GIUSEPPE G. L. BIONDI-ZOCCAI • GIACOMO MONTI • STEFANO TURI •
IMAD SHEIBAN • ELENA BIGNAMI • GIOVANNI LANDONI
Introduction. Acute renal failure and fluid retention are common problems in pediatric patients after cardiac surgery.
Furosemide, a loop diuretic drug, is frequently administered to increase urinary output. The aim of the present study was
to compare efficacy and complications of continuous infusion of furosemide vs bolus injection among pediatric patients
Methods. A systematic review and meta-analysis was performed in compliance with The Cochrane Collaboration and the
Quality of Reporting of Meta-Analysis (QUORUM) guidelines. The following inclusion criteria were employed for potentially
relevant studies: a) random treatment allocation, b) comparison of furosemide bolus vs continuous infusion, c) surgical
or intensive care pediatric patients. Non-parallel design randomized trials (e.g. cross-over), duplicate publications and
non-human experimental studies were excluded.
Results. Up to August 2008, only three studies were found, with 92 patients randomized (50 to continuous infusion and 42
to bolus treatment). Overall analysis showed that continuous infusion and bolus administration were equally effective in
achieving the predefined urinary output, and were associated with a similar amount of administered furosemide (WMD=-
1.71 mg/kg/day [-5.20; +1.78], p for effect=0.34, p for heterogeneity<0.001, I2=99.0). However, in the continuous infu-
sion group, patients had a significantly reduced urinary output (WMD=-0.48 ml/kg/day [-0.88; -0.08], p for effect=0.02, p
for heterogeneity <0.70, I2=0%).
Conclusions. Existing data comparing furosemide bolus injection with a continuous infusion are insufficient to confidently
assess the best way to administer furosemide to pediatric patients after cardiac surgery. Larger studies are needed before
volume fluctuations that it may cause in
an already labile circulatory system. (4)
nary output. Intravenous bolus injection
Acute renal failure and fluid retention are
is the traditional mode of administration
pediatric patients. The exclusion criteria
studies bias (including publication bias)
zed trials (i.e. cross-over), b) duplicate
hearth failure (CHF). (5-7) A recent revi-
CHF adult patients concluded that “the
existing data still does not allow definite
recommendations for clinical practice”.
criteria. Divergences from the selection
(8) Randomized controlled trials in criti-
criteria were resolved by consensus.
cally ill adult patients report conflicting
Data Abstraction and Study Characteri-
with those of bolus injection in pediatric
contacts with experts yielded a total of
population, clinical setting. At least two
ssed according to the selection criteria,
eight studies. A total of five studies were
tified three eligible randomized clinical
et al. (12) and is available in the appen-
the duration of intensive care unit (ICU)
Internal validity and risk of bias of inclu-
put in both groups (1ml/kg/h). Patients’
references of retrieved articles and per-
severity scores were not reported in any
tinent reviews). No language restriction
pendently examined at the title/abstract
testing and at the 0.10 for heterogeneity
level by two investigators (LC, GM), with
testing. According to Higgins et al., (15)
and then, if potentially pertinent, retrie-
Table 1. Characteristics, results and conclusions of three studies randomizing cardiac surgery pediatric patients after cardiopulmonary bypass to receive a continuous infusion (C group) or a bolus (B group) administration of furosemide.
ents had a significantly reduced urinary
ne levels. Patients’ characteristics, stu-
dies’ results and authors’ conclusions
effect=0.02, p for heterogeneity <0.70,
administration in pediatric patients after
Diuretic treatment is widely used in ICU
tion achieved a urinary output > 1 ml/
creatinine levels after treatment, survi-
to resolve fluid overload or to treat (or
stration of loop diuretics in adult patients
seems not to be associated with clinical
validity of our findings by exploring the
showed that diuretics administrations in
total furosemide dose or urine output.
critically ill patients with AKI is associa-
Figure 2. Forest plot for pooled estimates (A) and funnel plot for small study bias appraisal (B) for total use of furo-semide.
Figure 3. Forest plot for pooled estimates (A) and funnel plot for small study bias appraisal (B) for total urinary out-put.
furosemide excretion rate will be closer
me in adult patients with or at risk for
to the most efficient excretion rate over
acute renal failure, like critically ill pati-
ry, (26) especially cardiac surgery. (27)
efficacy of a continuous infusion: acute
of the literature on continuous infusion
uld have a better safety profile, allowing
of loop diuretics in critically ill patients
diuresis. Their receptor is on the inter-
action site, within the lumen, appears to
intuitively seems superior to bolus injec-
tions, evidence on this topic is still lac-
cally ill pediatric patients after cardiac
profile, during the research, is defined
this meta-analysis had conflicting results.
on in critically ill paediatric patients are
stability. In the study by Luciani, (20)
patients reported an ototoxicity rate of
known and include the level of uniformity
on criteria, while in Klinger’s (19) it was
an exclusion criteria. In Singh’s study,
for critically ill pediatric patients after
marked variability of hourly urine output
Continuous infusion resulted in a gentle
An additional limitation of our study is
way to eliminate fluid overload at least
higher (even if not significantly different)
according to the authors of all the three
continuous infusion in pediatric critically
Copeland in adult patients after cardiac
It should be noted that in critically ill
are insufficient to confidently assess the
tric patients after cardiac surgery. Both
unavailability of the research staff) twel-
desired urinary output, and safe. Larger
mic lability of these patients: the typical
(bolus AND (infus* OR perfusio*) AND (furosemide OR frusemide OR diuretic* OR diuresis)) AND (randomized controlled trial[pt] OR controlled clinical trial[pt] OR randomized controlled trials[mh] OR random allocation[mh] OR double-blind method[mh] OR single-blind method[mh] OR clinical trial[pt] OR clinical trials[mh] OR (clinical trial[tw] OR ((singl*[tw] OR doubl*[tw] OR trebl*[tw] OR tripl*[tw]) AND (mask*[tw] OR blind[tw])) OR (latin square[tw]) OR placebos[mh] OR placebo*[tw] OR random*[tw] OR research design[mh:noexp] OR comparative study[tw] OR follow-up studies[mh] OR prospective studies[mh] OR cross-over studies[mh] OR control*[tw] OR prospectiv*[tw] OR volunteer*[tw]) NOT (animal[mh] NOT human[mh]) NOT (comment[pt] OR editorial[pt] OR meta-analysis[pt] OR practice-guideline[pt] OR review[pt]))
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This study is part of a senior training project of the Meta-analysis and Evidence-based medicine Training in Cardiology (METCARDIO) Centre, based in Milan, Italy (http://www.metcardio.org).
We are indebted to Virzo I, RN, Chiappa C, RN, Giardina G, RN, Castelnuovo L, RN, Costantini M and Fichera M, for the careful data entry and revision of the paper.
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