Firstly, I would again like to thank everyone who took part in the discussion of the FEAST study. I would like to especially thank Annabelle South for her invaluable contribution.
Before the discussion I emailed Professor Kathryn Maitland and was delighted to receive an email back with some thoughts ahead of the discussion (posted in the introduction to the paper). Following the discussion I received another email from Professor Maitland with her thoughts for each of the discussion points and with her permission I have posted these below. I would like to thank her for taking the time to do this and to engage with the journal club and to Annabelle for her help with sending me a version my old laptop could cope with:
1. Was the inclusion group in this trial too wide, especially in regards to ages (from a 60 day old baby to a 12 year old child)?
Rational: The trial was designed to be pragmatic: the WHO classify children into age group: young infant (0‐60 days) and children thereafter. Guideline for shock management for children do not treat children < 1 year differently that older age groups.
A: Overall, age did not affect response to bolus: we specifically examined the age group < 1 year – outcome was the same in this group.
2. An editorial in the Archives of Disease of Childhood criticised the study and highlighted what they felt was the most harmful limitation, the reliance on one non-specific clinical feature for the diagnosis of hypovolaemic shock (see this BMJ rapid response for further details). Does this make the study invalid for evaluating fluid boluses in children with hypovolaemic shock?
How is shock diagnosed in the UK? With the same signs as were used in the FEAST trial – (delayed capillary response; temperature gradient and a weak pulse). We acknowledge problems with inter-observer variation and specificity of the bedside determination of shock, however these are the standard criteria that populate all international shock definitions. Whether one or more of these features were present the results were the same – boluses were harmful. The World Health Organization shock criteria (requiring all four parameters including a capillary refilling time of 4 or more seconds) identified very few children 65 (2%). Even so outcome was substantially worse in the bolus groups (see Appendix): 48% in bolus versus 20% in no bolus. This equates to an absolute risk of death of 28 % (95% CI 3.4% – 52.5%). In other words for every 100 children receiving fluid boluses this would result an extra 28 deaths compared to children not receiving boluses. Moreover, outcome was worse with fluid boluses even in children with observer-independent measures of shock (moderate hypotension) or poor tissue oxygenation (severe lactic acidosis > 5mmol/l) (see tables in FEAST). The remarkable consistency of these findings all point to the same conclusion. There have been a number of editorials: it’s a shame that these two were highlighted1-3.
3. How applicable are these results to the use of fluid boluses in the developed world?
The 2008 Surviving Sepsis Campaign Guidelines, informed by a modified Delphi process, graded the ACCM paediatric recommendation for fluid resuscitation as 2C, indicating weak recommendation based on low quality of evidence, largely from observational studies and expert opinion. There are no paediatric trials of fluid resuscitation outside of those conducted in malaria, dengue and a very small sepsis trial in India4. These recommendations together with the FEAST trial now raise questions about the commonly used treatment. Children in theUK have access to ICU – adverse consequences maybe masked by this.
The first response should be an audit of practice: who receives fluids and outcomes (including admission to ICU). Mortality is very low compared to adult sepsis: so would need a huge trial for this endpoint
4. Does there need to be a similar study in developed countries? If so, would such a study ever get ethical approval?
See above: Even if given ethical approval there may be insufficient uncertainty about risks of fluids. These data need to be generated (if they do exist) to create equipoise around current practice before clinicians would be happy to enrol a child into a controlled trial.
1. Duke T. What the African fluid-bolus trial means. Lancet 2011, Jun 15.
2. Myburgh JA. Fluid Resusciation in Acute Illness – Time to Reappraise the Basics. N Engl J Med. 2011, May 26
3. Hilton AK, Bellomo R. Totem and Taboo: Fluids in sepsis. Crit Care, 2011;15(3): 164
4. Akech S, Ledermann H, Maitland K. Choice of fluids for resuscitation in children with severe infection and shock: systematic review. BMJ. 2010;341:nc4 416.
I have to apologise in the delay in posting the summary for the FEAST paper. It turns out that starting a new job, revising for the first part of MRCP and having a life outside of work with its own trials and tribulations means that I either have to become superwoman or realise I can’t do everything at once. The post is nearly finished and will be posted as soon as I get a spare minute.