Med. J. Cairo Univ., Vol. 78, No.

2, June: 59-65, 2010

www.medicaljournalofcairouniversity.com

The Prevalence of Hypoxemia and Abnormal Ventilatory

Functions in Cirrhotic Patients With and Without Ascites
TAHER H. AL-ZANATY, M.D.; MONA A. HEGAZY, M.D.; SAMAR H. ABOULSOUD, M.D.;
HATEM M. EL-KHABERY, M.D. and SAMY O. MOHAMAD, M.Sc.
The Department of Internal Medicine, Faculty of Medicine, Cairo University.

Key Words: Hypoxemia Abnormal ventilatory functions

Liver cirrhosis Ascites.

Abstract
Objective: To investigate the frequency of hypoxemia
and impairment of pulmonary function tests in patients with
liver cirrhosis, and to examine the relationships of these
impairments with the presence, absence and grade of ascites
in cirrhotic.

Introduction
PATIENTS with cirrhosis develop complication
affecting multiple organs including the lung, the
heart and the kidney [1] . Pulmonary complications
such as hepatopulmonary syndrome and Porto
pulmonary hypertension are frequently observed
in cirrhotic patients [2] . Patients with cirrhosis have
a compromised lung function with a reduced transfer factor and ventilation/perfusion abnormalities
and arterial hypoxia is seen in 30%-70% of patient
with chronic liver disease, depending on the severity
[3] . The hypoxemia has been attributed to right to
left shunting through pulmonary arteriovenous
fistula and/or intrapulmonary vascular dilatation.
The restrictive pulmonary function could be due
to interstitial lung oedema, ascites, respiratory
muscle weakness and/or pleural effusion which
can be improved after treatment with diuretic and
paracentesis [4,5] .

Methods: A comparative study that included 100 patients

with liver cirrhosis divided into two groups according to
presence or absence of ascites. Patients with ascites were
further classified according to grade into mild, moderate and
massive ascites.
Results: Hypoxia was evident in thirty patients of both
groups (30%). Restrictive ventilatory function was the commonest pattern in patients with liver cirrhosis with or without
ascites, 46% of patients had restrictive ventilation and 3%
obstructive ventilatory function. Forced Vital Capacity (FVC),
Forced Expiratory Volume in 1 st second (FEV1) and Forced
Expiratory Flow (FEF 25-75%) were decreased in patients
with ascites when compared to patients without ascites.
Moreover, these parameters further decreased with advanced
grades of ascites. There was a trend of higher incidence of
restrictive ventilatory function with higher grades of ascites
(p<0.05).
Conclusion: Hypoxia is more common in cirrhotic patients
with ascites when compared to those without ascites. Moreover,
the degree of hypoxia correlates positively with the grade of
ascites. Restrictive pattern was the commonest observed
abnormality in patients with liver cirrhosis with or without
ascites.

Aim of the study: To investigate the frequency

of hypoxemia and impairment of pulmonary function tests in patients with liver cirrhosis and to
examine the relationships of these impairments
with the presence, absence and grade of ascites in
cirrhotic.

Abbreviations:
FVC : Forced Vital Capacity.
FEV1 : Forced Expiratory Volume in 1 st second.
FEF 25-75%: Forced Expiratory Flow.
ABG : Arterial blood gases.
PaO2 : Partial pressure of oxygen in arterial blood.
SaO2 : Oxygen saturation.
PCO2 : Partial pressure of carbon dioxide.
DLCO : Diffusion lung capacity for carbon monoxide.

Patients and Methods

This study was conducted in Kasr El-Aini Hospital, Internal Medicine Department.
Our study enrolled 100 patients with liver cirrhosis. The patients were divided into two groups
according to ultrasound findings:

Correspondence to: Dr. Taher H. Al-Zanaty, The Department

of Internal Medicine, Faculty of Medicine, Cairo University.

Group 1: 36 patients with no fluid collection.

59

60

The Prevalence of Hypoxemia & Abnormal Ventilatory Functions

Group 2: 64 patients with ascites. They were further

classified into 27 (42.1%) patients with
mild ascites, 20 (31.2%) patients with
moderate ascites and 17 (26.6%) patients
with massive ascites.
A written informed consent was obtained from
all participants.
Inclusion criteria:
Patients aged from18 to 60 years with liver
cirrhosis diagnosed by (history, clinical examination, laboratory findings and abdominal ultrasound).
Exclusion criteria:
1- All patients with chronic pulmonary diseases
such as bronchial asthma, chronic obstructive
pulmonary disease and pleural effusion.
2- Patients with heart diseases excluded by Echo
cardiography.
3- Smokers (current or ex smokers).
All the patients in this study were subjected to the
following:
History and Clinical examination:
All patients were subjected to full history taking
and were assessed clinically to detect stigmata of
liver cirrhosis.
Laboratory investigations:
Complete blood picture.
Fasting blood sugar
Liver profile including alanine aminotransferase (ALT), aspartate aminotransferase
(AST), serum albumin, total & direct billirubin, prothrombin time (PT), and International
normalized ratio (INR).
Hepatitis markers for Hepatitis B virus (HBs
Ag) and Hepatitis C virus (HCV Ab).
Chest X-ray and Electrocardiography:
To exclude the presence of pleural effusion and
heart diseases.
ECHO heart.

Two groups of pulmonary function tests were

performed:
Arterial blood gases (ABG):
The arterial blood gases were done using Radiometer Medical APS, DK-2700. The samples were
taken while the patients were lying in the recumbent
position and breathing room air. Blood sample was
drawn on heparinised syringe from the radial artery
of the non-dominant arm.
Measurements of ABG included: pH, partial
pressure of oxygen in arterial blood (PaO 2), Oxygen
saturation (SaO 2 ), and partial pressure of carbon
dioxide (PCO 2 ). Patients with PaO 2 values less
than 80 mmHg were considered hypoxemic.
Ventilation tests:
The ventilation tests were done using spirometry
[multispiro-Lt plus (TM) version 5.03]. Details of
the tests are out of the scope of this paper.
Forced vital capacity (FVC), forced expiratory
volume in the first second (FEV1) were measured
and FEV1/FVC ratio was calculated.
Restrictive ventilation disorder was determined
on the basis of the following parameters: A normal
or increased FEV1/FVC ratio markedly decreased
FVC and decreased FEV1.
Obstructive ventilation disorder was determined
on the basis of the following parameters: A
FEV1/FVC ratio below 70% and markedly decreased FEV 1.
Statistical analysis:
Data were presented as means SD. A p-value
0.05 was considered significant.
Chi-Square test X 2 was used to test the association variables for categorical data. Fisher exact
test was performed in table containing value less
than 5. Student's t-test was used to assess the
statistical significance of the difference between
two population means in a study involving independent samples. ANOVA (Analysis of variance)
evaluated the equality of several group means and
was used to test the difference about mean values
of some parameters among multiple groups.

Abdominal ultrasonography:
Abdominal ultrasound was performed to all
patients aiming at:

All calculations were done with SPSS for Windows version 15 (SPSS, Chicago, IL, USA).

Confirming the presence of liver cirrhosis.

Results

Diagnosis and detection of the amount of

ascitic fluid.

The study included 100 patients with liver

cirrhosis. The age of the patients ranged from 19-

Taher H. Al-Zana ty, et al.

60 years. There were 53 females (53%) and 47

males (47%).
Group (I): 36 cirrhotic patients with no ascites.
There were 22 females and 14 males with mean
age of 43.7 9.06 years.
Group (II): 64 cirrhotic patients with ascites (27
mild ascites, 20 moderate ascites and 17 massive
ascites). The group included 31 females and 33
males with mean age of 48.9 6.77 years.
Hepatitis markers results:
Twenty seven patients (27%) in both groups
were found to be positive for HBs Ag, and eightysix patients (86%) were found to be positive for
HCV Ab. Nineteen patients (19%) tested positive
for both HBV & HCV, and six patients (6%) had
negative markers for HBV or HCV.
Pulmonary function tests in patients with and
without Ascites:
On comparing the results of arterial blood gases
and ventilatory function among the two groups the
following was concluded:
Arterial blood gases:
PH: There was no statistical significant difference between the two groups as regards the mean
pH (p>0.05).
PCO2 : Patients with ascites showed significantly
lower PCo 2 when compared to patients without
ascites (p<0.05).
PO 2 : Patients with ascites showed significantly
lower Po 2 when compared to patients without
ascites (p<0.05).
SaO 2% : Oxygen Saturation in patients with
ascites showed significantly lower mean when
compared to patients without ascites (p<0.05).
Ventilatory functions:
FVC: FCV decreased below the predicted value
in 8 patients without ascites out of 36 patients
(22.2%) compared to 38 patients with ascites out
of 64 patients (59.3%). Patients with ascites showed
highly significant lower mean when compared to
patients without ascites (p<0.05).
FEV 1: FEV 1 decreased in 8 patients without
ascites (22.2%) and in forty-one patients with
ascites (64%). Group 2 patients showed significantly lower mean when compared to group 1
(p<0.05).
FEV1/FVC%: None of group 1 patients had
FEV1/FVC% less than 70% whereas 3 patients in

61

group 2 (4.6%) had ratio less than 70%. There was

no statistical significant difference between the
two groups as regards the mean value of FEV1/
FVC%.
FEF25-75%: Patients with ascites showed highly significant lower mean when compared to Patients without ascites (p<0.05).
Table (1): Results of arterial blood gases and ventilatory
functions.
Parameters

Patients
with ascites
(N=64)

Patients
without ascites
(N=36)

pH

7.420.05

7.380.17

0.12

PCO 2

30.006.02

32.613.78

0.02*

PO

80.2517.54

87.8910.28

0.02*

SaO 2 %

93.954.36

96.532.04

0.04*

FVC

71.6312.47

86.3913.83

<0.0001**

FEV1

73.3414.66

85.4415.16

<0.03**

FEV 1/FVC%

83.638.09

85.444.63

0.22

FEF25-75%

68.9819.76

84.6915.90

<0.0001**

Significance p<0.05.
** High Significance p<0.001.

Pulmonary function tests in different grades of

ascites:
Comparing the results of arterial blood gases
and ventilatory function in patients with mild,
moderate and massive ascites revealed the following:
Arterial blood gases:
PH: There was no statistical significant difference between the three groups as regards the mean
PH (p>0.05).
PCO 2 : There was no statistical significant difference between the three groups as regards the
mean value (p>0.05).
PO 2 : Patients with mild ascites showed significantly higher PO 2 when compared to cases with
moderate and massive ascites ( p<0.05), with no
statistical significant difference among cases with
moderate and massive ascites.
SaO 2% : Patients with mild ascites showed significantly higher mean when compared to cases
with moderate and massive ascites (p<0.05), with
no statistical significant difference between cases
with moderate and massive ascites (p>0.05).

62

The Prevalence of Hypoxemia & Abnormal Ventilatory Functions

100
90
80
70
60

Mild ascites (N=27)

Moderate ascites (N=20)
Massive ascites (N=17)

Fig. (1): Arterial blood gases results in

different grades of ascites.

50
40
30
20
10
0
pH

Ventilatory functions:
FVC: Patients with massive ascites showed
significantly lower mean when compared to cases
with mild and moderate ascites (p<0.05), and cases
with moderate ascites showed lower mean than
mild cases i.e. there was a significant reduction in
FVC with higher grades of ascites (p<0.05).
FEV 1: Patients with massive ascites showed
significantly lower mean when compared to patients
with mild and moderate ascites ( p<0.05), and
patients with moderate ascites showed lower mean
than mild patients i.e. there was a significant

PCO 2

PO 2

SaO 2

reduction in FEV 1 with higher grades of ascites

(p<0.05).
FEV1/FVC%: There was no statistical significant difference between the three groups (mild,
moderate, massive) as regards the mean value
(p>0.05).
FEF25-75%: Patients with massive ascites
showed significantly lower mean when compared
to cases with mild and moderate ascites ( p<0.05),
with no statistically significant difference between
cases with mild and moderate ascites (p>0.05).

Table (2): Arterial blood gases and ventilatory functions in different grades of Ascites.
Parameters

Mild Ascites
(N=27)

Moderate Ascites
(N=20)

Massive Ascites
(N=17)

pH
PCO 2
PO 2
SaO 2 %
FVC
FEV1
FEV 1/FVC%
FEF25-75%

7.41 0.05
31.11 5.49
87.48 16.57
95.81 2.68
77.74 13.26
79.22 13.26
82.788.95
72.1523.39

7.42 0.05
28.406.21
74.15 15.46
92.355.36
71.059.89
73.50 11.09
84.005.09
74.75 15.03

7.42 0.06
30.12 6.54
75.94 18.08
92.884.33
62.597.75
63.82 12.04
82.189.27
57.18 13.19

* Significance p<0.05.
** High Significance p<0.001.

Table (3): Numbers of patients presenting with hypoxia in

both groups.
No hypoxia
N (70)

Hypoxia
N (30)

Absent (36)

33 (91.7%)

3 (8.3%)

Mild (27)

21 (77.7%)

Parameters
Ascites:

Moderate (20)

10 (50.0%)

6 (22.2%)
10 (50.0%)

Massive (17)

6 (35.2%)

11 (64.8%)

p
0.87
0.32
0.02*
0.01*
<0.001**
0.002*
0.28
0.01*

Taher H. Al-Zana ty, et al.

63

presence of arterial venous shunt and changes in

the alveolar-arterial membrane [5] . Agusti, et al.
[7] reported that vasoparalysis of pulmonary vasculature is responsible for alteration of ventilatoryperfusion ratio and accounts for paradoxical phenomenon (low pulmonary vascular resistance associated with arterial hypoxemia). Besides, Chang,
et al. [8] suggested that the mechanical effect of
ascites, the interstitial pulmonary oedema and fluid
retention contribute additionally to gas exchange
impairment.

100
80

60
40
20
0
Absent

Mild

Moderate Massive
Ascitis

Normal ventilatory
Obstructive ventilatory function
Restrictive ventilatory function

In the current study we compared the ventilatory

function tests and arterial blood gases analysis in
into two groups of patients with liver cirrhosis
according to presence (64 patients) or absence (36
patients) of ascites.

Discussion

According to the results of arterial blood gases

analysis it was found that the mean of partial
arterial carbon dioxide (PCO 2 ) was lower in patients
with ascites when compared to patients without
ascites. This could be due to the hyperventilation
state in patients with ascites due to lung compression by the diaphragm. Hypoxia was detected in
thirty patients from the two groups (30%) according
to results of the partial arterial oxygen pressure
(PaO 2 ). On further analysis according to the presence or absence of ascites it was found that three
patients out of thirty-six patients without ascites
had hypoxia (8.3%) and twenty seven patients out
of sixty four patients with ascites had hypoxia
(42.2%). Therefore patients with ascites showed
significantly higher rate of hypoxia when compared
to patients without ascites. In different grades of
ascites, we found that six patients had hypoxia out
of twenty-seven patients with mild ascites (22.2%),
ten patients had hypoxia out of twenty patients
with moderate ascites (50%) and eleven patients
had hypoxia out of seventeen patients with massive
ascites (64.8%). This suggested that there was a
trend of higher rate of hypoxia with higher grades
of ascites. Oxygen saturation (SaO2%) showed
significantly lower mean in patients with ascites
compared to patients without ascites.

Pulmonary dysfunction is very common in

patients presenting with chronic liver disease, with
50-70% of cirrhotic patients complaining of shortness of breath [6] . The aetiology of pulmonary
dysfunction in liver cirrhosis may be due to, reduced transfer factor, ventilation/perfusion mismatching, and arterial hypoxemia which seen in
30%-70% of patients with chronic liver disease.
Various path physiological factors may be involved
in the reduced diffusing capacity, including an
abnormal ventilation/perfusion ratio (VA/Q), the

Our results agreed with Irem, et al. [9] who

studied the relation between liver cirrhosis and
pulmonary function tests and confirmed the presence of hypoxia in 33.3% of the included patients.
They stated that PaO 2 and SaO 2 values of patients
with ascites were lower in comparison to patients
without ascites. Konstantinos, et al. [10] confirmed
that PaO 2 and SaO 2 were decreased with advanced
liver cirrhosis and increasing grades of ascites.
Their results agreed with the present study. Our
results also agreed with a study of pulmonary

Fig. (2): Ventilatory function tests in different grades of ascites.

According to the results of ventilatory function in

patients with different grades of ascites:
Absent ascites (36 patients): Eight patients
without ascites (22.2%) showed restrictive pattern.
Mild ascites (27 patients): 11 patients (40.7%)
had restrictive pattern and 2 patients had obstructive
pattern (7.4%).
Moderate ascites (20 patients): A restrictive
pattern was found in 12 patients (60%).
Massive ascites (17 patients): There were 15
patients with restrictive pattern (88.2%), and one
patient with obstructive pattern (5.9%).
There was a trend of higher incidence of restrictive ventilatory function with higher grade of ascites
p<0.05.
Obstructive ventilatory function was insignificant with only three patients presenting with an
obstructive pattern in our study (3%).

64

The Prevalence of Hypoxemia & Abnormal Ventilatory Functions

function tests in forty five cirrhotic patients with

ascites [11] which stated that there was significant
decrease of PaO 2 and Sa O 2 in patients with liver
cirrhosis and increasing grades of ascites.

Hourani, et al. [14] stated that profuse ascites

and/or pleural effusion reduced lung expansion
and caused restriction of pulmonary volume and
capacity.

On the other hand, Djordje, et al. [12] studied

ventilatory-perfusion disorders in chronic liver
diseases and concluded that the presence of ascites
had no significant effect on the level of partial
oxygen pressure. Their results disagreed with our
study and previous studies.

Irem [9] studied the pulmonary function in 39

smokers with liver cirrhosis in this study diffusion
abnormality was determined using the DLco test.
The study revealed although the ventilatory function
test parameters FVC, FEV1, FEV1/ FVC and
FEF25-75% were lower in patients with ascites
compared to those without ascites. However, only
the differences between the EFV1 and FVC and
FEF25-75% values were statistically significant.
This data disagreed with our study. The disagreement can be due to the smoking status of the
participants and unclarity about the grades of ascites
in included patients.

According to analysis of the results of the

ventilatory function it was found that the restrictive
pattern was predominant in both groups. As 46%
of patients have restrictive pattern compared to
3% with an obstructive pattern. The obstructive
pattern was statistically insignificant. On comparing
the ventilatory function in the two groups we
observed that the Forced Vital Capacity (FVC),
Forced Expiratory Volume in 1 st second (FEV 1)
and Forced Expiratory Flow (FEF 25-75%) had
significantly lower mean in the patients with ascites
when compared to patients without ascites. These
values further decreased with increasing the grade
of ascites.
In concordance with our study Nagral, et al.
confirmed that pulmonary functions were impaired with cirrhosis and that ascites caused further
deterioration. They mentioned that in cirrhotic
patients without ascites, FVC, TLC, FEV 1 were
lower than predicted values and in patients with
ascites, these values were even significantly lower
as compared to predicted values. These values
decreased significantly with increasing grades of
ascites. Jameel, et al. [13] studied pulmonary dysfunction in advanced liver disease and stated that
25% of their patients had ventilatory restriction
and only 3% had airflow obstruction. Diffusion
abnormality was accompanied with restrictive
ventilatory defect in 35% and FEF was abnormally
reduced in about 27% of their patients. The study
revealed that many factors other than respiratory
muscle weakness like ascites or interstitial pulmonary abnormalities were responsible for restriction.
Their data agreed with our results.
[11]

In another study Djordje, et al. [12] reported a

significantly higher incidence of restrictive ventilatory disorders in cirrhotic patients with ascites
compared with those without ascites. The also
recommended evacuation of ascites as it resulted
in the improved total pulmonary capacity, functional
residual capacity and airway flow, the best improvement being noted in the expiratory reserve
volume.

Helmy, et al. [15] studied the interstitial pulmonary disease in hepatitis C virus patients and reported restrictive disorder in (16.6%) of patients
with hepatitis C virus infection which can even be
related to the development of several pulmonary
abnormalities despite absence of symptoms. In the
present study restrictive ventilatory function was
found in patients without ascites. Taking in consideration the high prevalence of hepatitis C virus
antibodies in our study (86%) we can suggest
interstitial pulmonary fibrosis; one of the extra
hepatic manifestation of hepatitis C virus; as a
possible aetiology.
Finally we believe that diffusion tests should
be performed in addition to the pulmonary function
tests as a further confirmatory tool for diagnosis
of the presence and extent of pulmonary involvements. We also consider the number of patients
included in the study as limited for a "prevalence"
study and large scale studies are suggested. Both
issues were considered as limitations of the current
study.
In conclusion, patients suffering from liver
cirrhosis and ascites, presented with reduction in
PaO 2 and SaO 2 in association with restrictive
pulmonary function pattern (59.3%). As a result,
pulmonary resistance is impaired and patients more
likely succumb to infection and adult respiratory
distress syndrome. Thus prognosis in those patients
is poor on the basis of both hepatic and pulmonary
disease.
Recommendations:
1- Arterial blood gases should be routinely done
for all patients of liver cirrhosis to detect hypoxia.

Taher H. Al-Zana ty, et al.

2- Pulmonary function tests should be considered

in all patients with liver cirrhosis who are candidates for liver transplantation in order to detect
pulmonary complications.
3- Follow-up studies should be done to detect the
effect of paracentesis or diuretics on pulmonary
functions and which of them yielded better
outcomes if any.
4- Large scale studies that investigate the path
physiological factors that are accused in abnormal ventilatory patterns in cirrhotic patients
with or without ascites should be encouraged.

65
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9- IREM P., SULEYMAN S., MELIH K., et al.: The relationship between severity of liver cirrhosis and pulmonary
function. Dig. Dis. Sici., 53: 1951-1956, 2008.

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