A Perner

B Mickiewicz

BM Paridon van

CW Seymour

D Gattas

M Cvetkovic

Mark J. Peters

Samiran Ray

SM Tibby

PubMed

Ray, S

Peters, MJ

UCL Discovery

Ray and Peters Critical Care  (2015) 19:394 DOI 10.1186/s13054-015-1122-3LETTER Open AccessTiming of antibiotics, volume andvasoactive infusions in children with sepsis:it is all in the timingSamiran Ray1 and Mark J. Peters1,2*See related research by van Paridon et al., http://www.ccforum.com/content/19/1/293We share the view of van Paridon et al. [1] that robustdata on fluid bolus therapy for sepsis resuscitation areneeded, and looked with interest to the Alberta SepsisNetwork’s recent report to add to our understanding.We note that the authors chose to exclude children whowere expected to die <24 hours from presentation. Wewould be grateful to know how many cases wereexcluded on this basis. The majority of the hazardfrom sepsis lies in this period. We recently definedthis risk in a similar cohort of children; 55 % of allsepsis deaths (78 % of these being previously healthychildren) occurred within the first 24 hours [2].Resuscitation interventions such as fluid and vasoactivedrugs are guided by changes in physiology. Inasmuch as* Correspondence: mark.peters@ucl.ac.uk1Respiratory, Critical Care and Anaesthesia Section, UCL Institute of ChildHealth, 30 Guildford Street, London WC1N 1EH, UK2Paediatric and Neonatal Intensive Care Unit, Great Ormond Street Hospital,London WC1N 3JH, UKAuthors’ responseBregje M van Paridon, Cathy Sheppard, Gonzalo Garcia Guerra© 2015 Ray and Peters. Open Access This artInternational License (http://creativecommonsreproduction in any medium, provided you gthe Creative Commons license, and indicate if(http://creativecommons.org/publicdomain/zephysiological variables are associated with mortality, theseinterventions are also likely to have an immediate effect onmortality. The authors suggest potential explanations forthe 1-year mortality effect seen with aggressive fluid admin-istration: while all are not only plausible but likely, the effectwill only be seen if the acute phase is overcome. By exclud-ing children dying early, the authors also reduce the poten-tial to propensity match children receiving similar levels ofinterventions. Pediatric Risk of Mortality (PRISM) scorescontrol for severity of illness, but information is lost giventhat the PRISM score utilises categories of haemodynamicvariables rather than age-standardised continuous variables[3]. We wonder whether the modest effect size differencewould persist with these alterations to the methodology.and Ari R JoffeWe thank Ray and Peters for their interest in our study.They point out that we excluded children who were ex-pected to die within 24 hours from presentation, and thatthese are the children who may be most likely to benefitfrom aggressive fluid resuscitation. They hypothesise thataggressive fluid administration may be non-beneficial onlyonce the ‘acute phase’ is overcome.We agree this is a limitation of our study. In our cohortof children screened for sepsis in the paediatric ICU, onechild was excluded because survival for >24 hours was notexpected and one child was excluded because palliativecare had been decided upon. Although we do not haveexact numbers, the number of children with sepsispresenting to our Children’s Hospital emergency depart-ment or referral area and dying before arriving in thepaediatric ICU is extremely small. In addition, althoughonly one patient in our cohort died in the paediatric ICU,six children required ECLS (extracorporeal life-support),an indicator of the severity of sepsis [4]. Thus, we believethe number of patients excluded from our study who diedwithin 24 hours after sepsis presentation is very small. Inaddition, we note that recent editorials continue to pointout the variability in fluid bolus therapy practice, the lim-ited data on effectiveness of fluid bolus therapy and thatthe ideal resuscitation target is a knowledge gap in sepsis[5–7]. Although we do not recommend a change in prac-tice at this time, we believe that further study of fluidbolus therapy and alternative strategies for resuscitation insepsis are warranted.AbbreviationsPRISM: Pediatric Risk of Mortality.icle is distributed under the terms of the Creative Commons Attribution 4.0.org/licenses/by/4.0/), which permits unrestricted use, distribution, andive appropriate credit to the original author(s) and the source, provide a link tochanges were made. The Creative Commons Public Domain Dedication waiverro/1.0/) applies to the data made available in this article, unless otherwise stated.Ray and Peters Critical Care  (2015) 19:394 Page 2 of 2Competing interestsThe authors declare that they have no competing interests.References1. van Paridon BM, Sheppard C, Guerra GG, Joffe AR, for the Alberta SepsisNetwork. Timing of antibiotics, volume, and vasoactive infusions in childrenwith sepsis admitted to intensive care. Crit Care. 2015;19:293.2. Cvetkovic M, Lutman D, Ramnarayan P, Pathan N, Inwald DP, Peters MJ.Timing of death in children referred for intensive care with severe sepsis:implications for interventional studies. Pediatr Crit Care Med. 2015;16:410–7.3. Tibby SM. Does PELOD measure organ dysfunction … is organ function avalid surrogate for death? Intensive Care Med. 2010;36:4–7.4. Mickiewicz B, Thompson G, Blackwood J, Jenne C, Winston B, Vogel H, et al.Development of metabolic and inflammatory mediator biomarkerphenotyping for early diagnosis and triage of pediatric sepsis. Crit Care.2015;19:320.5. Gattas D, Aneman A. Consistent inconsistency of fluid challenges in the ICU:we should reflect on extreme variation in our practice. Intensive Care Med.2015;4:1670–2.6. Perner A, Vieillard-Baron A, Bakker J. Fluid resuscitation in ICU patients: quovadis? Intensive Care Med. 2015;41:1667–9.7. Seymour CW, Rosengart MR. Septic shock: advances in diagnosis andtreatment. JAMA. 2015;314:707–17.

Timing of antibiotics, volume and vasoactive infusions in children with sepsis: it is all in the timing

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Timing of antibiotics, volume and vasoactive infusions in children with sepsis: it is all in the timing

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