Clin J Gastroenterol (2013) 6:390–394
DOI 10.1007/s12328-013-0411-0
CASE REPORT
Endotoxin adsorption therapy using polymyxin B-immobilized
fiber as a treatment for septic shock-associated severe acute
cholangitis
Yoshihiro Inoue • Yasuhisa Fujino • Makoto Onodera
Satoshi Kikuchi • Gaku Takahashi • Masahiro Kojika
Shigeatsu Endo
Received: 27 May 2013 / Accepted: 18 July 2013 / Published online: 15 August 2013
Ó Springer Japan 2013
Abstract The application of endotoxin adsorption ther-
apy for severe acute cholangitis is controversial. We
present a survival case of septic shock and multiple organ
failure due to severe acute cholangitis. The patient was
treated by endotoxin adsorption therapy using polymyxin
B-immobilized fiber because he continued to remain in
shock even after successful endoscopic nasobiliary drain-
age. The patient was an 84-year-old male diagnosed with
acute cholangitis and acute pancreatitis who was trans-
ferred to our department because of shock and severe
dyspnea. The patient had already developed acute respi-
ratory failure, acute renal failure, and disseminated
intravascular coagulation. We performed endoscopic na-
sobiliary drainage immediately, but the patient continued
to remain in shock and plasma endotoxin level was
markedly elevated at 133.6 pg/mL. Therefore, we per-
formed direct hemoperfusion with polymyxin B-immobi-
lized fiber. On starting the hemoperfusion, blood pressure
and urine volume increased, and the plasma endotoxin
level reduced considerably. On the basis of our experience
in this case, we think that direct hemoperfusion with
polymyxin B-immobilized fiber may be a useful modality
in the management of severe acute cholangitis.
Keywords Cholangitis
Septic shock
Endotoxin

Multiple organ failure
Polymyxin B
Y. Inoue
Y. Fujino (&)
M. Onodera
S. Kikuchi

G. Takahashi
M. Kojika
S. Endo
Department of Critical Care Medicine, Iwate Medical
University, 19-1 Uchimaru, Morioka, Iwate 020-8505, Japan
e-mail: yfujino-gi@umin.ac.jp
123
•
•
Introduction
Patients with severe acute cholangitis often present with
elevated blood endotoxin levels, multiple organ failure, and
septic shock [1]. In such severe cases, biliary drainage is
very important, and if performed at the appropriate time,
the patient’s condition can improve dramatically. However,
delayed or incomplete drainage can lead to multiple organ
failure, and the outcome may then be fatal. We report the
case of an elderly patient who was rescued with endotoxin
adsorption therapy using polymyxin B-immobilized fiber
(PMX) after developing multiple organ failure and
remained in shock despite undergoing endoscopic nasob-
iliary drainage (ENBD).
Case report
An 84-year-old male was admitted to a local hospital for
abdominal distension and dyspnea. On the following day,
he was diagnosed with acute cholangitis and acute pan-
creatitis on the basis of laboratory data and computed
tomography (CT) findings. He was transferred to our
department because of shock and severe dyspnea. At
83 years of age, the patient had experienced an episode of
cerebral infarction; however, afterwards he was able to
perform his daily activities independently.
At the time of admission to our department the patient
was disoriented, and his vital signs were blood pressure
92/54 mmHg, heart rate 102 beats/min, and body temper-
ature 40.2 °C. Abdominal examination revealed tenderness
and guarding in the right upper quadrant. Table 1 shows
the laboratory data on admission. The patient had signs of
systemic inflammatory reaction, liver dysfunction with
jaundice and elevated biliary enzyme levels, elevated
Clin J Gastroenterol (2013) 6:390–394 391

Table 1 Laboratory data on admission that emergency drainage was necessary. Written informed
Blood Arterial blood (O2 4 L/min)
consent for all the procedures was obtained from the
gas patient and his family. The patient was immediately
WBC count 15410/mm3 pH 7.343 administered antibiotics and a catecholamine. Endoscopic
RBC count 462 9 104/ PCO2 23.8 mmHg retrograde cholangiography showed the presence of stones
mm3 in the CBD (Fig. 2a) and stones and purulent material in
Hb level 14.1 g/dL PO2 71.1 mmHg the papilla of Vater (Fig. 2b). We performed ENBD
Ht 41.3 % HCO3- 12.6 mmol/L without removal of the stones. A 5-F nasobiliary drainage
Plt count 3.0 9 104/ Base excess -10.8 mmol/L catheter (Hanaco Medical, Saitama, Japan) was used for
mm3 ENBD. In addition, we administered an immunoglobulin
Chemistry Coagulation and gabexate mesilate. The acute respiratory failure was
TP level 5.9 g/dL APTT 40.5 s managed with mechanical artificial respiration and the
Alb level 3.6 g/dL PT 15.6 s acute renal failure with hemodiafiltration. Despite these
UN level 34.2 mg/dL (ratio) 1.23 treatments, the patient continued to remain in shock. The
Cr level 2.5 mg/dL Fibrinogen 511.9 mg/dL plasma endotoxin level on admission, as measured by the
AST level 529 IU/L FDP 80.1 lg/dL kinetic-turbidimetric Limulus assay, was markedly ele-
ALT level 409 IU/L AT III 63 % vated at 133.6 pg/mL. Therefore, we performed PMX-
LDH level 756 IU/L direct hemoperfusion (PMX-DHP). The endotoxin
c-GTP level 399 IU/L Plasma adsorption column used was PMX-20R (Toray Industries,
T-Bil level 4.1 mg/dL Endotoxin level 133.6 pg/mL Tokyo, Japan). PMX-DHP for 120 min was considered a
D-Bil level 3.5 mg/dL b-D-glucan level 7.1 pg/mL single session of therapy. Shortly after starting PMX-DHP,
AMY level 2475 IU/L his blood pressure and urine volume increased. The next
Ca level 8.7 mg/dL Bacteriology day, the plasma endotoxin level had reduced to 7.3 pg/mL,
CRP level 8.8 mg/dL Bile Klebsiella but still exceeded the criterion (1.1 pg/mL) [3], and the
oxytoca blood pressure again reduced slightly. Therefore, the
Glucose level 176 mg/dL Blood Klebsiella patient was recommended a second session of PMX-DHP.
oxytoca Immediately after the start of the session, the blood pres-
WBC white blood cells, RBC red blood cells, Hb hemoglobin, Ht sure increased and subsequently, the catecholamine dose
hematocrit, Plt platelets, TP total protein, Alb Albumin, UN urea was decreased. Five days after admission, the plasma
nitrogen, Cr creatinine, AST aspartate aminotransferase, ALT alanine endotoxin level decreased to 0.35 pg/mL. The signs of
aminotransferase, LDH lactate dehydrogenase, c-GTP c-glutamyl-
transpeptidase, T-Bil total bilirubin, D-Bil direct bilirubin, AMY
inflammatory reaction and liver dysfunction also improved
amylase, CRP C-reactive protein, APTT activated partial thrombo- gradually. Nine days after admission, the patient was
plastin time, PT prothrombin time, FDP fibrinogen degradation removed from mechanical artificial respiration, and
products, ATIII anti-thrombin III 28 days after admission, the CBD stone was removed.

pancreatic enzyme levels, and renal failure. The patient

met all 4 diagnostic criteria of systemic inflammatory
response syndrome (SIRS), including the typical findings
of physical examination [2]. SIRS signs—decreased
platelet count (3.0 9 104/mm3), increased prothrombin
time (PT-ratio 1.27), and abnormal levels of fibrinogen
degradation products (80.1 lg/mL)—were attributed to
disseminated intravascular coagulation (DIC). An abdom-
inal CT scan showed gallbladder stones, but abnormal
dilatation of the common bile duct (CBD) or stones in the
CBD were not visualized. Later, Klebsiella oxytoca was
isolated from the arterial blood and bile cultures.
Figure 1 shows the clinical course of the patient. The
patient was diagnosed with acute cholangitis because of
fever, pain in the right hypochondrium, jaundice, and ele-
vation of biliary enzyme levels; he had also developed
acute pancreatitis as a complication. In addition, he was
unconscious and had shock and DIC; therefore, we decided
Discussion
The Tokyo Guidelines 2007 (TG07) for the management of
acute cholangitis and cholecystitis, were adopted as the
international guidelines in 2007 [4] and updated in 2013
(TG13) [5]. According to the TG07, acute cholangitis is
diagnosed on the findings of blood tests and imaging
studies and a history of biliary disease in addition to the
presence of Charcot’s triad [6, 7]. Patients with organ
failure are classified as having severe acute cholangitis and
require urgent biliary drainage [7–10]. Endoscopic biliary
drainage is safer and more effective than open surgical
drainage [11]. At our institution, we perform ENBD for
patients with severe acute cholangitis. In patients with
marked dilatation of the bile ducts, the percutaneous tran-
shepatic route can be used for biliary drainage; however,
our patient did not show any dilatation. If endoscopic or

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392 Clin J Gastroenterol (2013) 6:390–394

Fig. 1 Clinical course of an ENBD

84-year-old male with severe
acute cholangitis. Because he

Blood pressure (mmHg)

HDF PMX-DHP
continued to remain in shock 140

Urine volume (mL/3h)

despite initial treatments, 120 800
including ENBD, we performed Blood pressure
100 600
PMX-DHP. After PMX-DHP,
Urine volume
the blood pressure and urine 80 400
volume increased, and plasma 200
60
endotoxin level dropped. WBC
count and AST level improved 0
gradually. ENBD endoscopic 140
nasobiliary drainage, PMX 120
polymyxin B-immobilized fiber,

Endotoxin (pg/mL)
PMX-DHP PMX-direct 100
Endotoxin
hemoperfusion, WBC white 16000 800 80
WBC count (/mm3)

blood cells, AST aspartate WBC

AST level (IU/L)
aminotransferase, HDF 12000 600 60 AST
hemodiafiltration 8000 400 40

4000 200 20

0 0 0
12 18 24 6 12 18 24 6 12 18 24 6 Time (o’clock)
0 1 2 5 days from admission

Fig. 2 a Endoscopic
retrograde cholangiography
showed stones (arrow) in the
common bile duct. b Endoscopy
showed stones (arrow) and
purulent material (arrowhead)
in the papilla of Vater

percutaneous transhepatic biliary drainage is contraindi- difficult [15]. When we performed ENBD, purulent mate-
cated because of a history of surgery, percutaneous tran- rial was discharged from the papilla of Vater; therefore, the
shepatic gallbladder drainage (PTGBD) might be chosen. patient, in fact, could have had acute obstructive suppura-
However, a previous report indicates that PTGBD did not tive cholangitis (AOSC) [16]. Nevertheless, studies indi-
yield favorable results for severe acute cholangitis because cate no statistically significant differences between the
of insufficient effect of drainage [12]. severity of suppurative cholangitis and that of nonsuppu-
Our patient had Reynolds’ pentad [13] (Charcot’s triad rative cholangitis [17, 18]; therefore, AOSC was not
plus shock and a decreased level of consciousness) in included in Tokyo Guidelines [7, 9].
addition to acute respiratory failure, acute renal failure, and In our case, the patient continued to remain in shock
DIC; therefore, he was diagnosed with sepsis-associated despite successful ENBD. At our institution, endotoxin
multiple organ failure. Akizuki et al. [14] reported that the levels could be analysed immediately, and we found that
number of dysfunctional organs is correlated with mortality his plasma endotoxin level was markedly elevated; there-
in patients with severe acute cholangitis, and that all fore, we performed PMX-DHP. This enabled the rescue of
patients with [4 dysfunctional organs had died. In addi- the patient. Although the Tokyo Guidelines do not discuss
tion, the age of the patient made his rescue even more PMX-DHP [8, 10], the mechanism of septic shock through

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Clin J Gastroenterol (2013) 6:390–394
endotoxins and cytokines has been elucidated to some
extent [19], and the blood levels of endotoxins and cyto-
kines have been reported to be correlated with the severity
of acute cholangitis [1, 20]. In addition, PMX-DHP has
been reported to be useful in the treatment of septic shock
[21]. A few reports have been published on the effective-
ness of PMX-DHP in cases of cholangitis. Hirose et al. [22]
stated that PMX-DHP may be useful for the treatment of
acute cholangitis if biliary drainage was impossible. Masui
et al. [23] reported a survival case of severe acute cho-
langitis associated with endotoxin shock that was treated
with ENBD and PMX-DHP.
Although immediate analysis of endotoxin levels is not
possible at every institution, Gram-negative bacilli are the
organisms most often implicated in acute cholangitis [17].
In addition, the validity of PMX-DHP for Gram-positive
bacterial infection has been verified [24]. Therefore, per-
forming PMX-DHP without the analysis of endotoxin
levels would be promising for the rescue of severely
affected patients who continue to remain in shock even
after sufficient drainage. At present, we suggest PMX-DHP
administration if the patient continues to remain in shock
6 h after successful ENBD.
Moreover, although PTGBD was inadequate in our case
of severe acute cholangitis, as reported previously, some
cases of successful treatment with PTGBD and PMX-DHP
have been reported [25, 26]. Therefore, PMX-DHP may be
a useful modality in the management of severe acute
cholangitis, and its application in a greater number of cases
may help confirm this.
Conflict of interest The authors declare that they have no conflict
of interest.
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