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Lactate/albumin ratio is more effective than

lactate or albumin alone in predicting clinical
outcomes in intensive care patients with sepsis

Esra Cakir & Isil Ozkocak Turan

To cite this article: Esra Cakir & Isil Ozkocak Turan (2021) Lactate/albumin ratio is more
effective than lactate or albumin alone in predicting clinical outcomes in intensive care patients
with sepsis, Scandinavian Journal of Clinical and Laboratory Investigation, 81:3, 225-229, DOI:
10.1080/00365513.2021.1901306

To link to this article: https://doi.org/10.1080/00365513.2021.1901306

Published online: 20 Mar 2021.

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SCANDINAVIAN JOURNAL OF CLINICAL AND LABORATORY INVESTIGATION
2021, VOL. 81, NO. 3, 225–229
https://doi.org/10.1080/00365513.2021.1901306

ORIGINAL ARTICLE

Lactate/albumin ratio is more effective than lactate or albumin alone in

predicting clinical outcomes in intensive care patients with sepsis
Esra Cakir and Isil Ozkocak Turan
Department of Anesthesiology and Clinical of Critical Care, Health Sciences University, Ankara Numune Education and Research Hospital,
Ankara, Turkey

ABSTRACT ARTICLE HISTORY

This study aimed to compare the value of lactate, albumin, and lactate/albumin ratio for the prediction Received 23 December 2020
of mortality in sepsis patients. Patients admitted to the intensive care unit (ICU) due to sepsis between Revised 1 February 2021
January 2016 and January 2019 were evaluated retrospectively. Lactate, albumin, and lactate/albumin Accepted 7 March 2021
ratio values were compared between surviving and non-surviving patients and their predictive value
KEYWORDS
for mortality was evaluated. A total of 1136 sepsis patients admitted to the ICU were included in the Albumin; lactic acid; lactate/
study. The mortality rate was 42.7% (485/1136 patients). In ROC analysis for mortality prediction, albumin ratio; sepsis;
the area under the curve and optimal cut-off values were 0.816 and >2.2 mmol/L for lactate, 0.812 intensive care
and
26 g/L for albumin, and 0.869 and >0.71 for lactate/albumin ratio, respectively. Our analysis of units; mortality
lactate, albumin, and lactate/albumin ratio in the largest patient sample to date showed that lactate/
albumin ratio was a stronger parameter than lactate or albumin alone in predicting mortality among
sepsis patients in the ICU. Lactate/albumin ratio is an easily obtained parameter with potential value
for critically ill patients.

Introduction also be affected by inflammatory events such as sepsis [4].

Severe sepsis and septic shock are among the leading causes
of morbidity and mortality worldwide. Mortality rates vary
between 20% and 30%, but may increase up to 60–98% in
patients with multiple organ dysfunction syndrome [1–3].
Despite advances in sepsis diagnosis and treatment, the inci-
dence of severe sepsis and septic shock has increased [1].
Therefore, biomarkers predictive of mortality are important
for the early diagnosis and timely treatment of patients with
septic shock [4].
In severe sepsis and septic shock, elevated blood lactate
levels often result from cellular hypoxia, tissue hypoperfu-
sion, and impaired oxidative phosphorylation secondary to
low oxygen concentration [5]. High lactate level is associated
with mortality and is widely used for the early diagnosis,
treatment, and risk classification of septic shock patients [6].
Moreover, because blood lactate concentration can be deter-
mined easily and rapidly, it is used as a marker of tissue
hypoperfusion in critical patients admitted to the emergency
department or ntensive care unit (ICU) [7,8]. However, an
optimal lactate cut-off value that can be used to predict
mortality in the critical patient population has not been
determined [1].
Albumin is produced in the liver and plays a role in
blood oncotic pressure (or colloid osmotic pressure) [9]. As
a negative acute phase protein, serum albumin can also
serve as a prognostic biomarker in patients with sepsis [10].
Similar to lactate level, serum albumin concentration can
Although lactate is an important parameter in patients with
severe sepsis and septic shock, using the ratio between lac-
tate and albumin may provide more valuable information
related to mortality, but this has not been researched suffi-
ciently [11]. The present study was designed to investigate
the value of lactate, albumin, and lactate/albumin ratio as
prognostic markers for mortality in sepsis patients admitted
to the ICU.
Materials and methods
Ethical approval
This study was a retrospective review of data from all
patients admitted to our ICU due to sepsis between January
2016 and January 2019. The study was approved before ini-
tiation by the hospital’s local clinical ethics committee and
was conducted throughout in accordance with the principles
outlined in the Declaration of Helsinki.
Patient data
Sepsis was diagnosed based on clinical and laboratory find-
ings according to the Third International Consensus
Definitions for Sepsis and Septic Shock [12]. All patients
diagnosed with sepsis were treated as per the International
Guidelines for Management of Sepsis and Septic Shock [6].

CONTACT Esra Cakir pavulonmouse@hotmail.com Department of Anesthesiology and Clinical of Critical Care, Ankara Numune Education and Research
Hospital, Health Sciences University, Talatpasa Street, Ankara 06130, Turkey
ß 2021 Medisinsk Fysiologisk Forenings Forlag (MFFF)
226 E. CAKIR AND I. O. TURAN
Patients admitted to the ICU with a primary diagnosis of
sepsis were included in the study. Patients admitted for
other reasons (e.g. trauma, intoxication, neurological and
metabolic disorders, myocardial infarction) were excluded.
The patients’ sex, age, their acute physiology and chronic
health evaluation (APACHE) II score, sepsis-related organ
failure assessment (SOFA) score, white blood cell (WBC)
count, and C-reactive protein (CRP), lactate, and albumin
levels at time of ICU admission, duration of mechanical
ventilation (MV), length of ICU stay, presence of bacter-
emia, and mortality data were recorded [13,14].
Determination of serum CRP, lactate, and albumin
levels, WBC count, and blood culture
At ICU admission, venous blood samples were collected in
tubes containing ethylenediamine tetra-acetic acid and WBC
count was determined. Blood samples were also centrifuged
at 3000 rpm for 10 min at room temperature and the serum
was used for CRP and albumin analyses. WBC count was
measured using a Cell-Dyn 3700 automated hemocytometer
(Abbott, Abbott Park, IL, USA) that was calibrated twice
daily. Serum CRP concentrations were measured by high-
sensitivity turbidimetric immunoassay using a Roche
Modular P analyzer (CRP latex HS, Roche kit, Roche
Diagnostics, GmbH, Mannheim, Germany). Arterial blood
samples obtained at time of admission were analyzed imme-
diately for lactate concentration (Radiometer ABL 700 auto-
mated blood gas analyzer, Copenhagen, Denmark). Positive
blood cultures (bacteremia) were identified using a
BACTEC FX (Becton Dickinson, Sparks, MD, USA) auto-
mated blood culture detection system.
Data analysis
Statistical analyses were performed in SPSS version 17.0
(SPSS, Chicago, IL). p Values less than .05 were considered
statistically significant. Comparisons between independent
groups were made using t-test and/or Mann–Whitney U-
test for non-normally distributed continuous variables and
chi-square test or Fisher’s exact test for categorical variables.
Spearman’s correlation analysis was used to evaluate correla-
tions between parameters. Results for continuous variables
were expressed as median (minimum–maximum) values.
Categorical variables were expressed as frequency and per-
centage distribution. Receiver operating characteristic (ROC)
curve analysis was performed to determine cut-off values for
lactate, albumin, and lactate/albumin ratio for the prediction
of mortality. Univariate analysis was performed including all
independent variables in the initial model, after which those
with p values less than .05 were selected for univariate logis-
tic regression analysis to identify the effect of each factor
independently (age, gender, SOFA score, APACHE II score).
Odds ratio (OR) and the corresponding 95% confidence
interval were calculated for each variable.
Results
A total of 1136 of 2340 patients who were admitted to our
ICU during the study period and met the inclusion criteria
were included. Of these 1136 patients, 485 patients died
(42.7%) and 651 were discharged (57.3%). The mean age of
the patients in the study was 76 years. Nonsurviving patients
had significantly higher APACHE II and SOFA scores, MV
duration, ICU length of stay, CRP and lactate level, and lac-
tate/albumin ratio and significantly lower albumin level
compared to surviving patients (p < .05). The groups were
similar in terms of age, sex, prevalence of bacteremia, and
WBC count (p > .05) (Table 1).
According to the results of ROC analysis for mortality
prediction, lactate had an area under the curve (AUC) of
0.816 and cut-off value of > 2.2 mmol/L, albumin had an
AUC of 0.812 and cut-off of
26 g/L, and lactate/albumin
ratio had an AUC of 0.869 and cut-off value of > 0.71. The
AUC, confidence interval, p, sensitivity, specificity, and posi-
tive and negative predictive values for lactate, albumin, and
lactate/albumin ratio are given in Figure 1. Lactate, albumin,
and lactate/albumin ratio were all significant predictors of
in-ICU mortality after correction for confounders (lactate:
OR 1.04, 95% CI 1.02–1.07, p < .001; albumin: OR 1.25,
95% CI 1.16–1.37, p < .001; lactate/albumin: OR 1.42, 95%
CI 1.21–1.64, p < .001).
Discussion
In this study, we observed higher APACHE II and SOFA
scores, serum CRP, lactate, and lactate/albumin ratio at
admission, longer MV duration and ICU stay, and lower
serum albumin level among sepsis patients who died com-
pared to those who survived. The AUC values for lactate
and albumin indicated comparable accuracy in mortality
prediction (0.816 and 0.812, respectively), while the AUC
for lactate/albumin ratio demonstrated significantly higher
accuracy (0.896). Admitting lactate > 2.2 mmol/L, albumin

26 g/L, and lactate/albumin ratio > 0.71 were determined
as optimal predictive thresholds for mortality.
High CRP levels and APACHE II and SOFA scores in
sepsis patients indicate that they are more critically ill and
have more inflammation. Consequently, these patients are
expected to have longer duration of MV and higher mortal-
ity rate, which was supported by our results [13–16].
Consistent with our findings, some previous studies have
demonstrated that lactate levels are higher and albumin lev-
els are lower in nonsurviving sepsis patients [1,17].
In acute conditions, hyperlactatemia is usually an indica-
tor of tissue hypoperfusion [8]. Clinical studies have empha-
sized that the increase in lactate levels in patients with
sepsis is caused by tissue hypoxia characterized by supply-
dependent oxygen consumption [18]. Although a blood lac-
tate level >4.0 mmol/L was identified as a determinant cut-
off value for resuscitation in sepsis, more recent evidence
suggests that lower lactate levels can also be used as cut-off
values [1]. Some studies reported that a lactate level
>4.0 mmol/L is an indicator of mortality [19,20]. In other
studies that determined predictive thresholds for mortality,
 SCANDINAVIAN JOURNAL OF CLINICAL AND LABORATORY INVESTIGATION 227

Table 1. Comparison of demographic and clinical features between mortality and non-mortality.
Variables Non- mortality (n ¼ 651) Mortality (n ¼ 485) p Value
Age, (years),a 76 (29–98) 76 (39–101) .143
Male gender, n (%) 338 (51.9) 248 (51.1) .421
APACHE II score,a 18 (9–35) 24 (13–47) <.001
SOFA score,a 8 (3–17) 11 (5–21) <.001
Duration of MV, (days),a 4 (2–42) 9 (1–45) <.001
ICU stay, (days),a 19 (4–55) 21 (4–59) <.001
Bacteremia, n (%) 151 (23.2) 129 (26.6) .212
WBC, (x10E9/L),a 12.3 (1.2–31.0) 9.4 (1.8–44.6) .274
CRP, (mg/L),a 51 (11–362) 141 (19–446) <.001
Lactate, (mmol/L),a 1.4 (0.3–7.1) 2.7 (1.1–8.8) <.001
Albumin, (g/L)a 30 (18–49) 24 (10–45) <.001
Lactate/albumin ratio 0.44 (0.10–2.45) 1.27 (0.35–5.82) <.001
a
Median (minimum-maximum), APACHE II: acute physiology and chronic health evaluation score; CRP: C-reactive protein; ICU:
intensive care unit; MV: mechanical ventilation; SOFA: sepsis-related organ failure assessment score; WBC: white blood
cell count.
Statistically significant p values.

Figure 1. ROC curve for lactate, albumin, lactate/albumin ratio predicting mortality in patients with sepsis in intensive care unit.

cut-off values for lactate ranged from 2.3 to 2.5 mmol/L.
These values are close to the optimal cut-off value in our
analysis (> 2.2 mmol/L). However, previous studies reported
lower AUC (0.660 and 0.700), sensitivity (60% and 55%),
and specificity (67% and 61%) values compared to those
obtained in our study (AUC ¼ 0.816, 78% sensitivity and
77% specificity) [1,21]. Although these studies were similar
to ours in terms of the patients’ ages, the difference in cut-
off and AUC values may be due to the smaller patient sam-
ples in those studies, the presence of different underlying
diseases, and differences in sepsis severity. Nevertheless, ini-
tial blood lactate level is commonly used in the ICU, as it
can provide clinicians information about the degree to
which high-risk septic patients require ICU admission,
hemodynamic monitoring, and organ support [1]. Although
lactate is a well-studied prognostic biomarker, interpretation
is complex due to the pathologic processes that can cause
elevated serum lactate levels. Normal lactate levels can also
be misinterpreted as an indicator of good prognosis in high-
risk patients [22].
Because impaired liver function disrupts albumin synthe-
sis, serum albumin level is below normal in patients with
hepatic dysfunction [4]. Moreover, albumin is a negative
acute phase protein that is rapidly down regulated in
response to inflammatory signals and can be a predictor of
negative clinical outcomes. Arnau-Barr
es et al. found that
albumin was a determinant of mortality in sepsis patients.
They reported that albumin level < 26 g/L was associated
with 30-day mortality, similar to our results [17]. In a study
including 348 patients, the AUC value of albumin for mor-
tality in sepsis patients was 0.755, while this value was 0.812
in our study. This difference might be related to the patient
sample of that study being smaller in number and younger
than ours (mean age 64 years vs. 76 years) [23]. Although
serum albumin level has prognostic value, it is affected by
chronic illness, dietary supplementation, and inflammation,
228 E. CAKIR AND I. O. TURAN
and a single measurement may have limited prognostic
value [4]. So, albumin is likely less volatile than lactate, and
is considered to be less valuable marker of frailty, especially
in the elderly. Thus, using additional indicators may provide
more valuable information.
Due to these limitations related to the use of lactate and
albumin alone as prognostic factors, lactate/albumin ratio
enhances the prognostic value in sepsis [22]. As a result,
serum lactate and albumin were combined and lactate/albu-
min ratio has started to be used as a prognostic factor. In a
study of 119 sepsis patients in a pediatric ICU, Moustafa
et al. determined that the AUC of admitting lactate/albumin
ratio in the prediction of mortality was 0.681 and the cut-
off value was > 1.17. The AUC increased for 6 and 24 h val-
ues (0.714 and 0.856, respectively), while cut-off values were
similar (> 1.07 and > 1.1, respectively) [24]. Similar to our
results, Wang et al. reported that the AUC of lactate/albu-
min ratio for predicting mortality was 0.844 and the cut-off
at 24 h was > 1.735 in adult ICU patients with sepsis [11].
Choi et al. determined a lactate/albumin ratio cut-off of >
1.016 for the prediction of mortality [25]. In a study includ-
ing 1381 sepsis patients admitted to the emergency depart-
ment, the cut-off and AUC were reported as > 1.22 and
0.670 [22]. In another emergency department study, Shin
et al. reported that lactate/albumin had an AUC of 0.690
and cut-off of > 1.32 for the prediction of mortality [4].
The predictive thresholds for lactate/albumin ratio in these
studies are higher than our results. In contrast, Lichtenauer
et al. determined a lactate/albumin ratio cut-off of 0.15 and
AUC of 0.700 for mortality in 348 adult ICU patients with
sepsis [23]. In our study, we determined the cut-off as >
0.71. The differences in AUC and cut-off values among pre-
vious studies and with our study may stem from differences
in the departments in which patients were being treated, the
size and mean age of the patient group, and the patients’
comorbidities. Our results indicated that lactate/albumin
ratio at admission had the highest predictive value for mor-
tality in ICU patients with sepsis, followed by lactate and
albumin. This supports the findings of earlier studies per-
formed in different departments [4,11,22–24]. To our know-
ledge, ours is the first study to evaluate lactate/albumin ratio
as a predictor of mortality in such a large sample of sepsis
patients admitted to the ICU.
Considering the fact that lactate is metabolized mainly by
the liver and to a lesser extent by the kidneys, these patients
often present to the emergency department with elevated
lactate levels. Furthermore, clinicians encounter persistently
high lactate levels in these patients due to impaired clear-
ance and are then faced with the question of when to stop
fluid resuscitation. In addition to the superior performance
of lactate/albumin ratio compared with lactate alone in this
population, it is also important to pay attention to patients
with poor nutritional status (albumin < 30 g/L). Therefore,
clinicians should consider relying on lactate/albumin ratio
rather than lactate or albumin alone [4].
Our study has certain limitations. The retrospective and
single-center design precludes generalization of our findings.
Additionally, the results were interpreted based on the
patients’ values at admission. Follow-up values and the rela-
tionship between these values and clinical outcomes could
not be evaluated. Finally, the patients’ nutritional status and
liver and kidney functions, which can affect lactate and
albumin levels, could not be evaluated.
Conclusion
Based on the results of our study in the largest ICU case
series to date, lactate and albumin alone were found to be
strong predictors of mortality in patients admitted to the
ICU due to sepsis. In addition, it was determined that lac-
tate/albumin ratio can be used alone as an even stronger
predictor of mortality than both parameters separately.
Studies that include follow-up measurements and monitor-
ing of additional parameters in a larger number of patients
are needed to confirm our findings.
Disclosure statement
No potential conflict of interest was reported by the author(s).
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