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DOI: 10.1177/1049909110384841

2011 28: 253 originally published online 7 November 2010AM J HOSP PALLIAT CARE

Silvio A. Ñamendys-Silva, María O. González-Herrera, Julia Texcocano-Becerra and Angel Herrera-GómezHypoalbuminemia in Critically Ill Patients With Cancer: Incidence and Mortality

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Hypoalbuminemia in Critically Ill PatientsWith Cancer: Incidence and Mortality

Silvio A. N ˜ amendys-Silva, MD, MSc, FCCP1,2,Marıa 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 todescribe the relationship of serum albumin levels to mortality. Design: An observational cohort study. There were nointerventions. Results: During the study period, 200 patients were eligible for inclusion. A total of 164 (82%) patients had aserum albumin concentration below 35 g/L, of which 91 (55.5%) patients had levels of albumin 20 g/L. The mean serumalbumin 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 patientswith cancer admitted to ICU was high.

Keywords

hypoalbuminemia, cancer, intensive care unit, critically ill patients, incidence, mortality

Introduction

Albumin is an important molecule under physiological and

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 albuminconcentration therefore decreases andcritically ill

patients are frequently hypoalbuminemic.1 Abnormally low

serum albuminlevels (<35 g/L) area frequent and early biochem-ical derangement in critically ill adults with a reported incidence

of30% to40%.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 relation-

ship of serum albumin levels to mortality.

Patients and Methods

Design and Setting

An observational cohort study was performed at the Instituto

Nacional de Cancerologıa, 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 Cancerologı a,

Mexico City, Mexico2 Department of Critical Care Medicine, Instituto Nacional de Ciencias Medicas y

Nutricion Salvador Zubiran, Mexico City, Mexico3Department of Surgical Oncology, Instituto Nacional de Cancerologıa, Mexico

City, Mexico

Corresponding Author:

Silvio A. N amendys-Silva, Department of Critical Care Medicine, Instituto

Nacional de Cancerologıa, Mexico. Av. San Fernando No. 22, Col. Seccion XVI,

Delegacion Tlalpan, 14080, Mexico City, Mexico

Email: [email protected]

American Journal of Hospice

& Palliative Medicine®

28(4) 253-257

ª The Author(s) 2011

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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 vaso-

pressor and mechanical ventilation, duration of mechanical

ventilation, length of stay in ICU, treatment (chemotherapy

within 8 weeks of ICU admission) prior surgery, and ICU mor-

tality rate.

The length of stay in the ICU was measured as the number

of days from admission to the ICU until discharge from theICU. 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 physiologi-

cal 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).

ResultsDuring 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 scoreand 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 <20g/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. TheICU survival by albu-

min levels is depicted in Figure 4.

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

VariablesAll Patients(n ¼ 164)

Albumins 20 g/L(n ¼ 73)

Albumin < 20 g/L(n ¼ 91) p

Age (years) 52.4 + 17.3 56.5 + 16.2 49.2 + 17.6 .007Women, n(%) 100 (61) 47 (64.3) 53 (58.2) .423

Need for MV, n(%) 129 (78.7) 56 (76.7) 73 (80.2) .002Length of MV (days) 1 (0.5-4) 1 (0.4-4) 2 (0.5-5) .452ARDS, n(%) 28 (17.1) 8 (10.9) 20 (22) .094Sepsis, n(%) 56 (34.1) 12 (16.4) 44 (48.3) <.001Need for vasopressors, n(%) 76 (46.3) 20 (27.3) 56 (61.5) <.001Length of stay in ICU (days) 3 (1-6) 3 (1-5) 2 (1-6) .695APACHE II score 12.5 (11-14) 12 (11-14) 13 (11-15) .300SOFA score 3 (1-8) 3 (1-6) 5 (2-10) .009Charlson comorbidity index > 2, n (%) 121 (73.8) 51 (69.9) 70 (77) .372Chemoteraphy, n(%) 49 (29.9) 17 (23.2) 32 (35.1) .123Prior surgery, n(%) 61 (37.2) 20 (27.4) 41 (45) .023Mortally, n (%) 37 (22.5) 10 (13.6) 27 (29.6) .023

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

254 American Journal of Hospice & Palliative Medicine® 28(4)








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 popula-

tions.13 The role of the hypoalbuminemia as a predictor of out-

come 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

those with the greatest rate of vascular permeability areassociatedwiththe highest mortality.The development anddegree

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 mostcommon postoperative complications after esophagect-

omy were pneumonia (16%), sepsis (12.5%), respiratory failure

(10%), and ARDS (7.5%) and the in-hospital mortality rate

was 8%.

Figure 1. Distribution and outcome of the study population.

Figure 2. Histogram of admission serum albumin concentration forall patients.

Figure 3. Mortality ratein relationto the serum albuminconcentration

on admission to intensive care unit. Numbers above the bars indicatemortality rate percentage.

Figure 4. Overall survivalconcerningthe serum albumin concentrationon admission to intensive care unit.

N amendys-Silva et al 255








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 consec-

utive 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, suggest-

ing 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 under-

stood. The so-called capillary leak syndrome postulates that the

capillary wall looses. The capillary leak syndrome phenom-

enon 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 extrava-sation 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 indepen-

dently 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 hyperme-

tabolism, 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 criti-

cally 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 ent-

eral feeding. These findings should be confirmed in a larger

multicentre study.

This study supports the fact that serum albumin levels areaffected 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 hypoalbumi-

nemia 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 measure-

ment 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.

AcknowledgmentWe 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, author-

ship, and/or publication of this article.

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