Embolism, Echocardiograpahy

1. CASE REPORT
Cerebral embolism following N-butyl-2-cyanoacrylate injection
for esophageal postbanding ulcer bleed: a case report
Asmarani Abdullah Æ Sharmila Sachithanandan Æ Ooi Keat Tan Æ
Yee Ming Chan Æ Dennise Khoo Æ Faizal Mohamed Zawawi Æ
Haniza Omar Æ Soek Siam Tan Æ Hamed Oemar
Received: 5 May 2008 / Accepted: 13 April 2009 / Published online: 6 May 2009
Ó Asian Pacific Association for the Study of the Liver 2009
Abstract Systemic embolization is a rare but serious
complication of variceal injection with cyanoacrylate. We
report a case of cerebral embolism a few hours after an
injection of Histoacryl into a bleeding esophageal post-
banding ulcer. Echocardiogram revealed patent foramen
ovale.
Keywords Histoacryl Á Esophageal post-banding ulcer Á
Cerebral embolism
Introduction
There have been a few reported cases of embolic compli-
cations of variceal injection with N-butyl-2-cyanoacrylate
(Histoacryl). Both pulmonary and systemic embolisms
have been reported. Table 1 shows the case series on the
incidence of various embolic complications following
gastric varices injection with Histoacryl in six centers
[1–6].
Cerebral embolism following variceal injection with
cyanoacrylate is rare. In these six case series, which
include 1,022 episodes of gastric varices injections, there
was only one case of cerebral embolism [1]. In addition,
there are three case reports on cerebral embolism associ-
ated with Histoacryl injection for gastric varices [7–9].
Table 2 summarizes the three case reports [7–9] on
cerebral embolism following Histoacryl–lipiodol injection
for gastric varices.
There is a paucity of data on the injection for esophageal
varices with cyanoacrylate. We found two reported cases of
cerebrovascular accidents after endoscopic injection for
esophageal varices with bucrylate [10].
We report a case of a patient who developed blindness
and limb weakness following Histoacryl–lipiodol injection
for a bleeding esophageal postbanding ulcer.
Case report
A 40-year-old man with Child’s C liver cirrhosis due to
chronic hepatitis C was admitted to the surgical ward with
Fournier’s gangrene and underwent wound debridement
under general anesthesia on November 6, 2007.
He had an index esophageal variceal bleed in the year
2000 and was subsequently placed on a banding program.
A.Abdullah(&) Á S.Sachithanandan Á O.K.Tan Á Y.M. Chan Á
D. Khoo Á F. Mohamed Zawawi Á H. Omar Á S. S. Tan
Hepatology Unit, Selayang Hospital, Lebohraya Selayang-
Kepong, 68100 Batu Caves, Selangor, Malaysia
e-mail: tamanani@hotmail.com
S. Sachithanandan
e-mail: sharmila@selayanghospital.gov.my
O. K. Tan
e-mail: okt72@yahoo.com
Y. M. Chan
e-mail: drymchan@hotmail.com
D. Khoo
e-mail: dennise@selayanghospital.gov.my
F. Mohamed Zawawi
e-mail: drfaizalmz@yahoo.com
H. Omar
e-mail: hanizao@selayanghospital.gov.my
S. S. Tan
e-mail: tanss@selayanghospital.gov.my
H. Oemar
Department of Medicine, University Institute Technology of
Malaysia, Faculty of Medicine, Selayang Hospital, Lebohraya
Selayang-Kepong, 68100 Batu Caves, Selangor, Malaysia
e-mail: oemarh@yahoo.com
123
Hepatol Int (2009) 3:504–508
DOI 10.1007/s12072-009-9130-5

2. The last esophaegal variceal banding was done in April
2007 and the subsequent upper gastrointestinal endoscopy
in May 2007 revealed two columns of grade I esophageal
varices. He was scheduled for a repeat upper gastrointes-
tinal endoscopy on November 16, 2007.
On November 16, 2007, which was 10 days after the
wound debridement, upper gastrointestinal endoscopy was
performed as scheduled and it showed three columns of
grade II esophageal varices with red-wale signs. Four band
ligations were placed (Cook, Six Shooter Saeed Multi-
Band Ligator MBL-6, Wilson-Cook Medical, Winston-
Salem, NC). No gastric varices were seen at any time
during his endoscopy. He was planned to have a repeat
upper gastrointestinal endoscopy after 2 weeks to reassess
the esophageal varices. At that time, we did not routinely
give any proton-pump inhibitor to patients following an
endoscopic variceal banding.
A day before his scheduled repeat upper gastrointestinal
endoscopy, he had hematemasis and became hypotensive.
Emergency upper gastrointestinal endoscopy under con-
scious sedation showed three columns of grade II esopha-
geal varices with a bleeding postbanding ulcer. A mixture
Table 1 Case series on the incidence of various embolic complications following gastric varices injection with Histoacryl
Author Publication
year
Country Number of gastric
varices cases in the
series
Indication for
Histoacryl
Volume ratio of
Histoacryl to lipiodol
Incidence of embolism
Cheng [1] 2007 China 635 Obliteration of
gastric varices
1:1 One cerebral embolism, three
splenic infarction, one
pulmonary embolism
Noophun
[2]
2005 Thailand 24 Bleeding gastric
varices
5:8 One small bowel infarction,
one pulmonary embolism
Sato [3] 2006 Japan 129 (45 emergency;
84 elective)
Obliteration of
gastric varices
Histoacryl mixed with 5%
lipiodol
Two splenic infarction, one
pulmonary embolism
Dhiman
[4]
2002 India 29 (18 bleeding
gastric varices; 11
prophylactic)
Obliteration of
gastric varices
1:1 in the first 10 cases and
undiluted Histoacryl in the
remaining
One case of embolism in pelvic
area
Jang [5] 2006 Korea 85 (65 within
1 week of gastric
varices bleeding)
Obliteration of
gastric varices
Not available Two pulmonary embolism, one
splenic infarction
Hwang
[6]
2001 Korea 120 Obliteration of
gastric varices
1:1 Six with radiological evidence
of pulmonary embolism
(four symptomatic; two
asymptomatic)
Total number of cases 1,022 Total number of embolic complications 20
Table 2 Case reports on cerebral embolism following Histoacryl–lipiodol injection for gastric varices
Author Age/
sex
Cause of portal
hypotension
Source of
GI bleeding
Histoacryl:lipiodol
volume ratio
Complications Imaging Cause of right to left
shunt
Appenrodt
[7]
68/F Liver cirrhosis Esophageal
and
gastric
varices
TIPS inserted, and during
the procedure, gastric
varices were injected
with 1 ml of
Histoacryl/lipiodol
(ratio 1:4)
Near complete
blindness;
weakness
left upper
extremity
MRI brain–multiple
infra and
supratentorial
infarction
Patent foramen ovale
on echocardiogram
Roesch [8] 66/F Mesenteric vein
thrombosis
due to
Polycythemia
Rubra Vera
Fundal
varices
1 ml of
Histoacryl:lipiodol
(ratio1:1) injected three
times
Comatose after
procedure
Multiple emboli in
lungs, coronary
arteries, cerebrum
and spleen
Presumed arterio-
venous
malformation (since
patent foramen
ovale was ruled out)
Upadhyay
[9]
65/M Non-cirrhotic
portal
hypertension
due to
bilharziasis
Gastric
varices
Histoacryl:lipiodol
1.5 ml/2.1 ml
Inferior
myocardial
infaction
and cortical
blindness
Multiple emboli in
cerebral arteries
and occipital
infarct
Patent foramen ovale
on echocardiogram
Hepatol Int (2009) 3:504–508 505
123

3. of N-butyl-2-cyanoacrylate (Histoacryl; B-Braun Surgical
GmbH, Melsungen, Germany) and lipiodol (Laboratoire
Guerbet, Aulnay-Sous-Bois, France) was injected into the
bleeding varix with a 21-gauge injector needle with a dead
space of 0.8 ml (Injector Force, NM-200L-0821, Olympus
Optical Co., Ltd., Tokyo, Japan). Each injection consisted
of 0.5 ml of Histoacryl and 0.5 ml of lipiodol mixture and
three injections were required to arrest the bleeding
The next morning, he complained of not being able to see
and weakness of the right limbs. On examination, his vision
was reduced to light perception. There was right upper
motor neuron palsy of cranial nerve VII. The power of the
right upper limb and the lower limb was 0/5 and 3/5,
respectively. Computed tomographic (CT) scan of the brain
revealed multiple hyperdense foci throughout the cerebral
cortex and multifocal infarcts (Fig. 1). Embolization of
Histoacryl–lipiodol was suspected in view of the Hounse-
field units of the hyperdense lesions (range = 80–
250 units). Contrasted transthoracic echocardiogram dem-
onstrated patent foramen ovale (Fig. 2). Over the next
month, the patient’s neurological symptoms showed
marked improvement.
Discussion
Our patient developed bleeding from an esophageal ulcer
formed after an elective variceal banding. There is a paucity
of data on the incidence of bleeding from such ulcers.
Results from secondary prophylaxis trials for esophageal
variceal bleed showed that bleeding from postbanding
ulcers is relatively uncommon [11, 12]. A study by de la
Pen˜a et al. (n = 80) [11] showed that four of the 20 reb-
leeding cases were due to bleeding esophageal ulcers.
Similarly, a study by Lo et al. (n = 122) [12] showed that
seven of the 71 rebleeding episodes were due to esophageal
ulcers.
Evidence on the management of an active esophageal
postbanding ulcer bleed remains lacking. In our practice,
intravariceal injection of Histoacryl is often used to arrest
active bleeding from such ulcers. However, it remains to be
determined whether this is the optimum treatment modality.
One study (n = 44) showed that intravenous pantop-
razole after variceal banding followed by daily oral pan-
toprazole for 9 days did not reduce the number of ulcers
but reduced the size of postbanding ulcers at day 10 [13].
All three postbanding ulcer bleed occurred in the placebo
group. Another study (n = 47) [14] showed that intrave-
nous pantoprazole for 3 days followed by oral pantoprazole
for 11 days after variceal banding resulted in smaller
postbanding ulcers at day 7 and day 14, respectively. Two
cases of postbanding ulcer bleeding also occurred in the
placebo group.
Seewald et al. [15] outlined that the risk of embolism is
increased if (1) more than 1 ml of Histoacryl–lipiodol
mixture is injected each time; (2) the volume of water used
to deliver the glue mixture is in excess of the dead space of
the injecting catheter; and (3) the catheter is flushed too
forcefully before the needle is withdrawn from the varix.
Seewald et al. [15] recommended that the volume ratio
(ml/ml) of Histoacryl to lipiodol used for variceal injection
to be 0.5:0.8. In the reported cases of systemic embolism
following variceal cyanoacrylate injection, the volume ratio
of cyanoacrylate to lipiodol ranged from 1:1 to 1:4 [1, 7–9,
Fig. 1 Noncontrasted CT scan of the brain showing multiple
hyperdense foci (shown by black arrows). Note: Multifocal infarcts
seen in other slices of the scan are not visible here
Fig. 2 Contrasted transthoracic echocardiogram showing microbub-
bles seen as white specks present mainly in the right-sided heart
chambers. This image, which was captured when the patient
performed Valsalva maneuver soon after intravenous agitated saline
injection, showed that the microbubbles escaped into the left atrium
via a defect (patent foramen ovale) in the inter-atrial septum
506 Hepatol Int (2009) 3:504–508
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4. 16–18]. In theory, using undiluted Histoacryl may prevent
distal embolization because the polymer solidifies rapidly
upon contact with blood. Undiluted Histoacryl was studied
in 80 patients with bleeding gastric, esophageal, and duo-
denal varices [19]. Distal embolization to distant abdominal
sites occurred in two patients. Therefore, using undiluted
Histoacryl does not preclude the risk of embolization.
Among the case reports on systemic Histoacryl embo-
lism, echocardiographic study showed either patent fora-
men ovale [7, 9] or no evidence of intracardiac shunt [8, 18].
Other authors did not report on echocardiographic findings
and have presumed that the paradoxical embolization
occurred via an arteriovenous pulmonary shunt [16, 17]. In
the case series, no echocardiographic study was mentioned
[1–6].
The most common form of intracardiac communication
in earlier reported cases of paradoxical embolism unrelated
to Histoacryl is patent foramen ovale [20]. Ventricular
septal defect and patent ductus arteriosus are rarely found
in cases of paradoxical embolism [20].
The detection rate of patent foramen ovale is 27.3% [21]
on direct inspection during cardiac surgery and 9.2% [22]
on transesophageal echocardiogram in general population.
More studies are needed before routine screening for patent
foramen ovale can be advocated in patients with portal
hypertension.
In our patient, excessive retching during upper gastroin-
testinal endoscopy might have caused transient rise in right
atrial pressure, causing right-to-left shunting. As a general
precaution, adequate sedation is important to prevent
patients from retching excessively during upper gastroin-
testinal endoscopy because this may prevent right-to-left
shunting in an undiagnosed patent foramen ovale.
Finally, we did not screen this patient for hypercoagul-
opathy to rule out hypercoagulable state as a predisposing
factor to the cerebral infarction.
To our knowledge, this is the first reported case of
cerebral embolism following Histoacryl injection for a
postbanding ulcer bleed. Care should be taken to minimize
the risk and patients undergoing Histoacryl injection should
be informed of the potential risk.
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