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Aires FT et al .
244 Rev Assoc M ed Bras 2016; 62(3):243-247
The study population included patients over 18 years
old and diagnosed with liver cirrhosis, regardless of etiol-
ogy, and gastrointestinal bleeding. Exclusion criteria were
patients who had used lactulose in the past six weeks, were
hemodynamically unstable or had severe comorbidities.
The intervention group included patients treated with
lactulose aiming to obtain two or three bowel movements
with pasty stools per day.
The analyzed primary outcome was the incidence of
hepatic encephalopathy during hospitalization. Mortal-
ity and adverse effects from the use of lactulose were also
evaluated.
Search strategies
The Medline database was searched via PubMed (http://
using the following search
strategy: (liver cirrhosis) AND (gastrointestinal bleeding)
AND (lactulose OR lactitol OR disaccharides) AND (he-
patic encephalopathy), until September 2014.
The references of the selected studies were also con-
sulted manually to select studies that may not have been
retrieved in electronic searches.
Statistical analysis
All data were examined based on intention to treat anal-
ysis, and patient assessment was conducted within each
randomization group, regardless of the treatment proto-
col and irregularities.
The measures of effectiveness or harm expressed in
absolute numbers were analyzed as the absolute risk dif-
ference using a 95% confidence interval. When there was
a statistical difference between the groups, the number
needed to treat (NNT) or number needed to harm (NNH)
was calculated.
Results
The electronic and manual searches resulted in a total of
28 studies. After reading their titles and summaries, two
studies that met the inclusion criteria were selected and
evaluated for methodology.
The results of this review were based on data provid-
ed by two controlled clinical trials8,9 totaling 200 patients,
100 in lactulose group and 100 in the control group.
Both articles describe randomization and patient al-
location to each group appropriately. Blinding of patients
was considered impossible due to the sweet taste and the
cathartic effect of lactulose. To minimize this bias, the
analysis of the incidence of hepatic encephalopathy was
carried out by independent evaluators. None of the pa-
tients were lost to follow-up. Therefore, both studies were
classified as score 3 on the Jadad scale (Table 1).
Demographic, laboratory and clinical data, etiology
of cirrhosis and bleeding source are described in Table 2.
There were no significant differences among patients ran-
domized to each group in each primary study.
Incidence of hepatic encephalopathy
The overall incidence of hepatic encephalopathy was 16.5%
(33 cases), ranging from 10 to 28.6% in primary studies.
In the lactulose group, one patient developed HE grade
1; three developed grade 2; two developed grade 3; and
one developed grade 4. In the control group, three pa-
tients developed HE grade 1; fourteen developed grade 2;
seven developed grade 3; and one developed grade 4. In
the group of patients who received lactulose, the inci-
dence of HE was 7% while in the control group it was 26%.
This means a reduction of 19% in absolute risk (95CI 0.04
to 0.33; p=0.01; I2=47%) so that six patients need to be
treated to obtain such benefit (Figure 1).
Mortality
The mortality rate was 5%, ranging between 0.7 and 12.9%
in the primary studies. Liver failure was the main cause
of death (70%) followed by failure to control bleeding
(30%). There was no difference in the incidence of mor-
tality between the group treated with lactulose and the
TABLE 1Characteristics of primary studies.
Reference
Period
Location
Lactulose Description of the randomization
and allocation methods
Description of
blinding
Description of
patient loss
Jadad
Wen J, 2013
2007 – 2011
Beijing, China
10-30 mL 2-3x/day for 7
days until 2-3 bowel
movements with pasty stools
Table of random numbers generated
by computer
Non-blinded Yes 3
Sharma P, 2011
2008 – 2010
New Delhi, India
30 mL 3-4x/day for 5 days
until 2-3 bowel movements
with pasty stools
Opaque envelopes numbered by
computer
Non-blinded Yes 3