Winston MacBride sat in the emergency room (ER)
and stared his mortality in the face. While vomiting streams of blood
into an emesis basin, he realized that maybe his "just one more
drink" adage hadn't been the smartest way to live. His body had
complied with his excesses once too often, and his liver was now
vehemently rebelling. The fear he saw in equal measure on the faces of
his wife and two young daughters, he knew, was mirrored on his own. Now,
while facing the consequences of his actions, he could only hope the
doctors could reverse the physical effects of his choices enough for him
to live to see his daughters grow into adulthood.
Although only one of the possible causes of
liver cirrhosis, alcohol abuse, with its consequent damage to the liver,
remains one of the ten leading causes of death in the United States
today.1
Cirrhosis of the liver is the third leading
cause of death after cancer and cardiovascular disease in people 25 to
65 years of age. In the United States, the leading cause of cirrhosis is
alcoholic liver disease, and is the cause of death for one-third of all
cirrhotic patients. Outside the western world, the major causes of
cirrhosis are the hepatitis B and C viruses.2
The liver, the largest organ in the body, weighs
from three to four pounds. It lies in the right upper quadrant of the
abdomen, under the right lung and immediately below the diaphragm. It is
a multi-faceted organ, as it performs several essential functions
simultaneously. These include eliminating waste materials from the body,
manufacturing vital proteins, producing cholesterol, storing and
releasing glucose, vitamin storage and metabolizing medications. The
liver also produces bile, which subsequently flows through the bile
ducts into the intestine, where it plays a role in metabolizing and
digesting food. Most of the clotting factors utilized in the body are
manufactured by the liver, including prothrombin, fibrinogen and
Heparin. It is also the organ that releases the vasopressors that
respond to hemorrhage.
The Liver's Rebellion -- Cirrhosis
Cirrhosis develops over a period of many years,
as a result of an insult to the liver that has resulted in scarring,
which, in turn, distorts the normal anatomy and structure of the liver's
cells. Consequently, blood flow to and from the liver is blocked, and
liver functions are hindered. While the causes of cirrhosis are
multiple, the damage sustained by the liver over a prolonged period of
time is synonymous, whether incurred due to alcohol abuse, a viral
infection, or a congenital disease. An additional cause of cirrhosis is
autoimmune hepatitis, a chronic inflammation of the liver that occurs
when the body's immune system fails to recognize the liver tissue as its
own, so it produces antibodies to injure these "foreign"
cells, causing the scarring and damage that leads to cirrhosis. A
chronic biliary duct blockage can also cause scar tissue formation in
the liver. This can either occur at birth as biliary atresia, or later
in life as primary biliary cirrhosis. Normal metal levels are present in
all cells of the body. When they accumulate in abnormal amounts,
however, as they do in Wilson's disease, which is the abnormal storage
of copper in the cells of the body, or in hemochromatosis, which is the
abnormal storage of iron, they can cause liver scarring, leading to
cirrhosis. Prolonged exposure to certain drugs or chemicals can scar the
liver, as can inherited diseases such as cystic fibrosis and alpha
1-antitrypsin deficiency.
In its initial stages, cirrhosis produces
minimal or no signs and symptoms, although fatigue, weakness, and a
decreased appetite may manifest and increase in their intensity over
time. When fully developed, however, it can present in a variety of
ways. This occurs when the healthy pathways for blood from both the
heart and the intestines to the liver become scarred and impassable,
thereby inhibiting much of the organ's vital functions.
The liver produces bile, which flows into the
intestine and is stored in the gallbladder. When cirrhosis is advanced,
the bile pathway becomes obstructed, causing it to back up in the blood.
This causes the skin and the eyes to turn yellow in color (jaundice),
and the urine to darken in response. Certain types of cirrhosis, such as
the type caused by a chronic biliary duct blockage, can cause intense
itching (pruritis). Since cirrhosis causes the abnormal metabolism of
the bile pigment, gallstones develop frequently with this condition. The
liver also produces a protein called albumin, which keeps fluid in the
blood vessels. When the blood level of this protein falls, fluid
proceeds to seep out of the tissues into the legs and abdomen, causing
edema and swelling (ascites). Since one of the functions of the liver is
to manufacture certain proteins that are involved in the clotting of
blood, when it can no longer adequately perform this function, causing a
deficiency of these proteins, excessive and/or prolonged bleeding can
occur. One of the primary functions of the liver is to filter toxins out
of the bloodstream. When the liver can no longer adequately perform this
function, and the toxins themselves escape into the bloodstream, changes
in mental status can develop, causing a hepatic encephalopathy.
Most often, the most therapeutic treatment of
cirrhosis of the liver is to remove the causative agent. Treatment
alternatives are initially dependent upon addressing the cause of the
cirrhosis and preventing both complications and further spread of the
disease. Alcoholic patients must abstain from alcohol. Excessive iron
deposits can be removed from the blood by frequent phlebotomies.
Cortisone is a therapeutic treatment for autoimmune hepatitis.
Decreasing dietary protein can prevent and/or slow changes in mental
status. Sodium restriction and diuretics can reduce edema and ascites.
Ursodiol (Actigall) and other drugs have been helpful in treating
primary biliary cirrhosis and primary sclerosing cholangitis. When
cirrhosis has progressed to its advanced stages, however, more
aggressive interventions are required.
A Hemodynamic Cascade -- Variceal Hemorrhage
In advanced cirrhosis, intestinal blood bypasses
the liver and flows up and around the esophagus to the heart. This
causes the veins in the esophagus and the upper part of the stomach to
dilate, and potentially rupture, leading to a massive and a potentially
life-threatening bleed. These esophageal varices, essentially varicose
veins in the esophageal area, are a life-threatening complication of
portal hypertension, which is an increased blood pressure in the portal
vein, and a direct result of chronic liver disease. When portal
hypertension occurs, the blood flow through the liver is decreased. In
response, the body increases the blood flow through the microscopic
blood vessels within the esophageal wall. As this blood flow increases,
the blood vessels begin to dilate to very large diameters, blowing up
like an overblown balloon until they rupture. The dilation can be
profound. An esophageal blood vessel is normally measured in
millimeters. An esophageal varix may dilate to as large as 1.0 cm or
larger in diameter, and increases in size over time.3
Although varices can remain asymptomatic for
long periods of time, and variceal bleeding is painless, if and when the
veins in the distal esophagus rupture, it can cause a life-threatening
bleed, which is both heavy and rapid. In its acute phase, the patient
vomits copious amounts of bright red blood, produces black, tarry stools
(melena) secondary to the bleeding in the gastrointestinal tract, and
manifests signs and symptoms of hypovolemia, in this instance caused by
a vastly decreased level of circulating blood in the body. This will
rapidly worsen liver function even more. The loss of approximately
one-fifth or more of the normal circulating blood volume produces
hypovolemic shock. The more rapidly the blood volume is diminished, the
more severely the symptoms of shock will manifest. The signs of shock
include an altered mental status, restlessness, increased anxiety,
pallor, cool and clammy skin, collapse of the peripheral neck veins, and
tachycardia.4,5
Treatment is focused on restoring tissue
perfusion and reducing peripheral vasoconstriction. Intervention must be
rapid and decisive to prevent mortality. The risk factors for a variceal
hemorrhage include the location of the varices, their size and
appearance, variceal pressure, and the underlying clinical status of the
patient.6
While cirrhosis is confirmed by a liver biopsy,
esophageal varices are confirmed by performing an upper endoscopy (EGD
-- esophagogastroduodenoscopy). During an EGD, the physician is not only
able to evaluate the risk of a variceal bleed, but to categorize the
existing varices on a scale of I to IV, based upon their size. Larger
varices, grades III and IV, carry a higher bleeding risk than the
smaller ones. In addition to size, there are several morphologic
features of varices that place them at an inherently greater risk of
bleeding. Several of these signs are noted on endoscopy, and include red
whale marks, which are longitudinal red streaks on varices, discrete red
cherry-colored flat spots that overlay the varices, hematocystic spots
that are raised discrete red spots that overly the varices and resemble
blood blisters, and diffuse erythema, which infuses the varices with a
red color over the totality of its length.7
25 percent to 40 percent of all patients who are
diagnosed with cirrhosis will develop esophageal varices, which enlarge
at a rate of 4 percent to 10 percent per year.8
Of that number, 30 percent will eventually bleed
from a variceal rupture in the first year after identification.9
An active variceal hemorrhage accounts for about
one-third of all cirrhosis-related deaths. A variceal hemorrhage will
stop spontaneously in approximately 62 percent to 70 percent of
patients. However, a recurrent bleed will occur in approximately 60
percent of patients within the first seven days of the initial bleeding
episode.10
The mortality rate for esophageal variceal
bleeding on the first event is between 30 percent and 50 percent.11
This can be due to a multitude of factors, which
include liver failure, sepsis, exsanguination, cerebral edema, and the
complications that are associated with anemia. Associated abnormalities
in the renal, pulmonary, cardiovascular and immune systems in patients
with esophageal varices contribute to 20 percent to 60 percent of the
mortality rate.12
A history of a previous variceal bleed increases
the likelihood of a subsequent bleeding episode.
Treatment goals are aimed at controlling and
subsequently ending the acute bleeding and to control the existing
varices so as to prevent rebleeding. A positive outcome of an active
hemorrhage is dependent upon emergent bleeding control and avoidance of
the major complications associated with this treatment, such as
infection. Medications used to treat the variceal bleeding can cause
electrolyte imbalances, allergic reactions, and/or hypotension. Blood
transfusions can cause allergic reactions or infections.
There are two phases in the course of a variceal
hemorrhage: the acute phase, and the later phase in which the risk
factors of a recurrent bleed remain high for approximately a six-week
time frame subsequent to the time of the active bleeding episode. The
greatest risk of rebleeding, however, occurs in the first 48 to 72
hours. Risk factors for a rebleeding episode are increased in patients
who are greater than 60 years of age, in the presence of renal failure,
and when the varices are especially large.13
The one-year survival rate for those patients
who survive for two weeks after a variceal bleed is approximately 52
percent.14
Without additional treatment, a patient has a
rebleed risk within the first year of 70 percent.15
These risk factors are additionally increased
with continued alcohol use, the grade of the varices, in the presence of
severe liver or renal failure, and in a patient who has hepatocellular
carcinoma.
Diagnostic laboratory studies include a complete
blood count, as anemia may be secondary to bleeding, nutritional
deficiencies, or bone marrow suppression secondary to alcoholism.
Diagnostic studies also include prothrombin time, as an impairment of
liver function can result in a prolonged prothrombin time, since it is
synthesized by the liver. Liver function tests may be normal or mildly
elevated in cirrhosis. Blood urea and creatinine levels may be elevated
in patients with esophageal bleeding, cirrhosis, and ascites. A stool
sample should be evaluated for melena. An ultrasound of the abdomen is
indicated if a biliary obstruction or liver cancer is suspected. An
upper endoscopy is required at an early stage in order to evaluate the
extent of the disease process and to formulate a treatment plan -- both
acute and long-term.
The Physician's Arsenal -- Therapeutic
Treatments
The objectives of intervention are to halt the
acute bleeding episode as quickly as possible, and to then plan
long-term management of persistent varices with both medical and
procedural alternatives. The most imperative treatment requirement
during the acute phase of bleeding is the hemodynamic stabilization of
the patient through adequate intravenous access, through which blood
products (colloids) and saline solution (crystalloids) can be emergently
instilled. Clotting status must be evaluated, and, if necessary, a
transfusion of fresh frozen plasma or platelets and vitamin K. A
nasogastric tube is placed to filter blood out of the abdominal cavity
and to monitor the extent of the bleeding. Acute bleeding can also be
treated by a balloon tamponade, which consists of the passage of a tube
through the nose and into the stomach, which is subsequently inflated
with air. The intent of passing a Sengstaken-Blakemore tube is to
produce pressure against the bleeding veins to stop the bleeding.
Although inherently a beneficial treatment for stabilization purposes,
it can also be associated with the complications of aspiration pneumonia
and/or esophageal rupture. It is commonly used in conjunction with
medications that decrease portal blood flow and bleeding, vasopressin
(Pitressin) and octreotide (Sandostatin).16
If extremely massive bleeding occurs, the
patient may be placed on a ventilator in order to protect the airway and
to prevent blood from aspirating into the lungs. One of the major
problems of balloon tamponade is the high risk of rebleeding that
follows the deflation of the balloon. This modality of treatment should
be used only as a temporary stabilization measure until more definitive
treatment interventions can be instituted, and must be performed by
experienced personnel.17
Once hemodynamic stabilization occurs, an
emergency upper endoscopy can be performed, during which the varices are
not only assessed, but during which therapeutic modalities of treatment
can be employed to control the bleeding.
The use of sclerosing agents, such as sodium
morrhuate or sodium tetradecyl sulfate, have been the historical
treatment of choice for acute bleeding episodes and subsequent
prophylactic treatment therapies. However, due to the advent of newer
treatment modalities, with lower complication rates and side effects,
sclerotherapy is rarely the current treatment of choice. Instilled into
the varices during the course of an EGD, the sclerosing agents deflate
the varices, causing variceal thrombosis, fibrosis and ultimately
obliteration, thereby reducing their potential for rupture. This agent
is introduced into the varices via a needle-tipped catheter that is
passed through the endoscope. Although it is a technique that has proven
effective in the prevention of an initial variceal hemorrhage, it
carries side effects that can include perforation, pleural effusion, and
the development of esophageal strictures. Complications of sclerotherapy
can be categorized into three major categories -- local, regional, and
systemic. Local complications include ulceration, bleeding, dysmotility,
stricture formation and portal hypertensive gastropathy. Regional
complications include esophageal perforation and mediastinitis, while
systemic complications include the development of sepsis, aspiration and
hypoxemia. These complications occur more frequently when endoscopy is
performed emergently rather than electively. Sclerotherapy is successful
in the initial control of variceal bleeding in 80 percent to 90 percent
of patients over a span of one to two treatment sessions. If a patient
continues to bleed after two successive procedures, alternative forms of
treatment should always be considered.
Endoscopic variceal ligation (EVL) has emerged
as an alternative treatment methodology to sclerotherapy.18
It has proven to be as efficacious in the
control of bleeding, and has ultimately fewer complications associated
with it. Performed through the suction channel of an endoscope, elastic
bands are placed around the varices. These bands ultimately cause
ischemic necrosis and eradication of the varices. Since patients with
ascites and variceal bleeding run a greater risk of bacterial
peritonitis, pre-procedural treatment with antibiotic prophylaxis is
desirable.
After the acute crisis has been addressed,
long-term medical treatment of esophageal varices includes the use of
two non-selective beta blockers, propranolol hydrochloride (Inderal) and
nadolol (Corgard). Although these medications reduce portal pressure and
thereby reduce portal venous flow, higher doses of these medications
decrease cardiac output. These medications reduce the risk of initial
variceal bleeding by approximately 45 percent. Doses must be titrated
carefully to individual patient response. If there is a contraindication
to the use of beta blockers, however, long-acting nitrates can be
employed as alternatives, such as isosorbide. This treatment should be
continued indefinitely.19
Another therapeutic procedure involves extending
a catheter through a vein into the liver where it will connect the
portal system to the systemic venous system. The goal of this
therapeutic treatment, called transjugular intrahepatic portosystemic
shunting (TIPS), is to decrease portal venous pressure and thereby
decrease pressure in the esophageal area. This procedure effectively
controls active bleeding in more than 90 percent of patients, even in
those who are critically ill. Immediate complications of this procedure
include rebleeding and an increasing encephalopathy. Long-term
complications are stent stenosis or occlusions requiring balloon
angioplasty. This procedure is proposed when treatment with medications
and endoscopic interventions have proven unsuccessful.
Although patients who are refractory to medical
treatments may need surgical intervention, these procedures carry with
them a high mortality rate. One such surgical alternative, which is
rarely performed, is the placement of a portacaval shunt, which passes
blood to the vena cava from the portal vein by means of a graft. An
alternative surgical procedure would be an esophageal resection of the
bleeding area.
Complications of treatment include recurrence of
the bleeding, hypovolemic shock from the loss of blood, and the
formation of an esophageal stricture after surgical interventions. The
outcome is usually poor unless a liver transplant is performed. A liver
transplant is the only way to permanently cure esophageal varices.20
To Live or To Die -- A Prognosis for Life
A person with esophageal varices usually
requires lifelong monitoring of both the varices and the underlying
liver disease. Variceal hemorrhage is one of the most serious
complications of portal hypertension. Although the optimum interval for
therapeutic screening has not been determined, screening at a minimum of
every two to three years is recommended. Vigilant screening and
lifestyle modifications are required to forestall potential variceal
rebleeding that leads to death. Long-term treatment goals are directed
at the prevention of rebleeding, chronic liver failure, and ultimately
death. Although liver transplantation has progressed to the stage where
it can be considered standard treatment for selected patients with
advanced cirrhosis of the liver, ongoing research holds the promise of
less drastic therapeutic alternatives in the future.
Cathy S. Birn, MA, RN, CGRN, CNOR, is an
endoscopy nurse at Memorial Sloan-Kettering Cancer Center in New York
City. For the last 15 years, she has worked in the specialty of
gastroenterology endoscopy nursing. As an active member of the Society
of Gastroenterology Nurses and Associates, she is committed to expanding
the educational horizons of all endoscopy personnel working in the field
today.
References
1. Worman H. Alcoholic Liver Disease. Available
at:
