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106 Because of the

potential for serious cardiovascular and dermatologic complications caused by

nonspecific vasoconstriction, vasopressin should be used only when necessary and

for a duration necessary to control bleeding. The duration of infusion should not

exceed 24 hours.

92

Interestingly, a meta-analysis of four randomized controlled trials

comparing vasopressin for the acute treatment of variceal bleeding with non-active

treatment or placebo found no difference in mortality.

100 Since efficacy of

vasopressin for treatment of esophageal bleeding is limited and adverse effects (e.g.,

abdominal cramping, arrhythmias, and gangrene) are of great concern (Table 25-2), it

has largely been replaced by octreotide. Nonetheless, some clinicians still prescribe

vasopressin.

Nitroglycerin can help to minimize the adverse vascular and cardiac effects of

vasopressin and enhance the reduction in portal pressure. When given by IV infusion,

the nitroglycerin dosage is 40 to 200 mcg/minute.

100,102,107 A randomized trial by

Gimson et al.

108

found a lower rate of complications in the vasopressin and

nitroglycerin group compared with vasopressin alone. At the end of the 12-hour study

period, variceal hemorrhage was controlled in 68% receiving combined therapy

versus 44% in those given vasopressin alone (p < 0.05). Major complications

requiring cessation of therapy were less common in those given nitroglycerin

compared with those given vasopressin alone (p < 0.02).

108

TERLIPRESSIN

Terlipressin, a synthetic analog of vasopressin and a pro-drug of lypressin (currently

not available in the United States), effectively controls acute bleeding from

esophageal varices in 80% of patients. Fewer cardiovascular side effects have been

associated with terlipressin than with vasopressin.

109 Octreotide, vapreotide,

vasopressin, and terlipressin have been shown to be effective in the control of acute

variceal hemorrhage.

110,111 Terlipressin, however, is the only medication for the acute

treatment of variceal hemorrhage that has been shown to improve patient survival. In

a meta-analysis of seven randomized, placebo-controlled trials, terlipressin led to

significant reductions in mortality as compared with placebo (relative risk [RR],

0.66; 95% CI, 0.49–0.88).

112

p. 547

p. 548

Table 25-2

Treatment of Acute Bleeding

Therapy Mechanism Side Effects and Risks

Octreotide Selective and potent vasoconstrictor

that reduces portal and collateral

blood flow by constricting

splanchnic vessels

Diarrhea, hyperglycemia,

hypoglycemia, constipation, rectal

spasms, abnormalstools, headache,

dizziness, fat malabsorption

Vasopressin Nonspecific vasoconstrictor of all

parts of the vascular bed

Abdominal cramping, nausea,

tremor, skin blanching, phlebitis,

hematoma at the site of the infusion,

worsening of hypertension, angina,

arrhythmias, myocardial infarction,

bowel necrosis, gangrene, dilutional

hyponatremia

Endoscopic variceal ligation (EVL) An elastic band is placed around

the mucosa and submucosa of the

esophageal area containing the

varix, leading to strangulation,

fibrosis, and ideally obliteration of

the varix

Moderate bleeding, hypotension,

gastrointestinal discomfort,

esophageal ulceration, perforation

Sclerotherapy Injection of 0.5–5 mL of a

sclerosing agent (e.g., concentrated

saline: 11.5% NaCl or ethanolamine

oleate) into each varix at points

Esophageal ulceration, stricture

formation, esophageal perforation,

retrosternal chest pain, temporary

dysphagia

about 2 cm apart to induce

immediate hemostasis (cessation of

bleeding within 2 to 5 minutes)

Balloon tamponade Bleeding is controlled by direct

compression of the varices at the

gastroesophageal junction or at the

bleeding site by a Sengstaken–

Blakemore tube or Linton tube

(gastric varices only). The tube is

passed through the mouth and into

the stomach. A balloon is then

inflated, which applies direct

compression to the varices

Aspiration (>10% incidence),

pressure necrosis, pneumonitis,

esophageal ulceration and rupture,

bleeding on balloon deflation, chest

pain, asphyxia (aspiration may be

minimized by endotracheal intubation

and continued aspiration of

oropharyngealsecretions)

Transjugular intrahepatic portal

systemic shunt (TIPS)

A conduit between the hepatic vein

and the intrahepatic segment of the

portal vein with an expandable

metalstent is placed during an

angiographic procedure. This

channel allows blood to return to

the systemic circulation and

reduces portal pressure

Bleeding, thrombosis, stenosis,

severe encephalopathy, hepatic

failure, shunt occlusion, shunt

migration

Sources: Goulis J, Burroughs AK. Role of vasoactive drugs in the treatment of bleeding oesophageal varices.

Digestion. 1999;60(Suppl 3):25; Wao T et al. Effect of vasopressin on esophageal varices blood flow in patients

with cirrhosis: comparisons with the effects on portal vein and superior mesenteric artery blood flow. J Hepatol.

1996;25:491; Law AW, Gales MA. Octreotide or vasopressin for bleeding esophageal varices. Ann Pharmacother.

1997;31:237; de Franchis R. Longer treatment with vasoactive drugs to prevent early variceal re-bleeding in

cirrhosis. Eur J Gastroenterol Hepatol. 1998;10:1041.

Pharmacologic therapy for C.V. (somatostatin or its analogs [octreotide or

vapreotide] or terlipressin) should be initiated as soon as variceal hemorrhage is

suspected and continued for 3 to 5 days after diagnosis is confirmed.

92

ENDOSCOPIC VARICEAL LIGATION AND SCLEROTHERAPY

CASE 25-2, QUESTION 3: Octreotide and vasopressin are nonspecific vasoconstrictors that require

continuous IV infusion and carry a risk of systemic side effects. What is the place of endoscopic variceal

ligation and sclerotherapy in the management of C.V.’s hemorrhage? What is a balloon tamponade? Are

alternative therapies such as TIPS appropriate?

After successful resuscitation, endoscopy should be performed within 12 hours to

establish the cause of bleeding.

92 Fiberoptic endoscopy allows direct visualization of

the esophagus and location of the bleeding. Those with actively bleeding varices can

be treated with endoscopic variceal ligation (EVL), sclerotherapy, or balloon

tamponade. EVL is a well-tolerated procedure (Table 25-2).

110,113–117 Villanueva et

al.,