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GIUSEPPE G. L. BIONDI-ZOCCAI • GIACOMO MONTI • STEFANO TURI • IMAD SHEIBAN • ELENA BIGNAMI • GIOVANNI LANDONI ABSTRACT
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])) 1.Gailiunas P Jr, Chawla R, Lazarus JM, Cohn L, Sanders J, Merrill JP. Acute renal failure following cardiac operations. J Thorac Cadiovasc 2.Baxter P, Rigby ML, Jones OHD, Lincoln C, Shinebourne EA. Acute renal failure following cardiopulmonary bypass in children: results of treatment. Int J Cardiol 1985;7:235-9.
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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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