Association between fluid overload and

SOFA score kinetics in septic shock

patients: a retrospective multicenter
study
BY: DELIYA ALI ABDU
Abstract

Background
Fluid infusion represents one of the cornerstones of resuscitation therapies in order to
increase oxygen delivery during septic shock. Fluid overload as a consequence of
excessive fluid administration seems to be linked to worse long-term outcome. However,
its immediate effect on patient’s clinical state is poorly described. The goal of this study
was to assess the impact of FO on SOFA score kinetics as a surrogate marker of organ
dysfunction from day 0 to day 5.

Material and methods

Retrospective, multicenter, investigator-initiated study. All adult patients (> 18 years
old) admitted from January 2012 to April 2017 in one of the three ICUs for septic shock,
secondary to peritonitis or pulmonary infection and mechanically ventilated, were
included. Univariate analysis was performed with Student’s t and chi-square test, for
continuous and categorical variables, respectively. A multivariate linear regression
model evaluated the impact of FO on delta SOFA score from day 0 to day 5. Secondly, a
multivariate mixed-model accounting for repeated measures analyzed the impact of FO
on SOFA score kinetics.

Results
One hundred twenty-nine patients met the inclusion criteria and were assigned into FO
and no FO groups. FO occurred in 39% of the patients. The difference between SOFA
score at day 0 and day 5 was more than twofold higher in the no FO group than in the
FO group with a difference of 2.37 between the two groups (4.52 vs. 2.15; p = 0.001).
Cumulative fluid intake at day 5 was higher in the FO group (2738 vs. 8715 ml, p < 
0.001). In multivariate analysis, FO was associated with delta SOFA score: aRR = 0.15
(95% CI 0.03–0.63; p = 0.009). In mixed model, the regression coefficient for fluid
overload status (r2 = 1.16; p = 0.014) indicated that the slope for SOFA score kinetic was
less pronounced for patients with FO than for patients without FO.

Conclusions
FO patients had a more prolonged multi-organ failure according to SOFA score kinetics
during septic shock from resuscitation phase to day 5.

Background

Sepsis is still a major cause of mortality over the world [1, 2]. A recent systematic review
reported an annual incidence of 256 hospital-treated sepsis cases per 100,000 person
and per year [3]. It represents nearly 10% of intensive care unit (ICU) admissions, with
an average ICU mortality of 18% and a 22% in-hospital mortality regardless of the
source of infection [4]. Sepsis management-related cost accounted for 5.2% of total US
health cost in 2011 [5].

Distinct phases of hemodynamic resuscitation have been described with different risks,
goals, and challenges: resuscitation, optimization, stabilization, and de-escalation
phases [6]. Fluid therapy represents one of the cornerstones of resuscitation treatments
in order to increase oxygen delivery during circulatory failure [7]. During the salvation
phase of septic shock, the current guidelines suggest that an aggressive fluid
resuscitation is the best initial therapy [8]. During the optimization phase, the goal is to
maintain adequate tissue perfusion and avoid the effects of fluid overload. During this
phase, “liberal” or uncontrolled fluid therapy can induce an increased positive fluid
balance with tissue fluid overload leading to potential harmful effects [9,10,11,12]. A
restrictive fluid therapy strategy could be used to decrease fluid overload (FO) during
the optimization phase in septic shock patients [13]. It is worth mentioning that
inappropriate use of fluid therapy can induce its own side effects.

Therefore, a paradigm shift is currently occurring as concerns have been raised about
the potential adverse effects of fluid therapy. Fluid overload is one of the major adverse
effects reported and an independent factor of worse outcome in intensive care unit
(ICU) patients [10]. It is now suggested that fluid administration should be conducted
cautiously to avoid an unnecessary increase in fluid intake but ensure an adequate tissue
perfusion. A patient goal-directed therapy may help to optimize fluid intake and avoid
the deleterious effects of an increased fluid balance [14].

Most studies on FO or cumulative fluid balance have reported impact on in-hospital or

28-day mortality. To date, there is no data on the impact of FO on organ dysfunction.
The aim of this pilot study was to describe the impact of FO on the kinetics of organ
dysfunction assessed by the sequential organ failure (SOFA) score between day 0 and
day 5 after the onset of septic shock.

Methods

Study design and population

We retrospectively analyzed data from three French ICUs at Brest and Morlaix Hospital
(France): two units of a teaching hospital (medical ICU and surgical ICU) and one
general ICU of a regional hospital. An approval of an institutional ethics committee was
obtained before recruitment (approval number: ADZ/Avis no 2017-1). From
institutional registries, we identified all adult patients (> 18 years) admitted from
January 2012 to April 2017 in one of the three ICUs for septic shock, secondary to
peritonitis or pulmonary infection and mechanically ventilated, were eligible for the
study. In our cohort, septic shock was defined according to recommendations published
in 2003 by Levy et al. [8]. We considered this definition because the more recent Sepsis-
3 definition published in 2016 was not already used in daily practice from 2012 to 2017
the participating ICUs [9]. Thus, in our study, septic shock was defined by a suspected
or documented infection, clinical/biological signs of systemic inflammatory response
syndrome (SIRS), signs of organ dysfunction, and a persistent hypotension (defined as a
systolic arterial pressure < 90 mmHg, mean arterial pressure < 65 mmHg, or a reduction
in systolic arterial pressure of more than 40 mmHg from baseline) despite fluid
challenge needed vasopressors. Diagnosis criteria of intra-abdominal and pulmonary
infection used were the one reported in the most recent international guidelines
[15,16,17]:

 Intra-abdominal infection was suspected when the following criteria were met:
digestive symptoms (acute abdominal pain, nausea, vomiting, anorexia), acute
abdominal contracture or splinting, diffuse abdominal rigidity, and/or
hyperthermia > 38.5 °C or hypothermia < 36 °C. Clinical suspicion was
systematically confirmed by abdominal CT scan. Then, diagnostic laparoscopy
confirmed peritonitis. Peritoneal fluid/tissue was systematically collected from
the site of infection for microbiological analysis to identify pathogens [16]
 Diagnosis of pulmonary infection was made using the following clinical criteria:
presence of respiratory symptoms (cough, sputum, dyspnea, thoracic pain),
hyperthermia > 38.5 °C or hypothermia < 36 °C, and signs of infection on chest
radiography. Respiratory samples (sputum, endotracheal aspiration, or
bronchoalveolar lavage) were performed to confirm diagnosis and identify
pathogens

Patients included in our cohort required mechanical ventilation because they had:

 An acute circulatory failure (defined by systolic arterial pressure < 90 mmHg or

mean arterial pressure < 65 mmHg despite fluid challenge and needing of
vasopressors > 0.3 μg/kg/min)
 An alteration of consciousness (defined by a Glasgow Coma Scale < 8)
 And/or an acute respiratory failure (defined by a respiratory rate > 35/min,
SpO2 < 92% despite non-invasive support and signs of dyspnea)

Patients admitted for septic shock without catecholamine and/or mechanical ventilation
were excluded. Patients firstly admitted for another reason were also excluded, even if
they presented septic shock during their stay in ICU.

Data collection
All data were collected from medical records. For eligible patients, the following data
were recorded: age, reason for ICU admission, source of infection, hemodynamic
support, and respiratory devices used. For enrolled patients, demographic data, baseline
body weight, and comorbidities were collected. We evaluated baseline severity with
SOFA score and APACHE II score. Initial hemodynamic status (mean blood pressure,
heart rate) and hemodynamic treatment received prior to admission (fluid challenge,
amount of each catecholamine received) were also recorded. Relevant biological data
were collected, especially data needed to obtain SOFA score and lactatemia.
Daily fluid intake from day 0 to day 10 (including fluid challenge, maintenance fluid,
and nutrition), daily fluid output (including urine output, insensible losses, drain fluid,
ultrafiltration rate, and estimated gastrointestinal losses), and daily fluid balance from
day 1 to day 5 (calculated by subtracting the daily fluid output from daily fluid intake)
were collected. Daily body weight was recorded. When the recorded body weight was
10% higher than the baseline one, FO was reported. Duration of FO was also recorded.
In case of missing baseline or daily body weight, FO status could not be obtained and
was marked as not available. All relevant clinical variables necessary to calculate daily
SOFA score were collected. For neurological SOFA sub-score, Glasgow coma scale (GCS)
was calculated with results of clinical examination. If daily GCS or neurological
information were not available and if a patient was sedated, we considered the last GCS
reported in the medical record. For non-survivors at day 5, delta SOFA score was
calculated taking into account the last observation. We also recorded daily organ
support (RRT, mechanical ventilation, amount of catecholamine), length of ICU stay,
and mortality (28-day and 90-day).

Study outcomes
The main pre-specified objective of this study was the impact of FO on SOFA score
kinetic from day 0 to day 5 following the onset of septic shock. The onset of septic shock
was defined by the time of first antibiotic administration. We chose to evaluate SOFA
score kinetics instead of other scores like MODS, SAPS II, and APACHE II because a
sequential assessment of organ dysfunction with the SOFA score is robust and has been
validated in ICU patients [18]. Several definitions of fluid overload (FO) were used. In
some studies, FO was defined by dividing cumulative fluid balance (in liters) by patient’s
baseline body weight; a cutoff value of 10% of fluid accumulation was used to define FO
[19, 20]. Other studies suggested that a 10% increase in body weight is also clinically
relevant [21]. In our study, we identified exposition to FO by dividing daily body weight
by baseline body weight. A cutoff value of 10% of weight gain associated with peripheral
edema was used to define FO. We hypothesized that FO increases the risk of persistent
organ dysfunction during the first 5 days of septic shock.

We also analyzed the impact of patient’s baseline variables on SOFA score kinetics and
the impact fluid overload on the following outcomes: 28-day and 90-day mortality,
length of stay in ICU, number of ventilator-free days at day 28, and number of
catecholamine-free days at day 10.

Statistical analysis
Population description was described as means and standard deviation for continuous
variables and percentages for categorical variables. For any variable with less than 20%
of data missing, multiple imputation was used with five iterations, except for categorical
variables. Bivariate analysis was performed using student t test or Wilcoxon test for
continuous variables and chi-square or Fisher’s exact test for categorical variables.
Variables with significant bivariate relation (p < 0.1) to FO status were considered for
multivariate analysis.
A multivariate linear regression model was performed to test the impact of FO on delta
SOFA score from day 0 to day 5. The results were presented with risk ratio (RR), 95%
confidence intervals (CI), and p value. Interactions between FO status and all variables
were included in the multivariate model if required. Sensitivity analysis was performed:
without outliers, without early dead patients (before day 5), and after being discarded to
test assumption after bootstrap replication.

A mixed model was used to evaluate the impact of FO and duration of FO (0 to 1 day, 2
to 5 days, or more than 5 days) on SOFA score kinetics. A “subject” random effect was
introduced into the model and was regarded as a fixed effect. “Time” variable was
introduced into the model and was regarded as a fixed effect. The mixed model was
adjusted for variables that were first in multivariate analysis and found significantly
associated with delta SOFA score. Results were presented as coefficients and
estimated p value (with Satterthwaite approximation method). For multivariate
analysis, we considered two-tailed p values of less than 0.05 as significant. All statistical
analysis was performed with R statistical software (version 3.3.2).

Results

Study population
From 1 January 2012 to 31 April 2017, 1209 patients were admitted in participating
ICUs for severe sepsis or septic shock. During the study period, 275 eligible patients had
septic shock with pneumonia or peritonitis. One hundred forty-six patients were
excluded, 61 because they were admitted in ICU for another reason and 55 did not
require mechanical ventilation. All included patients (129 over 275) were analyzed.
Additional file 1: Figure S1 displays the flow of patients in the study.

Overall population characteristics and outcomes

Baseline characteristics of patients are summarized in Table 1. The first source of
infection was pneumonia (75.2%), and the mean age was 65 years old. On ICU
admission, the mean lactate level was 4.37 mmol/l (SD = 4.19) and leucocyte count was
13.97 G/l (SD = 10.85). The overall 28-day mortality was 34.1%, and the mean ICU
length of stay was 17.15 days (SD = 19.06). About 39% of patients were exposed to FO
during their stay in ICU. Percentages of FO exposure according to ICUs are presented in
Additional file 2: Figure S2. For nine patients (7%), no weight was recorded during their
stay and FO status was not available. Fluid intakes in the whole cohort were 2017 ml
(SD = 2612), 13,320 ml (SD = 7018), and 24,307 ml (SD = 11,658) at day 0, day 5, and
day 10 respectively. Daily fluid balance was 1,604 ml (SD = 2806) at day 1 and
progressively decreased to 1263 ml (SD = 2955) at day 3 and 91 ml (SD = 1325) at day 5.
The cumulative fluid balance at day 5 was 5041 ml (SD = 6789). All studied patients
needed noradrenaline support during their ICU stay, 32 (25%) were treated with
dobutamine, and 19 (14.8%) were treated with adrenaline at least 1 day. At day 1, the
mean infusion rate was 0.4 μg/kg/min for noradrenaline and 5.6 μg/kg/min for
dobutamine. At day 5, 25 and 5 patients needed noradrenaline and dobutamine infusion
respectively. Mean catecholamine-free days at day 10 was 4.5 days (SD = 3.17).

Table 1 Characteristics of overall population according to fluid overload status

Full size table

Between-group differences according to fluid overload status

Patient’s characteristics according to fluid overload status are summarized in Table 1.
Patients exposed to FO had more cardiovascular comorbidities than the non-exposed
patients (59.7% vs. 34.8%, p = 0.014). At baseline, there was no difference in terms of
leucocyte count and lactate level between the two groups. Baseline SOFA score (8.60 vs.
9.09, p = 0.39) and APACHE II score (25.3 vs. 25.1, p = 0.88) were not statistically
different between the two groups. A number of patients treated with dobutamine (23.3%
vs. 25.5%, p = 0.95) and adrenaline (15.1% vs. 12.8%, p = 0.932) were comparable
between the two groups. The amount of norepinephrine infused was higher in patients
with FO; however, this difference did not reach statistical significance. There was no
difference in terms of dobutamine infusion. Fluid intake differences were respectively
1223 ml (p = 0.014), 5709 ml (p <  0.001), and 11,719 ml (p <  0.001) at day 0, day 5, and
day 10. Daily fluid balance differences were respectively 954 ml (p = 0.075), 1245 ml (p 
<  0.001), 1867 ml (p = 0.001), 953 ml (p = 0.002), and 963 ml (p <  0.001) from day 1 to
day 5. Cumulative fluid balance at day 5 was also more important in the FO group, with
a between-group difference of 5977 ml (2738 versus 8715 ml, p < 0.001). Distribution of
cumulative fluid balance and fluid intake at day 5 according to fluid overload status is
represented in Fig. 1. There were more transfusions in the FO group (p = 0.007).
Baseline measurement of SOFA score was similar in two groups (8.60 versus 9.09, p = 
0.390).

Fig. 1
Delta SOFA score, fluid intake, and cumulative FB at day 5 according to FO status. Delta
SOFA score from day 0 to day 5 was higher in the group of patients without FO
compared to the group of patients with FO (mean delta SOFA score: 4.52 (+/− 3.74) vs.
2.15 (+/− 3.50), p < 0.001). Fluid intake at day 5 was more important in the FO group,
with a between-group difference of 5709 ml (11,171 ml vs. 16,880 ml, p < 0.001).
Cumulative fluid balance at day 5 was more important in the FO group, with a between-
group difference of 5977 ml (2738 vs. 8715 ml, p < 0.001)
Full size image

Concerning clinical outcomes, patients without FO were more rapidly discharged from
ICU compared to patients with FO with a between-group difference of 6 days (p < 
0.001). The mean duration of mechanical ventilation was less important for patients
without FO than FO patients (13.84 days vs. 7.19 days, p = 0.001). The mean duration of
RRT was more important in patients without FO (5.21 days versus 3.85, p = 0.019). No
between-group difference in catecholamine free-days was found. There was no
statistically significant difference between groups in mortality at 28 days and 90 days.
Bivariate analysis results are displayed in Table 1.

Daily SOFA score kinetics according to fluid overload status

The difference between SOFA score at day 0 and day 5 (delta SOFA score) was more
than twofold higher in the no FO group than in the FO group with a difference of 2.37
between the two groups (p = 0.001). Delta SOFA score was also significantly different
between the two groups at day 3 (no FO 2.52 +/− 3.39 vs FO 1.11 +/− 3.47; p = 0.034)
and day 4 (no FO 3.74 +/− 3.39 vs FO 1.72 +/− 3.49; p = 0.003). Considering daily
measurement of the SOFA score, the main differences occurred from day 3, with
respectively a difference of 2.03 (p = 0.002), 2.69 (p < 0.001), and 2.83 (p < 0.001) in
day 3, day 4, and day 5. Distribution of delta SOFA score according to fluid overload
status is represented in Fig. 1. The mean daily SOFA score from day 0 to day 5 is
presented in Additional file 3: Table S1.

We also analyzed the changes in daily SOFA score according to the length of FO. These
results are presented in Fig. 2. There was an association between length of fluid overload
and daily SOFA score from day 3 to day 5 (p < 0.001). The delta SOFA score was also
higher in the group of patients without FO or 1 day of FO compared to the group of
patients with 2 or more days of FO (p < 0.001).

Fig. 2

Daily SOFA score from day 0 to day 5 according to the length of FO. Linear mixed model
was performed to identify any differences at each time between three sub-groups: No
fluid overload or 1 day of fluid overload, 2 to 5 days of fluid overload, more than 5 days.
Regression coefficient for the length of FO of 2.1 (p = 0.008) for patients with 2 to 5 days
of FO and 1.4 (p = 0.012) for patients with more than 5 days of FO. These results
indicated that the slope for SOFA score kinetics was less pronounced for patients with
more than 2 days of FO compared to patients without FO or 1 day of FO (*p < 0.05)
Full size image

Impact of fluid overload on SOFA score kinetics

Fixed effect model analysis
A multivariate analysis was used to evaluate the impact of fluid overload on delta SOFA
score. The independent variables which were imbalanced between FO and no FO
patients were tested in the fixed effect model: FO, age, weight at admission,
cardiovascular disease, chronic renal insufficiency, fluid intake at baseline, SOFA score
at baseline, heart rate at baseline, and length of hydrocortisone infusion. In the
unadjusted analysis, fluid overload status was significantly associated with changes in
delta SOFA score (RR = 0.09; 95% CI 0.023–0.38, p = 0.001). The other variables
significantly associated with delta SOFA score were age (p = 0.006), preexisting
cardiovascular disease (p = 0.011), and SOFA score at baseline (p < 0.001). After
adjustment, the association between FO status and delta SOFA score persisted (p = 
0.009). Results of multivariate analysis are presented in Table 2. All sensitivity analysis
confirmed this result (details are presented in Additional file 4: Table S2,
Additional file 5: Table S3).

Table 2 Results of multivariate linear regression model with delta SOFA score as
outcome and fluid overload as principal independent covariate

Full size table

Linear mixed model with random effect

Variables associated with delta SOFA score in the adjusted analysis were analyzed in the
mixed model after dichotomization (baseline SOFA score < or > 8, fluid overload or not,
cardiovascular disease or not). The regression coefficient for FO status of 1.16 (p = 
0.014) indicated that the slope for SOFA score kinetics was less pronounced for FO
patients than for patients without FO whatever the baseline SOFA score was and
preexisting cardiovascular comorbidity. The results of the mixed model are presented in
Table 3.

Table 3 Results of mixed-model analysis with SOFA score as main outcome

Full size table

Discussion

Our study investigates the association between FO and SOFA score kinetics in septic
shock. The main findings of this study are as follows: (1) 40% of our septic shock
patients experienced FO; (2) FO patients presented a more prolonged multi-organ
failure during septic shock from resuscitation phase to day 5; and (3) the longer the
duration of FO, the longer the duration of multi-organ failure.

Fluid therapy and the use of vasopressors are the cornerstones for hemodynamic
management from the salvation phase to the de-escalation phase during septic shock
[6]. After the resuscitation phase, the optimization phase should be characterized by a
cautious titration of fluid administration with a serial reassessment of hemodynamic
status [22]. “Liberal” fluid management has been shown to be deleterious for ICU and
surgical patients [9, 23, 24]. The SOAP (Sepsis Occurrence in Acute ill Patients) study
demonstrated that a positive fluid balance was associated with an increased mortality in
patients with acute lung injury and acute renal failure whatever baseline severity and
comorbidities were [23, 24]. Even if causality between fluid overload and mortality was
not strictly proved, many studies confirmed the statistical association between positive
fluid balance and mortality and reinforced this hypothesis [11, 12, 25,26,27,28]. In our
study, there was no association between FO and 28-day mortality in the bivariate
analysis. There is a trend of an increase of 90-day mortality in FO patients, but this
result is not statistically significant. However, our study was not designed to test this
hypothesis and therefore lack of statistical power.

To our knowledge, our study is the first report demonstrating FO early influence on
multiple organ failure kinetic (measured with daily SOFA score). In our cohort, no
therapeutic intervention other than fluid management was different between the two
groups. In a prospective cohort, Sakr and colleagues identified an association between
higher fluid balance (measured at 72 h) and higher mean/maximum SOFA score;
however, the authors did not evaluate dynamic SOFA score evolution [11]. In our cohort,
a length of fluid overload beyond 2 days seems to be an important determinant of the
SOFA score kinetic as the longer FO duration, the longer lasting organ dysfunction.
Serial SOFA score measurement is clinically meaningful and reflects global patient’s
deterioration or improvement during the course of sepsis. Such association reinforced
the link between FO and morbidity during sepsis. These findings are of interest as
designing sepsis trial based on non-fatal outcomes (as short-term organ dysfunction)
was recently encouraged by experts position paper [29].

In our study, given the longer ventilator-free days and shorter ICU stay, patients without
FO had better short-term outcomes. These results were in line with several studies
[30,31,32,33]. In a recent meta-analysis, considering a mixed population of septic and
ARDS patients, Silversides et al. demonstrated that patients included in “liberal” fluid
management group had higher mortality, length of stay in ICU, and length of
mechanical ventilation [34]. The FACCT study tested in ARDS patients two fluid
management strategies [30]. This study found a benefit in terms of ventilator free-days
and ICU stay for patients included in the “conservative” strategy. On the other hand,
compared to patients without FO, length of RRT was more important in the FO group
despite a better SOFA score kinetic (p = 0.019). We hypothesized that the use of
prolonged dialysis session helped clinicians to avoid FO in maintaining zero or negative
net fluid balance. We cannot confirm this hypothesis because we did not collect
specifically renal SOFA score and daily diuresis.

To our knowledge, only two pilot studies concluded that a protocolized fluid
management can reduce fluid administration without harmful effects during septic
shock [31, 32]. In the CLASSIC trial, Hjortrup et al. investigated a fluid restriction
protocol compared to the standard care group [31]. Patients included in the
interventional group received 250–500 ml of crystalloid boluses in case of severe
hypoperfusion. In the standard group, patients received fluid as long as hemodynamic
indices improved. Patients included in the fluid “restrictive” group received significantly
less fluid during the first 5 days with a mean difference of − 1241 ml. Cumulative fluid
balance was also less important: − 1148 ml. There were no differences in the 90-day
mortality, but more patients had a new or worsening AKI and ischemic events in the
“standard care” group [31]. Chen et al. evaluated a targeted fluid minimization protocol
based on passive leg raising. Cumulative fluid balance at day 5 was less important in the
interventional group. There were no statistically significant differences in the duration
of mechanical ventilation, maximal dose of vasopressor, or in-hospital mortality [32].

Considering the target population of our study, we followed the recommendation

underlined by a recent review which criticized the past design of trials focusing on septic
patients [29]. In this review, Mebazaa et al. emphasized that designing sepsis trials
without considering baseline risk resulted in lower event rates than expected and
decreased statistical power. Therefore, we excluded low-risk patients (urosepsis,
skin/soft tissue infection) and chose to enroll a homogeneous group of patients with a
reported mortality and organ dysfunction consistent for between patients [35].

We acknowledge some limitations of this study. We chose to include septic shock

patients according to the sepsis-2 definition because we considered that the more recent
Sepsis-3 definition could not be implemented in daily practice in participating ICUs.
This is a limitation of our cohort. Then, including only mechanically ventilated patients
limits the external validity. Further studies are needed to confirm these results in
patients without mechanical ventilation. Therefore, being observational and
retrospective, our study results cannot be conclusive in regard to the correlation
between FO and SOFA score kinetic. Then, the relatively small number of patients
lowers the statistical power of the study. Finally, early death induced missing data in the
collection of daily SOFA score. However, we performed a mixed modeling showing the
same results, and a sensitivity analysis without missing data was performed. Results
were consistent throughout the entire analysis.

Availability of data and materials

The dataset supporting the conclusions of this article is fully available. To have an access
on it, please contact the corresponding author (O.H.)

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Reflection paper:

Lactate can predict ScvO2 when patients are at or below the critical oxygen delivery
threshold, but relatively few shock patients meet this criterion. In the overall population
of critically ill patients, serum lactate predicts ScvO2 poorly, even after controlling for
factors that may affect lactate production. Lactate and ScvO2 should not be assumed to
be interchangeable markers of tissue oxygenation/perfusion.

Based on the results of this single-center retrospective cohort study, lactate has very
little predictive ability for ScvO2 in the vast majority of critically ill patients, even after
accounting for factors that could interfere with such a relationship. In the clinical
setting, lactate should not be used interchangeably with ScvO 2 as a marker of tissue
hypoxia.