Page 1484 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 106: Acute Liver Failure 1023

investigations of all patients are pivotal in this diagnosis demonstrating with a fulminant course of acute liver failure. This can be prevented by
loss of flow on the hepatic veins. pretreatment with antivirals (eg, lamivudine, entecavir, tenofovir); if a
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Hypoxic hepatitis has a prevalence of between 1.2% and 11% in patient presents in this manner, antivirals should be commenced. CMV
intensive care with three etiological subgroups: respiratory failure, and HSV should be considered and treated.
cardiac failure, and septic shock. It is a secondary form of ALF and N-acetylcysteine (NAC) is recommended in patients with
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as such the primary presenting organ failure needs to be addressed acetaminophen-induced ALF/injury. This drug is highly effective if
and managed to facilitate liver recovery; transplantation of the liver should used within 16 hours of drug ingestion. The Rumack-Matthew treatment
not normally be considered. An essential component to this presenta- nomogram should be followed utilizing a high-risk treatment line if
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tion appears to be conditioning of the liver with passive congestion and the patients fall into high-risk groups (eg, chronic alcohol use, malnour-
then a subsequent insult of hypotension and/or hypoxia. Transaminase ished status, or enzyme inducting drugs). Acetaminophen levels should
elevations, as can be seen with acetaminophen and ecstasy, are frequently be interpreted with caution; they are not useful if the time of ingestion
greater than 7000 to 10,000 IU/L with an associated coagulopathy. is unclear or staggered. In these circumstances, treatment should be
Pregnancy related liver disease is a spectrum of disease presenta- offered while awaiting further investigations; likewise, if patients pres-
tion where an individual patent may have features of all or only one ent late, treatment should be commenced while awaiting acetaminophen
component. Preeclampsia is a systemic disease of the microcirculation levels. Patients who have ingested acetaminophen, either as a single dose
with hypertension and proteinuria. A liver-specific complication of or staggered, and present with coagulopathy with or without encepha-
preeclampsia is that of liver rupture presenting with right upper quad- lopathy (ie, usually after 48 hours) will not have elevated acetaminophen
rant pain and transaminitis. Large subcapsular hematoma can result in levels. The characteristic picture is a significantly elevated transamini-
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secondary ischemic injury to the liver and potential limitation of hepatic tis (usually >5000 IU/L) and a history compatible with acetaminophen-
venous outflow. HELLP syndrome is characterized by hemolysis, abnor- induced hepatotoxicity. The evidence for using NAC after 16 hours is
mal liver function tests, and low platelets. Fatty liver disease of preg- based on relatively old studies showing decreased incidence of organ
nancy is characterized by hypoglycemia in addition to other features failure, as well as a mortality benefit. There are also data showing the
and is often complicated by other organ failure including pancreatitis. beneficial effects of NAC on oxygen extraction, cytokine modulation,
Elevated urate levels are also seen. and cGMP levels. NAC is, however, an inhibitor of NFKB and as such
■ INITIAL INVESTIGATIONS AND MANAGEMENT is an immune-modulating agent. Accordingly, most intensive care clini-
cians use NAC for a maximum of 5 days.
Patients should be screened for the etiology of their acute liver injury The role of NAC in non-acetaminophen-induced ALF is supported
or failure. This includes routine liver blood tests and full coagulation by the randomized control trial of the USA ALF group. This showed
screen. Viral screening should be undertaken for acute hepatitis A (IgM), benefit in those patients in grade I or II coma but not in deeper grades
8
hepatitis E (IgM), hepatitis B (IgM core Ab, surface Ab, and hepatitis B of coma. This finding is not surprising given that those with a high
DNA). Viral PCR for CMV and HSV should also be considered. Immune level of encephalopathy in this cohort of non-acetaminophen-induced
screening should be undertaken in the form of immunoglobulin and auto- ALF will frequently require transplantation, and as such an expectation
antibodies. Hemolysis screen should be undertaken if there is unconju- that NAC may alter outcomes is probably unrealistic. In a recent study
gated component with a DAT negative screen raising the consideration of of children with non-acetaminophen-induced ALF, NAC was not found
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Wilson disease. Elevated alkaline phosphatase and lactate dehydrogenase to be effective ; this should be considered in the context that the cohort-
raise the possibility of infiltrative processes within the liver. included patients with inborn errors of metabolism, a circumstance
All patients should undergo an ultrasound of the abdomen, with where NAC would not likely be effective.
interrogation of the hepatic and portal veins, assessment of spleen size Any drug with potential hepatotoxicity should be withdrawn. If a patient
and texture, and reflectivity of the liver. While the liver ultrasound is has evidence of hypoxic hepatitis, management of the cardiovascular and/
being undertaken, assessment of pancreas, ascites, and kidneys should or respiratory systems needs to be optimized.
especially if there is concern for malignancy or a nodular outline of liver ■ CARDIOVASCULAR MANAGEMENT
be performed. Axial imaging in the form of CT may also be required—
when further information is required to assess perfusion, liver contour, Most patients presenting with ALF have developed systemic vasodilation
and presence of nodes. The role of liver biopsy is controversial. It may with a decrease of effective central blood volume. Early presentation with
be required to define the presence or absence of cirrhosis or a specific lactic acidosis is likely to reflect volume depletion and will respond to
aetiology, which is amenable to therapeutic intervention. Examples appropriate volume loading. Following effective volume challenge ongo-
include autoimmune or alcoholic hepatitis, which may be treated with ing lactic acidosis is likely to reflect liver failure and severity of disease.
corticosteroids, or hepatosplenic lymphoma, which would be offered Assessment of volume status can be achieved through echocar-
chemotherapy. Though there have been some suggestions that a liver diographic techniques or utilizing invasive monitoring, usually pulse
biopsy assessing percentage necrosis allows assessment of prognosis, this contour or other similar techniques (see Chap. 34 on Judging Fluid
is now thought to be less appropriate given the risk of sampling error. Responsiveness). Caution should be exercised to avoid significantly
Echocardiography should be considered in patients where there is increased right-sided pressures as this may be detrimental to liver
any concern of hypoxic hepatitis (HH) and allows assessment of right venous outflow and hence liver function/recovery.
and left heart function. The presence of hepatopulmonary syndrome The cohort of patients with subacute liver failure and those with
may also be sought as this can be seen in some 50% of patients with HH. acute Budd-Chiari syndrome may present with elevated intra-abdominal
■ EARLY MANAGEMENT AND REFERRAL PRACTICE pressure. This may alter response to volume loading which will need
to be assessed on an individual level (see Chap. 114 on Abdominal
Presenting features are likely to be very different depending on nature Compartment Syndromes).
of disease process. It is important to consider early discussion with a Following volume loading, persistent hypotension requires institution
tertiary center to obtain guidance on investigations and management. of vasoactive support, given the normal clinical picture of an elevated
Removal and treatment of potential aetiological agents is essential. cardiac output and decreased vascular tone. The usual initial medication
Particular issues to consider are those patients with carriage of hepatitis B would be norepinephrine, with consideration for addition of low dose
who are otherwise asymptomatic and are then in receipt of chemotherapy vasopressin at 20 to 40 mU/min. Concern had been raised in the litera-
or immunological therapy such as Rituximab. 12,13 Such patients are at high ture that use of vasopressin may be detrimental with regard to cerebral
risk of developing ALF or injury (coagulopathy and no encephalopathy) complications. However, a study comparing terlipressin and norepineph-
as a result of reactivation of hepatitis B. Such reactivation may present rine showed that terlipressin increased cerebral perfusion pressure (CPP)

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