Rinella, M.D.1and 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
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EVALUATION AND MANAGEMENT OFSHOCK/AXLER 239
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Trang 4Intensive Management of Hepatic Failure
Mary E Rinella, M.D.1and 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
and often involves the combined efforts of many
special-ists 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 end-stage decompensated cirrhosis Both sides of this
spectrum present clinical challenges that involve many
organ systems Although both sides in acute and chronic
liver failure can have a poor prognosis, careful and
comprehensive intensive care can improve outcome and
bridge eligible patients to liver transplantation Because
acute and chronic liver failure are very distinct clinical
entities, they will be discussed separately
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
patient with no prior history of liver disease.1,2In recent
years, advancements in supportive care have improved
survival and provided a more effective bridge to
trans-plantation Although ALF remains one of the most acute serious illnesses, thoughtful intensive management can optimize the patient’s chances for spontaneous hepatic regeneration or a successful liver transplant.3 When possible, etiology-targeted therapy should be initiated (Table 1) The goal of management should be focused
on the prevention of systemic infection, multiorgan fail-ure, hepatic encephalopathy (HE), and ultimately the development of brain edema.4–6At this time liver trans-plantation is the only definitive therapy for those who fulfill criteria for poor prognosis7–9 (Table 2) The challenge to the clinician is selection of patients for 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:
INITIAL EVALUATION AND MANAGEMENT Early diagnosis and identification of the subject that is unlikely to improve spontaneously constitute a critical first step in the management of ALF The initial triage
1
Division of Hepatology, Northwestern University, Chicago, Illinois;
2 Division of Gastroenterology, Department of Internal Medicine,
Virginia Commonwealth University, Richmond, Virginia.
Address for correspondence and reprint requests: Arun Sanyal,
M.D., Division of Gastroenterology, Department of Internal
Med-icine, Virginia Commonwealth University, MCV Box 980341,
Richmond, VA 23298-0341 E-mail: ajsanyal@hsc.vcu.edu.
Non-pulmonary Critical Care: Managing Multisystem Critical Ill-ness; Guest Editor, Curtis N Sessler, M.D.
Semin Respir Crit Care Med 2006;27:241–261 Copyright # 2006
by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York,
NY 10001, USA Tel: +1(212) 584-4662.
DOI 10.1055/s-2006-945528 ISSN 1069-3424.
241
Trang 5of a patient with acute liver injury to an intensive care
unit (ICU) is based on the presence of altered mental
status and the degree of coagulopathy It is imperative
to admit most subjects with acute liver injury with an
international normalized ratio (INR) > 1.5 and all
subjects with mental status changes Rapid
deteriora-tion can occur and is often irreversible in the patient
with ALF It is therefore imperative that decisions
regarding prognosis and appropriateness for liver
trans-plant be made early, and potentially suitable patients
should be referred to a liver transplant center early in
the evaluation process
The management of patients in liver failure
requires a multidisciplinary approach involving
hepatol-ogists, transplant surgeons, intensivists, and other
sub-specialists The importance of a thorough physical exam
and an accurate history cannot be overemphasized be-cause both treatment and prognosis are significantly affected by the underlying etiology A detailed account
of the psychiatric history, including suicidal ideation and family support, is essential to assess suitability for transplantation The timing of the psychiatric evalua-tion is of particular importance, given the rapid deterio-ration in mental status that occurs in such patients
DISEASE-TARGETED THERAPY
A thorough discussion of the differential diagnosis of ALF is beyond the scope of this review; however, Table 1 provides a summary of common etiologies of ALF for which potential therapies exist Only acetami-nophen will be discussed in more detail because it is the most common etiology of liver failure in the United States and has an effective antidote
Acetaminophen Idiopathic and drug-related liver injuries are the most common causes of ALF in the United States.10 Of the drug-related causes, acetaminophen overdose is the most common cause of ALF in the United Kingdom and United States Overdose can be either intentional or unintentional.11–13The patient, family, and close contacts must be questioned about regular alcohol use, dieting, diet pills, medications, or recent illness that may have resulted
in poor nutrition These factors greatly affect toxicity either through upregulating cytochrome p450 (alcohol and other drugs) promoting the formation of toxic inter-mediates, or through glutathione depletion Such details are important because as little as 2.6 to 4.0 g of acetami-nophen can lead to liver failure in this setting.14–17
It is worth noting that, at the time of presenta-tion, a patient with acetaminophen-induced liver failure may have undetectable blood levels of acetaminophen This is particularly true when the toxicity manifests itself several days after ingestion of acetaminophen for ther-apeutic purposes in a susceptible subject However, in the majority of cases, detectable acetaminophen levels are present at the time of presentation When acetami-nophen overdose is confirmed, N-acetylcysteine (NAC) must be initiated in a timely manner, ideally within
16 hours of ingestion, to have a significant impact on survival NAC decreases injury through enhancement of glutathione synthesis resulting in less formation of acetaminophen’s hepatotoxic intermediate.18,19 Even if the patient is delayed in reaching the hospital or the diagnosis is not forthcoming, there is evidence that late administration of NAC can be beneficial.20NAC may also improve outcome through its effects on micro-circulatory function A large multicenter study (the ALF study group) is currently addressing the utility of NAC in nonacetaminophen-induced ALF
Table 1 Etiology-Targeted Therapy
Etiology Potential Therapies
TOXIC
Acetaminophen N-acetyl cysteine
Amanita poisoning Penicillin and silibinin
VIRAL
Herpes simplex virus Acyclovir
Acute heptatitis B Antivirals?
METABOLIC
Wilson’s disease Transplant
Autoimmune hepatitis Corticosteroids
VASCULAR
Acute Budd-Chiari syndrome Directed thrombolysis,
transjugular intrahepatic portosystemic shunt PREGNANCY
Acute fatty liver of
pregnancy/HELLP
Urgent delivery
HELLP, hemolysis elevated liver enzymes low platelets.
Table 2 King’s College Criteria for Acute Liver Failure
Acetaminophen induced
Arterial blood pH < 7.3 (regardless of degree of
encephalopathy)
If no acidosis then all three of the below criteria:
Prothrombin time > 100 seconds
Serum Creatinine > 2.5 mg/dL
Grade 3 or 4 encephalopathy
Nonacetaminophen induced
Prothrombin time > 100 seconds
If prothrombin time < 100 seconds, then any of the below
criteria (regardless of degree of encephalopathy):
Drug-induced, non-A, non-B, halothane hepatitis
Time from jaundice to encephalopathy > 7 days
Age < 10 or > 40 years
Prothrombin > 50 seconds
Bilirubin > 17.5 mg/dL
Trang 6MONITORING AND GENERAL GUIDELINES
Acute hepatic dysfunction has profound effects on many
organs Therefore, one must remain cognizant of the
ramifications of specific therapies on other systems The
mental status must be documented several times daily, in
addition to frequent assessment of hepatic synthetic
function and blood glucose (Table 3) Although a liver
biopsy may be helpful if the diagnosis is in question, it can
be unreliable in predicting outcome and is risky given the
presence of underlying coagulopathy.21Low serum
phos-phate and elevateda fetoprotein can be encouraging signs
of hepatic regeneration.22,23In a retrospective analysis of
ALF patients, 74% of patients with phosphate levels
< 2.5 were alive at 1 week, in contrast to none in those
with a serum phosphate> 5.24
Coagulopathy in ALF does not usually require
correction unless an invasive procedure is planned or
overt bleeding is present because the use of fresh frozen
plasma (FFP) can mask deterioration of liver function A
common indication for the correction of coagulopathy
is placement of a central line Traditionally, FFP and
cryoprecipitates have been used for the correction of
coagulopathy in subjects with ALF This is only partially
effective in correcting coagulopathy and its effects are
short-lived It is also associated with a risk of transmitting
cytomegalovirus infection and may contribute to volume
overload and pulmonary edema, especially when renal function begins to deteriorate Alternate approaches in-clude the use of plasmapheresis where a volume of plasma equal to the amount infused is removed to prevent volume overload Recently, recombinant factor VII (40 mg/kg) has been used in conjunction with FFP to rapidly correct coagulopathy prior to either intracranial pressure monitor or central line placement in patients with ALF.25
MECHANICAL VENTILATION Mechanical ventilation should be initiated once ence-phalopathy deteriorates to grade 3 (West Haven cri-teria) to protect the airway.26,27In addition to preventing aspiration in the patient with compromised mental status, intubation and sedatives help control agitation, which can lead to surges in intracranial pressure Patients with encephalopathy beyond grade 3 are very difficult to manage without intubation and sedation.28
Sedation is best achieved with a short-acting sedative alone or in combination with a short-acting narcotic Recent evidence supports the use of propofol for this purpose In a small study, propofol was given to seven patients with ALF and profound encephalopathy
Intracranial pressure (ICP) remained normal in six of
Table 3 Acute Liver Failure: General Management Guidelines
On Admission Daily Tid Hourly If Indicated Monitoring IV access, CVP and arterial
line, Foley catheter
Blood sugar Mental status Mechanical intubation,
ICP monitoring
Thorough history
and physical
Interview family members
Laboratories Liver panel, renal panel,
CBC, PT, Hep A,B,C serologies, HSV, CMV, EBV, ceruloplasmin, ANA, anti-sm Ab, SPEP, HIV, acetaminophen level, toxicology screen, cosyntropin stimulation test, TSH, blood type, blood cultures
Basic laboratories, AFP, arterial ammonia (or more if mental status deteriorating phosphate, factor V level
Blood gas Changes in
ICP monitor
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 Ab, antismooth muscle antibody; CBC, complete blood count; CMV,
cytomegalo-virus; CT, computed tomography; CVP, central venous pressure; EBV, Epstein-Barr cytomegalo-virus; HSV, herpes simplex cytomegalo-virus; HIV, human
immunode-ficiency virus; ICP, intracranial pressure; IV, intravenous; PT, prothrombin time; SPEP, serum protein electrophoresis; TSH, thyroid stimulating
hormone; US, ultrasound.
INTENSIVEMANAGEMENT OFHEPATIC FAILURE/RINELLA, SANYAL 243
Trang 7seven patients with ALF given propofol at 50 mg/kg/
min, suggesting propofol may have independent
benefi-cial effects on ICP.29 Paralytics are usually avoided
because they can mask seizure activity However, they
may be used in specific cases to facilitate management
when the subject does not respond appropriately to
sedation In such cases, it is imperative to consider the
possibility of seizure activity if the clinical picture
continues to deteriorate H2 antagonists or proton
pump inhibitors may decrease the incidence of ulcer
disease in mechanically ventilated patients30; however,
the theoretical risk of increasing the incidence of
pneumonia has not been studied in this population
PREVENTION AND MANAGEMENT
OF COMPLICATIONS
Circulatory Dysfunction
Derangements in circulatory function manifest early in
ALF and are often progressive They are characterized by
generalized vasodilation, increased cardiac output,
de-creased systemic vascular resistance, and a low mean
arterial pressure (MAP).31–33It is challenging to
distin-guish this clinical picture from the hemodynamics of
sepsis, particularly given that infection is common and
often a fatal complication.34 Factors such as adrenal
insufficiency also complicate management by making
the vasculature less responsive to vasopressive agents.35,36
In general terms, fluids and vasopressors should
be used to maintain adequate cerebral perfusion pressure
(CPP) (50 mm Hg to 65 mm Hg) while avoiding
cerebral hyperemia from hyperperfusion.37,38 Because
the circulatory disturbance in ALF is characterized by
vasodilation and increased cardiac output,
norepinephr-ine is frequently the vasopressor of choice
Infection
Patients with ALF are particularly susceptible to severe
infection due to many immunological defects such as
defective phagocytic function and decreased
comple-ment levels.39–42Bacterial or fungal sepsis is a frequent
cause of death in this population Much like other
immunocompromised hosts, their response to infection
is atypical in that signs such as fever or leukocytosis are
absent in 30% of cases.43 Thus sepsis is both frequent
and difficult to diagnose in subjects with ALF In a
prospective study of 887 patients with ALF, one or more
bacterial infections occurred in 37.8%; however, an
incidence of up to 80% has been reported.44 Of these,
gram-positive cocci were the most common organisms
isolated, although Escherichia coli and Klebsiella were also
frequent pathogens.45 Overall, pneumonias make up
50% of bacterial infections in ALF with bacteremia
and urinary tract infections occurring in 20 and 25%,
respectively These infections presented at a median of
5, 3, and 2 days after the onset of ALF.44 Given the frequency of both gram-negative and gram-positive infections in this population, broad spec-trum antibiotic coverage should be administered avoid-ing aminoglycosides due to their nephrotoxicity.34 Although no randomized controlled trials have demon-strated improved survival with prophylactic antibiotics, parenteral antibiotics are associated with a lower inci-dence of infection46 (Fig 1).47 Given these data, pro-phylactic broad-spectrum antibiotics seem justifiable given that uncontrolled infection in such patients is often catastrophic.48,49
Systemic Inflammatory Response Syndrome Even in the absence of documented infection, systemic inflammatory response syndrome (SIRS) is common in those with ALF and is likely due to a surge of cytokine release.50 In a study from King’s College, 57% of 887 patients with ALF developed SIRS The presence of SIRS on admission was independently associated with more severe illness, worsening of encephalopathy, and subsequent death In those patients that were infected (54%), mortality increased with each additional compo-nent of SIRS At this point it remains unclear how additional infection contributes or which component of the observed inflammatory response originates from humoral factors released by the necrotic liver.34,46,51
Adrenocortical Insufficiency Adrenocortical insufficiency can worsen hyperdynamic cardiovascular collapse typical of ALF or septic shock.52 This should be considered when the patient fails
Figure 1 The effect of antibiotic prophylaxis on the prevalence
of documented infection patients with acute liver failure (Adapted from Salmeron et al.47)
Trang 8to respond to volume resuscitation.35 In sepsis,
supra-physiological doses of steroids in patients with adrenal
insufficiency have been shown to reduce vasopressor
requirements and improve outcome.36,53 Adrenal
dysfunction appears to also be prevalent in patients
with ALF; 62% of patients with ALF were found to
have an abnormal response to high-dose corticotrophin
stimulation The patients with pronounced
hemody-namic instability had more marked evidence of adrenal
insufficiency, suggesting that it may contribute to the
pattern of cardiovascular collapse seen in liver failure.54
The benefit of stress-dose steroids in this population
needs to be tested in a randomized-controlled trial;
however, given these data, it is reasonable to look for
and consider treating adrenal insufficiency in patients
with ALF
Renal Failure
Renal failure is common in those with advanced liver
failure and is multifactorial in etiology Common causes
of renal failure in this population include prerenal
azotemia, renal ischemia, acute tubular necrosis, and
hepatorenal syndrome A majority of patients with
ALF complicated by profound hypotension and cerebral
edema will require renal replacement therapy.31Due to
the marked vasodilation that characterizes such patients,
continuous venovenous hemofiltration (CVVH) tends to
be better tolerated and may have more beneficial effects
on ICP.55,56 Moreover, intermittent hemodialysis has been associated with increases in ICP and decreases in CPP, whereas the opposite has been shown in patients receiving CVVH.55,57
Hepatic Encephalopathy and the Development
of Intracranial Hypertension The development of HE and subsequent cerebral edema and intracranial hypertension (ICH) define prognosis in patients with ALF.2,7,58 Treatment options for such patients are limited As a result, 30% of patients with ALF and cerebral edema succumb to cerebral herniation while awaiting an organ.7,31Without urgent transplantation, mortality can exceed 90% in those who have uncontrolled ICH
The pathogenesis of cerebral edema is complex (Fig 2) ALF leads to many hemodynamic changes, including impairment of cerebrovascular autoregulation and blood flow This impairment makes the standard assumption that CPP¼ MAP ICP less reliable.38
Other factors such as high arterial ammonia levels contribute to brain edema through the accumulation
of glutamine and alanine in astrocytes In response to swelling, a vasodilating factor is released that leads to increased CBF and thus increased ICP.59
Arterial ammonia levels > 200 mmol/L in the setting of ALF have been shown to herald impending cerebral herniation and poor outcome.60,61 Other
Figure 2 Factors leading to the development of brain edema and potential therapeutic interventions.
INTENSIVEMANAGEMENT OFHEPATIC FAILURE/RINELLA, SANYAL 245
Trang 9markers of brain cell dysfunction and damage such as
s100-b and neuron-specific enolase (NSE) have also
been evaluated as potential predictors of impending
herniation in the setting of ALF and acute on chronic
liver failure with negative results.62Currently, no serum
markers of brain cell dysfunction reliably demonstrate
neurological injury and poor outcome
Unfortunately, it can be difficult to predict which
patients are likely to develop elevated ICP Clinical signs
such as arterial hypertension, fever, and agitation can
precede episodes of severe ICH; however, these are not
reliable predictors because elevated ICP is often
clin-ically silent.63Although a computed tomographic (CT)
scan is usually used to look for cerebral edema, a normal
scan does not exclude the presence of edema because its
appearance on imaging may be delayed
INTRACRANIAL PRESSURE MONITORING
A significant clinical challenge in the management of
ALF is the decision to place an ICP monitor There are
no strict guidelines related to the use of these monitors
and experience across institutions is highly variable
Noninvasive techniques have not proven to be
benefi-cial and direct ICP monitoring is the only reliable
modality for the measurement of ICP The benefit
that can be derived from ICP monitoring is twofold
First, it allows for the early detection and treatment of
ICH because it can be clinically silent.63Second, it can
provide invaluable information about the likelihood of
neurological recovery when deciding whether to
pro-ceed with liver transplantation, such as when CPP is
persistently low Sustained CPP< 40 mm Hg predicts
a high likelihood of ischemic brain injury that typically
results in a poor neurological outcome after
transplan-tation.64,65Figure 3 proposes an algorithm for the use
of ICP monitors in ALF
Although treatments aimed at reducing ICP can
be used without an ICP monitor, an accurate ICP reading permits targeted therapy to optimize CPP and detect abrupt surges in pressure that necessitate addi-tional therapy Concomitant measurement of jugular bulb oxygen saturation,32,66which allows measurement
of brain oxygen utilization, can also be useful in the management of these patients.32 Jugular bulb oxygen saturation > 80% or < 60% predicts elevation in ICP with good sensitivity and specificity.31Jugulovenous O2
saturations < 50% may herald an increase in anaerobic cerebral glycolysis, increased lactate:pyruvate ratio, and worsening cerebral edema.67
When and in Whom to Insert an Intracranial Pressure Monitor
To justify the risks of ICP monitor placement, the monitor needs to be placed under controlled circum-stances, when increased ICP is likely to rise but before uncontrolled ICH and herniation occur ICP monitor-ing should be considered for mechanically ventilated patients with grade 3 or 4 encephalopathy with poor prognosis (Table 2) but who are otherwise good candi-dates for liver transplant (Fig 3) Other predictors of increased ICP such as arterial ammonia> 150 mmol/L could be used to time monitor placement In those with poor prognosis without orthopedic liver transplant (OLT), ICP monitoring can guide therapy and prevent surges in ICH before and during OLT
Risks of Intracranial Pressure Monitoring
As with all interventions, the risks of ICP monitor placement need to be balanced against the accuracy and usefulness of the information to be gained No random-ized, controlled trial is available to compare different
Figure 3 Proposed algorithm for the use of an intracranial pressure monitor.
Trang 10catheters in the setting of ALF Types of catheters include
epidural, subdural, parenchymal, and intraventricular
catheters Blei et al performed a survey of transplant
centers across the United States They estimated that
20% of ICP monitoring resulted in intracranial bleeding
Epidural catheters had the lowest rate of bleeding
com-plications (3.8%) and subdural and parenchymal catheters
the highest; 20% and 22%, respectively.68A recent
multi-center study from the ALF study group showed that ICP
monitors were only used in 92/332 patients (28%) with
ALF and severe encephalopathy; however, the frequency
of monitoring differed between centers Ten percent had
intracranial bleeding as a result of the ICP monitor In
two of these patients, ICP monitoring was directly
associated with the patient’s death.69Although the risk
of complications is greater,70 subdural catheters give a
more reliable estimate of ICP than epidural catheters.68
Bleeding complications can be decreased
signifi-cantly with the use of recombinant factor rVIIa given
immediately before the procedure.25 The frequency of
factor VII dosing was variable in this study; however, as a
group all patients that received factor VII normalized
their prothrombin time (PT) and were able to have ICP
monitors placed (compared with 38% in the FFP alone
group) The ideal initial dose and subsequent doses of
factor VII necessitates further study.71 The data show
that ICP monitoring can be an effective tool for
manag-ing elevated intracranial pressure; however, ICP
mon-itors have not been shown to improve survival Currently
there is no consensus about the use of ICP monitoring or
whether the more accurate but higher-risk subdural
catheters or the less accurate but safer epidural catheter
should be used Individual centers will continue to use
what they are comfortable with; however, their decision
may be influenced by the decreased availability of
epi-dural catheters
Prevention and Treatment of Increased
Intracranial Pressure
Routine measures such as elevation of the head of the
bed to 30 degrees,55sedation, minimal stimulation, and
mechanical ventilation to minimize cerebral stimulation
should be adhered to whenever possible The
manage-ment should be focused on maintaining an adequate
CPP (> 50 mm Hg) while minimizing elevations in ICP
(< 20 mm Hg) Blood pressure should be maintained to
achieve a CPP between 50 and 65 mm Hg Prolonged
CPP below 50 mm Hg in the setting of ICH or an ICP
greater than 40 mm Hg is associated with poor
out-come.65
HYPERTONIC SALINE
The use of hypertonic saline is thought to help restore
the osmotic gradient across the astrocyte membrane A
randomized, controlled trial recently demonstrated that
induction and maintenance of hypernatremia (145 to
155 mmol/L) in patients with grade 3 or 4 encephalop-athy resulted in a decreased incidence and severity of ICH.72 Other techniques to reduce brain water accu-mulation through the reduction of arterial ammonia remain under investigation.73–75
MANNITOL
Mannitol administration leads to increased plasma os-molality in brain capillaries, resulting in movement of water out of the brain according to Starling’s law It has been shown to decrease episodes of cerebral edema and result in improved survival in a cohort of patients with ALF (47.1 and 5.9%, respectively, p ¼ 008).76 Its use, however, is limited in renal failure and can lead to a paradoxical increase in brain swelling if osmolality is not controlled If more than two doses are to be used, plasma osmolality must be checked to assure that it remains
< 320 Osm/L
HYPERVENTILATION
Hyperventilation is an effective technique to decrease cerebral blood flow (CBF) and ICP It does so through precapillary hypocapnic vasoconstriction and helps re-store CBF autoregulation.61,77–79Although prophylactic hyperventilation appears to be ineffective in preventing the development of ICH,77it can be useful in controlling acute surges in ICP
INDOMETHACIN
Indomethacin leads to cerebral vasoconstriction effects via altering cerebral temperature and extracellular pH and inhibition of the endothelial cyclooxygenase path-way.80 Its effectiveness has been proven in an animal model81and in a small cohort of patients with ALF.82 However, due to its multiple systemic side effects in patients with ALF, its routine use cannot be supported
THIOPENTAL SODIUM
In a small, uncontrolled study, thiopental sodium was effective in reducing ICP.83 Unfortunately, its use is associated with significant hemodynamic derangements that may necessitate escalation of vasopressor or inotropic support Thus thiopental use should be reserved for surges of ICH unresponsive to standard medical therapy
HYPOTHERMIA
Moderate hypothermia (32 to 33C) in animal models of ALF has been effective in improving encephalopathy and reducing brain water.84,85Clinical studies of hypo-thermia have also shown significant reduction in ICP
Jalan et al were able to demonstrate that cooling patients with refractory ICH to 32C decreased ICP to< 20 mm
Hg Subsequently they demonstrated a reciprocal in-crease in ICP with rewarming.86 Since this study, the same and other groups have also shown that moderate INTENSIVEMANAGEMENT OFHEPATIC FAILURE/RINELLA, SANYAL 247