Lucas-Herald, Angela

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1Lucas-Herald AK, Robertson KJ Arch Dis Child Educ Pract Ed Month 2017 Vol 0 No 0STRUCTURED ABSTRACTS OF SENTINEL ARTICLES: PICKETCritically ill children did not benefit from tight glycaemic controlStudy deSignDesign: Randomised controlled trial.Allocation: Computer generated block design.Study queStionSetting: Thirty-five paediatric intensive care unit (ICU) centres.Patients: Three hundred and sixty patients (median age 5.5 years, IQR 1.4–12.5 years) in the lower target group; 353 patients (median age 6.7 years, IQR 1.7–12.8 years) in the higher target group.Intervention: Randomisation to low target glycaemic control group (80–110 mg/dL (3.3–6.1 mmol/L)) or higher target glycaemic control group (150–180 mg/dL (8.3–10 mmol/L).Outcomes: Primary outcome: number of ICU-free days to day 28. Prespecified secondary outcomes: 90-day mortality, severity of organ dysfunction, the number of ventilator-free days to day 28, incidence of healthcare-associated infection and incidence of hypoglycaemia.Patient follow-up: Patient was followed up for 90 days. Recruitment stopped at 50% due to low likelihood of benefit and potential of harm.Main reSultSVariable low target (n=349)Higher target (n=349)p ValueMedian (IQR), no of ICU-free days through day 2820 (1–24) 19.4 (7.1–23.9) 0.8690-day hospital mortality (%)52 (14.9) 40 (11.5) 0.6Incidence of healthcare-associated infection(no/no of days with a CVC/UTI/ventilator)12 (3.4) 4 (1.1) 0.04Catheter-associated bloodstream infection5/2577 0/2784 0.03Catheter-associated UTI 5/2287 4/2230 1.0Ventilator-associated pneumonia3/3182 0/3371 0.11Hypoglycaemia (%) 79 (22.8) 33 (9.5) <0.001CVC, central venous catheter; UTI, urinary tract infection.ConCluSionMaintaining tight glycaemic control (80–110 mg/dL, 4.4–6.1 mmol/L) for critically ill children with hyperglycaemia in paediatric ICU did not infer any benefit in terms of number of ICU-free days or mortality; severity of organ dysfunction or number of ventilator-free days. Infection rates were increased.Abstracted from Agus MSD, Wypji D, Hirshberg EL, et al. Tight glycaemic control in critically ill children. New Engl J Med 2017 [Epub ahead of print, 24 Jan 2017].CoMMentary The need to maintain tight glycaemic control in critically unwell patients has been a hot topic in intensive care medicine in recent years. One single-centre randomised controlled trial in adult surgical patients demonstrated a reduction in morbidity and mortality (van den Berghe et al, 2001), but this result was not shown consistently in other trials. It is known that there is a wide variation in practice in paediatric intensive care units; with the advent of continuous glucose monitoring it is now easier than ever before to track blood sugar readings and adjust insulin or fluid therapy as required. This study was therefore important and necessary in the effort to improve care and outcomes for critically ill children.The study demonstrates that there was no benefit in the tight glycaemic control of critically ill children and that morbidity and 90-day mortality were increased in the low-target group. A rise in blood glucose is a normal physi-ological response to critical illness and a forced reduction in this may there-fore do more harm than good. However, the increased risk secondary to the maintenance of tight glycaemic control may represent the administration of insulin therapy with its other metabolic effects as opposed to the absolute blood glucose levels.The finding that there was an increase in healthcare-associated infections should be noted. Of course, this study was not powered to detect this effect and may reflect the sample size rather than a true finding.In conclusion, this study shows that there is no clinical benefit for main-taining blood glucose control between 80 and 110 mg/dL (0.4–6.1 mmol/L) in critically unwell children. This is of relevance to any paediatricians caring for such children. Guideline development to standardise management for affected children would be useful.angela Katrina lucas-Herald,1 Kenneth J robertson21Developmental Endocrinology Research Group, University of Glasgow, Glasgow, UK2Royal Hospital for Children, Glasgow, UKCorrespondence to Dr Angela Katrina Lucas-Herald, Developmental Endo-crinology Research Group, University of Glasgow, 1345 Govan Road, Glasgow G51 4TF, UK;  angela. lucas- herald@ glasgow. ac. ukContributors AKL-H and KJR contributed equally to the preparation of the submitted manuscript.Provenance and peer review Not commissioned; internally peer reviewed.© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.to cite Lucas-Herald AK, Robertson KJ Published Online First: [please include Day Month Year]. doi:10.1136/archdischild-2017-313012Arch Dis Child Educ Pract Ed 2017;0:1.doi:10.1136/archdischild-2017-313012 Education & Practice Online First, published on May 23, 2017 as 10.1136/archdischild-2017-313012Copyright Article author (or their employer) 2017. Produced by BMJ Publishing Group Ltd under licence. group.bmj.com on August 22, 2017 - Published by http://ep.bmj.com/Downloaded from glycaemic controlCritically ill children did not benefit from tightAngela Katrina Lucas-Herald and Kenneth J Robertson published online May 23, 2017Arch Dis Child Educ Pract Ed  http://ep.bmj.com/content/early/2017/05/22/archdischild-2017-313012Updated information and services can be found at: These include:Open Accesshttp://creativecommons.org/licenses/by/4.0/provided the original work is properly cited. See: distribute, remix, adapt and build upon this work, for commercial use,Creative Commons Attribution (CC BY 4.0) license, which permits others to This is an Open Access article distributed in accordance with the terms of theserviceEmail alertingbox at the top right corner of the online article. Receive free email alerts when new articles cite this article. Sign up in theCollectionsTopic Articles on similar topics can be found in the following collections  (16)Open accessNoteshttp://group.bmj.com/group/rights-licensing/permissionsTo request permissions go to:http://journals.bmj.com/cgi/reprintformTo order reprints go to:http://group.bmj.com/subscribe/To subscribe to BMJ go to:group.bmj.com on August 22, 2017 - Published by http://ep.bmj.com/Downloaded from 

Critically ill children did not benefit from tight glycaemic control

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1Lucas-Herald AK, Robertson KJ Arch Dis Child Educ Pract Ed Month 2017 Vol 0 No 0
STRUCTURED ABSTRACTS OF SENTINEL ARTICLES: PICKET
Critically ill children did not 
benefit from tight glycaemic 
control
Study deSign
Design: Randomised controlled trial.
Allocation: Computer generated block design.
Study queStion
Setting: Thirty-five paediatric intensive care unit (ICU) 
centres.
Patients: Three hundred and sixty patients (median 
age 5.5 years, IQR 1.4–12.5 years) in the lower target 
group; 353 patients (median age 6.7 years, IQR 
1.7–12.8 years) in the higher target group.
Intervention: Randomisation to low target glycaemic 
control group (80–110 mg/dL (3.3–6.1 mmol/L)) or 
higher target glycaemic control group (150–180 mg/
dL (8.3–10 mmol/L).
Outcomes: Primary outcome: number of ICU-free 
days to day 28. Prespecified secondary outcomes: 
90-day mortality, severity of organ dysfunction, the 
number of ventilator-free days to day 28, incidence 
of healthcare-associated infection and incidence of 
hypoglycaemia.
Patient follow-up: Patient was followed up for 90 days. 
Recruitment stopped at 50% due to low likelihood of 
benefit and potential of harm.
Main reSultS
Variable low target 
(n=349)
Higher target 
(n=349)
p Value
Median (IQR), no of 
ICU-free days through 
day 28
20 (1–24) 19.4 (7.1–23.9) 0.86
90-day hospital 
mortality (%)
52 (14.9) 40 (11.5) 0.6
Incidence of healthcare-
associated infection
(no/no of days with a 
CVC/UTI/ventilator)
12 (3.4) 4 (1.1) 0.04
Catheter-associated 
bloodstream infection
5/2577 0/2784 0.03
Catheter-associated UTI 5/2287 4/2230 1.0
Ventilator-associated 
pneumonia
3/3182 0/3371 0.11
Hypoglycaemia (%) 79 (22.8) 33 (9.5) <0.001
CVC, central venous catheter; UTI, urinary tract infection.
ConCluSion
Maintaining tight glycaemic control (80–110 mg/
dL, 4.4–6.1 mmol/L) for critically ill children with 
hyperglycaemia in paediatric ICU did not infer 
any benefit in terms of number of ICU-free days or 
mortality; severity of organ dysfunction or number of 
ventilator-free days. Infection rates were increased.
Abstracted from Agus MSD, Wypji D, Hirshberg EL, et 
al. Tight glycaemic control in critically ill children. New 
Engl J Med 2017 [Epub ahead of print, 24 Jan 2017].
Co
M
M
en
ta
ry The need to maintain tight glycaemic control in critically unwell patients has been a hot topic in intensive care medicine in recent years. One single-centre randomised controlled trial in adult surgical patients 
demonstrated a reduction in morbidity and mortality (van den Berghe et al, 
2001), but this result was not shown consistently in other trials. It is known 
that there is a wide variation in practice in paediatric intensive care units; 
with the advent of continuous glucose monitoring it is now easier than ever 
before to track blood sugar readings and adjust insulin or fluid therapy as 
required. This study was therefore important and necessary in the effort to 
improve care and outcomes for critically ill children.
The study demonstrates that there was no benefit in the tight glycaemic 
control of critically ill children and that morbidity and 90-day mortality were 
increased in the low-target group. A rise in blood glucose is a normal physi-
ological response to critical illness and a forced reduction in this may there-
fore do more harm than good. However, the increased risk secondary to the 
maintenance of tight glycaemic control may represent the administration of 
insulin therapy with its other metabolic effects as opposed to the absolute 
blood glucose levels.
The finding that there was an increase in healthcare-associated infections 
should be noted. Of course, this study was not powered to detect this effect 
and may reflect the sample size rather than a true finding.
In conclusion, this study shows that there is no clinical benefit for main-
taining blood glucose control between 80 and 110 mg/dL (0.4–6.1 mmol/L) 
in critically unwell children. This is of relevance to any paediatricians caring 
for such children. Guideline development to standardise management for 
affected children would be useful.
angela Katrina lucas-Herald,1 Kenneth J robertson2
1Developmental Endocrinology Research Group, University of Glasgow, 
Glasgow, UK
2Royal Hospital for Children, Glasgow, UK
Correspondence to Dr Angela Katrina Lucas-Herald, Developmental Endo-
crinology Research Group, University of Glasgow, 1345 Govan Road, Glasgow 
G51 4TF, UK;  angela. lucas- herald@ glasgow. ac. uk
Contributors AKL-H and KJR contributed equally to the preparation of the 
submitted manuscript.
Provenance and peer review Not commissioned; internally peer reviewed.
© Article author(s) (or their employer(s) unless otherwise stated in the text of 
the article) 2017. All rights reserved. No commercial use is permitted unless 
otherwise expressly granted.
to cite Lucas-Herald AK, Robertson KJ Published Online First: [please include 
Day Month Year]. doi:10.1136/archdischild-2017-313012
Arch Dis Child Educ Pract Ed 2017;0:1.
doi:10.1136/archdischild-2017-313012
 Education & Practice Online First, published on May 23, 2017 as 10.1136/archdischild-2017-313012
Copyright Article author (or their employer) 2017. Produced by BMJ Publishing Group Ltd under licence. 
group.bmj.com on August 22, 2017 - Published by http://ep.bmj.com/Downloaded from 
glycaemic control
Critically ill children did not benefit from tight
Angela Katrina Lucas-Herald and Kenneth J Robertson
 published online May 23, 2017Arch Dis Child Educ Pract Ed 
 http://ep.bmj.com/content/early/2017/05/22/archdischild-2017-313012
Updated information and services can be found at: 
These include:
Open Access
http://creativecommons.org/licenses/by/4.0/
provided the original work is properly cited. See: 
distribute, remix, adapt and build upon this work, for commercial use,
Creative Commons Attribution (CC BY 4.0) license, which permits others to 
This is an Open Access article distributed in accordance with the terms of the
service
Email alerting
box at the top right corner of the online article. 
Receive free email alerts when new articles cite this article. Sign up in the
Collections
Topic Articles on similar topics can be found in the following collections 
 (16)Open access
Notes
http://group.bmj.com/group/rights-licensing/permissions
To request permissions go to:
http://journals.bmj.com/cgi/reprintform
To order reprints go to:
http://group.bmj.com/subscribe/
To subscribe to BMJ go to:
group.bmj.com on August 22, 2017 - Published by http://ep.bmj.com/Downloaded from 


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Critically ill children did not benefit from tight glycaemic control

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