled intracranial hypertension in acute liver failure

    Lancet

    (1999)
  • R. Jalan et al.

    Moderate hypothermia in patients with acute liver failure and uncontrolled intracranial hypertension

    Gastroenterology

    (2004)
  • A.J. Ellis et al.

    Subclinical seizure activity and prophylactic phenytoin infusion in acute liver failure: a controlled clinical trial

    Hepatology

    (2000)
  • V. Bhatia et al.

    Prophylactic phenytoin does not improve cerebral edema or survival in acute liver failure—a controlled clinical trial

    J Hepatol

    (2004)
  • Z. Liu et al.

    Effect of temperature on kainic acid-induced seizures

    Brain Res

    (1993)
  • R.J. Ede et al.

    Controlled hyperventilation in the prevention of cerebral oedema in fulminant hepatic failure

    J Hepatol

    (1986)
  • E.F.M. Wijdicks et al.

    Propofol to control intracranial pressure in fulminant hepatic failure

    Transplant Proc

    (2002)
  • R. Harry et al.

    The clinical importance of adrenal insufficiency in acute hepatic dysfunction

    Hepatology

    (2002)
  • M. Eefsen et al.

    Comparison of terlipressin and noradrenalin on cerebral perfusion, intracranial pressure, and cerebral extracellular concentrations of lactate and pyruvate in patients with acute liver failure in need of inotropic support

    J Hepatol

    (2007)
  • J. Vaquero et al.

    Infection and the progression of hepatic encephalopathy in acute liver failure

    Gastroenterology

    (2003)
  • S.P. Pereira et al.

    Pharmacokinetics and efficacy of oral versus intravenous mixed-micellar phylloquinone (vitamin K1) in severe acute liver disease

    J Hepatol

    (2005)
  • N. Rolando et al.

    Fungal infection: a common, unrecognised complication of acute liver failure

    J Hepatol

    (1991)
  • A. Skwarek et al.

    The use Prometheus FPSA system in the treatment of acute liver failure: preliminary results

    Transplant Proc

    (2006)
  • S. Sen et al.

    Albumin dialysis and molecular adsorbents recirculating system (MARS) for acute Wilson's disease

    Liver Transpl

    (2002)
  • Trey et al.

    The management of fulminant hepatic failure

    Prog Liver Dis

    (1970)
  • A. Rutherford et al.

    Acute liver failure: mechanisms of hepatocytes injury and regeneration

    Semin Liver Dis

    (2008)
  • S. Strand et al.

    Hepatic failure and liver cell damage in acute Wilson's disease involve CD95 (APO-1/Fas)-mediated apoptosis

    Nat Med

    (1998)
  • M.J. Smilkstein et al.

    Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985)

    N Engl J Med

    (1988)
  • F. Hawker

    Liver dysfunction in critical illness

    Anaesth Intensive Care

    (1991)
  • G. Ostapowicz et al.

    Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States

    Ann Intern Med

    (2002)
  • J. Polson et al.

    Etiologies of acute liver failure: location, location, location

    Liver Transpl

    (2007)
  • L.F. Prescott

    Paracetamol, alcohol and the liver

    Br J Clin Pharmacol

    (2000)
  • C.S. Lieber

    Susceptibility to alcohol-related liver injury

    Alcohol Alcohol Suppl

    (1994)
  • B. Pearce et al.

    Acute liver failure following therapeutic paracetamol administration in patients with muscular dystrophies

    Anaesthesia

    (2008)
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