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Archimedes

Towards evidence based medicine for paediatricians Edited by Bob Phillips

QUESTION 1 Is the use of furosemide beneficial in the treatment of acute kidney injury in the paediatric population including neonates? SCENARIO 1 A 2-year-old boy is admitted to the paediatric ward with a significant history of diarrhoea and vomiting, reduced urine output and signs of dehydration on examination. Despite giving adequate fluid replacement and maintenance, his urine output does not improve. Serial blood chemistry and urine analysis confirms evidence of worsening AKI. In this scenario, you wonder if administration of furosemide may help to ‘kick start’ and maintain urine output, ameliorate the need for dialysis and prevent long-term renal insufficiency.

STRUCTURED CLINICAL QUESTION In paediatric populations including neonates with AKI (Patient), is administration of intravenous furosemide subsequent to adequate intravascular volume replenishment (Intervention) in comparison with an expectant approach after adequate fluid replenishment associated with any short-term or long-term benefits or reduction in renal complications (Outcome)?

SEARCH STRATEGY AND OUTCOME No relevant reviews were found in the Cochrane Library. A search in Medline and Embase completed in October 2014 produced 1023 titles using the following entry terms and strategies: [(‘ACUTE KIDNEY INJURY’[Mesh] OR ‘acute renal failure’[tiab]) AND (‘furosemide’[tiab] OR ‘FUROSEMIDE’[Mesh])] AND Limit to: (Age Groups Newborn Infant birth to 1 month or Infant 1 to 23 months or Preschool Child 2 to 5 years)+[(‘ACUTE KIDNEY INJURY’ [Mesh] OR ‘acute renal failure’ [tiab]) AND (ANOXIA [Mesh) OR hypoxi×OR ISCHEMIA [Mesh]] AND Limit to: (Age Groups Newborn Infant birth to 1 month or Infant 1 to 23 months or Preschool Child 2 to 5 years). (The differing search terms used in Embase were substituted from the original Medline search). Reviewing the articles obtained by the above strategy highlighted the limitation of the number of paediatric relevant studies. Therefore, a separate search in Embase and Medline using no age limit or start date was used and a recent large adult meta-analysis looking at furosemide use in AKI in adults which was completed in 2006 was identified. A further search was undertaken looking at all relevant studies (including all age ranges) from 2006 onwards. Of the 1023 titles identified, 329 abstracts and 19 complete papers were obtained. Of these, 12 were referenced in the final article. A further five relevant articles were identified from the reference lists of the original 19.

SUMMARY See table 1.

Commentary AKI (previously known as acute renal failure) is a relatively common problem in neonates and children characterised by abrupt

When is enough enough? I know that is a tricky question, and could make you think of cream pouring on apple crumble, discussions about chemotherapy, or episodes of Octonauts depending on exactly what frame of mind you are in and background you have. Within a clinical research setting however, the question is, ‘How do we decide when something has been researched so much and folk have repeatedly found no/minimal effect, that we should just give it up?’ How do we conclude that it just does not work (enough). This is a key decision to be made, and relies on a mixture of elements. Take furosemide in acute renal failure—as explored in the Archimedes topic in this issue.1 As you will know, the idea of kick-starting the kidney comes from the observation that anuric renal failure is worse than oliguric renal failure. Start weeing, improve survival. Micturire ergo sum. At what point, undertaking research or considering a guideline recommendation, would you conclude that there is enough evidence of non-effect to stop studying anymore? The analogy is in considering equivalence and non-inferiority;2 work out with patients, carers, parents and clinicians what would be a meaningful difference and see if you have reasonably excluded it. Add to those ideas, the cost of intervention, the cost of more research (both doing it, and the ‘cost’ of not studying other stuff while you are engaged doing this), then you can settle on an answer. Then you would know exactly when enough is enough. Bob Phillips Correspondence to Dr Bob Phillips, Centre for Reviews and Dissemination, University of York, York YO10 5DD, UK; [email protected] Competing interests None declared. Provenance and peer review Commissioned; internally peer reviewed. Received 14 May 2015 Accepted 16 May 2015

▸ http://dx.doi.org/10.1136/archdischild-2015-308472 ▸ http://dx.doi.org/10.1136/archdischild-2015-308821 Arch Dis Child 2015;100:713. doi:10.1136/archdischild-2015-308978

REFERENCES 1 2

Is the use of furosemide beneficial in the treatment of acute kidney injury in the paediatric population including neonates? this issue! Phillips R. It’s all the same. Arch Dis Child 2012;97:750.

increases in blood levels of creatinine and nitrogenous waste products. An overall incidence of 0.8 per 100 000 of the total population has been proposed with age-related incidence being highest in the neonatal period.7 Pre-renal causes (following hypotension, hypovolaemia) and intrinsic damage due to ischaemia or nephrotoxins are the most common causes; AKI resulting from obstruction to urine flow (post-renal AKI) is less common.8

Arch Dis Child July 2015 Vol 100 No 7

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Towards evidence based medicine for paediatricians Bob Phillips Arch Dis Child 2015 100: 713

doi: 10.1136/archdischild-2015-308978 Updated information and services can be found at: http://adc.bmj.com/content/100/7/713.2

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Towards evidence based medicine for paediatricians.

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