American Journal of Hospice and Palliative

Medicine
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Hypoalbuminemia in Critically Ill Patients With Cancer: Incidence and Mortality

Silvio A. amendys-Silva, Mara O. Gonzlez-Herrera, Julia Texcocano-Becerra and Angel Herrera-Gmez
AM J HOSP PALLIAT CARE 2011 28: 253 originally published online 7 November 2010
DOI: 10.1177/1049909110384841
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Hypoalbuminemia in Critically Ill Patients

With Cancer: Incidence and Mortality

American Journal of Hospice

& Palliative Medicine
28(4) 253-257
The Author(s) 2011
Reprints and permission:
sagepub.com/journalsPermissions.nav
DOI: 10.1177/1049909110384841
http://ajhpm.sagepub.com

amendys-Silva, MD, MSc, FCCP1,2,

Silvio A. N
Mara O. Gonzalez-Herrera, MD1, Julia Texcocano-Becerra, RN1,
and Angel Herrera-Gomez, MD3

Abstract
Purpose: The aim of this study was to investigate the incidence of hypoalbuminemia in critically ill patients with cancer and to
describe the relationship of serum albumin levels to mortality. Design: An observational cohort study. There were no
interventions. Results: During the study period, 200 patients were eligible for inclusion. A total of 164 (82%) patients had a
serum albumin concentration below 35 g/L, of which 91 (55.5%) patients had levels of albumin 20 g/L. The mean serum
albumin was 18.17 g/L. The crude mortality rate was 22.5%. The highest mortality rate (73%) was seen in the group of
patients whose serum albumin levels were <20 g/L. Conclusion: The incidence of hypoalbuminemia in critically ill patients
with cancer admitted to ICU was high.
Keywords
hypoalbuminemia, cancer, intensive care unit, critically ill patients, incidence, mortality

Introduction

Patients and Methods

Albumin is an important molecule under physiological and Design and Setting
pathophysiological conditions, with multiple effects, including
regulation of osmotic pressure; carrier of poorly water soluble
molecules, such as hormones, cholesterol, calcium, iron,
bilirubin, free fatty acids, and drugs; and anti-oxidant
properties and anti-inflammatory effects.1 The normal serum
concentration of albumin in healthy adults is approximately
35 to 50 g/L.2 Albumin synthesis is decreased as a result of
malnutrition and liver dysfunction but also in response to
reprioritization of protein synthesis in favor of acute reactant
proteins.3 Increased microvascular permeability can be observed,
particularly in conditions associated with an inflammatory
response, such as sepsis,4 and alters the normal distribution of
albumin between intravascular and extravascular compartments.
Serum albumin concentration therefore decreases and critically ill
patients are frequently hypoalbuminemic.1 Abnormally low
serum albumin levels (<35 g/L) are a frequent and early biochemical derangement in critically ill adults with a reported incidence
of 30% to 40%.4-6 Reinhardt et al6 reported that a serum albumin
concentration of less than 34 g/L was associated with a 30-day
mortality of 24.6%. This increased to 62% if the serum albumin
concentration was 20 g/L or below during hospitalization.
There are no studies that reported data on the incidence and
significance of hypoalbuminemia in critically ill patients with
cancer admitted to intensive care unit (ICU). The aim of this
study was to investigate the incidence of hypoalbuminemia
in critically ill patients with cancer and to describe the relationship of serum albumin levels to mortality.

An observational cohort study was performed at the Instituto

Nacional de Cancerologa, Mexico City, from January to
August 2007. The hospital has 130 beds and specializes in the
care of patients with cancer. The medical-surgical ICU has
6 beds that are exclusively for oncology patients, with medical
and nursing staff who are qualified in intensive care. Data on
the characteristics and organization of the ICU have been
previously reported.7 The last year, 277 patients were admitted
to the ICU, and the mortality rate was 13.7%. The present study
was observational and descriptive. The Institutional Review
Board approved this study and the need for informed consent
was waived.

1
Department of Critical Care Medicine, Instituto Nacional de Cancerologa,
Mexico City, Mexico
2
Department of Critical Care Medicine, Instituto Nacional de Ciencias Medicas y
Nutricion Salvador Zubiran, Mexico City, Mexico
3
Department of Surgical Oncology, Instituto Nacional de Cancerologa, Mexico
City, Mexico

Corresponding Author:
amendys-Silva, Department of Critical Care Medicine, Instituto
Silvio A. N
Nacional de Cancerologa, Mexico. Av. San Fernando No. 22, Col. Seccion XVI,
Delegacion Tlalpan, 14080, Mexico City, Mexico
Email: snamendys@incan.edu.mx

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American Journal of Hospice & Palliative Medicine 28(4)

254

Table 1. Demographic and Clinical Characteristics for Patients With and Without Levels of Albumin < 20 g/L
Variables

All Patients
(n 164)

Albumins  20 g/L
(n 73)

Albumin < 20 g/L

(n 91)

Age (years)
Women, n(%)
Need for MV, n(%)
Length of MV (days)
ARDS, n(%)
Sepsis, n(%)
Need for vasopressors, n(%)
Length of stay in ICU (days)
APACHE II score
SOFA score
Charlson comorbidity index > 2, n (%)
Chemoteraphy, n(%)
Prior surgery, n(%)
Mortally, n (%)

52.4 + 17.3
100 (61)
129 (78.7)
1 (0.5-4)
28 (17.1)
56 (34.1)
76 (46.3)
3 (1-6)
12.5 (11-14)
3 (1-8)
121 (73.8)
49 (29.9)
61 (37.2)
37 (22.5)

56.5 + 16.2
47 (64.3)
56 (76.7)
1 (0.4-4)
8 (10.9)
12 (16.4)
20 (27.3)
3 (1-5)
12 (11-14)
3 (1-6)
51 (69.9)
17 (23.2)
20 (27.4)
10 (13.6)

49.2 + 17.6
53 (58.2)
73 (80.2)
2 (0.5-5)
20 (22)
44 (48.3)
56 (61.5)
2 (1-6)
13 (11-15)
5 (2-10)
70 (77)
32 (35.1)
41 (45)
27 (29.6)

.007
.423
.002
.452
.094
<.001
<.001
.695
.300
.009
.372
.123
.023
.023

Abbreviations: APACHE, acute physiology and chronic hearth evaluation; ARDS, acute respiratory distress syndrome; ICU, intensive care unit; MV, mechanical
ventilator; SOFA, sequential organ failure assessment.

Selection of Participants, Data Collection, and Definitions

During the study period, all patients older than 16 years
requiring ICU admission were evaluated. Patients with an ICU
stay of <24 hours and readmissions were not considered. The
following variables were collected: age, gender, need for vasopressor and mechanical ventilation, duration of mechanical
ventilation, length of stay in ICU, treatment (chemotherapy
within 8 weeks of ICU admission) prior surgery, and ICU mortality rate.
The length of stay in the ICU was measured as the number
of days from admission to the ICU until discharge from the
ICU. The presence of organ dysfunction was assessed using the
sequential organ failure assessment (SOFA) score recorded
before admission or on the day of admission to the ICU.8 The
acute physiology and chronic health evaluation (APACHE) II
score was recorded using the worst score for acute physiological variables in the first 24 hours after admission to the ICU.9
Acute respiratory distress syndrome was defined based on
the American-European consensus conference.10 Sepsis was
defined according to standard criteria.11 Comorbidity scores
were determined using the Charlson comorbidity index.12
Albumin levels were recorded for each patient on the day of
admission to the ICU (in the first 24 hours). An albumin level
was considered to be abnormally low if it was recorded as
<35 g/L.2 The albumin levels were used to divide the patients
into 2 groups: >20 g/L and 20 g/L.

Data Presentation and Statistical Analyses

Continuous variables are expressed as means + standard
deviation or as medians and interquartile ranges (IQR) if the
distribution was skewed. Categorical variables are expressed
as percentage. Student t test or the Mann-Whitney U test were
used to compare continuous variables according to the data
distribution (normal or nonnormal, respectively, determined

using the Kolmogorov-Smirnov test), and the chi-square or

Fisher exact test was used to compare categorical variables.
Survival curves were estimated using the Kaplan-Meier
method. The log-rank test was used to compare overall survival
data. Statistical significance was defined as P < .05. Statistical
analyses were performed using the Statistical Package for
the Social Sciences software (version 15.0; SPSS, Chicago,
Illinois, USA).

Results
During the study period, 200 patients were eligible for
inclusion. The mean age was 52.5 + 17.3 years and 100 were
women (61%; Table 1). A total of 164 (82%) patients had a
serum albumin concentration below 35 g/L, of which
91 (55.5%) patients had levels of albumin 20 g/L (Figure 1).
The mean serum albumin was 18.17 + 6.87 g/L (Figure 2).
Of those patients who had levels of albumin <20 g/L, 29.7% had
a gastrointestinal malignancy. There were 129 (78.7%) patients
who required mechanical ventilation during their stay in the
ICU, with a median duration of 1 day (IQR 0.5 to 4 days). The
median length of stay in the ICU was 3 days (IQR 1 to 6 days),
and 34.1% of the patients had sepsis. The median SOFA score
and APACHE II score were 3 (IQR 1 to 8) and 13 (IQR 11 to
14), respectively. The crude mortality rate was 22.5% (37 of
164) and increased with lower levels of albumin. The highest
mortality rate (73%) was seen in the group of patients whose
serum albumin levels were <20 g/L (Figure 3). Patients admitted
with and without serum albumin levels <20 g/L were similar for
gender, incidence of ARDS, APACHE II score, and length of
stay in the ICU (Table 1). However, significant differences were
found between the 2 groups in relation to age, sepsis, need for
vasopressors and mechanical ventilation, SOFA score, prior
surgery, and mortality rate in the ICU. The ICU survival by albumin levels is depicted in Figure 4.

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Namendys-Silva et al

255

Figure 3. Mortality rate in relation to the serum albumin concentration

on admission to intensive care unit. Numbers above the bars indicate
mortality rate percentage.
Figure 1. Distribution and outcome of the study population.

Figure 2. Histogram of admission serum albumin concentration for

all patients.

Discussion
The incidence and mortality related with hypoalbuminemia in
critically ill patients with cancer admitted to ICU has not been
documented to date. The hypoalbuminemia is associated with
increased complications and worse prognosis in many populations.13 The role of the hypoalbuminemia as a predictor of outcome in the ICU is reflected in its incorporation as a component
of the APACHE III score.14 The decrease in albumin is a result
of a combination of factors including hemodilution during fluid
resuscitation, and capillary leakage into the interstitial space.
The degree of capillary permeability is proportional to the
inflammatory response mounted by the patient, and therefore

Figure 4. Overall survival concerning the serum albumin concentration

on admission to intensive care unit.

those with the greatest rate of vascular permeability are

associated with the highest mortality. The development and degree
of hypoalbuminemia thus relates to the severity of the underlying
traumatic insult and therefore to the ultimate outcome.15
Ryan et al15 reported 200 patients who underwent upper
gastrointestinal surgery for malignancy and observed that a
serum albumin level of <20 g/L on the first postoperative day
was an independent predictor of complications. In total,
62 patients (31%) developed a major postoperative complication.
The most common postoperative complications after esophagectomy were pneumonia (16%), sepsis (12.5%), respiratory failure
(10%), and ARDS (7.5%) and the in-hospital mortality rate
was 8%.

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American Journal of Hospice & Palliative Medicine 28(4)

256
McCluskey et al16 studied the prognostic value of serial
measurements of serum albumin concentration during the first
72 hours after admission to a general adult ICU in 348 consecutive critically ill patients. The nonsurvivor group (29.3%) had
lower serum albumin concentrations on admission to the ICU,
and their albumin concentrations decreased more rapidly in the
first 24 to 48 hours. The hypoalbuminemia was also associated
with prolonged length of stay in ICU. The serum albumin
concentrations on admission were not a sensitive indicator of
outcome.
Two important findings were obtained in the current study
of hypoalbuminemic critically ill patients with cancer who
were admitted to an oncological ICU: (1) A high incidence
of hypoalbuminemia and (2) the highest mortality rate (73%)
and greater SOFA score was seen in the group of patients whose
albumin levels were <20 g/L. Sepsis, need for vasopressors and
need for mechanical ventilation was observed more frequently
in patients with serum albumin concentrations <20 g/L, suggesting that low albumin levels may increase the incidence of organ
dysfunction and infections in critically ill patients with cancer.
Fleck et al4 studied the movement of albumin across the
capillary wall. They showed that the transcapillary escape rate
of radiolabelled albumin was increased in different disease
states (sepsis, shock, surgery, cancer). However, the reasons for
this increased transcapillary escape rate are not fully understood. The so-called capillary leak syndrome postulates that the
capillary wall looses. The capillary leak syndrome phenomenon exists in the sense that fluid and plasma proteins escape
across its barrier function (probably a cytokine-mediated
injury), allowing rapid shift of plasma protein from the vascular
toward the interstitial space, which increases the interstitial
colloid oncotic pressure, which, in turn, promotes the extravasation of fluid.17
Serum albumin can maintain physiologic homeostasis. At
reduced albumin levels, homeostatic functions may be
impaired, resulting in the development or progression of
pathologic processes and poor outcome. The inflammatory
processes during acute illness may induce hypoalbuminemia,
and inflammatory mediators can increase vascular permeability
to promote escape of circulatory albumin into the extravascular
space. Inflammatory mediators can also directly inhibit the
gene transcription responsible for albumin synthesis.18
In this study, prior surgery was observed more frequently
in patients with serum albumin concentrations <20 g/L.
Hypoalbuminemia preoperatively or pretrauma is independently associated with the possibility of postoperative
complications.19-21 The relationship between a low serum
albumin concentration on admission to the ICU and the
development of complications as sepsis, need for vasopressors
and mechanical ventilation, organ dysfunction, and mortality
may be a sign of systemic immunoinflammation and hypermetabolism, a marker of the host response to a critical illness.15
Despite the fact that the low serum albumin concentration is
an independent predictor of morbidity, there is no evidence to
support the use of albumin to treat hypoalbuminemia in critically ill patients.22 We did not use albumin to restore

albumin levels. A randomized prospective control trial23

showed that treating intensive care patients with albumin is
associated with an improvement in the SOFA score who also
had a less positive fluid balance and a greater tolerance to enteral feeding. These findings should be confirmed in a larger
multicentre study.
This study supports the fact that serum albumin levels are
affected by critical and chronic illnesses and the result confirm
that lower serum albumin levels in critically ill patients with
cancer are related to higher mortality rate. Our study has some
limitations in that it only included critically ill patients with
cancer admitted to a single oncological ICU, representing the
experience of a single centre, and we reported a single
measurement of serum albumin concentration. Some caution
is needed with the extrapolation of our results because of
possible selection biases.

Conclusion
In conclusion, we have shown a high incidence of hypoalbuminemia in critically ill patients with cancer admitted to ICU. The
data suggest that albumin levels <20 g/L the day of admission
to the ICU may be associated with higher risks of organ
dysfunction, infection, morbidity, and mortality. The measurement of serum albumin on admission to the ICU could be used
as a biomarker clinical to facilitate identification of high-risk
groups of patients. There is a need for further prospective
randomized controlled trials in critically ill patients with cancer
to evaluate the precise place of albumin in the ICU.
Acknowledgment
We thank the nurses and medical staff of the intensive care unit at the
Instituto Nacional de Cancerologia, Mexico City, who were involved
in the care of these patients for their assistance. We are indebted to
Jose A. Baltazar-Torres for critical reading of this manuscript.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to
the research, authorship, and/or publication of this article.

Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.

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