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Keywords:
Lactate/albumin ratio
Severe sepsis and septic shock
MODS
Resuscitation
Inammation
a b s t r a c t
Background: This study examines the clinical utility of the increased lactate/albumin ratio as an indicator of
multiple-organ dysfunction syndrome (MODS) and mortality in severe sepsis and septic shock.
Methods: We designed a prospective cohort study in an intensive care unit, and 54 patients with severe sepsis or
septic shock were included. Data were used to determine a relationship between lactate/albumin ratio and the
development of MODS and mortality. These associations were determined by the Mann-Whitney test, multiple
logistic regression, plotting the receiver operating characteristic curve and Spearman test.
Results: Lactate/albumin ratio level was higher in MODS patients on day 1 (median [interquartile range, or IQR],
2.295 [1.818-3.065]; n = 30, P b .0001) than in those without (median [IQR], 1.550 (1.428-1.685); n = 24), and
on day 2, (median [IQR], 1.810 [1.377-2.448]; n = 26, P = .0022) it was higher than in those without (median
[IQR], 1.172 (1.129-1.382); n = 23) on day 2. We found that lactate/albumin ratio was an independent predictor
of the development of MODS (odds ratio, 5.5; P = .033; 95% condence interval, 1.1-26.1) during intensive care
unit stay. The area under the receiver operating characteristic curve showed that lactate/albumin ratio
could predict MODS (0.8458) and mortality (0.8449). Furthermore, the higher the Acute Physiology and
Chronic Health Evaluation II score, the more lactate/albumin ratio was discovered on day 1 (r = 0.5315,
P b .0001) and day 2 (r = 0.5408, P b .0001), whereas the lower partial pressure of oxygen in arterial
blood/fraction of inspired oxygen ratio, the more lactate/albumin ratio was illustrated on day 1 (r = 0.5143,
P b .0001) and day 2 (r = 0.5420, P b .0001).
Conclusions: Increased lactate/albumin ratio correlates with the development of MODS and mortality in patients
with severe sepsis and septic shock.
2014 Elsevier Inc. All rights reserved.
1. Introduction
Sepsis is a major cause of intensive care unit (ICU) admission and is
associated with high morbidity and mortality rates [1]. Severe sepsis
and septic shock are frequently complicated by multiple-organ dysfunction syndrome (MODS). When 3 or more organs are involved, MODS
causes 60% to 98% death [2,3]. Certainly, the severity of organ dysfunction is an important determinant of prognosis in sepsis [4].
When oxygen delivery fails to meet tissue oxygen demand in critical
illness, there are oxygen debt, global tissue hypoxia, anaerobic metabolism, and lactate production. Numerous studies have established that
the lactate level was a diagnostic, therapeutic, and prognostic marker of
global tissue hypoxia in circulatory shock [57]. Previous studies have
shown that a lactate concentration greater than 4 mmol/L in the presence
of the systemic inammatory response syndrome (SIRS) criteria signicantly increases mortality rate in normotensive patients [8].
Corresponding authors at: Department of Critical Care Medicine, The Afliated Suzhou
Municipal Hospital, Nanjing Medical University, 16 Baida West Rd, Suzhou, Jiangsu
215001, PR China. Tel.: +86 512 62364071.
E-mail addresses: biaowangsz@163.com (B. Wang), icuwu@163.com (Y. Wu).
1
These authors contributed equally to this work.
http://dx.doi.org/10.1016/j.jcrc.2014.10.030
0883-9441/ 2014 Elsevier Inc. All rights reserved.
272
2.2. Denition
Severe sepsis was dened as sepsis-induced tissue hypoperfusion or
organ dysfunction [12]. Septic shock was dened as sepsis-induced
hypotension persisting despite adequate uid resuscitation. Sepsisinduced tissue hypoperfusion is dened as infection-induced hypotension,
elevated lactate, or oliguria [12]. Multiple-organ dysfunction syndrome
was dened as the development of potentially reversible physiologic
derangement involving 2 or more organ systems not involved in the
disorder that resulted in ICU admission, and arising in the wake of a
potentially life-threatening physiologic insult [13]. Six-hour lactate
clearance (percent) was dened using the following formula: lactate at
ICU admission (hour 0) minus lactate at hour 6, divided by lactate at
ICU admission, then multiplied by 100 as day 1 lactate clearance, whereas
24-hour lactate clearance was dened as day 2 lactate clearance.
Table 1
Baseline characteristics of patients with severe sepsis and septic shock
Variables
Age (y)
Male sex (%)
APACHE II score
SOFA score
Albuin (g/dL)
Platelet (109/L)
WBC (109/L)
Fluid balance (/L)
Lactate (mmol/L)
Lactate clearance (%)
Temperature (C)
Heart rate (beats/min)
PaO2/FIO2 ratio
MAP (mm Hg)
CVP (mm Hg)
Hematocrit (%)
Creatinine (mg/dL)
ScvO2 (%)
Mechanical ventilation (%)
PRBC transfusion (%)
Vasopressor (%)
Prothrombin time (s)
D-Dimer (ng/mL)
Lactate/albumin ratio
Day 1
Day 2
MODS (n = 30)
MODS (n = 26)
75.5 (69.75-81.25)
21 (70)
26 (25-28)
10 (8-11)
2.9 (2.6-3.125)
143.5 (112.8-184)
15.95 (12.95-18.3)
3 (2.6-3.5)
5.95 (5.075-8.525)
17.92 (15.3-21.3)
37.25 (36.8-37.6)
92.5 (82.75-102.8)
147.5 (128.3-173)
69.5 (64.5-74)
5.75 (5.3-6.2)
32 (30-35.25)
2.5 (1.45-2.8)
46 (42-49)
16 (53.3)
6 (20)
9 (30)
16.2 (14.68-17.45)
3559 (1503-4639)
72 (68-75.75)
15 (62.5)
23 (20.25-25.75)
9 (8-10)
3.0 (2.7-3.275)
151 (122.5-225.3)
15.65 (12.73-18.23)
2.65 (2.425-2.9)
4.55 (4.4-5.6)
10.9 (9-11.3)
37.2 (36.8-37.75)
85.5 (75.25-100.3)
182.5 (158-206)
72.5 (66.25-76)
6.2 (5.3-6.9)
31 (29.25-33)
2.5 (1.5-2.775)
51.5 (48-56.75)
11 (45.8)
4 (16.7)
6 (25)
16.85 (15.38-18.68)
3439 (1267-4457)
NS
NS
.0002
.0821
.4473
.5479
.632
.0128
.0006
b.0001
.8821
.111
.004
.1526
.1478
.3098
.6947
.0353
.5839
.754
.6836
.226
.5083
75.5 (71.25-81.25)
19 (73)
26 (25-28.25)
9.5 (8-11)
2.85 (2.6-3.125)
150.5 (122-185.3)
15.85 (12.73-18.3)
2.15 (1.8-2.525)
4.5 (4.05-7.025)
24.4 (17.7-26.6)
37.25 (36.8-37.68)
95 (84.75-105.3)
177.5 (152-207)
79 (72.75-81.25)
8.2 (7.75-8.525)
31 (29-35.25)
2.3 (1.825-2.525)
65 (64-70)
13 (50)
2 (8)
5 (19.2)
17 (15.75-18.75)
3574 (1535-4667)
72 (68-76)
14 (60.9)
23 (21-26)
9 (8-10)
3.0 (2.7-3.3)
152 (130-235)
15.6 (12.5-18.6)
1.8 (1.6-2.1)
3.6 (3.4-4.7)
21.8 (17.6-22.8)
37.2 (36.8-37.6)
86 (75-102)
192 (163-220)
79 (74-82)
8.7 (7.8-9.4)
31 (29-33)
2 (1.5-2.3)
68 (64-72)
10 (43.4)
1 (4)
3 (13)
17.2 (15.6-18.7)
3426 (1536-4159)
NS
NS
.0001
.2041
.3928
.5611
.7258
.0803
.0097
.1024
.6586
.0712
.3164
.5466
.2248
.3864
.0753
.3986
.648
.9498
.4421
.944
.4229
2.295 (1.818-3.065)
1.550 (1.428-1.685)
b.0001
1.810 (1.377-2.448)
1.172 (1.129-1.382)
.0022
SOFA indicates Sequential Organ Failure Assessment score; WBC, white blood cell; MAP, mean arterial pressure; CVP, central venous pressure; PRBC, packed red blood cell; NS,
nonsignicant (P N .05).
Odds ratio
95% CI
Lactate/albumin ratio
PaO2/FIO2 ratio
APACHE II score
ScvO2
Lactate clearance
Fluid balance
Lactate
5.5
0.4
2.6
1.1
0.7
1.4
0.6
1.1-26.1
0.2-1.0
1.0-6.6
0.4-2.2
0.3-1.6
0.6-3.2
0.2-2.3
.033
.043
.049
.991
.456
.485
.453
3. Results
Fifty-four patients aged 74 years (68.75-80.25 years) were enrolled
in this study. There were 30 (55.6%) patients with MODS on day 1 and
26 (53%) on day 2. The mortality rate was 9% (n = 5; 4 patients in
MODS group) on day 1. The characteristics of patients with and without
MODS on days 1 and 2 are listed in Table 1.
In Table 1, although the lactate clearance and uid balance were
signicantly different on day 1 but not on day 2, lactate/albumin ratio
was higher in patients with MODS on days 1 and 2. The results support
that the lactate clearance and uid balance are not the main reason for
a high lactate/albumin ratio in patients with MODS. In addition, 27
patients required mechanical ventilation on day 1. PaO2/FIO2 ratio and
ScvO2 of patients with MODS were lower than those without MODS
on day 1 rather than day 2.
Univariate analyses were primarily used for the selection of variables,
based on a P value less than .05 (Table 1). The selected variables including
lactate/albumin ratio, PaO2/FIO2 ratio, APACHE II score, ScvO2, lactate
clearance, uid balance, and lactate were further analyzed by multiple
logistic regression analysis. The results are presented in Table 2.
Lactate/albumin ratio (OR, 5.5; P = .033; 95% CI, 1.1-26.1), PaO2/FIO2
ratio (OR, 0.4; P = .043; 95% CI, 0.2-1.0), and APACHE II score (OR,
2.6; P = .049; 95% CI, 1.06.6) remained signicant predictors of
MODS after controlling for other variables. ScvO2, lactate clearance,
uid balance, and lactate failed to maintain their prognostic value for
the MODS development in the adjusted analysis.
Fig. 1 shows lactate/albumin ratio levels in patients with and without
MODS and mortality on day 1. Lactate/albumin ratio was higher in
patients with MODS (2.514 0.165, n = 30, P b .0001) than in those
without (1.703 0.094, n = 24). Similarly, the patients with mortality
had increased levels of lactate/albumin ratio (2.876 0.235, n = 5)
compared with without (2.080 0.119 mL/kg, n = 49, P = .0122).
Fig. 2 illustrates the relationship between lactate/albumin ratio and
APACHE II score (A, day 1, r = 0.5315, P b .0001; B, day 2, r = 0.5408,
273
Fig. 1. Lactate/albumin ratio in severe sepsis or septic shock patients with (n = 30) and without (n = 24) MODS (A), and in patients with (n = 5) and without (n = 49) mortality (B).
P value was expressed.
274
Fig. 2. The relationship between lactate/albumin ratio and APACHE II score (A, day 1, r = 0.5315, P b .0001; B, day 2, r = 0.5408, P b .0001), or PaO2/FIO2 ratio (C, day 1, r = 0.5143,
P b .0001; D, day 2, r = 0.5420, P b .0001) in patients with severe sepsis by Spearman test.
Table 4
Diagnostic sensitivity, specicity, and predictive value of lactate/albumin ratio N 1.735 for
MODS and mortality
Table 3
Areas under the ROC curves for variables on day 1
Area Under ROC curve
Lactate/albumin ratio
PaO2/FIO2 ratio
APACHE II score
0.8458 (0.7389-0.9527)
0.7306 (0.5938-0.8673)
0.7951 (0.6740-0.9163)
0.8449 (0.7231-0.9667)
0.7857 (0.6492-0.9222)
0.8041 (0.6273-0.9809)
Sensitivity
Specicity
Positive predictive valve
Negative predictive valve
MODS (%)
Mortality (%)
80
79
83
76
100
51
17
100
Acknowledgments
This project was supported by Science and Education of Public
Health of Suzhou, China (KJXW2013028).
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