PostScript
Arch Dis Child: first published as 10.1136/archdischild-2020-319117 on 3 August 2020. Downloaded from http://adc.bmj.com/ on August 4, 2020 at The Sheppard Library - Middlesex
Letter
Management of fluids in
paediatric diabetic
ketoacidosis: concerns over
new guidance
In January 2020, the British Society for
Paediatric Endocrinology and Diabetes
(BSPED) published new guidance for
the management of children <18 years
with diabetic ketoacidosis (DKA).1 Fluid
management is significantly different
from their previous guideline2 and current
National Institute for Health and Care
Excellence (NICE) guidance.3 The 2020
guideline moved away from the concept
of cautious fluid replacement towards
a liberal approach for resuscitation and
maintenance fluids. It recommends that all
patients receive an initial 10 mL/kg bolus
and those presenting with shock receive
a 20 mL/kg bolus. Concerningly, delayed
capillary refill time is used to define shock;
however, in DKA this sign is confounded
by hypocapnoeic vasoconstriction, which
is common.4
A 20 mL/kg fluid bolus is also recom-
mended for ‘reduced conscious level/
coma’, without considering that this may
indicate cerebral oedema which can be
aggravated by additional fluid adminis-
tration. Junior staff are enabled to give
Figure 1  Comparison of potential fluid
volumes administered over the first 24 hours to
a child presenting with DKA. Assumptions are
pH <7.1, 10% dehydration, and maximum fluid
bolus administered as 10 mL/kg in the NICE
guideline compared with 40 mL/kg in the new
BSPED guideline. Total fluid administered (L) in
24 hours is shown on the left y-­axis (BSPED and
NICE guidelines), and fold increase in BSPED
compared with NICE two fluid regimens shown
on rightward y-­axis (dashed line). BSPED,
British Society for Paediatric Endocrinology
and Diabetes; DKA, diabetic ketoacidosis;
NICE, National Institute for Health and Care
Excellence.
Figure 2  Total annual referrals (line)
and subsequent percentage requiring PICU
admission (dots) for diabetic ketoacidosis to
the South Thames Retrieval Service (STRS).
PICU, paediatric intensive care unit.
boluses of up to 40 mL/kg, contrasting
starkly with NICE guidance, which
recommends a single 10 mL/kg bolus only
in those who are shocked. Full mainte-
nance fluid is recommended in addition
to replacing estimated losses, further
increasing the volume of fluid administra-
tion. Figure 1 demonstrates the increase
in 24-­hour fluid administration, which is
precisely the time when a child is at greatest
risk of cerebral oedema. The percentage
increase is greatest in younger patients
who are again at the greatest risk. Cere-
bral oedema remains the leading cause of
death in paediatric DKA, with a mortality
of 25%. The pathophysiology of cerebral
oedema is poorly understood, with debate
as to whether it is due to hypoperfusion
or fluid shifts. However, the likely exac-
erbating effect of rapid fluid administra-
tion was accepted previously by BSPED
and NICE.5 Changes made between their
2009 and 2015 DKA guidelines prevented
routine fluid boluses and reduced mainte-
nance fluid rates significantly.
The BSPED guideline authors admit
this ‘permissive’ regimen is ‘a signif-
icant change’, but has been recom-
mended without presenting evidence
for its benefit. The International Society
Table 1  Demographic, biochemical and therapeutic variables at presentation to the DGH,
2016–2019
Age (years)
Female (%)
First presentation of diabetes (%)
pH
pCO2 (kPa)
Base excess (mEq/L)
Glucose (mmol/L)
Received osmotherapy (%)
Mechanical ventilation (%)
Continuous variables are expressed as mean (SD).
DGH, district general hospital; pCO2, partial pressure of carbon dioxide; PICU, paediatric intensive care unit.
Arch Dis Child Month 2020 Vol 0 No 0
for Pediatric and Adolescent Diabetes
consensus guideline referred to by BSPED
also concludes that current evidence is
lacking.6 The Paediatric Emergency Care
Applied Research Network (PERCAN)
Fluid trial, comparing fast and slow rates
of DKA rehydration in a population where
the average pH was 7.2, showed no differ-
ence in neurological outcome between the
regimens; however, concerns remain over
the effect of administering more fluid in
the sickest patients.7 Caution about over-
liberal fluid replacement has recently
been raised in other settings; in fact, the
current Surviving Sepsis fluid recommen-
dations are now more conservative than
the BSPED guideline.8
The South Thames Retrieval Service
receives critical care referrals from 20
district general hospitals (DGHs) serving
a population of 2.4 million children. Our
2008 ‘restrictive fluid’ DKA guideline9 was
introduced following three deaths from
cerebral oedema in our region (figure 2).
Since this time the percentage of DGH
DKA referrals requiring admission to
University. Protected by copyright.
intensive care has remained constant, at
approximately 20% (figure 2), and there
have been no deaths. Of note, the DGHs
are now comfortable managing severe
DKA (table 1), with the most common
indications for paediatric intensive care
unit (PICU) admission being lack of neuro-
logical response to osmotherapy, need
for mechanical ventilation and suspected
coexistent pathology (eg, sepsis). We have
concern that the major differences in the
new BSPED guideline will produce confu-
sion and treatment inconsistencies for
our referring clinicians, without apparent
benefit.
Jon Lillie ‍ ‍,1 Elizabeth Boot,2
Shane M Tibby ‍ ‍,1 Marilyn McDougall,1
Andrew Nyman,1 Benedict Griffiths,1
Miriam Fine-­Goulden,1 Maja Pavcnik,1
Ariane Annicq,1 Shelley Riphagen1
Admitted to PICU Remained at DGH
(n=28) (n=96) P value
9.8 (5.9) 10.7 (4.8) 0.36
82.8 52.6 0.005
69.0 61.9 0.52
6.90 (0.11) 6.96 (0.13) 0.03
2.5 (0.8) 2.9 (1.0) 0.04
−27.7 (3.8) −25.5 (4.8) 0.03
34.1 (11.5) 32.6 (8.7) 0.44
79 33 <0.001
25 0 <0.0001
   1
 PostScript
1
South Thames Retreival Service and Paediatric
Intensive Care, Evelina London Children’s Hospital,
London, UK
2
Paediatrics, Epsom and St Helier Hospital NHS Trust,
Carshalton, UK
Correspondence to Dr Jon Lillie, Paediatric Intensive
Care, Evelina London Children’s Hospital, London SE1
7EH, UK; ​Jonathan.​Lillie@​gstt.​nhs.u​ k
Twitter Jon Lillie @DrJonLillie, Marilyn McDougall
@docmcdevelina and Miriam Fine-­Goulden @
finegoulden
Contributors  All authors contributed to the
acquisition of DKA data for the South Thames Retrieval
Service. All authors were involved in drafting or
revising the letter and have given approval for this final
submission.
Funding  The authors have not declared a specific
grant for this research from any funding agency in the
public, commercial or not-­for-­profit sectors.
Competing interests  None declared.
Patient consent for publication  Not required.
Provenance and peer review  Not commissioned;
externally peer reviewed.
© Author(s) (or their employer(s)) 2020. No
commercial re-­use. See rights and permissions.
Published by BMJ.
2 Arch Dis Child Month 2020 Vol 0 No 0
To cite Lillie J, Boot E, Tibby SM, et al. Arch Dis Child
Epub ahead of print: [please include Day Month Year].
doi:10.1136/archdischild-2020-319117
Accepted 26 May 2020
►► http://​​dx.​​doi.​​org/​​10.​​1136/​archdischild-​2020-​
319746
Arch Dis Child 2020;0:1–2.
doi:10.1136/archdischild-2020-319117
ORCID iDs
Jon Lillie http://​orcid.​org/​0000-​0003-​1776-​5184
Shane M Tibby http://​orcid.​org/​0000-​0001-​7774-​8656
References
1 British Society for Paediatric Endocrinology and
Diabetes. Interim guideline for the management of
children and young people under the age of 18 years
with diabetic ketoacidosis, 2020. Available: https://
www.​bsped.​org.​uk/​media/​1712/​new-​dka-​guideline-​v6-​
final.​pdf
2 British Society for Paediatric Endocrinology and
Diabetes. Recommended guideline for the management
Arch Dis Child: first published as 10.1136/archdischild-2020-319117 on 3 August 2020. Downloaded from http://adc.bmj.com/ on August 4, 2020 at The Sheppard Library - Middlesex
of children and young people under the age of 18 years
with diabetic ketoacidosis, 2015. Available: https://
www.​bsped.​org.​uk/​media/​1629/​bsped-​dka-​aug15_.​
pdf
3 National Institute for Health and Care Excellence.
Diabetes (type 1 and type 2) in children and young
people:diagnosis and management, 2015. Available:
https://www.​nice.​org.​uk/​guidance/​ng18/​chapter/​1-​
Recommendations#​diabetic-​ketoacidosis-2
4 Fleishman M, Scott J, Haddy FJ. Effect of pH change
upon systemic large and small vessel resistance. Circ
Res 1957;5:602–6.
5 Durward A, Ferguson LP, Taylor D, et al. The temporal
relationship between glucose-­corrected serum sodium
and neurological status in severe diabetic ketoacidosis.
Arch Dis Child 2011;96:50–7.
6 ISPAD Clinical Practice Consensus Guidelines
2018. Diabetic ketoacidosis and the hyperglycemic
hyperosmolar state. Pediatric Diabetes
2018;19:155–77.
7 Kuppermann N, Ghetti S, Schunk JE, et al. Clinical trial
of fluid infusion rates for pediatric diabetic ketoacidosis.
N Engl J Med 2018;378:2275–87.
8 Weiss SL, Peters MJ, Alhazzani W, et al. Surviving sepsis
campaign international guidelines for the management
of septic shock and sepsis-­associated organ dysfunction
in children. Pediatr Crit Care Med 2020;21:e52–106.
9 . Available: https://www.e​ velinalondon.​nhs.​uk/​
resources/​our-​services/h​ ospital/​south-​thames-​retrieval-​
service/d​ iabetic-​ketoacidosis-​jan-​2018.​pdf
University. Protected by copyright.