566

Critical Care Management of Gastrointestinal

Bleeding and Ascites in Liver Failure
Kapil Rajwani, MD1 Brett E. Fortune, MD, MSc2 Robert S. Brown Jr., MD, MPH2

1 Division of Pulmonary and Critical Care, Weill Cornell Medical
College, New York, New York
2 Division of Gastroenterology and Hepatology, Center for Liver
Diseases and Transplantation, Weill Cornell Medical College,
New York, New York
Address for correspondence Robert S. Brown Jr., MD, MPH, Division
of Gastroenterology and Hepatology, Weill Cornell Medical College,
1305 York Avenue, 4th Floor, New York, NY 10021
(e-mail: Rsb2005@med.cornell.edu).

Semin Respir Crit Care Med 2018;39:566–577.

Abstract Gastrointestinal (GI) bleeding and ascites are two significant clinical events that
frequently present in critically ill patients with chronic liver failure or decompensated
cirrhosis. GI bleeding in patients with cirrhosis, particularly portal hypertensive-
associated bleeding, carries a high short-term mortality (15–25%) and requires early

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initiation of a vasoactive agent and antibiotics as well as timely endoscopic manage-
ment. Conservative transfusion strategies and adequate airway protection are also
imperative to assist in bleeding control. The presence of ascites among hospitalized
cirrhotics requires early analysis of ascitic fluid to diagnose spontaneous bacterial
Keywords peritonitis and initiate appropriate antibiotics and albumin to reduce patients’ high
► chronic liver failure associated mortality rates of greater than 25%. Appropriate utilization of portal
► gastrointestinal decompression using transjugular intrahepatic portosystemic shunt placement for
bleeding selected patients with failure to control bleeding or ascites and early consideration for
► varices liver transplantation referral is critical to improve patient survival. This review will aim
► portal hypertension to elucidate the current strategies for the management of critically ill patients with
► ascites chronic liver failure presenting with GI bleeding or ascites.

Gastrointestinal (GI) bleeding and ascites are common life-
threatening problems seen in patients presenting with decom-
pensated cirrhosis or chronic liver failure. Portal hypertensive-
related bleeding, particularly gastroesophageal varices,
accounts for 50 to 90% of bleeding in patients with liver
dysfunction with peptic ulcers being the second most common
etiology.1 Appropriate management of GI bleeding in patients
with liver disease focuses on a variety of issues including blood
product transfusion, mitigating issues associated with trans-
fusions, and endoscopic identification and control of bleeding.
The short-term mortality from an episode of variceal bleeding
can range from 15 to 30% with higher mortality associated with
more severe liver dysfunction.
The presence of abdominal free fluid or ascites is a con-
sequence of severe portal hypertension and hypoalbuminemia
and is a common clinical event observed in hospitalized
patients with decompensated cirrhosis. The development of
ascites secondary to cirrhosis is associated with a 1-year
mortality rate of 15 to 20%, and the acute infection of ascitic
fluid, called spontaneous bacterial peritonitis (SBP), is asso-
ciated with an in-hospital mortality of 10 to 20%.2,3 Early
detection and treatment of SBP and appropriate management
of volume and ascites are critical for hospitalized cirrhotic
patients. This review will address the general principles of
management for GI bleeding, particularly portal hypertensive-
associated bleeding, as well as examine strategies to control
ascites in patients hospitalized with chronic liver failure.
A General Approach to Manage GI Bleeding
in Patients with Chronic Liver Failure
The general approach to manage GI bleeding in a patient with
chronic liver failure involves establishing adequate intrave-
nous (IV) access, providing adequate volume resuscitation

Issue Theme Hepatic Failure and Critical Copyright © 2018 by Thieme Medical DOI https://doi.org/
Care; Guest Editors, Igor Barjaktarevic, Publishers, Inc., 333 Seventh Avenue, 10.1055/s-0038-1672200.
MD, PhD, Ram Subramanian, MD, and New York, NY 10001, USA. ISSN 1069-3424.
Tisha Wang, MD Tel: +1(212) 584-4662.
 Critical Care Management of GI Bleeding and Ascites in Liver Failure
with IV fluids and blood products, and obtaining control of
the bleeding source. One must assess the degree of volume
loss using a combination of physical exam findings, vitals,
and laboratory values. In addition, assessment of other
comorbidities that may be contributing to bleeding, such
as uremia, vitamin K deficiency, and severe thrombocytope-
nia, must be assessed.
Large bore IV access (e.g., 16-gauge IV) allows for rapid
infusion of crystalloid and blood products. A rapid infuser
may be necessary to infuse large volumes of blood products
expeditiously to restore lost blood volume as well as keep up
with ongoing blood loss until adequate source control is
achieved. In many situations, a patient may require massive
transfusion, defined as transfusion of 10 units of red cell in 24
hours or 3 units within 1 hour.4 Crystalloid can be adminis-
tered as a volume expander initially to help maintain hemo-
dynamic stability followed by transfusion of red cells.
Excessive crystalloid infusion, however, should be avoided
as it has been shown to result in worse outcomes.5–7
Complications of Large Volume Transfusion
Massive transfusion requires the appropriate mix of the
various blood components to be administered to prevent
the worsening of coagulopathy and thrombocytopenia. How-
ever, clinicians must be careful to avoid overtransfusion.
There are many complications associated with the use of
large volumes of blood products including changes in ionized
calcium, potassium, and acid–base balance. Lower transfu-
sion goals for GI bleeding in general and especially in those
with portal hypertension have been supported in various
studies.8,9 In one trial, 921 patients with acute upper GI
bleeding were randomly assigned to receive a transfusion
when the hemoglobin fell below 7 versus 9 g/dL. Patients in
the lower trigger group (7 g/dL) had a higher probability of
survival at 6 weeks, less continued bleeding, and fewer
complications relative to the liberal transfusion group. Of
note, however, patients with massive exsanguinating bleed-
ing were excluded from the trial.8 Another important con-
sideration supporting limiting transfusion specifically in
patients with portal hypertensive-associated bleeding is
the risk of rebound portal hypertension with increases in
central venous pressure and induction of rebleeding.8,10–12
Electrolyte Abnormalities Seen in Transfusions
Serum ionized calcium concentration should be monitored
as precipitous drops can occur from citrate binding of ionized
calcium. This can lead to cardiac arrhythmias and paresthe-
sias.13,14 Calcium is also an important part of the coagulation
cascade.
Hyperkalemia may be a consideration especially in situa-
tions of large rapid transfusion of older blood products,
particularly in patients with renal impairment.15 The potas-
sium of stored blood supernatant increases by 1 mEq/day,
from a baseline of approximately 3 mEq/L at the time of
donation. This rate can be increased to 1.5 mEq/day with
irradiation. The overall volume of the supernatant is small;
so, the actual amount infused within a unit of RBC is
Rajwani et al. 567
approximately 7 mEq. This can be mitigated by using fresher
blood products as well as washing red cells to remove the
extracellular potassium.15
Hypothermia
Rapid transfusion of chilled blood can lead to a drop in the
core temperature. Six units of RBCs at 4°C will reduce the
body temperature of a 70-kg adult by 1°C. This drop of body
temperature can increase coagulopathy as well as increase
risk of cardiac arrhythmias.16 Hypothermia can reduce the
activity of coagulation proteins as well as prevent the activa-
tion of platelets.17,18 This effect has been demonstrated at
core temperatures of 34°C and below. A fluid warmer device
should be used when large volume transfusions are required.
Coagulopathy
Coagulopathy in the setting of massive bleeding may be
preexisting due to the underlying liver disease. It can also be
exacerbated by dilution of factors from infusion of large
quantities of crystalloid and massive transfusion of red cells.
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In addition, a consumptive coagulopathy can occur secondary
to tissue injury or from reduction of activity of coagulation
factors from hypoxia, shock, or hypothermia as above.19 Fresh
frozen plasma (FFP) should be administered if the prothrom-
bin (PT) or activated partial thromboplastin time (aPTT) values
exceed 1.5 times control if not due to liver disease.20 Tests such
as the PT and international normalized ratio (INR) in patients
with liver disease are less predictive of bleeding risk, but FFP
should be administered in the setting of large volume transfu-
sion to help prevent a dilutional coagulopathy.21 An ideal ratio
remains controversial with the trauma literature demonstrat-
ing benefits at a ratio of 1:1:1 of red cell, FFP, and platelets.22–25
However, some literature may support a somewhat modified
ratio and it is unknown if the same ratio would apply to
nontraumatic bleeding.26–28 Consideration should also be
given to empiric vitamin K repletion especially in patients
with cholestatic disease, poor nutrition, or recent antibiotics.
Similar to the dilution and consumption of other coagula-
tion factors, fibrinogen deficiency also needs to be addressed
during resuscitation of the bleeding patient. Early attention
to fibrinogen replacement is of even greater importance in
cirrhotic patients since baseline production is reduced. In
addition, patients with liver disease may have increased
fibrinolysis or a dysfibrinogenemia.21 Cryoprecipitate or
fibrinogen concentrate should be administered when fibri-
nogen levels are less than 100 mg/dL or when the lack of
functional fibrinogen is demonstrated on a viscoelastic
test.29,30 One should also consider using antifibrinolytics
especially if there is evidence of hyperfibrinolysis on viscoe-
lastic tests. Available agents include tranexamic acid and
epsilon aminocaproic acid. The optimal dosing in liver dis-
ease is not known but can be extrapolated from other causes
of hemorrhage. Ongoing studies will hopefully provide
further guidance for treating this patient population in the
near future.
Human recombinant factor VIIa infusion has not been
shown to have a meaningful benefit in nontraumatic bleed-
ing. There has been some trend toward lower transfusion
Seminars in Respiratory and Critical Care Medicine Vol. 39 No. 5/2018
568 Critical Care Management of GI Bleeding and Ascites in Liver Failure
requirements, but conflicting results were seen in two
studies involving Child-Pugh class B and C patients and there
is a potential increased risk for thrombosis.31,32 Due to
limited evidence of efficacy, in addition to its high cost,
routine use is therefore not recommended.33,34
In regard to monitoring, as alluded earlier, PT, aPTT, and
fibrinogen have limitations for clinical interpretation due to
patients with decompensated liver disease having baseline
prolongations of PT and aPTT along with preexisting throm-
bocytopenia, elevated D-dimer, and reductions in fibrinogen.
Therefore, these tests are not helpful in predicting bleeding
risk at baseline or during massive transfusion.35,36 Compre-
hensive viscoelastic testing such as thromboelastography
(TEG) or thromboelastometry (ROTEM) may be more helpful
in this population. These tests trace out the changes in clot
formation and lysis utilizing changes in torque between a pin
and a cup that occur as the blood clots. These tests have
reduced the use of blood products in patients with liver
disease, although the overall evidence remains limited.37–40
Further exploration in viscoelastic testing is necessary to
better understand their clinical utility.
Thrombocytopenia
Massive transfusion can also lead to a dilution of platelets
potentially exacerbating bleeding; 10 to 12 units of trans-
fused RBCs can result in a 50% fall in the platelet count. Each
unit of platelets can increase the platelet count by 5,000/µL or
30,000/µL for a full six-unit adult dose. In the setting of active
bleeding, it has been recommended to maintain a platelet
count of at least 50,000/µL.41
Respiratory Failure
Brisk upper GI bleeding can potentially lead to aspiration
especially in settings where protective upper airway reflexes
may be compromised (e.g., overt hepatic encephalopathy). In
addition, situations of either hemorrhagic shock or the down-
stream effects of massive transfusion, namely upper airway
edema, or volume overload may necessitate endotracheal
intubation for airway protection and/or mechanical ventila-
tion.42 However, whether preemptive endotracheal intubation
is protective against aspiration pneumonia remains unclear.
One study suggested that it may increase the aspiration risk
which may not have existed earlier but may become an issue in
the setting of sedation, airway manipulation, and flattening of
the patient.43 The risk–benefit equation must be evaluated on a
case-to-case basis, especially prior to endoscopy.
Placement of a nasogastric (NG) tube to prevent aspiration
has not been well studied. However, a NG tube can help
empty the stomach and assist in clearing of blood for sub-
sequent endoscopy. If the decision is made to proceed with
intubation, certain precautions can be taken to reduce
complications. Koenig et al utilized ultrasound to evaluate
for a filled stomach prior to intubation attempt—if a patient
was found to have a full stomach, a NG tube was placed prior
to intubation attempt.44 Rapid sequence intubation (RSI)
should also be considered when attempting intubation dur-
ing an upper GI bleed. RSI is the administration of an
induction agent and a neuromuscular blocking agent to
Seminars in Respiratory and Critical Care Medicine Vol. 39 No. 5/2018
Rajwani et al.
rapidly place an endotracheal tube. Preoxygenation is
required to provide a reservoir of oxygen to allow tolerance
of the apnea during intubation without desaturation. Bag-
ventilation is therefore avoided to reduce risk of gastric
insufflation and potential risk of subsequent aspiration.
The technique also prevents stimulation of the oropharynx
and resultant gag that may result in emesis and aspira-
tion.45,46 Adequate monitoring, IV access, suction, and alter-
native intubating devices should be on hand to optimize
success rates.
Transfusion-Associated Lung Injury and
Transfusion-Related Cardiac Overload
In addition to the causes of respiratory failure discussed earlier,
transfusions have also been associated with a diffuse lung
injury that usually occurs within 6 hours of transfusion.47,48
The rate of transfusion-associated lung injury (TRALI) seems to
be relatively low at approximately 1 in 5,000 units transfused,
but 34% of deaths related to transfusions reported to the FDA
between 2012 and 2016 were due to TRALI.49 The risk seems to
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be the highest in the setting of platelet transfusion, followed by
transfusion of FFP.50,51 An increased risk has been linked to
products from female donors, those with an increased volume
of transfused anti–human neutrophil antigen antibody, and an
increased volume of highly reactive transfused anti–human
leukocyte antigen (HLA) class II antibody.52 The diagnosis is
based on findings of acute hypoxemia and bilateral pulmonary
infiltrates on chest X-ray without evidence of left atrial hyper-
tension or preexisting lung injury. The exact mechanism of
injury is unknown, but a two-hit mechanism is generally
accepted. The first hit is the sequestration and priming of
neutrophils in the lung microvasculature due to recipient
factors such as endothelial injury. The second hit is activation
of these neutrophils by a blood product factor leading to
damage of the pulmonary capillary endothelium.53–55 Treat-
ment is mainly supportive similar to that of other causes
of acute lung injury and acute respiratory distress syn-
drome (ARDS) including use of lung-protective ventilation
strategies.56
Difficult to differentiate from TRALI, transfusion-related
cardiac overload (TACO) is related to fluid overload from
hydrostatic forces causing pulmonary edema. Risk factors
include patients with reduced cardiac function, renal dys-
function, and rapid blood product administration among
others. These patients present similar to those with TRALI;
however, certain features such as hypertension, distended
neck veins, and elevated brain natriuretic peptide (BNP)
levels may point to a diagnosis of TACO. Therapy is focused
on minimizing further fluid administration, respiratory sup-
port with oxygen and possibly noninvasive positive pressure
ventilation, and the use of diuretics.57–59
Portal Hypertensive-Associated Bleeding
The previously mentioned general principles can be applied
to all forms of bleeding seen in patients with chronic liver
failure. However, the most common cause of GI bleeding is
portal hypertensive-associated bleeding. Gastroesophageal
 Critical Care Management of GI Bleeding and Ascites in Liver Failure Rajwani et al. 569

variceal bleeding occurs in 25 to 35% of cirrhotics with
varices.60 Since local vascular changes and elevated portal
pressure are thought to be the most important factors
resulting in hemorrhage, interventions to reduce portal
pressure and ligate bleeding varices should be the primary
goal. As opposed to other forms of upper GI bleeding that
have a greater than 90% rate of spontaneous cessation,
variceal bleeding spontaneously stops only in approximately
50% of patients.60,61 In addition to the basic management of
GI hemorrhage outlined earlier, additional strategies should
be instituted for portal hypertensive-associated bleeding
(see ►Fig. 1).
Pharmacological Therapy
The first step is initiation of pharmacological therapy with
vasoactive agents. These drugs should be started empirically
in patients known to have or at risk of having portal hyper-
tension at the time of their upper GI bleed presentation.62
Vasoactive medications decrease portal inflow and have
been shown to obtain bleeding control. Options include
tory mediators, such as glucagon.66 It is administered as a
bolus followed by a continuous infusion. Octreotide is a
longer acting version of somatostatin that is available in
the United States. Usual octreotide dosing is an initial 50 µg
bolus followed by a continuous infusion of 50 µg per hour.
Somatostatin and octreotide have been shown to aid in
hemostasis and prevent rebleeding; however, no clear mor-
tality benefit has been demonstrated.67,68 Initial hemostasis
is achieved in 60 to 100% of patients with use of somatostatin
or octreotide either alone or in combination with endoscopic
intervention.69–73 Rebleeding occurs in approximately 9 to
30% of patients.74–77 The combination of somatostatin or
octreotide with endoscopic sclerotherapy has been shown to
be more effective than using either alone.75,78,79 Similarly,
combination therapy with somatostatin or octreotide
and endoscopic variceal ligation was more effective when
compared with endoscopic variceal ligation alone.67,80 When
compared with terlipressin, somatostatin and octreotide
showed similar rates of initial hemostasis, rebleeding, and
mortality.81 Somatostatin and its analogs are tolerated well

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vasopressin, terlipressin, and somatostatin and its analogs
such as octreotide. One agent, terlipressin, is associated with
less mortality but is not currently available in the United
States.63,64 The typical duration of vasoactive therapy after
control of bleeding is 3 to 5 days.65
Somatostatin and Its Analogs
Somatostatin decreases portal inflow by indirectly causing
splanchnic vasoconstriction via the inhibition of vasodila-
with few side effects.82
Terlipressin
Terlipressin is a synthetic analog of vasopressin that is
administered at an initial dose of 2 mg IV bolus every 4 hours
and can be titrated down to 1 mg IV every 4 hours once
hemorrhage is controlled. It has been shown to reduce all-
cause mortality.63 Terlipressin has a more sustained hemo-
dynamic effect on portal pressure and portal blood inflow

Patient with chronic liver failure presenting with GI bleeding

Hospital triage, airway protection as needed, fluid resuscitation

Maintain hemoglobin 7-8 g/dL, restrictive transfusion

Vasoactive agent (e.g., octreotide) and antibiotic (e.g., ceftriaxone)

Endoscopy within 12 h or less

Confirm presence of bleeding varices and treat CTP score 10-13

with banding ligatures

Balloon tamponade and rescue TIPS if banding fails TIPS candidate?

Assess for liver transplantation candidacy

Fig. 1 Suggested management of acute GI bleeding in patients with chronic liver failure. CTP, Child–Turcotte–Pugh; GI, gastrointestinal; TIPS,
transjugular intrahepatic portosystemic shunt.

Seminars in Respiratory and Critical Care Medicine Vol. 39 No. 5/2018

570 Critical Care Management of GI Bleeding and Ascites in Liver Failure
than octreotide.64,83 Adverse effects include hyponatremia,
necessitating at least daily sodium level monitoring. How-
ever, though widely available outside the United States,
terlipressin remains unavailable in the United States.
Vasopressin
Vasopressin constricts mesenteric arterioles and decreases
portal venous inflow.84 It has been shown to help with initial
hemostasis in 60 to 80% of patients. It has not been shown to
improve survival or reduce rebleeding however.63 Usual
dosing is a 0.4-unit bolus followed by an infusion of 0.4 to
1 units/min, and can be used with IV nitroglycerin to
decrease its systemic hemodynamic effects.85–88 Complica-
tions related to vasopressin include the possibility of myo-
cardial, cerebral, bowel, and limb ischemia. Therefore,
vasopressin is rarely used for the first-line management of
variceal hemorrhage in the United States.
Antibiotics
Infection is associated with an increased risk of bleeding and
mortality; up to 20% of patients with cirrhosis and GI
bleeding have a bacterial infection. Upward of 50% develop
an infection while in the hospital.89 Common infections
include SBP, urinary tract infections, respiratory infections,
and primary bacteremia.
Prophylactic antibiotics in cirrhotic patients who are
hospitalized with GI bleeding have shown a reduction in
infectious complications and mortality.89–95 Antibiotics also
may reduce the risk of recurrent bleeding.96 The specific
choice of antibiotics, duration of therapy, and patient selec-
tion remain unclear. There is a wide variation in different
studies in terms of choice and duration of therapy. Common
choices in most studies include quinolones or cephalosporins
for an average duration of approximately 7 days.97,98 Local
resistance patterns should be considered when choosing a
regimen; quinolone resistance is an increasing problem in
patients at some centers.90
Proton Pump Inhibitors
Proton pump inhibitors (PPIs) have been shown to reduce the
rate of rebleeding from peptic ulcers and should be started
routinely on any patient presenting with signs and symp-
toms concerning for an upper GI hemorrhage.99,100 PPIs have
also been shown to be useful to reduce the size of esophageal
ulcers after endoscopic band ligation and potentially reduce
early rebleeding as well. The exact duration of therapy post–
endoscopic band ligation, without other indications for a PPI,
remains unclear.101–103 However, chronic PPI use appears to
be associated with decreased survival for hospitalized cir-
rhotics and assessment of PPI duration should be performed
prior to hospital discharge.104
Endoscopic Management of Gastrointestinal
Bleeding
Urgent endoscopy, usually within 12 to 24 hours of bleeding
presentation, has been recommended to assess and manage
acute GI hemorrhage.65 Proper fluid resuscitation and airway
Seminars in Respiratory and Critical Care Medicine Vol. 39
Rajwani et al.
protection will depend on the extent of bleeding and cogni-
tive level of the patient. Airway protection with endotracheal
intubation is often considered, particularly in large transfu-
sion requirements and in patients with hepatic encephalo-
pathy. Initiation of vasoactive therapy prior to endoscopic
intervention is important, as one of the benefits is to improve
endoscopic visualization. If visualization is difficult, motility
agents, such as erythromycin, have been used with some
success.105 Use of endoscopic band ligatures has replaced
sclerotherapy as the preferred modality for endoscopic
management of esophageal varices, and should be placed
over the most distal portion of the varix column as well as
over any high-risk lesions until obliteration. Sclerotherapy
should be reserved for patients only where varices or post-
banding ulcers cannot be lifted with the endoscopic cap as
band ligation is superior to sclerotherapy with higher effi-
cacy and lower complication rates.65
If the source of GI bleeding is not portal hypertensive
related, endoscopic management will vary on the source,
such as a peptic ulcer. Potential endoscopic therapies
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include cautery, injection of epinephrine, endoscopic clips,
or combination. For nonportal hypertensive bleeding,
vasoactive treatment can be discontinued immediately,
although it is generally given for at least 72 hours after
endoscopic control of variceal bleeding. Nonselective β-
blockers (e.g., nadolol or propranolol) or carvedilol can
then be started for secondary prophylaxis with dose titra-
tion to achieve a goal heart rate
60 beats per minute if
systolic blood pressure is greater than 90 mm Hg. Repeat
endoscopy should be performed after 1 to 2 weeks until
variceal obliteration.65
Balloon Tamponade
Failure to achieve initial hemostasis with endoscopy can
occur in up to a one-fifth of cases and may require tampo-
nade therapy to stabilize the patient until portal decompres-
sion can be accomplished, such as with transjugular
intrahepatic portosystemic shunt (TIPS) placement. Cur-
rently, balloon tamponade is a secondary therapy and can
achieve high rates of hemostasis but also carries high mor-
bidity and mortality in up to 20% of patients.65 It is critical to
know that the gastric balloon must be reduced after 24 hours
to prevent significant tissue necrosis or perforation and the
esophageal balloon should be used rarely, if ever. Early
clinical trials, mostly outside the United States, have
demonstrated high rates of hemostasis with the use of
transendoscopic esophageal stents as a new method for
tamponade therapy.106 However, further trials are needed
to elucidate their utility in this setting.
Transjugular Intrahepatic Portosystemic Shunt
The risk of rebleeding after initial variceal bleed remains high
over the next 6 weeks, and especially in the first 48 to
72 hours, with over half occurring within the first
10 days.107 Placement of TIPS has been the mainstay of
rescue therapy for patients with refractory bleeding related
to portal hypertension. Access to the hepatic vein is obtained
through the transjugular route and a needle is advanced
No. 5/2018
 Critical Care Management of GI Bleeding and Ascites in Liver Failure
through the liver parenchyma into the portal vein after
which a metal stent is deployed connecting the two vascular
beds and thus causing portal decompression. A TIPS proce-
dure has been shown to be very successful in controlling
bleeding especially in high-risk patients.108,109 In addition to
control of acute bleeding, TIPS has been shown to be effective
in prevention of recurrent variceal hemorrhage.110–114 How-
ever, there is increasing literature to support the earlier use
of TIPS in patients who are stratified as high risk for rebleed-
ing or hemostatic failure. A pivotal study demonstrated high
bleeding control rates and improved survival for cirrhotics
with Child–Turcotte–Pugh (CTP) class B with active endo-
scopic bleeding and CTP class C patients (CTP score: 10–13)
receiving “early” TIPS versus matched patients receiving the
standard of care.115 These findings have been further vali-
dated in large prospective studies and have further refined
the ideal population of greatest benefit from “early” TIPS to
include bleeding patients with CTP class C (score: 10–13) at
presentation.116,117
Complications from a TIPS placement can occur during or
postprocedure. Issues with procedural sedation, difficulty in
accessing the portal vein, liver capsule transgression, and
bleeding related to the procedure are some of the main
procedural concerns. The direct procedural morbidity and
mortality rates remain low.118 Postprocedural complications
include hepatic encephalopathy, shunt migration, and early
occlusion among others. Acute encephalopathy can occur in
5 to 35% with most controlled with medical interventions
such as lactulose.119 If persistent and severe encephalopathy
occurs, a reduction of the stent diameter or total TIPS
occlusion may be considered.120–123 Recent stent device
enhancements may potentially allow TIPS placement with
smaller stent diameters that will not self-expand over time,
and there is hope to reduce encephalopathy rates without
compromising the rate of control of clinical symptoms.124,125
Absolute contraindications to TIPS include uncontrolled
infection, severe tricuspid regurgitation or pulmonary
hypertension, or anatomical barriers such as extensive
malignancy, polycystic liver disease, or vascular thrombosis
of the portal venous system.
Management of Gastric Variceal Bleeding
Bleeding gastric varices pose an additional management
challenge due to the technical difficulty involved with treat-
ment. Options for therapy include medical therapy followed
by endoscopic cyanoacrylate injection, TIPS placement, or
portal decompressive surgery (e.g., distal splenorenal shunt).
If the varices are located along the lesser curvature, endo-
scopic ligation can be used.
Cyanoacrylate glue can be injected directly into varices
and has been shown to be successful in small trials.126,127
Glue injection has also been shown to reduce rebleeding in
one trial.128–130 Overall complications remain low with glue
extrusion being the most common.131
Given that endoscopic therapy is more limited for gastric
varices, interventional radiologic therapy is generally the
first-line intervention for most gastric variceal bleeding.
Rajwani et al. 571
Similar to the management of esophageal varices, TIPS can
also be utilized in those who fail endoscopic intervention.
The initial success rate has been shown to be high, though
rebleeding rates remain high, as well as the risk of post-TIPS
encephalopathy.132–137
Balloon-occluded retrograde transvenous obliteration
(BRTO) is another interventional technique that has demon-
strated some success in the management of bleeding gastric
varices. A catheter is introduced via a spontaneous shunt
(e.g., splenorenal or gastrorenal) into a draining vessel
where a balloon is then inflated followed by sclerosant
injection or coil proximal to the balloon. Excellent bleeding
control has been achieved (90–100%), but technical failure
rates remain an issue.138–141 BRTO can be considered
upfront or in those patients in whom a TIPS may be
contraindicated or when concern for encephalopathy is
high.
Various other therapies such as endoscopic coils, throm-
bin injection, and vascular plugs among others have
been tried and are being studied to help in the manage-
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ment of gastric varices. In addition, combination therapy
may be appropriate based on center expertise and patient
selection.
The General Management of Ascites
Ascites is the most common complication in hospitalized
patients with cirrhosis. Primary evaluation begins with an
abdominal paracentesis to confirm the etiology of ascites
formation with appropriate fluid testing (see ►Table 1).
Usual fluid analysis for portal hypertension due to cirrhosis
demonstrates a high serum-ascites albumin gradient (> 1.1),
<250 polymorphonuclear (PMN) leukocytes/µL, and a low
ascites total protein (< 2.5 g/dL). Initial management consists
of dietary sodium restriction (<2,000 mg) and dual diuretic
therapy with a loop diuretic plus a potassium sparing
diuretic, such as spironolactone and furosemide at a starting
ratio of 100:40 mg daily.142–144 A suggested algorithm to
manage ascites is provided in ►Fig. 2. Recommended treat-
ment goal is to achieve approximately 0.5 to 1 pound of fluid
removal per day. Urine electrolytes may be helpful to deter-
mine adequate diuresis by obtaining a reverse potassium to
sodium ratio (i.e., UNa > UK). Nutrition consultation to edu-
cate patients regarding sodium restriction as well as self-
monitoring of daily weights may lead to improved patient
compliance, especially after hospital discharge. Therapeutic
large volume paracentesis (LVP) should be considered for
patients presenting with symptoms of dyspnea or painful
abdominal girth.
Patients with refractory ascites, defined as unresponsive
to sodium-restricted diet and high-dose diuretics (spirono-
lactone 400 mg/day and furosemide 160 mg/day) or rapidly
recurrent ascites after therapeutic paracentesis, have a poor
prognosis as it usually signals progression of their liver
disease.145,146 They should also be evaluated for other
causes of refractory ascites including portal vein thrombosis
and hepatocellular carcinoma. Nephrotoxic drugs such as
nonsteroidal anti-inflammatory agents should be stopped
Seminars in Respiratory and Critical Care Medicine Vol. 39 No. 5/2018
572 Critical Care Management of GI Bleeding and Ascites in Liver Failure Rajwani et al.

Table 1 Laboratory evaluation of ascitic fluid in the cirrhotic Spontaneous Bacterial Peritonitis
patient All patients with ascites admitted to the hospital, or those
with signs and symptoms of infection, abdominal pain,
Routine Send based on Not encephalopathy, renal failure, or variceal bleeding at any
clinical scenario helpful time, should undergo a diagnostic paracentesis to evaluate
Cell count with Cytology Lactate for SBP. The fluid should be sent for cell count with
differential differential and placed in blood culture bottles at bedside;
Bacterial culture Mycobacterial smear pH an ascitic fluid PMN leukocyte count  250 cells/mm3 or a
and culture positive ascitic fluid culture is diagnostic of SBP if there are
Albumina Adenosine no secondary causes of peritonitis. A diagnosis of SBP
deaminase should result in the administration of empiric antibiotics
Total proteina Amylase as a delay in antibiotics can result in development of shock
and increase mortality.157 Most causes of SBP are due to
Triglycerides
gram-negative agents such as Escherichia coli, with occa-
Bilirubin
sional infections due to streptococcal or staphylococcal
Glucose bacteria.158 Antibiotic choices include a third-generation
Gram stain cephalosporin or a quinolone, and the duration is typically 5
a
to 7 days.159–163 IV albumin (1.5 g/kg body weight within
Always needed on initial paracentesis to determine presence and
6 hours of diagnosis, and 1.0 g/kg on day 3) should be
etiology of portal hypertension. May not be required on subsequent
paracenteses. administered to patients with a creatinine >1 mg/dL, blood

Downloaded by: Universitätsbibliothek. Copyrighted material.

and β-blockers should be discontinued if patients have low
systolic blood pressures (< 90 mm Hg). Oral midodrine can
be administered to help with improvement in renal per-
fusion and management of refractory or recurrent
ascites.147 These patients should be evaluated for liver
transplantation whenever appropriate. Patients with refrac-
tory ascites usually require serial abdominal paracent-
eses.148,149 Albumin should be infused concurrently with
large volume paracentesis when greater than 4 to 5 L are
removed (6–8 g of 25% albumin per liter of fluid
removed).150–153 A TIPS may also be considered in select
patients with refractory ascites.154–156
urea nitrogen >30 mg/dL, or total bilirubin >4 mg/dL to
help reduce the risk of renal failure (►Fig. 2).164–166 Many
experts recommend repeating diagnostic paracentesis after
48 hours of antibiotics. Failure to have a >50% reduction in
the PMN count may suggest that the responsible agent is
not susceptible to the antibiotic regimen chosen. After
resolution of infection, patients who have had any prior
episode of SBP should be on secondary antibiotic prophy-
laxis with trimethoprim–sulfamethoxazole or a fluoroqui-
nolone. In addition, those patients who have an ascitic fluid
protein <1.5 g/dL and at least one of the following should
also be considered to receive primary prophylaxis to pre-
vent a first episode of SBP: serum creatinine 1.2 mg/dL,
blood urea nitrogen 25 mg/dL, serum sodium
130 mEq/
L, or Child–Pugh 9 points with bilirubin 3 mg/dL.152

Patient with chronic liver failure presenting with ascites

Assess for liver transplantation candidacy

Diagnostic paracentesis, send fluid for cell count with diff; fluid culture; fluid albumin,
total protein

SBP Absent SBP Present

Start diuretics; typically furosemide Albumin (1.5 g/kg on day 1 and 1 g/kg
and spironolactone; dietary sodium on day 3) and Antibiotic (e.g.,
restriction (2,000 mg/d) ceftriaxone) for 5-7 d

Yes
Diuretic response? SBP resolved?
If not, consider LVP
No
Change antibiotics and evaluate for
TIPS vs. serial LVP if refractory organism resistance; consider antifungal
abdominal imaging to rule out
ascites secondary cause or peritonitis

Fig. 2 Suggested management of ascites in a hospitalized patient with chronic liver failure. LVP, large volume paracentesis; SBP, spontaneous
bacterial peritonitis.

Seminars in Respiratory and Critical Care Medicine Vol. 39 No. 5/2018

 Critical Care Management of GI Bleeding and Ascites in Liver Failure
However, increasing microbial resistance may lead to reas-
sessment of current prophylaxis guidelines.
Summary
Outcomes related to patients with chronic liver failure pre-
senting with acute GI bleeding or ascites have improved over
time, as management strategies and risk stratification to
predict potential treatment failures have evolved. Portal
hypertensive-associated bleeding, particularly gastroeso-
phageal variceal hemorrhage, has decreased in prevalence
and is associated with lower mortality likely due to increased
screening and advancements in medical and interventional
treatments.167 These advancements include the combination
of antibiotics and vasoactive therapies as well as standar-
dized use of endoscopic band ligation of esophageal varices.
In addition, improving recognition of patients at high risk for
treatment failure has led to early intervention with TIPS
placement, leading to improved bleeding control and survi-
val with manageable adverse effects, such as hepatic ence-
phalopathy. Further studies to enhance our knowledge of
proper risk stratification will lead to improved patient
selection for personalized treatment strategies and use fewer
“one-size-fits-all” treatment regimens. In addition,
improved adherence to guidelines to use prophylactic non-
selective β-blockers in patients with nonbleeding varices on
screening endoscopy appears to demonstrate reduced mor-
tality from bleeding.
However, the presence of ascites remains an ongoing
complication with substantial morbidity and mortality and
without recent dramatic advances in management. Providers
continue to follow older guidelines, but recent literature
addressing the early utilization of TIPS for patients with
refractory ascites and long-term administration of albumin
may provide new schemes to address ascites with improved
outcomes.168,169 Ongoing research is still needed as these
patients still carry high mortality rates and proper patient
selection and effects of portal decompression warrant
further investigation.
Early consideration of liver transplantation referral is
imperative, as liver transplantation remains the only cura-
tive option for patients with chronic liver failure presenting
with portal hypertensive-related GI bleeding or ascites.
Some literature has demonstrated better hospital outcomes
when patients with chronic liver failure are cared for at
liver transplant centers.170 However, improved standardi-
zation of universal guidelines and increased education to
providers and patients/caregivers will hopefully improve
national outcomes at all hospitals. Ongoing enhancement
in the management of these complex patients and
improved universal implementation of guidelines will
need to be the mainstay for improved care of these
critically ill patients.
Conflicts of Interest
K.R.: nothing to disclose.
B.E.F.: Gore, speaker’s bureau.
R.S.B.: Consulting for Shionogi, Dova, Salix.
Rajwani et al. 573
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