Journal of Cardiothoracic and Vascular Anesthesia ] (]]]]) ]]]–]]]

Contents lists available at ScienceDirect

journal homepage: www.jcvaonline.com

Review Article

Continuous Infusion versus Intermittent Bolus

Injection of Furosemide in Critically Ill Patients:
A Systematic Review and Meta-analysis
Ka Ting Ng, MB ChBn,1, Aslinah Velayit, MBBS†,
Delton Kah Yeang Khoo, MBBS†, Amirah Mohd Ismail‡,
Marzida Mansor, MAnaesn
n
Department of Anaesthesiology, Faculty of Medicine, University of Malaya, Jalan Universiti,
Kuala Lumpur, Malaysia
†
International Medical University, Kuala Lumpur, Malaysia
‡
Jeffrey Cheah School of Medicine and Heath Sciences, Monash University Malaysia, Selangor, Malaysia

Objective: Fluid overload is a common phenomenon seen in intensive care units (ICUs). However, there is no general consensus on whether
continuous or bolus furosemide is safer or more effective in these hemodynamically unstable ICU patients. The aim of this meta-analysis was to
examine the clinical outcomes of continuous versus bolus furosemide in a critically ill population in ICUs.
Data Sources: MEDLINE, EMBASE, PubMed, and the Cochrane Database of Systematic reviews were searched from their inception until June
2017.
Review Methods: All randomized controlled trials, observational studies, and case-control studies were included. Case reports, case series,
nonsystematic reviews, and studies that involved children were excluded.
Results: Nine studies (n ¼ 464) were eligible in the data synthesis. Both continuous and bolus furosemide resulted in no difference in all-cause
mortality (7 studies; n ¼ 396; I2 ¼ 0%; fixed-effect model [FEM]: odds ratio [OR] 1.15 [95% confidence interval (CI) 0.67-1.96]; p ¼ 0.64).
Continuous furosemide was associated with significant greater total urine output (n ¼ 132; I2 ¼ 70%; random-effect model: OR 811.19 [95% CI
99.84-1,522.53]; p ¼ 0.03), but longer length of hospital stay (n ¼ 290; I2 ¼ 40%; FEM: OR 2.84 [95% CI 1.74-3.94]; p o 0.01) in
comparison to the bolus group. No statistical significance was found in the changes of creatinine and estimated glomerular filtration rate between
both groups.
Conclusions: In this meta-analysis, continuous furosemide was associated with greater diuretic effect in total urine output as compared with
bolus. Neither had any differences in mortality and changes of renal function tests. However, a large adequately powered randomized clinical
trial is required to fill this knowledge gap.
& 2018 Elsevier Inc. All rights reserved.

Key Words: continuous; furosemide; intermittent; length of stay; loop diuretic; mortality; critically ill

FLUID OVERLOAD often is encountered in critically ill
patients and has been demonstrated to be associated with
1
Address reprint requests to Ka Ting Ng, Department of Anaesthesiology,
Faculty of Medicine, University of Malaya, Jalan Universiti, 50603 Kuala
Lumpur, Malaysia.
E-mail address: katingng1@gmail.com (K.T. Ng).
adverse outcomes, namely cardiac failure, pulmonary edema,
poor tissue healing, and impaired bowel function.1–4 The
outlook of recovery after these complications is poor and
contributes to significant healthcare cost due to prolonged
duration of ventilation and length of intensive care unit (ICU)
stay.3,5 A loop diuretic is the fundamental pharmacologic

https://doi.org/10.1053/j.jvca.2018.01.004
1053-0770/& 2018 Elsevier Inc. All rights reserved.

Please cite this article as: Ng KT, et al. (2018), https://doi.org/10.1053/j.jvca.2018.01.004

2 K.T. Ng et al. / Journal of Cardiothoracic and Vascular Anesthesia ] (]]]]) ]]]–]]]
therapy to increase urine output to minimize the risk of
multiorgan dysfunction in these hemodynamically unstable
patients in ICUs.6 To date, there is no general consensus on
whether continuous infusion or intermittent bolus injection of
furosemide is superior in terms of safety and efficacy profiles
in these critically ill patients.
Furosemide is one of the most commonly used loop
diuretics in ICUs. The half-life of furosemide varies between
1 and 1.5 hours.7 Continuous infusion of furosemide is
believed to confer additional benefits over bolus injection
with less variability in the peak plasma furosemide concentra-
tion, leading to a constant predictable urine output and lower
risk of electrolyte disturbance.7,8 In addition, continuous
infusion can be titrated easily to meet the expected diuresis
effect as the fluid status of these critically ill patients fluctuates
rapidly throughout the day due to multiorgan failure.9
In the literature, the findings of the only existing meta-
analysis examining the optimal mode of furosemide adminis-
tration in ICUs in 2011 were inconclusive, based on 4 small
heterogeneous studies with a sample size of only 129 patients.6
In recent years, several randomized controlled trials (RCTs)
were published with conflicting results.10–13 Intravascular
volume fluctuation, drug toxicity, and tolerance from the
different modes of furosemide administration remain
unclear.14,15 The clinical characteristics of the ICU population
are unique and different from other hospitalized patients due to
their vulnerable and already compromised hemodynamic
status. Any fluid or electrolyte imbalance secondary to
injudicious use of furosemide can be detrimental. The authors
hypothesized that continuous furosemide was more physiolo-
gically friendly with better diuretic effects and lesser adverse
effects than bolus injection in ICU patients.
The primary aim of this systematic review and meta-
analysis was to examine the clinical outcomes of continuous
infusion versus bolus injection of intravenous furosemide on
mortality and length of hospital stay in critically ill patients
with fluid overload. The secondary aim was to examine the
diuretic effects and changes in estimated glomerular filtration
rate (eGFR) and creatinine of continuous versus bolus
furosemide in critically ill patients.
Methods
This review was conducted and reported according to the
Preferred Reporting Items for Systematic Review and Meta-
Analysis (PRISMA) statement 2015.16 The review protocol
was registered on the global public database of systematic
reviews, PROSPERO (www.crd.york.ac.uk), with the refer-
ence number CRD42017067722. The research questions were
formulated using a PICO approach (Supplemental Table 1).
Search Strategy
According to Mehta and Bouchard, fluid overload implies a
degree of pulmonary edema or peripheral edema in critically ill
patients.1 It also is defined as Z 15% in men and Z 13% in
women of fluid excess in relation to the extracellular volume.17
Please cite this article as: Ng KT, et al. (2018), https://doi.org/10.1053/j.jvca.2018.01.004
Ovid, MEDLINE, EMBASE, PubMed, and the Cochrane
Database of Systematic Reviews were searched from their
inception until June 2017. The search strategy and terms used
are provided in the online digital supplement (Supplemental
Table 2). Publications not written in the English language were
excluded. The bibliographies of included papers and relevant
systematic reviews were hand-searched for additional papers.
Experts and authors of papers identified in the search strategy
were contacted for additional data or missing data.
Outcomes
Co-primary outcomes were all-cause mortality and length of
hospital stay. Prespecified secondary outcomes were total urine
output in the first 24 hours and changes in serum creatinine
during the duration of treatment. Other relevant outcomes were
considered for the meta-analysis if they were measured in
more than one of the included studies. On this basis, changes
in eGFR also were included. However, the incidence of acute
kidney injury and need for renal replacement therapy were not
reported in this review due to lack of sufficient data.
Study Selection and Data Extraction
Titles and abstracts were independently screened against
eligibility criteria by 2 authors (A.L. and A.V.). The same
2 reviewers independently screened full texts of qualifying
papers. Any disagreements at any stage were resolved by the
third reviewer (K.N.). Inclusion criteria were (1) RCTs;
(2) case-control studies; and (3) observational studies compar-
ing the effects of continuous versus bolus injection of
furosemide on the outcomes of mortality, length of hospital
stay, total urine output, changes of creatinine, and eGFR
in the critically ill population with fluid overload in the setting
of ICUs.
Case reports, case series, and nonsystematic reviews were
excluded. Studies involving patients younger than 16 years of
age also were excluded. All the included RCTs and observa-
tional studies were assessed for risk of bias using the Cochrane
Collaboration Risk of Bias Assessment Tool (https://hand
book.cochrane.org) and the Newcastle-Ottawa Quality Assess-
ment Scale (http://www.ohri.ca), respectively. In the New-
castle-Ottawa scale, studies with scores Z7, 4 to 6, and o 3
were considered as having a low, moderate, and high risk of
bias, respectively. In addition to the measured outcomes, the
data fields, namely citation, year of publication, study design,
country, population, sample size, and mean daily dose of
furosemide, were extracted. Continuous outcomes presented as
median (range) were converted to mean (standard deviation).18
Statistical Analysis
Statistical analyses were undertaken using RevMan Review
Manager version 5.3 (The Cochrane Collaboration, Copenha-
gen, Denmark). Analyses of funnel plots were not undertaken
for all co-primary and secondary outcomes because there
fewer than 10 studies for each measured outcome to assess
 K.T. Ng et al. / Journal of Cardiothoracic and Vascular Anesthesia ] (]]]]) ]]]–]]]
the risk of publication bias.19 The I2 test was used to assess the
heterogeneity of studies. Values of less than 40%, 40%
to 60%, and more than 60% were used to determine low,
moderate, and substantial heterogeneity, respectively.20
A p value of o 0.05 was considered to denote statistically
significant heterogeneity.
In line with standard methodology (https://handbook.
cochrane.org), if no significant heterogeneity was noted, a
fixed-effect model (FEM) analysis (Mantel–Haenszel method)
was used to pool estimates. If evidence of substantial hetero-
geneity (I2 4 50%) was observed, a random-effects model
(REM) analysis (DerSimonian–Laird) method was used.
Findings were reported as odds ratios (ORs) or mean
difference with 95% confidence intervals (CIs). Subgroup
analysis was conducted by stratifying all included studies into
RCTs and non-RCTs (observational study, case-control study)
to investigate for high heterogeneity. Sensitivity analysis was
performed to assess the robustness and applicability of present
findings by switching from fixed-effect to random-effect
models or vice versa and withdrawing nonrandomized studies
from data analysis.
Results
The results of the literature search and study selection process
are outlined in the PRISMA flow chart (Fig 1). The titles and
abstracts of 4,264 nonduplicate articles were screened, and 41
articles were retrieved. After applying inclusion and exclusion
criteria, 9 articles with a total of 464 subjects were included in the
final data analysis. Details of the excluded studies are outlined the
online digital supplement (Supplemental Table 3).
Fig 1. PRISMA diagram.
Please cite this article as: Ng KT, et al. (2018), https://doi.org/10.1053/j.jvca.2018.01.004
3
Study Characteristics
The clinical characteristics of all included studies comparing
the outcomes of continuous infusion versus bolus injection of
furosemide in critically ill patients are illustrated in Table 1. A
single-centred RCT21 was excluded from data analysis because
its data were inadequate for pooling. Out of the 9 studies,
79,10,13,21–24 were RCTs, 111 was a case-control study, and 112
was an observational study. Among the 7 RCTs, 510,13,21,23,24
were single centered and 29,22 were multicentered. The study
design of the majority of included studies9,11,12,22–24 was goal-
directed diuresis, except for 3 RCTs10,13,21 that adopted a fixed
dose of intravenous furosemide in both continuous and bolus
groups. None of the studies was commercially sponsored, and
there were no conflicts of interest.
Overall, the risk of bias assessment for all the included
RCTs9–12,23 was rated as unclear, where 3 RCTs13,22,24 had all
their patients receive a standardized dose of bolus furosemide
(either 20 mg or 40 mg) before the randomization process,
which potentially could introduce variance into the authors’
interpretation (Supplemental Table 4). For both nonrando-
mized studies,11,12 their Ottawa-Newcastle assessment scored
7 stars, which indicated low risk of bias (Supplemental
Table 5). Given the limited number of RCTs in critically ill
patients, nonrandomized studies11,12 were included for data
analysis in this review.
Co-Primary Outcomes: Mortality and Length of Hospital Stay
Seven studies examined the mortality rate in critically ill,
fluid-overloaded patients: a total of 369 patients who received
4 K.T. Ng et al. / Journal of Cardiothoracic and Vascular Anesthesia ] (]]]]) ]]]–]]]

Table 1
Characteristics of Included Studies

First Author Year Design Mean Dose of Loop Diuretic Setting Country n Outcomes Used in
(SD) Meta-analysis

Copeland17 1984 Single-centered Fixed dose for both groups Cardiac intensive United States 18 -
RCT Continuous: Furosemide 45.8 care unit
mg/12 hours
Bolus: Furosemide 45.5
mg/12 hours
Schuller18 1997 Multicentered Goal-directed diuresis Medical or cardiac United States 33 Mortality
RCT 40 mg furosemide bolus intensive care unit Changes in creatinine
before randomization
Continuous: not reported
Bolus: not reported
Makhoul19 1997 Single-centered Goal-directed diuresis Medical intensive Israel 20 Total urine output in the
RCT Continuous: furosemide 329 care unit first 24 hours
(186.7) mg/day
Bolus: furosemide 324
(110.8) mg/day
Mojtahedzadeh20 2004 Single-centered Goal-directed diuresis Medical intensive Iran 22 Mortality
RCT 20 mg furosemide bolus care unit
before randomization
Continuous: not reported
Bolus: not reported
Ostermann10 2007 Multicentered Goal-directed diuresis Medical or surgical Canada 59 Mortality
RCT Continuous: furosemide 9.2 intensive care unit Changes in creatinine
mg/hour
Bolus: furosemide 24.1 Changes in eGFR
mg/hour
Shah21 2014 Single-centered Fixed dose for both groups Cardiac intensive India 90 Mortality
RCT 40 mg furosemide bolus care unit Hospital length of stay
before randomization
Continuous: furosemide 100 Total urine output in the
mg/day first 24 hours
Bolus: furosemide 100
mg/day in 2 divided doses
Palazzuoli11 2015 Single-centered Fixed dose for both groups Cardiac para- Italy 57 Mortality
RCT Continuous: furosemide 188 intensive unit Length of hospital stay
(70) mg/day
Bolus: furosemide 170 (80) Total urine output in the
mg/day first 24 hours
Changes in creatinine
Changes in eGFR
Yeh12 2015 Prospective case- Goal-directed diuresis Surgical intensive United States 55 Mortality
control study Continuous: furosemide 59.4 care unit Length of hospital stay
(30.5) mg/day 1
Bolus: furosemide 25.4 (32.0) Total urine output in the
mg/day 1 first 24 hours
Changes in creatinine
Caetano22 2015 Prospective cohort Goal-directed diuresis Cardiac intensive Portugal 110 Mortality
observational Continuous: not reported care unit Length of hospital stay
study Bolus: not reported Changes in creatinine

Abbreviations: RCT, randomized controlled trial; SD, standard deviation.

either continuous infusion or intermittent bolus injection of
furosemide.9–13,22,24 Overall, statistical heterogeneity was
assessed as low in the pooled effect. There was no statistically
significant effect on mortality rate in either continuous and
bolus groups (p ¼ 0.61, I2 ¼ 0%; FEM:OR 1.15; 95% CI
0.67-1.96) (Fig 2). Subgroup analysis showed the outcome of
mortality rate was similar across randomized and nonrando-
mized studies, which suggested that mortality rate did not
differ between continuous and bolus groups.
Four studies investigated the duration of hospital stay
in a total of 290 patients.10–13 The authors found that the
continuous infusion group was associated with a statistically
significant longer duration of hospitalization as compared with
the intermittent bolus group (p o 0.01, I2 ¼ 40%; FEM:
OR 2.84; 95% CI 1.74-3.94) (Fig 3). Overall, statistical
heterogeneity was assessed as moderate across the studies.
To investigate for this moderate heterogeneity, a sub-
group analysis was performed and it reported similar findings

Please cite this article as: Ng KT, et al. (2018), https://doi.org/10.1053/j.jvca.2018.01.004

 K.T. Ng et al. / Journal of Cardiothoracic and Vascular Anesthesia ] (]]]]) ]]]–]]] 5

Fig 2. Mortality.

across these subgroup studies, where continuous furosemide
resulted in longer length of hospital stay in comparison
with the bolus arm with significant subgroup differences
(p ¼ 0.04).
Secondary Outcomes: Total Urine Output in the First 24
Hours; Changes in Creatinine; Changes in eGFR
Three studies measured the total urine output in the first 24
hours in critically ill patients randomized to treatment with
either continuous or bolus intravenous furosemide.10,11,23 The
continuous infusion of furosemide resulted in a statistically
significant greater urine output in the first 24 hours than the
intermittent bolus injection (p ¼ 0.03, I2 ¼ 70%; REM:OR
811.19; 95% CI 99.84-1,522.53) (Fig 4). The high hetero-
geneity was contributed by the only case-controlled study, and
the outcome of total urine output in the first 24 hours remains
unchanged where continuous furosemide was associated with
a greater diuresis effect as compared with the bolus arm.
Four studies investigated changes in creatinine during the
period of randomization in a total of 281 patients.9–12
Statistical heterogeneity was assessed as high. There was no
significant difference in the changes in creatinine in critically
ill patients who received either continuous infusion or
intermittent bolus injection of furosemide (p ¼ 0.39, I2 ¼
86%; REM:OR 0.09; 95% CI –0.11 to 0.29) (Fig 5). Subgroup
analysis showed a similar trend of nonsignificant findings in
both subgroup studies.
Only 2 RCTs investigated the changes of eGFR in critically
ill patients after randomization to either continuous or bolus
furosemide to treat fluid overload, with a total of 116
patients.9,10 In this meta-analysis, the authors reported no
statistical significance in this outcome in either groups
(p ¼ 0.12; I2 ¼ 0%; FEM:OR 1.09; 95% CI –0.28 to 2.45)
(Fig 6). No significant heterogeneity was found among these
studies.
Discussions
Positive fluid balance in critically ill patients is known to be
associated with poor prognosis.1,4,25,26 The optimal mode of
furosemide administration in critically ill patients remains
topic of debate among clinicians and intensivists. To the
authors’ knowledge, this is the first meta-analysis to summar-
ize the current findings in the literature since the first meta-
analysis published in 2011.6 In this meta-analysis, the authors’
main findings were that continuous furosemide yielded to a
greater total urine output but with longer duration of hospital

Fig 3. Length of hospital stay.

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6 K.T. Ng et al. / Journal of Cardiothoracic and Vascular Anesthesia ] (]]]]) ]]]–]]]

Fig 4. Urine output in the first 24 hours.

stay than bolus arm. However, neither continuous nor bolus
regimes differed in mortality rate or in changes in serum
creatinine and eGFR.
Furosemide acts on the thick ascending loop of Henle to
promote natriuresis and diuresis in patients with fluid over-
load.27,28 All loop diuretics have to be filtered and secreted to
the luminal side of the loop of Henle to exert its diuresis effect
to improve symptoms of fluid congestion.6,8 The authors found
that the association of greater urine output in the first 24 hours
with the continuous group was in line with all published
RCTs, non-RCTs, and meta-analyses.6,29–32 It is believed that
continuous furosemide may be associated with lesser fluctua-
tion of serum furosemide concentration, resulting in a pre-
dictable and more constant urine output. In addition, the risk of
diuretic resistance is lower as the chance of serum furosemide
dropping below the therapeutic threshold was lower in a
continuous dose than in a bolus dose.8 The continuous regime
may provide better hemodynamic stability and lesser adverse
effects of furosemide in vulnerable adult patients in ICUs.
However, a meta-analysis based on 3 small trials (n ¼ 92
patients) reported no significant changes in urine output among
pediatric patients after cardiac surgery.33 Given the lack of
power and suboptimal quality of all 3 included studies, the
findings of that meta-analysis need to be interpreted with
caution.33
Changes in body weight have been suggested by Ng et al as a
better indicator of diuretic effect than urine output in the acute
decompensated heart failure population.34 In the ICU setting, the
authors believe that the majority of patients will be catheterized
with a urinary catheter for close monitoring of fluid balance,
which should minimize the potential risk of reporting bias
among ICU patients. Six out of the 9 included studies adjusted
the dose of furosemide to match the goal-targeted diuresis effects
for all their critically ill patients.9,11,12,22–24 Several studies have
pointed out that protocol-driven, goal-directed strategy was
better than fixed-dose strategy in hemodynamic labile critically
ill patients.6,22,35,36 Schuller et al revealed a subgroup analysis
that a non-protocol-driven group was associated with lesser net
diuresis and longer ICU and hospital stay than the protocol-
driven group.22 The most recent comprehensive meta-analysis
suggested that goal-directed fluid therapy reduces mortality,
morbidity, and hospital length of stay.17 However, there were
insufficient studies for data analysis in comparing goal-directed
and fixed-dose furosemide strategies in this review. Given that
the majority of ICU patients are malnourished, the co-adminis-
tration of albumin with intravenous furosemide is often at the
discretion of physicians to increase the oncotic pressure to
remove fluid. The difference of strategies and adjuvant use of
albumin in all included studies were not standardized, and it may
introduce variances to the authors’ findings.
The authors demonstrated no difference in mortality between
continuous and bolus furosemide, which was in agreement with
the only meta-analysis examining these 2 regimes in ICU
patients.6 However, the findings of the previous meta-analysis
had to be interpreted with caution as it was derived from 4 small
heterogenous studies, which may be insufficient to provide
recommendations on whether continuous dose is better than
bolus dosing.6 The authors’ subgroup analysis was consistent
with a nonsignificant mortality rate among randomized and
nonrandomized studies that administrated a continuous versus

Fig 5. Changes in creatinine.

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 K.T. Ng et al. / Journal of Cardiothoracic and Vascular Anesthesia ] (]]]]) ]]]–]]]
Fig 6. Changes in estimated glomerular filtration rate.
bolus dose. In a non-ICU setting, 2 recent meta-analyses of RCTs
published in 2014 reported no difference in mortality in either
groups.29,30 In contrast, an observational study conducted by
Caetano et al showed that the continuous group was associated
with a higher mortality rate, which was speculated to be due to
higher rate of nosocomial infection in that population.12 The
authors believe that the total sample size in their data analysis
was insufficient to justify the insignificant difference in mortality
rate between continuous and bolus groups. Thus, an adequately
powered multicentered RCT would be required to determine
whether the continuous arm is better than the bolus arm in terms
of mortality rate.
Although there was no difference in mortality, the contin-
uous group was found to have longer duration of hospitaliza-
tion as compared with the bolus group. Along with no changes
in serum creatinine and eGFR in either continuous or bolus
groups, the authors postulated that duration of hospital stay
was multifactorial and there were many confounders that they
were unable to control or adjust in the original studies at this
review level. Injudicious use of continuous furosemide may
cause intravascular volume contraction and tip the fluid
balance toward hypovolemia, resulting in tissue and organ
underperfusion. Palazzuoli et al found that the continuous
group was associated with significantly poorer basal renal
function before randomization, which may interfere with the
interpretation of the length of hospitalization.10 The duration
of randomization in the majority of RCTs lasted for only 72
hours, except 1 study21 that lasted for only 12 hours. A longer
duration of continuous furosemide may be needed to manifest
its clinical benefits to alleviate the symptoms of fluid overload,
especially in patients who are diuretic-resistant.
Dorman et al demonstrated that the continuous arm had a
better safety profile in terms of lower risk of raised creatinine
and impaired eGFR than the bolus arm.37 However, the
authors found no differences in changes of creatinine and
eGFR in these 2 regimes. The type 2 error may have occurred
due to small sample size of the authors’ included studies. In
addition, this also potentially could be masked by intense
monitoring and active correction of any electrolyte imbalance
in the ICU setting.6 Nevertheless, the interpretation of the
changes in eGFR and creatinine could be complicated as the
majority of admitted ICU patients are frail with multiorgan
failure, namely acute kidney injury, acute or chronic kidney
disease, liver failure, and gastrointestinal dysfunction. None-
theless, careful monitoring of kidney function during the
administration of furosemide is still recommended by the
experts, although few clinical studies have reported that the
continuous regime was associated with lower risk of electro-
lyte imbalance and renal impairment.6,15,31,37
Please cite this article as: Ng KT, et al. (2018), https://doi.org/10.1053/j.jvca.2018.01.004
7
This review provided a comprehensive and up-to-date
analysis of studies examining the clinical outcomes of
continuous versus bolus furosemide in critically ill patients
in the ICU setting. The authors conducted an exhaustive
literature search, and all included studies were subjected to a
rigorous assessment of methodologic quality. The only meta-
analysis on this topic was conducted in 2011, which only
included the 4 small heterogeneous studies with small sample
size.6 The current review added 5 studies into the pooled data
analysis.10–13,23 The addition of this meta-analysis could
summarize the current evidence to inform future clinical
practice and research directions on the optimal mode of
intravenous furosemide administration in the critically ill
population with fluid overload in ICUs.
Limitations of this study were common to other meta-analysis
of RCTs, namely differences in population clinical character-
istics, diuretic dosage, and schedules of administration and
small patient numbers. The largest sample size of the included
RCTs never exceeded 100 patients, which had inadequate
power to make any strong justification of the authors’ co-
primary measures. In spite of the low statistical heterogeneity in
all-cause mortality, the authors’ pooled estimates were unad-
justed and should be interpreted with caution. Unfortunately, the
authors were not able to control for confounding factors in all
included studies at this review level. For instance, some of the
studies were performed in cardiac ICUs, with patients who may
have had cardiogenic renal dysfunction and received inotropic
support in addition to furosemide. Different causes of and
treatments for renal dysfunction (cardiogenic and noncardio-
genic) may introduce variance in the outcomes of continuous
and bolus furosemide in these critically ill patients. All of these
differences may contribute to the high heterogeneity of some
measured variables in this review. There is currently a dearth of
evidence regarding whether either continuous or bolus furose-
mide is better in critically ill patients with fluid overload. Given
the potential theoretical benefits of continuous furosemide in
hemodynamically unstable patients, a large, adequately pow-
ered, multicenter RCT should be designed to clarify the authors’
hypotheses in the administration of furosemide in ICU patients,
with an agreed definition of fluid overload and normal renal
function.
In this meta-analysis, continuous infusion of furosemide had
greater diuretic effect in total urine output without any
significant reduction in mortality rate and changes of eGFR
and creatinine. In the absence of high-quality, adequately
powered studies, the authors were unable to make any further
recommendations at this time regarding whether continuous or
bolus furosemide is safer or more effective in critically ill
patients with fluid overload.
8 K.T. Ng et al. / Journal of Cardiothoracic and Vascular Anesthesia ] (]]]]) ]]]–]]]
Appendix A. Supporting information
Supplementary data associated with this article can be found in
the online version at https://doi.org/10.1053/j.jvca.2018.01.004.
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