Ethanolamine Oleate
Ethanolamine is a clear colourless or pale yellow moderately
viscous liquid with a slight ammoniacal odour. It is alkaline
to litmus.Miscible with water, alcohol, acetone, chloroform, and glycerol; it is immiscible with petroleum spirit and fixed oils but it will dissolve many essential oils. Ph. Eur. has slightly soluble in ether while USNF has immiscible with ether. Store in airtight containers. Protect from light.
Adverse Effects and Precautions
Ethanolamine oleate is irritant to skin and mucous mem-
branes. Local injection may cause sloughing, ulceration, and,
in severe cases, necrosis. Pain may occur at the site of injection. Patients receiving treatment for oesophageal varices may develop pleural effusion or infiltration. Hypersensitivity reactions have been reported.
When used to treat varicose veins of the legs, ethanolamine
oleate and other sclerotherapeutic agents should not be used
in patients with thrombosis or a tendency to thrombosis: acute phlebitis: marked arterial, cardiac, or renal disease; local or systemic infections; or uncontrolled metabolic disorders such as diabetes mellitus. In the USA ethanolamine oleate is not recommended for the treatment of varicose leg veins.
Effects on the kidneys. Acute renal failure, which cleared
spontaneously within 3 weeks, occurred in 2 obese women
given sclerosing injections of 15 to 20 mL of a solution con-
taining ethanolamine oleate 5% and benzyl alcohol 2%.
Uses and Administration
Ethanolamine oleate is used as a sclerosing agent in the injection treatment of varicose veins and oesophageal varices. For sclerotherapy of varicose veins, 2 to 5 mL of a 5% solution of ethanolamine oleate is injected into empty isolated sections of vein. divided between 3 or 4 sites. Injection into full veins is also possible. For sclerotherapy of oesophageal varices, a suggested dose is 1.5 to 5 mL of a 5% solution per varix to a maximum total dose of 20 mL per treatment session. Treatment may be repeated at intervals until the varices are occluded.
Sclerotherapy. Sclerosants are used in the management of
varicosities including varicose veins and oesophageal varices
(see below). The mechanisms by which injection sclerothera-
py works are not completely understood but are thought to
involve damage to the intima, intraluminal thrombosis, and
intravascular fibrous organization, resulting in occlusion of
the vein. Sclerosants used include ethanolamine oleate, lau-
reth , sodium tetradecyl sulphate and sodium morrhuate. Direct intravariceal injection of sclerosant is less likely to cause local necrosis, ulcer or stricture formation than paravariceal injection.
Variceal haemorrhage. Portal hypertension, one defini-
tion of which is an increase in resting portal venous pressure
above 12 mmHg, may occur in many pathological conditions
affecting the liver, and leads lo the development of collateral
channels linking the portal and systemic circulations. En-
largement of such blood vessels beneath the oesophageal and
gastric mucosa produces varices which have about a 30% risk
of rupture and bleeding. Oesophageal varices are more often
a cause of haemorrhage than gastric varices. Capillaries and
veins in the gastric mucosa may also become swollen, a con-
dition known as portal hypertensive gastropathy, and clinical-
ly important bleeding may occur in severe cases.
Variceal haemorrhage is usually severe with mortality as high
as 50% for the initial episode and the recurrence rate may be
as high as 100% within two years. Bleeding stops spontane-
ously in many patients, but in those who continue to bleed
control of haemorrhage is difficult and patients should be re-
ferred lo a centre with appropriate specialist facilities. Treatment to stabilise the patient may be necessary before they can be safely transferred.
Acute management. Initially treatment is supportive and re-
quires measures to prevent aspiration and maintain a clear airway, and volume replacement with colloid and blood.
Emergency endoscopy should be performed to establish the
site of haemorrhage and exclude non-variceal sources of
bleeding. The choice of treatment depends on the site of
haemorrhage. Endoscopic methods are favoured for initial
management with injection sclerotherapy or banding ligation
being used in bleeding oesophageal varices. The optimum
management of bleeding gastric varices remains to be de-
fined. Injection sclerotherapy is a suitable method for controlling bleeding from varices on the lesser curve of the stomach or within a hiatus hernia, but is not so effective in haemorrhaging fundal gastric varices. Intravariceal injection of bovine thrombin and cyanoacrylate tissue adhesives has been
used in such cases. Where the source of haemorrhage is non-
variceal and due to gastropathy, portal decompressive surgery
is effective although it is associated with a high incidence of
encephalopathy in cirrhotic patients. Small studies have
shown propranolol to be effective in arresting haemorrhage.
Injection sclerotherapy for variceal haemorrhage may be
performed during the emergency endoscopy procedure.
Intravariceal injection, paravariceal injection or a combina-
tion of the two have been used. The most widely-used sclero-
sams are ethanolamine oleate and sodium tetradecyl sulphate
for intravariceal injection and laureth 9 for paravariceal injection. Sclerotherapy controls bleeding in up to 95% of cases.
Ulceration and stricture formation occur frequently following
injection sclerotherapy.
An alternative technique is endoscopic banding
ligation where elastic bands are placed around the varic-
es. The tissue subsequently necroses to leave a superficial ulcer. This technique has a similar efficacy to injection
sclerotherapy but may be more difficult to perform if active
bleeding is occurring. Procedures may be repeated if bleeding continues or restarts.
Where endoscopy is unavailable drug therapy or balloon tam-
ponade may be used until the patient can be transferred to a specialist centre. These techniques may also have a role when sclerotherapy fails. Drug therapy using vasoconstrictors is ineffective in massive haemorrhage and its effects cease once
the drug is stopped. Drugs that are used include vasopressin
and its analogue terlipressin and, more recently, somatostatin
and its analogue octreotide. Vasopressin controls haemor-
rhage in 60 to 70% of patients. It is given by continuous intravenous infusion together with glyceryl trinitrate which counteracts the adverse cardiac effects of vasopressin. while
potentiating its reduction of portal pressure. Terlipressin, has the advantage of a longer therapeutic action enabling bolus
doses to be given. However, somatostatin and particularly oc-
treotide. which may be given by bolus injection, are now gen-
erally preferred as they have similar efficacy to vasopressin
but fewer side effects.-Octreotide is as effective as injection
sclerotherapy in the control of acute variceal bleeding.
For Octreotide or somatostatin may also have a role as ad-
juncts to sclerotherapy or ligation but no mortality benefit has yet been shown.
Balloon tamponade controls bleeding by direct pressure on
the varices. Although it is a very effective means of controlling haemorrhage there is a high incidence of rebleeding once pressure is removed and the incidence of complications is
high. It is useful in cases of massive haemorrhage when drug therapy is ineffective and sclerotherapy is difficult,
Surgery, such as the formation of a shunt or oesophageal
transection, may be necessary if the above measures fail to
control the bleeding. However, such techniques have been as-
sociated with high mortality in some series. Formation of a
transjugular intrahepatic portal-systemic shunt is now generally preferred. It may be particularly useful in candidates for liver transplantation.
Long-term management. Once the acute bleeding has been
controlled measures are needed to prevent rebleeding. Endo-
scopic therapy is widely used, with injection sclerotherapy or banding ligation being repeated until the varices are obliterated. Banding ligation is now (he treatment of choice; it eradicates varices in fewer treatment sessions than injection sclerotherapy and reduces the risk of ulceration and stricture formation. Sucralfate has been given following sclerotherapy as it may reduce the frequency of stricture formation and
reduce bleeding from treatment-related ulcers. It seems to
have no influence on ulcer healing following banding liga-
lion. Some practitioners carry out regular endoscopic
checks and repeat sclerotherapy or banding ligation when
varices reappear, although this approach is no more effective
in terms of improving survival than giving treatment once
bleeding occurs. Drug therapy may be an alternative to endo-
scopic methods. Beta blockers (mainly propranolol) reduce
the incidence of recurrent variceal bleeding in some patients
although patients with poor liver function, who form a large
proportion of the population with variceal haemorrhage, do
not seem to benefit. A combination of nadolol with isosorbide
mononitrate has been reported to reduce the risk of rebleeding
more than repeated sclerotherapy. although there was no sig-
nificant effect on mortality. Drug therapy has also been used as an adjunct to endoscopic methods to control rebleeding in
the period before variceal obliteration has occurred, or for
long-term management following endoscopic therapy. Sever-
long-term management following endoscopic therapy.
several studies have compared Trans jugular intrahepatic porto
systemic shunting with endoscopic treatment but no clear
benefit has been demonstrated and there may be an increased
risk of encephalopathy with the use of shunts. Surgery, in
cluding liver transplantation, should be considered in patients
with recurrent life-threatening haemorrhage. Propranolol
may also have a role in patients with portal hypertensive gastropathy. In a controlled study propranolol reduced the inci
dence of recurrent bleeding from portal hypertensive
gastropathy in patients with cirrhosis.
Prophylaxis of a first bleed in patients with portal hyperten-
sion is controversial since about 70% of patients who have
varices will never bleed, but should probably be given to pa-
tients with cirrhosis and varices thought to be at high risk of
bleeding. A reliable system that will identify those at high
risk of haemorrhage has yet to be devised. The NIEC (North
Italian Endoscopic Club) system is probably the best so far.
Sclerotherapy had been considered as a method of prophylax-
is, but its value has not been clearly established. Studies show that beta blockers decrease the incidence of a first bleed and are probably the treatment of choice if prophylaxis is to be given.
It is postulated that a reduction in portal pressure to below
12 mmHg is necessary to reduce the incidence of variceal
bleeding and that treatment with beta blockers alone does not
achieve this. More effective drugs are being sought and iso-
sorbide mononitrate (as adjunctive therapy with a beta
blocker) and clonidine are under investigation for the proph-
ylaxis of a first bleed and prevention of recurrent haemor-
rhage in patients with portal hypertension.