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. https://adc.bmj.com/content/104/5/426
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
“YOU HAVE TO WAIT 1 SECOND BEFORE SAYING “ONE”!!!” #DFTB_JC @apsmunro
“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
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
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 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!
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!