ADVANCED JOURNAL OF EMERGENCY MEDICINE. 2017; 1(1): e7
Abootalebi et al
DOI: 10.22114/ajem.v1i1.17
Original Article
Comparing the Effects of Hydroxyethyl Starch and Albumin in Cirrhotic
Patients with Tense Ascites; a Randomized Clinical Trial
Alireza Abootalebi1*, Sepideh Khazaei2, Mohammad Minakari1, Mohammad Nasr-Isfahani1, Mehrdad Esmailian3,
Farhad Heydari3
1. Department of Emergency Medicine, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
2. Student Research Committee, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
3. Emergency Medicine Research Center, Department of Emergency Medicine, Al-Zahra Research Institute, Isfahan University of Medical
Sciences, Isfahan, Iran.
*Corresponding author: Alireza Abootalebi; Email: a_abootalebi@yahoo.com
Published online: 2017-10-12
Abstract
Introduction: Large-volume paracentesis is one of the usual treatments for cirrhotic patients with tense
ascites, which may cause different complications including decreased cardiac preload, suppressed renin
angiotensin system, inactivation of sympathetic nervous system, electrolyte imbalances, etc.
Objective: The aim of this study was to compare the effects of administrating hydroxyethyl starch (HES) and
albumin in cirrhotic patients with tense ascites in order to reduce the paracentesis complications.
Methods: In the present randomized clinical trial, 108 cirrhotic patients with tense ascites were enrolled. The
patients were randomly divided into 3 groups. In group A, albumin 20% with 5 g/L dose of paracentesis fluid,
in group B, HES 6% dissolved in saline were administered, and in group C, a combination of albumin 20% and
HES 6% with half the dosage administrated to two other groups were prescribed. Then biochemical panel, and
liver function tests and renal and electrolyte complications were compared between the groups.
Results: The results obtained after intervention did not show significant differences between the groups
regarding weight (p=0.102), heart rate and platelet count (both p=0.094), hematocrit (p=0.09), creatinine
(p=0.421), serum sodium (p=0.743) and potassium (p=0.147), total bilirubin (p=0.375) and urine volume
(p=0.421). Additionally, we concluded that mean arterial pressure of patients who had received albumin was
higher than the other 2 groups (p < 0.001).
Conclusion: The results of the present study showed the similar effects of HES and albumin in cirrhotic
patients with tense ascites undergoing large-volume paracentesis.
Key words: Albumins; Ascites; Hydroxyethyl starch derivatives; Liver cirrhosis; Serum albumin
Cite this article as: Abootalebi A, Khazaei S, Minakari M, Nasr-Isfahani M, Esmailian M, Heydari F. Comparing the Effects of Hydroxyethyl
Starch and Albumin in Cirrhotic Patients with Tense Ascites; a Randomized Clinical Trial. Adv J Emerg Med. 2017;1(1):e7.
INTRODUCTION
Ascites is defined as accumulation of more than 25
cc liquid in the peritoneal cavity, which has various
reasons including cirrhosis, anomaly, congestive
heart failure, Budd-Chiari syndrome, tuberculosis,
and pancreatitis. Ascites is one of the most common
complication that manifests in about 60% of
cirrhotic patients within 10 years (1, 2). Various
treatment methods have been proposed including
diuretics,
paracentesis,
and
trans-jugular
intrahepatic
portosystemic
shunt
(TIPS)
placement, but none improved the survival of
cirrhotic patients (3, 4). Among the treatment
options, paracentesis is the most common one that
could lead to various problems in the circulatory
system by increasing cardiac output and
decreasing cardiac preload (5). Thus, finding other
treatment methods for these patients is still
necessary. Albumin is the most common protein
found in blood and has various functions such as
maintaining intravascular volume and colloid
osmotic pressure, anti-oxidant, anti-inflammation,
stabilizing endothelial wall, and might play an
important role in treatment of ascites caused by
cirrhosis (6-8). The effects of albumin in cirrhotic
patients with tense ascites vary and include
prevention of dysfunction after paracentesis,
decreased autonomous bacterial peritonitis,
prevention of kidney injury and increasing
survival. On the other hand, hydroxyethyl starch
(HES) is used for treatment and prevention of
hypovolemia by sustaining water in the plasma and
increasing blood volume. It has recently been used
as plasma expander in cirrhotic patients with tense
ascites (9). Considering the complications caused
Copyright © 2017 Tehran University of Medical Sciences
This open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 License (CC BY-NC 4.0).
1
ADVANCED JOURNAL OF EMERGENCY MEDICINE. 2017; 1(1): e7
by paracentesis, the need to find a safe, noninvasive and cheap treatment method is still
present. In addition, to the best of our knowledge,
there are not enough prospective studies in this
regard and moreover, contradicting results have
been presented in this era. Therefore, the present
study aimed to evaluate and compare the results of
HES and albumin in cirrhotic patients with tense
ascites in order to reduce the paracentesis
complications.
METHODS
Study design
This randomized clinical trial was performed in
Alzahra Hospital, Isfahan, Iran, from January to
May 2017. The study protocol was approved by the
ethical committee of Isfahan University of Medical
Sciences and the code of 395092 was assigned to it.
All the participants signed the written consent
form. The authors were fully adhered to the
Declaration of Helsinki Principles throughout the
study.
Abootalebi et al
Study population
Inclusion criteria consisted of cirrhotic patients
with tense ascites that were diagnosed by the
emergency physician based on clinical criteria and
ultrasonography findings (including cirrhosis of
patients and presence of ascites fluid) and referred
to the hospital, serum creatinine <1.4 mg/dL,
serum sodium >120 mEq/dL, giving consent for
participation in the study.
Having any comorbid diseases in addition to
cirrhosis, history of gastrointestinal (GI) bleeding
in the past 2 weeks, presence of portosystemic
anastomosis or peritoneal shunt, receiving plasma
expander or paracentesis in the past 10 days,
creatinine increasing to more than 2 mg/dL during
the study, hepatic anomaly encephalopathy, severe
cardiac, pulmonary, and renal diseases, infectious
disease, hypotension (systolic blood pressure
(SBP) <80 mmHg), severe hemodynamic disorder,
withdrawing from participation in the study and
patients’ data not being complete were all
considered as the exclusion criteria.
Figure 1: CONSORT flowchart of studied patients
Copyright © 2017 Tehran University of Medical Sciences
This open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial 3.0 License (CC BY-NC 4.0).
2
ADVANCED JOURNAL OF EMERGENCY MEDICINE. 2017; 1(1): e7
The eligible patients were divided into 3 groups:
group A received albumin, group B received HES,
and group C received a combination of albumin and
HES. Allocation of patients was via blocks,
therefore since our studies included 3 groups,
blocks of 12 included 4 participants that were
allocated to albumin group, 4 participants in HES
group and 4 participants of albumin and HES
group, and this pattern went on until sample size
was reached. CONSORT flowchart of the study has
been shown in figure 1. Overall, 114 patients with
the diagnosis of cirrhosis with tense ascites were
eligible and 110 cases were allocated for each
group: 36 in albumin group, 37 in HES group and
37 in albumin and HES group. In the end, 6 patients
were excluded and 108 participated in the study.
Those who prescribed the drugs were independent
from those who gathered patient data and both
were blind to the type of drugs prescribed
Intervention
Patients did not receive diuretics and vasoactive
agents for at least 5 days before paracentesis.
Liquid intake before paracentesis was not more
than 115 L per day. Patients were fasting before
paracentesis and electrolyte levels, serum
creatinine, complete blood count (CBC), and liver
function tests were evaluated before paracentesis.
Ascites fluid samples were sent to the hospital
laboratory for undergoing routine tests such as
culture, cell count, and biochemical tests.
Group A: Albumin 20% with 5 g/L dose of
parasynthesized liquid (5g/L albumin in each liter
of parasynthesized liquid) was injected
intravenously (to prevent liquid increase in
vessels, half of the required albumin was
prescribed during paracentesis and the other half
during 6-8 hours after paracentesis) (10).
Group B: HES 6% with 5 g/L dose of
parasynthesized liquid (5g/L HES in each liter of
parasynthesized liquid) was injected intravenously
(to prevent liquid increase in vessels, half of the
required HES was prescribed during paracentesis
and the other half during 6-8 hours after
paracentesis) (10).
Group C: A combination of albumin 20% and HES
6%, with half the dose injected in groups A and B,
was given. This means that each of the compounds
(albumin 20 and HES 6%) were prescribed with 2.5
g/L dose and similar to protocol A.
Four days after paracentesis, weight, mean arterial
pressure, heart rate, urinary output, and level of
consciousness were evaluated. In addition, in this
time period biochemical tests (platelet, hematocrit,
24-hour urine volume, fasting blood sugar (FBS),
potassium, sodium, albumin, bilirubin, and
Abootalebi et al
prothrombin time) and liver function tests were
done for all the patients.
The complications that manifested after
paracentesis and were important to us included:
renal failure defined as more than 50% increase in
serum creatinine (> 1.5mg/dL), hyponatremia
where sodium concentration was less than
130mEq/dL,
hyperkalemia
(potassium
concentration > 5.5mEq/dL), infection, especially
spontaneous bacterial peritonitis, encephalopathy,
and cardiac diseases associated with paracentesis.
Statistical analysis
All patient data including demographic factors and
paraclinical symptoms were recorded in a checklist
designed by the researcher and entered to SPSS 22
software; statistical analyses were presented in
descriptive and analytic sections. In the descriptive
section, mean and standard deviation of the
laboratory variables and frequency of side effects
were presented as the main variable in different
groups and all demographic and clinical data of the
patients were reported based on descriptive
criteria. In the analytic section, based on statistical
assumptions, proper parametric and nonparametric tests were applied. To analyze
qualitative findings chi-square and for comparison
of quantitative data independent t-test were used.
If the initial assumptions, such as normality of data,
were not true, non-parametric Mann-Whitney test
was used. All tests were evaluated at 5% error level
and p-value < 0.05 considered significant.
RESULTS
Finally, 108 patients completed the survey. The
mean age of studied patients was 45.48±3.95 years
and 62 cases (57.4%) were male. Table 1 reports
values of the studied variables in the 3 groups of
patients before and after intervention. The mean
age (p=0.218) and sex ratio (p=0.767) were not
statistically different. Before intervention, there
was no significant difference between the groups
regarding the variables except for prothrombin
time index, which stayed the same after
intervention (p=0.001).
In the results obtained after intervention, there
was no significant difference in the variables such
as weight, 24-hour urine volume, bilirubin, heart
rate, platelet, hematocrit, sodium, and potassium
(p>0.05), but mean arterial pressure was
significantly different in the albumin receiving
group compared to the other 2 groups, which
indicates that albumin is good for patients with
hemodynamic disorders. In addition, no dangerous
and negative side effect was detected in any of the
groups.
Copyright © 2017 Tehran University of Medical Sciences
This open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial 3.0 License (CC BY-NC 4.0).
3
ADVANCED JOURNAL OF EMERGENCY MEDICINE. 2017; 1(1): e7
Table 1: Values of studied variables in the 3 groups of patients before and after intervention
Albumin group
HES group
(n=36)
(n=36)
Variable
Mean ± SD
77.36 ± 12.91
81.61 ± 14.43
Before
Weight (Kg)
72.19 ±12.71
76.16 ± 14.22
After
83.81 ± 3.09
84.35 ± 2.41
Before
Mean arterial pressure (mmHg)
84.67 ± 2.59
82.24 ± 2.43
After
80.11 ± 6.49
78.33 ± 5.70
Before
Heart rate (/min)
77.05 ± 5.72
74.61 ± 5.49
After
250.14 ± 57.1
226.78 ± 61.47
Before
Platelet count (/mm3)
301.41 ± 61.11
273.52 ± 61.12
After
36.68 ± 3.32
37.13 ± 3.30
Before
Hematocrit (%)
38.05 ± 3.34
38.49 ± 3.33
After
135 ± 2.98
134.67 ± 2.96
Before
Serum sodium (mEq/L)
134.16 ± 3.07
133.58 ± 3.05
After
4.36 ± 0.32
4.46 ± 0.32
Before
Serum potassium (mEq/L)
4.21 ± 0.32
4.30 ± 0.34
After
5.76 ± 1.57
6.22 ± 1.99
Before
Total bilirubin (mg/dL)
4.3 ± 1.59
4.88 ± 2.02
After
62.22 ± 14.17
70.44 ± 8.85
Before
Prothrombin time index (%)
59.5 ± 13.96
67.63 ± 8.67
After
1065.37 ± 282.54
1044.44 ± 257.67
Before
Urine volume (ml/day)
1358.33 ± 281.7
1358.33 (±287.72)
After
DISCUSSION
Based on the obtained results, there was no
significant difference between the groups
regarding the studied variables. However, we
concluded that in patients with hemodynamic
disorders, albumin is a better choice. This study
showed that prescription of HES, albumin and even
both simultaneously has the same effects in
treatment of cirrhotic patients with tense ascites.
A study by Abdel-Khalek, et al. showed that in
cirrhotic patients with tense ascites who have
undergone paracentesis HES 6% is as effective and
safe as albumin for prevention of renal and
electrolyte complications and just like the current
study they concluded that transients hypotension
after paracentesis is more common in HES group
(10).
In a study performed by Alsebaey et al. it was
shown that Terlipressin and HES have the same
effects as low dose albumin regarding prevention
of hemodynamic disorder following large-volume
paracentesis, but they cost less than albumin.
Additionally, they concluded that plasma renin
activity in HES group increases less than the other
groups and urinary output was significantly higher
than baseline at the time of discharge, but there
was no significant difference between the groups in
this regard (11).
Altman et al. also showed that in cirrhotic patients
HES is tolerated better than albumin. They also
found out that there is no difference between HES
and
albumin
regarding
prevention
of
complications associated with large-volume
Abootalebi et al
HES and albumin group
(n=36)
p
74.05 ± 15.09
69.05 ± 14.93
84.16 ± 1.90
80.56 ± 3.05
81.55 ± 6.76
77.5 ± 6.69
228.86 ± 81.87
275.66 ± 82.29
35.29 ± 4.34
36.63 ± 4.35
134.75 ± 3.43
133.88 ± 3.47
4.28 ± 0.36
4.13 ± 0.38
5.75 ± 2.11
4.35 ± 2.15
63.97 ± 12.43
61.22 ± 12.15
1129.16 ± 268.69
1434.72 (±281.02)
0.081
0.102
0.651
<0.001
0.102
0.094
0273
0.166
0.093
0.09
0.896
0.743
0.094
0.147
0.494
0.375
0.011
0.011
0.385
0.421
paracentesis. They also concluded that weight loss
occurs less in HES group (12). Fernandez et al.
showed that albumin, but not HES, improves the
hemodynamic status of patients with spontaneous
bacterial peritonitis (13). These results were
similar to our findings, which showed that albumin
prescription is better in patients with
hemodynamic disorder and did not show any
differences
between
HES
and
albumin
administration regarding biochemical, and liver
function tests and renal complications.
In a meta-analysis performed by Bernardi et al. it
was shown that albumin decreases the morbidity
and mortality of cirrhotic patients with tense
ascites undergoing large-volume paracentesis. In
addition, they compared replacement treatments
such as dextran 70, 6%, gelatin 3.5%, HES 6%,
dextran 40, 10%, Terlipressin 3mg, saline 3.5%,
norepinephrine 0.5-3 mg, and Midodrine 12.5 mg
(14). These results are in line with our findings.
However, we followed patients for a shorter period
of time, which was one of the limitations of this
study and there is a need for further studies and
increased follow-up period to evaluate the patients
regarding mortality rate with various methods. The
results of the present study showed the similar
positive effects of HES and albumin in cirrhotic
patients with tense ascites undergoing largevolume paracentesis. We concluded that in patients
with hemodynamic disorders, albumin is better
and based on the patients’ condition it should be
used as an additional treatment on the side of
standard treatment, which leads to a significantly
Copyright © 2017 Tehran University of Medical Sciences
This open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial 3.0 License (CC BY-NC 4.0).
4
ADVANCED JOURNAL OF EMERGENCY MEDICINE. 2017; 1(1): e7
Abootalebi et al
better control of biochemical and liver function
tests and renal and electrolyte complications.
Limitations
Since there are many items on the exclusion
criteria of this study (so that the results of the study
will not be affected and confounding factors are
eliminated) it is difficult to generalize the aforementioned findings to emergency patients.
Therefore, it is suggested to carry out a study with
a bigger sample size and include patients with
various clinical statuses to generalize the findings
of the study and evaluate the effects of the drugs
applied in this study more accurately. Among other
limitations of the study is the lack of long-term
evaluation of the drugs’ effects (1 week and 1
month later) regarding need for re-admission, or
re-injection of the drug and the required dose to
determine the real effects of both drugs. Therefore,
another study is suggested to evaluate and follow
the patients for a long period of time.
with hemodynamic disorders based on the status
of the patients and as an adjunct treatment in
addition to standard treatment.
CONCLUSIONS
The results of the present study showed the similar
effects of HES and albumin in cirrhotic patients
with tense ascites undergoing large-volume
paracentesis. Therefore, it can be concluded that
albumin should better be prescribed for patients
C ONFLICT OF INTEREST
None declared.
ACKNOWLEDGEMENTS
The present study is derived from a research
project approved by Isfahan University of Medical
Sciences. Hereby, we thank the vice-chancellor of
research and technology of Isfahan University of
Medical Sciences for supporting this project. We
also thank the researchers, coordinators, patients
who volunteered to participate in this study and
clinical research and development unit (CRDU) of
Alzahra Hospital, Isfahan, Iran.
AUTHORS’ CONTRIBUTION
All authors passed four criteria for authorship
contribution based on recommendations of the
International Committee of Medical Journal
Editors.
FUNDING
None declared.
REFERENCES
1. Ahmed F. Comment on ‘Ascitic Fluid Analysis in the Differential Diagnosis of Ascites: Focus on Cirrhotic
Ascites’. J Clin Transl Hepatol. 2017;5(2):184.
2. Pedersen JS, Bendtsen F, Møller S. Management of cirrhotic ascites. Ther Adv Chronic Dis.
2015;6(3):124-37.
3. Wiest R, Lawson M, Geuking M. Pathological bacterial translocation in liver cirrhosis. J Hepatol.
2014;60(1):197-209.
4. Chinchilla-López P, Hamdan-Pérez N, Guerrero-Ixtlahuac J, Barranco-Fragoso B, Méndez-Sánchez N. The
Role of TIPS in Patients with Refractory Ascites and Portal Vein Thrombosis. Ann Hepatol. 2017;16(4):61920.
5. Facciorusso A, Cosimo Nacchiero M, Rosania R, Laonigro G, Longo N, Panella C, et al. The use of human
albumin for the treatment of ascites in patients with liver cirrhosis: item of safety, facts, controversies and
perspectives. Curr Drug Saf. 2011;6(4):267-74.
6. Wong F. Drug insight: the role of albumin in the management of chronic liver disease. Nat Clin Pract
Gastroenterol Hepatol. 2007;4(1):43-51.
7. Martin DK, Walayat S, Jinma R, Ahmed Z, Ragunathan K, Dhillon S. Large-volume paracentesis with
indwelling peritoneal catheter and albumin infusion: a community hospital study. J Community Hosp
Intern Med Perspect. 2016;6(5):32421.
8. Widjaja FF, Khairan P, Kamelia T, Hasan I. Colloids Versus Albumin in Large Volume Paracentesis to
Prevent Circulatory Dysfunction: Evidence-based Case Report. Acta Med Indones. 2016;48(2):148-55.
9. Wilkes MM, Navickis RJ, Sibbald WJ. Albumin versus hydroxyethyl starch in cardiopulmonary bypass
surgery: a meta-analysis of postoperative bleeding. Ann Thorac Surg. 2001;72(2):527-33.
Copyright © 2017 Tehran University of Medical Sciences
This open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial 3.0 License (CC BY-NC 4.0).
5
ADVANCED JOURNAL OF EMERGENCY MEDICINE. 2017; 1(1): e7
Abootalebi et al
10. Abdel-Khalek EE, Arif SE. Randomized trial comparing human albumin and hydroxyethyl starch 6% as
plasma expanders for treatment of patients with liver cirrhosis and tense ascites following large volume
paracentesis. Arab Journal of Gastroenterology. 2010;11(1):24-9.
11. Alsebaey A, Abdel-Razek W, Bassuni A, Rewisha E, Khalil M, Waked I. Prevention of paracentesisinduced circulatory dysfunction: could we use other albumin alternatives? Egypt Liver J. 2013;3(4):11825.
12. Altman C, Bernard B, Roulot D, Vitte R-L, Ink O. Randomized comparative multicenter study of
hydroxyethyl starch versus albumin as a plasma expander in cirrhotic patients with tense ascites treated
with paracentesis. Eur J Gastroenterol Hepatol. 1998;10(1):5-10.
13. Fernández J, Monteagudo J, Bargallo X, Jiménez W, Bosch J, Arroyo V, et al. A randomized unblinded
pilot study comparing albumin versus hydroxyethyl starch in spontaneous bacterial peritonitis.
Hepatology. 2005;42(3):627-34.
14. Bernardi M, Caraceni P, Navickis RJ, Wilkes MM. Albumin infusion in patients undergoing large‐volume
paracentesis: a meta‐analysis of randomized trials. Hepatology. 2012;55(4):1172-81.
Copyright © 2017 Tehran University of Medical Sciences
This open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial 3.0 License (CC BY-NC 4.0).
6