ADC/DFTB Journal Club – May – Restrictive fluid boluses in shock

Cite this article as:
Charlotte Durand. ADC/DFTB Journal Club – May – Restrictive fluid boluses in shock, Don't Forget the Bubbles, 2019. Available at:

Rapid fluid rehydration is a key component in the management of paediatric patients presenting with septic shock. The 2009 American College of Critical Care Medicine – Paediatric Advanced Life Support (ACCM-PALS) guideline recommends boluses of 20mL/Kg up to 200mL/kg in the first hour. Results from the 2011 Fluid Expansion As Supportive Therapy (FEAST) trial showed an increased mortality in patients receiving bolus therapy in low-income countries, though it continues to be debated whether these findings are applicable to higher-income countries.

The Fluids in Shock (FiSh) pilot trial compared restricted bolus (10mL/kg) with the current recommendation (20mL/kg) to determine if a larger scale trial would be feasible in the UK. We discussed the paper in the May #DFTB_JC with expert input from author Dr David Inwald (@dlwanI)

Inwald DP, et al. Restricted fluid bolus volume in early septic shock: results of the Fluids in Shock pilot trial. Archives of Disease in Childhood 2019;104:426-431.

What was this study about?

The FiSh pilot was an open, multi-centre randomised controlled trial (RCT) involving 13 UK hospitals. 75 children were enrolled based on the presence of shock entry criteria (CRT ≥3s or systolic blood pressure <5th percentile for age) after an initial fluid bolus of 20mL/kg. Patients were randomised if they showed signs of shock after an initial 20mL/kg bolus to select for sicker patients. If they improved after the initial bolus they were excluded from the study group.

Boluses were delivered every 15mins (max 500mL of 10mL/kg group, or 1000mL for the 20mL/kg group) until patients’ signs of shock resolved.
79% of boluses were delivered per protocol in the 10 mL/kg arm and 55% in the 20 mL/kg arm. The volume of study bolus fluid after 4 hours was 44% lower in the 10 mL/kg group. There were no significant differences between the groups with regards to length of hospital stay, paediatric intensive care unit (PICU) admissions and PICU-free days at 30 days.

The twitter jury is still out on the reliability of capillary refill time, particularly in a resuscitation scenario. Dr Inwald gave an authors perspective on how they decided on shock criteria…

“It was difficult…in the end we went for hypotension OR prolonged CRT >=3s, in context of suspected infection – after 20 mL/kg. We didn’t use HR as too many confounders in ED. We were surprised that CRT was the main criterion in so many patients.” @Dlawni

Many had issues with inter-observer variability and confounding patient factors. Most participants emphasised not relying on CRT in isolation, but interpreting results in the context of other clinical features.

We’re in an LMIC – so, for a well nourished child, a LOT of emphasis. But – for severe malnutrition, they all have delayed CRT so no emphasis. I think even in HICs, in a case of poverty or neglect, I take it super seriously unless the child comes in looking scrawny. #DFTB_JC @mardi_steere

It’s a subjective measure, and needs to be kept in context of other signs of peripheral vasoconstriction. A CRT of 3s in a warm, perfusing child is likely either to be a) a sign I can’t count properly or b) this is a hot, annoyed child” #DFTB_JC @edd_broad


I’ve found seconds to be an extraordinarily flexible measure of time, especially in the high stakes environment of a child potentially in circulatory collapse. See also 5 second ice bath dunks in SVT – unless someone is timing, it’s usually 2 seconds tops!” @edd_broad

It’s too subjective in my opinion. Plenty of evidence there is a lot of interobserver variability. I don’t put a lot of emphasis on CRT when resuscitating.” #DFTB_JC @davidking83

This trial contained an ‘embedded perspectives’ study which allowed researchers to collect qualitative information about the randomisation process from parents and carers. Trained site staff explained the process of RWPC and the nature of the intervention, which appeared to elicit support from parents. No parents refused consent during the study. The twittersphere vibe was one of support for this methodology, with the caveat that studies using RWPC must have sound ethical oversight to ensure interventions are of equal risk/potential benefit. The wonderful @kerry_woolfall spoke about this in more detail during her talk at #DFTB19

I think it’s the only way to get good quality research in time-critical topics. The lack of patients withdrawing is a good sign that this it is acceptable to families. It needs robust ethical oversight, though, to ensure true equipoise.” #DFTB_JC @DrSarahMcNab

It’s the only way we will get answers about dealing with critically ill children in the resuscitative phase of treatment. Not necessarily the future, I think that randomisation prior to inclusion carries more scientific weight, but a useful tool in the research arsenal” #DFTB_JC @edd_broad

Crucial for resus studies, but strong ethics board to make sure both interventions truly seem equal risk / potential benefit #DFTB_JC @mardi_steere

Dr Inwald explained the process of preparing for a trial involving RWPC…

RWPC is becoming more and more common in emergency care trials. We did a lot of work in our feasibility study to make sure our process had proper steer from parents and families and was also acceptable to staff. I was blessed with great co-investigators, particularly @kerry_woolfall who led the qualitative work. “#DFTB_JC @dlawnI

Adherence to the fluid bolus volume and timing was better in the 10mL/kg group, when compared to the 20mL/kg group. Authors proposed two principal reasons for this. Firstly, the technical difficulty in delivering the larger volume of fluid in 15mins; secondly, suggestions from the embedded perspectives study that clinicians favoured the 10mL/kg boluses.

Responses from journal club participants varied widely, with a range of responses and reasoning behind their preferred bolus volume. Interestingly, these responses reflected the lack of clinician equipoise identified in the study. Twitter is not the place to go for a consensus on a topic, but the variety of responses does highlight the disconnect between current guidelines and clinical practice across the world.

I use 20mL/kg in most kids needing a bolus, but I’ve noticed many people use 10mL/kg.” #DFTB_JC @DrSarahMcNab

I personally would never give 20ml/kg, I don’t see the need. Draw up 2x 10ml/kg, give one and reassess. Esp as most pt we bolus are babies and there’s always a cardiogenic shock hiding in there”. #DFTB_JC @apsmunro

It’s not my practice but it seems to have crept in. Have seen 5 mls/kg in DKA for example.” #DFTB_JC @davidking83

I give 20ml/kg if think they need a bolus with the exception of cardiac, DKA and trauma” @begley_roisin

Kidney docs say 10 Heart docs say 10 10 very easily repeatable Sketchy science for 20>10 I like 20/kg- always have – but #DFTB_JC has led to introspection for me” @pea88

I wouldn’t criticise anyone for using 20 mL/kg as a first bolus in an ED setting though. The evidence is weak both ways. FEAST was conducted in a setting without PICU so I think has limited applicability in a high income countries.” #DFTB_JC @Dlawni

Again a biased tweet from Kenya – but FEAST was impactful for us. So well nourished kids now we tend to 10-20/kg; malnourished no bolus – and early peripheral pressors (PIV or IO). Honestly, FEAST has helped us not be scared of pressors in the ED, which is good.” #DFTB_JC @mardi_steere

Though the workings of the trial were feasible, the lack of severe illness in the study population (due to reduced burden of vaccine-preventable disease) means a large scale trial could not be completed. What part of the study to we change? Some suggested altering the inclusion criteria to include all children needing a bolus

To change practice may need an earlier intervention study including the less sick patients (more reflective of true practice?). Randomise at first bolus to 10 vs 20ml/kg. Accept we can’t demonstrate diff in mortality, but that in itself may justify changing guidelines to 10ml/kg @apsmunro

Problem is that then there will too many well kids in the study who just get 1 bolus and go to the ward. All outcomes will be good in this population whatever you do, so it’s not useful to investigate. This is kind of what happened to an extent in FiSh… #DFTB_JC @dlawnI

We discussed how to look at sicker kids by using PICU as the study site rather than purely ED or non-PICU sites.

In rural/remote Australia we pick up a decent number of septic kids with @MedSTAR_SA – maybe we need to do a better job of studying multicentre aeromed retrieval platforms. @docjohncraven @AmyKKeir #DFTB_JC @mardi_steere

So probably a multicentre study looking at early resus in multidisciplinary children’s hospitals with integral PICU and ED. If you do a study in PICU it will be too late – all the resus fluid will have already been given and there will be no separation between the arms…#DFTB_JC @dlawnI

Multinational studies. Stratify according to access? FEAST is criticised as “not our population”, but really maybe its about access & timing, not genetics. #PedsICU based studies are risky as pre-diagnosed, pre-treated rather than de novo arrivals IMO #DFTB_JC @mardi_steere

Some suggested altered end points given how difficult it is to prove mortality difference – after all, when working with these children we are considering so much more in the risk/benefit analysis than just mortality.

I don’t think it will be feasible to show a difference in mortality in a high resource setting. There seemed to be a trend towards a difference in length of PICU stay and mechanical ventilation, though. #DFTB_JC @DrSarahMcNab

Difficult one – I think community acquired sepsis is becoming a rare disease in the post vaccine age so if a study was to be done in a high income setting it would need to include “all comers” with sepsis – including HCAI. #DFTB_JC @dlawnI

Inevitably, with any discussion on fluids and sepsis we must talk about pressors, too. There is always more research to be done!

We all need to talk more about peripheral pressors and peds sepsis bundle #ED implementation 🙂 #DFTB_JC @mardi_steere

This is more likely to be the future, as underlying issue isnt true hypovolaemia, its relative to vasodilation (in most sepsis groups). Pressers correct the deficit more truely than just pumping saline in (but we need some evidence to prove it!) #DFTB_JC @apsmunro

A big thank you to everyone who participated in the chat. If you missed out, please feel free to add your thoughts via the comments below. Keep an eye out on Twitter for the date + time of the next #DFTB_JC. We will see you there!

Awakening the FEAST: Why did fluid boluses kill?

Cite this article as:
Alasdair Munro. Awakening the FEAST: Why did fluid boluses kill?, Don't Forget the Bubbles, 2019. Available at:

In paediatric medicine, it sometimes feels like we talk about sepsis more than anything else. We’ve all become familiar with the “sepsis bundles”, including a generous portion of intravenous fluid given as a rapid bolus in resuscitation.

This is why the FEAST trial blew everyone’s minds when it was published in 2011. This large RCT in East Africa of over 3000 children was stopped early when it demonstrated an increase in mortality for children given a fluid bolus of either 0.9% saline or 5% albumin instead of just maintenance fluids. It sparked huge controversy and various groups trying to explain away this effect with limited success. Guidelines however were not changed on the basis of this trial, because of concerns that it wasn’t applicable to a high resource setting, because the trial included children without measurement of blood pressure, and partially because no-one could come up with a good explanation for why this would be the case (see this breakdown in The Lancet). Why would giving a fluid bolus increase mortality in sepsis?

This is the question a new paper in The Lancet Respiratory Medicine tries to answer, using data from the FEAST trial (and others), and including members of the original FEAST team.

Levin M, Cunnington A, Wilson C, Nadel S, Lang H, Ninis N et al. Effects of saline or albumin fluid bolus in resuscitation: evidence from re-analysis of the FEAST trial. Lancet Respir Med. Epub June 2019

This study is a little complicated, but we can break it down to make it a bit easier to digest. Let’s start with the most important thing:

Research Question

We want to know why a fluid bolus increased mortality in FEAST.

To get to that, there are 2 questions asked in this study:

  1. Are changes in cardiovascular, neurological or respiratory function, or blood oxygen carrying capacity or biochemistry associated with adverse outcomes in children with sepsis?
  2. In the FEAST trial, were fluid boluses associated with changes in these parameters?

In order to address these 2 questions, the populations analysed were a mix from several studies of childhood sepsis, including:

3170 patients from the FEAST trial (children with sepsis from East Africa)

502 patients from the UK with meningococcal sepsis

448 from Malawi with cerebral malaria

61 children from South Africa with presumed sepsis/gastroenteritis (unpublished)

18,863 children attending a UK emergency department (unpublished)


The authors developed novel physiological scores for cardiovascular, neurological and respiratory function which could be assessed in a low/middle income setting. They didn’t use existing scores, as these are not single organ specific and require monitoring or tests which are not available in these settings, so could not be applied to the FEAST population

The scores were:

The cohorts other than FEAST were essentially just used to test their scoring system. They performed logistic regression to see if an increasing score (i.e. worsening on function) correlated with an “adverse outcome”. Basically testing if their score had any clinical relevance.

In the FEAST population, physiological scores and Hb, lactate, base excess, pH and electrolytes were measured at baseline (prior to any fluids) and then at several time points after fluid administration (either bolus or maintenance). Distributions of these scores were compared in the fluid bolus vs no bolus groups in FEAST to see if this could account for the increased mortality.

Other analyses

To cut a long study short – there are a huge number of different comparative analyses performed in this study. Feel free to spend days wading through the data (I know I will), but for now we’ll stick to the headlines which are the answers to our 2 big questions.

1.    Are changes in cardio, neuro or resp function, or blood oxygen carrying capacity or biochem associated with adverse outcomes?

The answer is yes.

In the FEAST trial, for every 10 units increase (worsening) in score, the odds ratio for death was; respiratory 1.09, neurological 1.26 and cardiovascular 1.09. So they’ve developed a new score, and looks like it tells is what we want.

In the other cohorts analysed, worsening of almost every physiological parameter was also associated with adverse outcomes (see pg 22 supp appendix)

2.    In the FEAST trial, were fluid boluses associated with changes in these parameters?

Yes they were.

Giving a fluid bolus increased (worsened) respiratory score by 3.45 at 1hr and neurological score by 2.64 at 1hr. These differences disappeared at 12h.

Fluid bolus decreased (improved) cardiovascular score by 2.17 at 1h. This difference disappeared at 12h.

Fluid bolus decreased Hb by 0.33g/dL at 8hrs

Fluid bolus did not change lactate

Fluid bolus decreased bicarbonate by 0.96mmol/L and decreased base excess by 1.41mEq/L

Additional points of interest

It made no difference if they received albumin or saline boluses, which is expected as there was no mortality difference either.

Higher volume fluid boluses (≥30mL/kg) were associated with worse respiratory and neurological scores at 4h then lower volume boluses, but high or low volume bolus made no difference in cardiovascular scores.

Significantly, in a post hoc principle component analysis (stay with me – this is not complicated I promise) – differences in physiological scores at 1h explain all the differences in mortality observed between bolus and no-bolus groups of the trial. The major determinants were neurological score, base excess and respiratory score. This is important as although differences between the groups were only apparent at 1h, this was enough to completely account for the differences in mortality.

There is some exciting cluster analysis (1. Mild derangement of scores, 2. Severe anaemia, high lactate and CV score, 3. High resp and neuro scores), but we will ignore this for now as the answer to our main questions didn’t differ among any of the clusters.

So how does a fluid bolus increase mortality in sepsis?

Whilst this question cannot be definitively answered through this study, the authors have presented a bioplausible explanation of their results. They have summarised it in an amazing picture, but if you like bullet points…

A fluid boluses causes:

  1. Haemodilution, causing anaemia, reducing O2 delivery and worsening metabolic acidosis
  2. Hyperchloraemia and bicarbonate dilution, worsening metabolic acidosis
  3. Worsening of respiratory function (partially through increased acidosis), causes decreased CO2 excretion, which both worsens metabolic acidosis and causes cerebral vasodilation, increasing intracranial pressure
  4. Cerebral oedema, causing raised intracranial pressure.

Limitations of the study

Should we all stop giving fluid boluses to children with sepsis now? Some limitations to consider from this study include:

  • This resource limited setting without intensive care may not be directly applicable to high income settings, as mechanical ventilation and neuro intensive care may be able to mitigate some of the adverse effects of bolus
  • Their scores are not independently validated and were not initially derived from the data
  • The influence of large volume fluid boluses may suffer from confounding by indication
  • Acid-base data was only available at 24hrs, by which time most deaths had occurred. Some analysis was performed using imputations.
  • Some of the statistics are almost impenetrable to us mere mortals


In the FEAST trial of children with sepsis in East Africa, a fluid bolus of either 0.9% saline or 5% albumin was associated with a worsening of respiratory and neurological function, anaemia and metabolic acidosis, which in turn was associated with increased mortality. There was a transient increase in cardiovascular function.

The implications of this according to the authors:

Particular care should be taken if considering giving fluid boluses to children with sepsis and respiratory or neurological compromise at presentation

Resuscitation with buffered solutions may be preferable in severely unwell children to avoid worsening of metabolic acidosis (trials in adults currently underway to assess this)

Where next?

As the authors state, it is unlikely ethical approval will be given for further trials of fluid boluses in a low/middle income setting following the increased mortality shown in FEAST. Conversely, trials in higher income countries are difficult because fluid boluses are seen as standard of care for sepsis, and as demonstrated recently in the FISH trial, sepsis has become so rare that trials of fluid management are difficult, even approaching unfeasible. We may find people become generally more cautious when implementing fluid bolus resuscitation as time goes on, perhaps with 10mL/kg boluses becoming preferable to the historically recommended 20mL/kg.

For further reading, check out the great accompanying editorial here, and check out references 3 – 14 in the paper for some of the heated controversy surrounding FEAST.

Through the looking glass: intravenous fluids use in children by Sarah McNab

Sarah  is a General Paediatrician working at The Royal Children’s Hospital, Melbourne, and is the Clinical Lead of the Short Stay Unit. During her PhD, she was the lead investigator on the PIMS (Paediatric Intravenous Maintenance Solution) study: a large, randomised controlled trial comparing isotonic and hypotonic fluids for maintenance hydration in children. The study findings have led to practice change, both in Australia and internationally. 

Don't Forget the Bubbles
Don't Forget the Bubbles
Through the looking glass: intravenous fluids use in children by Sarah McNab


PAC conference: McNab on a fluid solution

Cite this article as:
Lawton, B. PAC conference: McNab on a fluid solution, Don't Forget the Bubbles, 2015. Available at:

The DFTB team have teamed up with APLS to share the videos from their Paediatric Acute Care Conferences. These videos have never been open access before, so if you weren’t able to attend the conferences, then now’s your chance to catch up.

The PAC Conference is run each year by APLS and consists of presentations on a range of topics relevant to paediatric acute and critical care.

ILCOR 2015 – paediatric summary

Cite this article as:
Ashley Towers. ILCOR 2015 – paediatric summary, Don't Forget the Bubbles, 2015. Available at:

The International Liaison Committee on Resuscitation (ILCOR) is a collaboration between resuscitation groups worldwide. Every few years, they do an enormous evidence based review of resuscitation science which informs resuscitation guidelines all over the world.

The 2015 ILCOR consensus document (International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations) was published on 15th October 2015 and covers all aspects of resuscitation for all patient populations.

If you’re anything like me, you’ll agree that wordy documents like this can’t be read quickly (in this case even the Executive Summary is 31 pages!) so to save us all some time, I’ve summarised the recommendations with a focus on paediatrics.