Anaesthesia 2020, 75 (Suppl. 1), e134–e142 doi:10.1111/anae.

14908

Original Article

Impact of loop diuretics on critically ill patients with a

positive fluid balance
 rio,1 M. L. Barbosa,2 V. B. Sa
A. B. Libo 3 and T. T. Leite4

1 Professor, Medical Sciences Postgraduate Program, 2 Masters Student, 3 Graduate Student, Medical Course
Universidade de Fortaleza – UNIFOR, Fortaleza, Ceara, Brazil
4 PhD student, Medical Sciences Postgraduate Program, Department of Clinical Medicine, Universidade Federal do
Ceara, Fortaleza, Cear
a, Brazil

Summary
The impact of the use of loop diuretics to prevent cumulative fluid balance in non-oliguric patients is
uncertain. This is a retrospective study to estimate the association of time-averaging loop diuretic exposure
in a large population of non-cardiac, critically ill patients with a positive fluid balance (> 5% of body
weight). The exposure was loop diuretic and the main outcomes were 28-day mortality, severe acute
kidney injury and successful mechanical ventilation weaning. Time-fixed and daily time-varying variables
were evaluated with a marginal structural Cox model, adjusting bias for time-varying exposure and the
presence of time-dependent confounders. A total of 14,896 patients were included. Patients receiving loop
diuretics had better survival (unadjusted hazard ratio 0.56, 95%CI 0.39–0.81 and baseline variables
adjusted hazard ratio 0.53, 95%CI 0.45–0.62); after full adjusting, loop diuretics had no association with
28-day mortality (full adjusted hazard ratio 1.07, 95%CI 0.74–1.54) or with reducing severe acute kidney
injury occurrence during intensive care unit stay – hazard ratio 1.05 (95%CI 0.78–1.42). However, we
identified an association with prolonged mechanical ventilation (hazard ratio 1.59, 95%CI 1.35–1.89). The
main results were consistent in the sub-group analysis for sepsis, oliguria and the study period (2002–2007
vs. 2008–2012). Also, equivalent doses of up to 80 mg per day of furosemide had no significant
association with mortality. After adjusting for time-varying variables, the time average of loop diuretic
exposure in non-cardiac, critically ill patients has no association with overall mortality or severe acute
kidney injury; however, prolonged mechanical ventilation is a concern.

.................................................................................................................................................................
Correspondence to: A. B. Lib
orio
Email: alexandreliborio@yahoo.com.br
Accepted: 2 October 2019
Keywords: acute kidney injury; fluid balance; loop diuretic

Introduction recent evidence that circulatory overload is associated

Loop diuretics, most commonly furosemide, are with a poor prognosis and that a conservative strategy
frequently prescribed to patients in the intensive care for fluid management has beneficial effects [7], an
unit (ICU) [1–3], in spite of contradictory evidence on increase in loop diuretic use in critically ill patients has
their efficacy and safety [4]. In addition to the classical been used to avoid a positive fluid balance [8].
indication of acute pulmonary oedema, loop diuretics However, a restrictive fluid strategy in patients
are also used in the setting of acute kidney injury (AKI) undergoing high-risk abdominal surgical was associated
[5] and circulatory overload [6]. Moreover, together with with a higher rate of AKI [9].

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orio et al. | Loop diuretics in critically ill patients
Studies evaluating loop diuretic use in ICU have been
non-conclusive [4, 10, 11]. It has been demonstrated that
their use is ineffective in preventing or treating AKI [5, 12–
14] and can further complicate the fluid accumulation–
mortality association [6]. Also, several studies have
demonstrated associations between loop diuretics and
renal non-recovery/death [2, 15]; whereas others suggest
loop diuretics have a protective effect on survival,
probably mediated by reduced fluid balance [5, 6, 16].
The conclusions of studies evaluating diuretics in critically
ill patients are limited by several shortcomings which
need to be considered: clinical trials restrict the study
populations (generally, only including patients with
incipient or actual AKI [17] or those admitted with acute
cardiac failure [18]); whereas observational studies have
insufficient statistical power to adjust for all measured
biases, mainly the inability to control for time-dependent
variables [19].
Statistical limitations are very important
evaluating the effects of loop diuretics in critically ill
patients because it is a time-dependent exposure (i.e. the
patient can receive a loop diuretic on one day, but not on
the following day, increasing bias in studies that considers
never/always treatment approaches). Moreover, many
confounders of the association between loop diuretic
exposure and outcomes are also time varying (renal
function, fluid balance, serum electrolytes and others). An
important example is urine output: it is a time-varying
confounder of loop diuretic exposure and is affected by
loop diuretic use in itself (so-called treatment–confounder
feedback). For example, reduced urine output on day 1
can influence the administration of loop diuretics on day
2 which, in turn, affects urine output on day 2. This is an
important point, because in the presence of treatment–
confounder feedback, conventional methods
confounder adjusting (multiple regression, stratification
and even propensity score matching) do not work [20]. In
this situation, the use of inverse probability weighting to
fit a marginal structural Cox model is a possible
alternative. The marginal structural model was recently
developed for such data to take into account time-
dependent confounders impacting both choice
treatment and outcome [20, 21]. Hence, it
substantially decrease biases resulting from
confounders in observational longitudinal data analysis –
see Appendix S1 for detailed explanation. In this study,
we aimed to estimate the effects of time-averaging loop
diuretic use in a large population of non-cardiac critically
ill patients with a positive fluid balance, using data
obtained during the first 28 days of ICU stay.
© 2020 Association of Anaesthetists
Anaesthesia 2020, 75 (Suppl. 1), e134–e142
Methods
The Multiparameter Intelligent Monitoring in Intensive
Care 3 (MIMIC-3) project, maintained by the Laboratory
for Computational Physiology at the Massachusetts
Institute of Technology, contains data on patients
admitted to ICU at Beth Israel Deaconess Medical Center
from 2001 to 2012 [22]. The database is freely available,
so that any researcher who accepts the data use
agreement and has attended ‘protecting human subjects
training’ can apply for permission to access it. This study
was approved by the Institutional Review Boards of the
Massachusetts Institute of Technology and Beth Israel
Deaconess Medical Center and was granted a waiver of
informed consent.
We included all adult patients with ICU length of
stay > 24 h. The MIMIC-3 project includes five adult ICU
units (medical, surgical, trauma-surgical, coronary and
cardiac-surgery). In this study, only patients first admitted
when to the general units were considered. Also, we did not
include cardiac patients, for whom loop diuretic use has
specific indications. We selected patients with a fluid
balance > 5% of body weight during ICU stay. Patients
receiving renal replacement therapy or with serum
creatinine ≥ 4 mg.dl 1
before having a cumulative fluid
balance < 5% of body weight were not included. Data
were collected daily during the first 28 days of ICU stay.
Patients lacking baseline data for more than two
consecutive days were not included.
The following variables were extracted from the MIMIC-3
database. Time-fixed variables included: sex; age;
admission body weight; admission type (elective or
emergency); ICU type (medical or surgical); previous use of
furosemide; Elixhauser comorbidity index [23]; and sepsis
defined by suspicion of infection and sequential organ
for failure assessment (sequential organ failure assessment,
SOFA score) ≥ 2, thereby meeting the Sepsis-3 criteria [24].
To extract data about previous loop diuretic use, we
developed a natural language processing algorithm that
searched in discharge summaries for a discrete medication
section within the ‘History’ and ‘Physical examination’
performed on admission. We performed a validation of the
of natural language processing algorithm through a formal
can examination of the discharge summaries of 100 random
such patients and demonstrated concordance of 98%. Time-
dependent variables were collected daily during the first 28
days of ICU stay and included: mechanical ventilation
support; fluid balance; urine output; need for vaso-active
drugs; non-renal SOFA score; need for renal replacement
therapy; and laboratory variables (serum bicarbonate,
serum creatinine, potassium, sodium and urea). For patients
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receiving mechanical ventilation of their lungs, we also
collected daily oxygenation index and positive end-
expiratory pressure (PEEP) values. If a variable was
measured more than once in a 24-h period, the value
associated with the greatest disease severity was used.
For each day, we considered that patients had received
a loop diuretic if a minimum equivalent dose of 20 mg
furosemide was administered intravenously – see Table S1
for dose conversion. Other loop diuretics considered in the
study, in addition to furosemide, were bumetanide,
ethacrynic acid and torsemide.
The main outcome was 28-day mortality. Other
considered outcomes were severe AKI during ICU stay and
successful mechanical ventilation weaning. Severe AKI was
defined using serum creatinine AKI stage 2/3 Kidney
Disease Improvement Global Outcome (KDIGO) definition
[25]. We did not use urine output criteria because it is
directly influenced by loop diuretic use. Since we aimed to
evaluate a possible association of loop diuretic with renal
function, baseline serum creatinine was considered at day
1 when patients had a cumulative fluid balance > 5% body
weight. For successful mechanical ventilation weaning, we
considered only patients requiring mechanical ventilation
of their lungs on the first day of ICU admission. To be
considered successfully weaned, patients have to stay at
least 24 h free of mechanical ventilation after extubation.
To identify a potential category of patients that could more
specifically benefit from loop diuretics, or a change in
clinical decision to administer loop diuretics with time, the
following sub-group analyses were planned: (1) patients
with sepsis vs. no-sepsis; (2) oliguric vs. non-oliguric
patients – because it is unlikely that shorter periods of
oliguria would be a common motivation to prescribe
diuretics, we defined oliguria as urine output less than
1
0.5 ml.kg.h for at least 12 h; and (3) patients admitted
from 2002 to 2007 vs. from 2008 to 2012. These time
periods were chosen because although all dates in the
MIMIC-3 database have been changed to protect patient
confidentiality, it is possible to identify patients admitted in
these two different lag times; and these periods are close
to the release of the fluid and catheter treatment trial [26],
whose results support the use of a conservative fluid
management strategy in patients with acute lung injury and
could change decisions about the prescription of loop
diuretics for critically ill patients.
Variables were assessed for normality using the
Kolmogorov–Smirnov test and compared using the t-test or
Wilcoxon’s test, respectively. Qualitative variables were
compared with the Chi-square test. Impossible values, such
as negative values of urine output, were censored and then
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Lib
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replaced by multiple imputations. Missing values were
imputed using the Amelia-2 multiple imputation software
[27]. Multiple imputation (n = 5) for time series data was
used including linear effects of time on variation of variable
of interest. The number of missing/censoring values is
provided in Table S2. For continuous variables, outliers
were winsorised at percentile 99. Outcomes were available
for all patients.
Marginal structural models use inverse probability
of treatment-weighting estimators to create a
pseudopopulation where treatment is independent of
baseline and time-dependent confounding factors are
introduced into the weights. Marginal structural models
allow the estimation which is asymptotically unbiased of
longitudinal treatment effect. The association between
treatment and outcome can be determined in the
pseudopopulation. Provided that all model assumptions are
satisfied, the association can be extrapolated to the first
population. Marginal structural models can be conducted in
intention-to-treat or in as-treated analyses [28]. Due to
frequent cross-overs in loop diuretic treatment in ICU, we
chose to perform an as-treated analysis. The marginal
structural model is a longitudinal extension of the use of
inverse probability of treatment-weighting estimator,
allowing the modelisation of changes in the treatment
regimen. When calculating daily inverse probability of
treatment-weighting estimators, patients’ treatments were
not considered as fixed over time, and time-dependent
variables influencing treatment cross-over during patients’
ICU stay were taken into account [29] – see Fig. S1 for a
summarised version of the directed acyclic graph used in
this analysis. Also, inverse probability of treatment-
weighting estimators was obtained by multiplying the
weight calculated on a given day by those of previous days,
thus containing the patient’s treatment history. We also
calculated inverse probability weighting to handle
informative censoring resulting from the discharge of
patients that were alive, for whom longitudinal data are no
longer available and competing outcomes (in this study,
death was considered a competing outcome for developing
severe AKI and successful mechanical ventilation weaning).
The final weight was the multiplication of the stabilised and
inverse probability of treatment weighting. Afterwards, a
marginal structural Cox model was used to assess the
association of loop diuretic administration with outcomes [30].
Data about inverse probability of treatment weighting and
the marginal structural model positivity assumptions are
present in Appendix S1, Table S3 and Fig. S2. We used R
package ipw [31], survival [32] and ggplot2 [33] to perform
the analysis.
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Results diuretic use was associated with higher serum

The MIMIC-3 database contains the records of 46,520
patients, of whom 38,605 were aged ≥ 15 years at the
time of admission and 25,320 were admitted to the
general medical or surgical ICU. A total of 454 were
excluded due to missing baseline data or missing data for
two or more subsequent days; 247 patients were
undergoing renal replacement therapy; and 1981 were
not included because ICU length of stay < 24 h. An
additional 4248 patients were not analysed because they
had a history of previous heart failure or were admitted
due to pulmonary oedema and 3226 because cumulative
fluid balance was < 5% of body weight. Finally, another
268 patients were excluded due to baseline serum
creatinine 354 lmol.l 1
. After all exclusions, 14,896
patients were available for the final analysis (Fig. S3).
A total of 3055 (20.5%) patients received loop
diuretics on at least one day during their ICU stay and
967 (6.5%) for at least half of their ICU stay. The peak of
loop diuretic use was on day 6 after reaching a fluid
balance > 5% of body weight, when approximately 32%
of patients received loop diuretics (Fig. S4). The median
(IQR [range]) equivalent dose of furosemide was 40 (20–
80 [20–240]) mg.day 1
. The main baseline characteristics
of the population according to loop diuretic use are
shown in Table 1. Figure 1 displays time-dependent
variables according to loop diuretic administration. Loop
creatinine, sodium, bicarbonate and urea levels over
time. Daily fluid balance was consistently lower in
patients receiving loop diuretics during ICU stay.
In all patients, the 28-day mortality rate was 9.4%
(n = 1405). At the crude analysis, patients receiving loop
diuretics had better survival (unadjusted hazard ratio
0.56, 95%CI 0.39–0.81). After adjusting for baseline
variables only, loop diuretic use remained associated with
a better 28-day survival (baseline adjusted variables
hazard ratio 0.53, 95%CI 0.45–0.62). However, when time-
variable confounders were included in the model through
inverse probability of treatment-weighting estimators, we
could detect no significant association between loop
diuretics and survival (full adjusted hazard ratio 1.07, 95%
CI 0.74–1.54).
Regarding worsening renal function up to day 28 of ICU
stay, there was no significant association between loop
diuretics and severe AKI (full adjusted hazard ratio 1.05
(95%CI 0.78–1.42)). Another evaluated outcome was
mechanical ventilation weaning. For this analysis, we
included daily PEEP and oxygenation index. When
considering only patients under mechanical ventilation on
the first day with a cumulative fluid balance > 5% of body
weight (n = 5827), loop diuretic administration was
associated with prolonged mechanical ventilation (full
adjusted hazard ratio 1.59, 95%CI 1.35–1.89).

Table 1 Baseline characteristics of no time-dependent variables stratified by loop diuretics. Values are mean (SD), number
(proportion) or median (IQR [range]).
All patients No loop diuretic Loop diuretic
n = 14,896 n = 11,841 n = 3055 p value
Age; y 59.9 (18.9) 58.8 (19.2) 64.1 (17.0) < 0.001
Sex; male 8163 (54.8%) 6557 (55.3%) 1606 (52.6%) 0.006
Elixhauser index 0 ( 1 to 5 [ 23 to 32]) 0 ( 1 to 5 [ 23 to 27]) 3 ( 1 to 7 [ 21 to 32]) < 0.001
Surgical admission 7441 (49.9%) 5921 (50.0%) 1520 (49.8%) 0.835
Sepsis 6801(45.6%) 5419 (45.7%) 1382 (45.2%) 0.62
Non-renal SOFA 2 (1–4 [0–17]) 2 (1–4 [0–17]) 4 (2–6 [0–17]) < 0.001
1
Sodium; mEq.l 141.2 (4.5) 141.1 (4.4) 141.4 (4.9) 0.001
1
Potassium; mEq.l 4.4 (4.0–4.8 [2.7–9.8]) 4.3 (4.0–4.7 [2.7–9.8]) 4.5 (4.2–4.9 [3.2–9.4]) < 0.001
Serum bicarbonate; 21.6 (4.4) 21.8 (4.3) 21.1 (4.8) < 0.001
mEq.l 1
Serum creatinine; 88.4 (70.7–114.9 [8.8–344.8]) 88.4 (70.7–106.1 [70.7–344.8]) 97.2 (70.7–141.4 [17.7–344.8]) < 0.001
lmol.l 1
1
Serum urea; mg.dl 33.9 (18.6) 32.6 (17.8) 38.0 (20.1) < 0.001
Mechanical ventilation 5827 (39.1%) 3902 (32.9%) 1925 (63.0%) < 0.001
Vaso-active drugs 2012 (13.5%) 1241 (10.5%) 771 (25.2%) < 0.001
Length of ICU stay; 2 (1–4 [1–102]) 2 (1–3 [1–102]) 6 (3–13 [1–98]) < 0.001
days

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orio et al. | Loop diuretics in critically ill patients

5000 80

150
4000

60

Serum creatinine (mg.dl)

3000
Fluid balance (ml)

Serum urea (mg.dl)

100

2000

40

50

1000

0 0 20

0 10 20 0 10 20 0 10 20
ICU day ICU day ICU day
32.5
160
5

30.0

4
150

Serum bicarbonate (mEq.l)

27.5
Serum potassium (mEq.l)
Serum sodium (mEq.l)

140

25.0
2

130
22.5
1

120 0 20.0

0 10 20 0 10 20 0 10 20
ICU day ICU day ICU day

Figure 1 Daily evolution of fluid balance, urine output and laboratory variables according to loop diuretic use. For this
univariate analysis, patients were allocated to the loop diuretic group if they received loop diuretics during 50% or more
of their ICU stay ( ) no loop diuretic; ( ) loop diuretic.

We also evaluated patients’ sub-groups according to the Discussion

presence of sepsis, the study period and the presence of In the present study, we evaluated whether loop diuretics
oliguria. None of the sub-groups had a survival advantage with have beneficial effects on non-cardiac critically ill patients
loop diuretics. Regarding developing severe AKI, the results with a positive fluid balance and observed no association
were very similar, except for a trend in association between with mortality or incidence of severe AKI during ICU stay.
loop diuretics and severe AKI in septic and non-oliguric However, patients receiving loop diuretics had longer time
patients. Finally, all sub-groups of patients had a consistent on mechanical ventilation. We also found that results were
association between loop diuretics and prolonged mechanical similar in all analysed sub-groups and with different loop
ventilation. Figure 2 displays main outcomes according to diuretic doses.
loop diuretic administration in the global and sub-group Several studies have evaluated the effects of loop
populations. We also evaluated if different equivalent doses of diuretics in the ICU setting, mostly observational ones [2, 6, 16].
furosemide would have any impact on 28-day mortality. Mehta et al. reported that loop diuretics were associated
Equivalent dosages up to 80 mg per day of furosemide had no with poor prognosis in patients with kidney injury [2],
significant association with mortality (Fig. 3). while another multicenter observational study found no

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28-day mortality
Oliguric (n=1919)

Non oliguric (n=12,950)

Period 2002-2007
(n=7828)

Period 2008-2012
(n=7041)

Sepsis (n=6801)

No sepsis (n=8068)

All patients (n=14,896)

0 0,5 1 1,5 2

Loop diurec protecon Loop diurec risk

Severe acute kidney injury

Oliguric (n=1919)

Non oliguric (n=12,950)

Period 2002-2007
(n=7828)

Period 2008-2012
(n=7041)

Sepsis (n=6801)

No sepsis (n=8068)

All patients (n=14,896)

0 0,5 1 1,5 2

Loop diurec protecon Loop diurec risk

Prolonged mechanical venlaon

Oliguric (n=582)

Non oliguric (n=5245)

Period 2002-2007
(n=3230)

Period 2008-2012
(n=2597)

Sepsis (n=2656)

No sepsis (n=3171)

All patients (n=5827)

0,8 1,3 1,8 2,3

Figure 2 Adjusted marginal structural Cox model hazard ratio values for outcomes in patients receiving or not receiving a loop
diuretic according to the sub-groups.

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2.5

Hazard rao for 28-day mortality

2

1.5

0.5

0
No diurec (reference) 20mg.day-1 40mg.day-1 80mg.day-1

Figure 3 Adjusted marginal structural Cox model hazard ratio values for 28-day mortality according to daily administered
equivalent dose of furosemide.

association between loop diuretic use and mortality in the association between loop diuretics and severe AKI in septic
same type of patients [15]. More recent studies have and non-oliguric patients. Although there was no significant
demonstrated a potential benefit of loop diuretic use, difference in severe AKI, patients receiving loop diuretics
suggesting it could be mediated by reducing fluid balance had higher serum creatinine levels during their ICU stay.
[6, 16]. Our study expands the analyses from previous Also, similar to a previous randomised trial [17], we
studies, as we also investigated time-dependent variables. observed patients receiving loop diuretics had higher
Another main limitation when evaluating the impact of serum sodium, urea and bicarbonate levels. Although the
loop diuretics in retrospective studies is the diverse clinical prognostic consequences for some of these metabolic
reasons to administer them in the critical care setting. We alterations are not yet established, other metabolic
have tried to limit this bias by not including patients with alterations, such as increased serum bicarbonate, should be
heart disease and pulmonary oedema, clinical situations of concern [36].
where loop diuretic use has a class-1 recommendation [34]. Surprisingly, in patients undergoing mechanical
According to our data, there was no beneficial association ventilation on day 1, there was a negative association of
between loop diuretics and survival. It is important to clarify loop diuretics with successful weaning. It could be that, with
that although we controlled loop diuretic exposure to urine reduced cumulative fluid balance, patients are less
output and fluid balance, the hazard ratio of the marginal dependent on mechanical ventilation. Although several
structural Cox model estimates the total effects of mean studies describe an association between less cumulative
administration time of loop diuretics on mortality. Thus, one fluid balance and reduced time of mechanical ventilation
can suggest that in non-cardiac critically ill patients with a [37], promoting more negative fluid balance with diuretics is
positive fluid balance, a de-resuscitation approach with a controversial issue [38]. First, it is noteworthy that patients
loop diuretics has no association with 28-day mortality. It in our study receiving loop diuretics consistently had serum
1
has been recently suggested that fluid de-resuscitation bicarbonate levels of 2 mEq.l above the others. In healthy
measures (diuretic and/or renal replacement therapy) are subjects, metabolic alkalosis decreases the neural
associated with better survival [35]. However, there are respiratory drive and minute ventilation [39]. Also, in
differences between the aforementioned study and ours critically ill patients, metabolic alkalosis is associated with
since our study did not include cardiac patients and only prolonged mechanical ventilation. In a randomised,
baseline confounders and de-resuscitation manoeuvres up controlled study, acetazolamide decreased serum
1
to day 3 were evaluated in the aforementioned study. It is bicarbonate levels by only 0.8 mEq.l and patients had a
important to reinforce that loop diuretic use in our cohort median decrease of 16 h of mechanical ventilation,
was also associated with better 28-day survival when considered clinically relevant [40]. Although controversial,
evaluating only baseline variables, but not after using the metabolic alkalosis, a known complication of loop diuretics,
marginal structural model. can lead to mechanical weaning difficulties [36]. Although
Regarding the development of severe AKI, patients our data suggest a negative association of loop diuretics
receiving loop diuretics showed no difference regarding with mechanical ventilation, it is possible that their judicious
severe AKI incidence during ICU stay, except for a trend in use and care to prevent and/or treat adverse events related

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orio et al. | Loop diuretics in critically ill patients
to them can overcome this issue. For instance, it has
been demonstrated that diuretic use was associated with a
more negative fluid balance and reduced duration of
mechanical ventilation [41]. However, contrary to our
findings, in that trial, there was no difference regarding
metabolic alkalosis between the groups and almost half of
those randomly allocated to the treatment group also
received acetazolamide.
Our study has several limitations. First, it is the first to
adjust for time-varying confounders but it is possible that
unknown confounders could bias our results. Second, even
after not including cardiac patients, loop diuretic use in the
ICU setting is far from standardised and physicians’
motivations to prescribe them can be considered an
unmeasured bias [8]. Our study also has several strengths.
We used a large database with high granularity, making it
possible to collect data up to ICU day 28. More importantly,
loop diuretic use is the prototypal case where the traditional
statistical approach cannot eliminate all potential biases,
and this is the first study to evaluate loop diuretics in the ICU
setting with a marginal structural model approach.
In conclusion, loop diuretic time-average exposure in
non-cardiac critically ill patients with a positive cumulative
fluid balance has no association with overall mortality or the
incidence of severe AKI. Prolonged mechanical ventilation
is, however, a possible concern when using loop diuretics.
Acknowledgements
No external funding or competing interests declared.
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Supporting Information
Additional supporting information may be found online in
the Supporting Information section at the end of the article.
Figure S1. Causal directed acyclic graph corresponding
to the structure of analysed data.
Figure S2. Calculation of the inverse probability of
treatment-weighting (IPTW) estimators – Log distribution of
untruncated (a) and (b) truncated weights.
Figure S3. Patient distribution in the MIMIC-III
database and exclusion criteria.
Figure S4. Distribution of patients receiving loop
diuretics during ICU stay.
Table S1. Loop diuretics dose equivalent to 20 mg of
intravenous furosemide.
Table S2. Frequency of missing/censoring values
imputed (considering 14,896 patients and 59,515 days of
ICU stay). No further variables had missing values, except for
those shown in table.
Table S3. Calculation of inverse probability of
treatment-weighting (IPTW) estimators for the IPTW model:
Probability of receiving loop diuretic for ICU patients.
Appendix S1. Marginal structural models (MSM).
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