American Journal of Emergency Medicine 33 (2015) 186189

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American Journal of Emergency Medicine

journal homepage: www.elsevier.com/locate/ajem

Original Contribution

Fluid balance in sepsis and septic shock as a determining factor

of mortality
Josep-Maria Sirvent, MD, PhD a,, Cristina Ferri, MD b, Anna Bar, MD a,
Cristina Murcia, MD a, Carolina Lorencio, MD a
a
b

Department of Intensive Care (ICU), University Hospital of Girona Doctor Josep Trueta, IDIBGI, CIBERES, Girona, Spain
Department of Intensive Care (ICU), University Hospital of Tarragona Joan XXIII, Tarragona, Spain

a r t i c l e

i n f o

Article history:
Received 11 October 2014
Received in revised form 25 October 2014
Accepted 7 November 2014

a b s t r a c t
Objective: The objective was to assess whether uid balance had a determinant impact on mortality rate in a
cohort of critically ill patients with severe sepsis or septic shock.
Design: A prospective and observational study was carried out on an inception cohort.
Setting: The setting was an intensive care unit of a university hospital.
Patients: Patients admitted consecutively in the intensive care unit who were diagnosed with severe sepsis or
septic shock were included.
Interventions: Demographic, laboratory, and clinical data were registered, as well as time of septic shock onset,
illness severity (Simplied Acute Physiology Score II, Sepsis-related Organ Failure Assessment), and comorbidities. Daily and accumulated uid balance was registered at 24, 48, 72, and 96 hours. Survival curves representing
28-day mortality were built according to the Kaplan-Meier method.
Results: A total of 42 patients were included in the analysis: men, 64.3%; mean age, 61.8 15.9 years. Septic shock
was predominant in 69% of the cases. Positive blood cultures were obtained in 17 patients (40.5%). No age, sex,
Sepsis-related Organ Failure Assessment, creatinine, lactate, venous saturation of O2, and troponin differences
were observed upon admission between survivors and nonsurvivors. However, higher Simplied Acute Physiology Score II was observed in nonsurvivors, P = .016. Nonsurvivors also showed higher accumulated positive uid
balance at 48, 72, and 96 hours with statistically signicant differences. Besides, signicant differences (P = .02)
were observed in the survival curve with the risk of mortality at 72 hours between patients with greater than 2.5
L and less than 2.5 L of accumulated uid balance.
Conclusions: Fluid administration at the onset of severe sepsis or septic shock is the rst line of hemodynamic
treatment. However, the accumulated positive uid balance in the rst 48, 72, and 96 hours is associated with
higher mortality in these critically ill patients.
2014 Elsevier Inc. All rights reserved.

1. Introduction
In severe sepsis and septic shock, the main elements of treatment are
intravenous uids, appropriate antibiotics, source control, vasopressors,
and ventilatory support [1]. For more than 10 years, the administration
of intravenous uids has been known as a key in the initial stages of
sepsis resuscitation, as proven by a classic article on goal-based treatments [2]. Anyway, it is now recognized that the administration of
excess uid in sepsis may lead to worsened respiratory function,
increased intraabdominal pressure, worsened coagulopathy, and
increased probability of cerebral edema [3]. Some authors observed difculty in uid balance management in critically ill patients, and positive
uid balance is associated with increased mortality rates in patients

Corresponding author. Department of Intensive Care (ICU), University Hospital of

Girona Doctor Josep Trueta, Avda de Frana s/n, E-17007 Girona, Spain. Tel.: +34 972
940 288; fax: +34 972 940 296.
E-mail address: jsirvent.girona.ics@gencat.cat (J.-M. Sirvent).
http://dx.doi.org/10.1016/j.ajem.2014.11.016
0735-6757/ 2014 Elsevier Inc. All rights reserved.

with acute lung injury and septic shock [4,5]. For all these reasons, the
present observational study was designed to assess whether uid
balance has a determinant impact on mortality in a well-dened cohort
of patients with severe sepsis or septic shock.
2. Methods
2.1. Population and data collection
Our study includes the patients admitted consecutively in the intensive care unit (ICU) of a teaching hospital for 4 months (from October
2012 to January 2013) that were diagnosed with severe sepsis or septic
shock. It is a prospective and observational study on an inception cohort.
Patients with septic shock were identied by a specic team of
intensivists. Demographic, laboratory, and clinical data were registered:
age, sex, time of septic shock onset, focus of infection, presence of initial
acute kidney injury, severity of illness based on the Simplied Acute
Physiology Score (SAPS) II score [6], the Sepsis-related Organ Failure

J.-M. Sirvent et al. / American Journal of Emergency Medicine 33 (2015) 186189

Assessment (SOFA) score [7], and comorbidities. The kind of uids used
in the volume resuscitation of patients was always balanced electrolyte
solution (Plamasmalyte 148) at the doses proposed by Surviving Sepsis
Campaign Guidelines [1]. Daily and accumulated uid balance was
registered at 24, 48, 72, and 96 hours. Initial echocardiogram (within
the rst 24 hours) was completed on 26 patients to evaluate percentage
ejection fraction (EF). Patients were excluded if they had developed
septic shock outside hospital requiring uid management and vasopressor drugs before their transfer to ICU. Data collection and patient inclusion in the study were performed after obtaining informed consent.
2.2. Denitions
Severe sepsis was dened by the presence of acute infection and
organ dysfunction. Septic shock was dened by acute organ dysfunction
(acute renal failure, respiratory failure) in the presence of an infection
and the need of vasopressor treatment for more than 6 hours [1]. The
initial time of severe sepsis and septic shock was determined upon
ICU admission by this diagnosis. When EF was less than 45%, patients
were classied as having cardiac dysfunction.

Descriptive statistics of demographic and clinical variables included

means and standard deviations for quantitative variables and percentages for qualitative variables. For unadjusted comparisons between or
among groups, continuous variables were compared by using Student
t test in case of normally distributed data or Mann-Whitney U test for
nonnormally distributed data. Categorical variables were compared by
using the 2 test or Fisher exact test where appropriate. Comparative
variables for mortality at 28 days were studied by means of bivariate
analysis. Survival curves representing mortality at 28 days were constructed according to the Kaplan-Meier method and compared with

Table 1
Characteristics of the study population

Demographics
Age, y
Sex, male, n (%)
SAPS II upon admission, points
SOFA upon admission, points
Coexisting conditions, n (%)
Smokers
Alcohol abuse
Liver disease
Congestive heart failure
Cerebral stroke
Chronic kidney disease
Diabetes mellitus
Immunosuppression
Clinical data, n (%)
Severe sepsis
Septic shock
Bacteremia
Cardiac dysfunction
Infective focus, n (%)
Abdomen
Respiratory
Soft tissues
Urinary tract
Others
Outcome
Length of ICU stay, d
Length of hospital stay, d
ICU mortality, n (%)
Mortality at 28 d, n (%)
Hospital mortality, n (%)
Data are expressed as mean (SD).

Echocardiogram performed in 26 out of 42 patients.

Table 2
Fluid balance and variables between survivors and nonsurvivors
Variable

Survivors
(n = 27)

Non-survivors
(n = 15)

P value

Age, y
Sex, male, n (%)
SAPS II upon admission, points
SOFA upon admission, points
Initial creatinine (mg/dL)
Initial lactate (mg/dL)
Initial SatvO2 (%)
Troponin T hs (ng/dL)
Fluid balance (mL) within 24 h
Fluid balance (mL) within 48 h
Fluid balance (mL) within 72 h
Fluid balance (mL) within 96 h
Fluid balance 24 h N2.0 L
Fluid balance 48 h N2.5 L
Fluid balance 72 h N2.5 L
Fluid balance 96 h N2.5 L
Severe sepsis
Septic shock
Bacteremia

58.9 (17.6)
17 (62.9)
40.2 (14.9)
6.9 (3.2)
1.5 (1.3)
18.9 (14.7)
77 (9)
32.5 (36.3)
1710.4 (1955.4)
1791.6 (2349.1)
1128.1 (3312.6)
4612.8 (4220.0)
10 (37.0)
12 (44.4)
11 (40.7)
10 (37.0)
13 (48.1)
14 (51.8)
11 (40.7)

66.9 (11.3)
10 (66.6)
52.5 (15.4)
7.6 (3.6)
1.9 (1.7)
28.6 (18.6)
72 (9)
115.6 (180.4)
3153.5 (3118.9)
4394.3 (3477.6)
5401.6 (3961.4)
6678.6 (4656.5)
11 (73.3)
11 (73.3)
12 (80.0)
12 (80.0)
0 (0.0)
15 (100.0)
6 (40.0)

.122
.810
.016
.518
.452
.072
.118
.099
.096
.020
.002
.001
.024
.071
.014
.008
.001
.980
.963

Data are expressed as mean (SD).

2 de Pearson or Fisher test for qualitative data and Student t or Mann-Whitney U test
for quantitative data.

2.3. Statistical analysis

Variable

187

All patients (N = 42)

61.8 (15.9)
27 (64.3)
44.6 (16.1)
7.1 (3.4)
16 (38.1)
9 (21.4)
4 (9.5)
8 (19.0)
4 (9.5)
2 (4.8)
8 (19.0)
6 (14.3)
13 (31.0)
29 (69.0)
17 (40.5)
5/26 (19.2)
20 (47.6)
7 (16.7)
4 (9.5)
3 (7.1)
8 (19.1)
11.5 (15.4)
23.2 (20.7)
14 (33.3)
15 (35.7)
18 (42.9)

the Mantel-Haenszel log-rank test. P b .05 was considered statistically

signicant for all comparisons. Statistical analyses were performed
using SPSS (version 12; SPSS Inc, Chicago, IL).
3. Results
A total of 42 patients were included in the analysis. Epidemiologic
results were as follows: predominance of men (64.3%); mean age was
61.8 15.9 years; cases of septic shock were predominant (69%).
Positive blood cultures were obtained in 17 patients (40.5% of the
cases). The most frequent initial infectious focus was abdominal
(48%), followed by respiratory (17%). Infections were community
acquired in almost 70% of the cases. Severity scores upon ICU admission
were 44.6 16.1 and 7.1 3.4 points in SAPS II and SOFA, respectively.
Besides, 28-day mortality was observed in 15 patients (35.7%), all of
them in the septic shock group. Five out of 26 patients (19.2%) were
classied as having cardiac dysfunction by EF less than 45% (see population characteristics in Table 1).
Table 2 presents differences in uid balance and variables between
survivors and nonsurvivors. No age, sex, SOFA score, creatinine, lactate,
venous saturation of O2 (SatvO2), and troponin T differences were reported upon admission between survivors and nonsurvivors. However,
higher SAPS II score was observed in nonsurvivors (52.5 15.4 vs 40.2
14.9, P = .016). Nonsurvivors also showed higher accumulated positive uid balance at 48, 72, and 96 hours with signicant differences.
Fig. 1 shows a box plot with the greater daily accumulated uid
balance in milliliters at 48, 72, and 96 hours in nonsurvivors, with statistically signicant differences. Fig. 2 shows the survival curve with the
risk of survival at 72 hours between patients with greater than 2.5 L
and less than 2.5 L of accumulated uid balance, compared by log-rank
test with signicant differences (P = .02).
4. Discussion
Our observational study shows that the accumulated positive uid
balance at 48, 72, and 96 hours is associated with higher mortality in
ICU-admitted patients with sepsis or septic shock.
These results are consistent with those by Boyd et al [5], who
showed that higher positive uid balance in resuscitation over the
rst 4 days was associated with increased risk of mortality in septic
shock patients. Other factors such as creatinine, lactate, SatvO2, and

J-M. Sirvent et al. / American Journal of Emergency Medicine 33 (2015) 186189

Fluid Balance (mL)

188

Fig. 1. Comparative box plot showing accumulated uid balance in milliliters at 24, 48, 72,
and 96 hours between survivors and nonsurvivors.

troponin showed no statistical differences between survivors and

nonsurvivors in our study.
Micek et al [8] studied the cardiac function and accumulated uid
balance in septic shock in a recent work and concluded that cumulative
uid balance and cardiac dysfunction predict outcome in septic shock
patients. Cardiac function was studied only in 26 out of 42 patients in
the present work; and therefore, no conclusions could be drawn on
this issue, but these data should be taken as preliminary and analyze
in future studies.
Cordemans et al [9] observed that uid balance and extravascular
lung water index were mortality predictors in critically ill patients
requiring mechanical ventilation. Thus, clinicians treating septic shock
patients should carefully assess the need for intravenous uids both in
the immediate resuscitation period and over the subsequent days of
treatment. The use of more conservative uid administration protocols

Accumulated Fluid Balance

72h < or >2,5L

Fig. 2. Survival curve with the risk of survival at 72 hours between patients with greater
than 2.5 L and less than 2.5 L of accumulated uid balance.

in patients with severe sepsis and septic shock needs further study to
determine their relative efcacy compared to standard care therapy [8].
Associations between increased cumulative positive uid balance
and long-term adverse outcomes have been reported in sepsis patients
[5]. In tests of liberal vs goal-based treatments or restrictive uid strategies in patients with acute respiratory distress syndromeparticularly in
perioperative patients [3,4]restrictive uid strategies were associated
with reduced morbidity. However, because there is no consensus on
the denition of these strategies, high-quality tests in specic patients
populations are required [10].
The mechanisms by which positive uid balance can adversely
inuence outcomes remain unknown. However, hypervolemia or
hyperosmolarity might exacerbate capillary leak in septic shock patients,
thus contributing to pulmonary edema. Positive uid balance could also
result in intraabdominal hypertension, thus contributing to organ hypoperfusion development and subsequent organ failure [11,12]. Acute
renal failure coexisting with sepsis may worsen outcomes as well as
lead to positive uid balance [13].
Our study has important limitations. Firstly, it was performed in one
only middle-sized and university hospital and may therefore have no
external validity for other institutions. Secondly, our observational design and the lower number of studied patients tan other studies of
uid balance, limit our ability to determine a causal relationship between uid balance and outcomes. And thirdly, the fact that cardiac
function was only studied in 26 of the 42 patients leaves out an important predictor of mortality. Finally, other factors such as antibiotic therapy, focus control, and some other unmeasured clinical parameters may
have contributed to our ndings. Recommendations in the guidelines
for sepsis treatment are well known to have recently been questioned,
specically the early goal-directed treatment [14]. The same applies to
the recommendations of the type of uid used for sepsis and septic
shock. For all these reasons, it is difcult to standardize a single treatment protocol for these critically ill patients, as well as to draw clear
conclusions from observational studies.
Lastly, selection, timing, doses, and uid balance in sepsis and septic
shock should also be evaluated very carefully with the aim of maximizing
efcacy and minimizing iatrogenic toxicity [15].
In conclusion, uid administration upon the onset of severe sepsis or
septic shock is the rst line of hemodynamic treatment in this clinical
situation. There is no doubt that the study of cardiac function by echocardiography helps us better understand the prognosis of these
patients. However, the accumulated positive uid balance in the rst
48, 72, and 96 hours is associated with higher mortality in these critically
ill, ICU-admitted patients.

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