cardiac arrest

1. THE BRASS TACKS: CONCISE REVIEWS OF PUBLISHED EVIDENCE
Intensive Glucose Control for Critically Ill
Patients
John Conway1
, and Benjamin Friedman, MD2
NNT color
recommendation
Black (harm > benefit)
Summary heading Intensive glucose control in critical care
patients offers no benefit and
increases hypoglycemia
Benefits in NNT No significant benefits
Benefits in
percentages
NA
Harms in NNT (NNH) NNH = 12 for severe hypoglycemia
Harms in percentages 8.3% higher risk of severe hypoglycemia
Efficacy endpoints 3- to 6-month mortality, short-term
mortality, sepsis, new dialysis
Harm endpoints Severe hypoglycemia
Who was in
the studies
17,582 adults hospitalized in critical
care settings and enrolled in 27 trials
NARRATIVE
In the past decade, emergency department (ED) to
intensive care unit (ICU) admissions increased by 79%
to 2.2 million admissions annually, reflecting the
increasing role of emergency medicine physicians in pro-
viding care for critically ill patients.1
Optimal glucose
control in critical care patients has been a topic of con-
tention for decades. In 2001 a single-center trial of
mechanically ventilated surgical patients found intensive
glucose control (maintaining glucose at 80–110 mg/dL)
reduced mortality compared to conventional control
(180–200 mg/dL only if glucose exceeded 215).2
Subse-
quent studies provided conflicting data, and in 2009,
the multicenter NICE-SUGAR trial, the largest trial yet,
demonstrated increased mortality with intensive glucose
control.3
Current American Diabetes Association
(ADA) guidelines, reflecting concern about harms asso-
ciated with intensive glucose control, recommend con-
ventional glucose control with a target glucose range of
140 to 180 mg/dL for critically ill patients who experi-
ence persistent hyperglycemia.4
The meta-analysis summarized here provides an
updated review of intensive glucose control effects on
critical care patients.5
A total of 27 randomized trials
enrolling 17,582 patients compared intensive with con-
ventional glucose control in adult medical, surgical, and
mixed critical care settings. Most had similar glucose tar-
gets. The primary outcomes were 3- to 6-month and
short-term mortality (mainly within 28 days). Secondary
outcomes were severe hypoglycemia (defined as serum
glucose < 40 mg/dL: associated with increased mortal-
ity in multiple studies),6–8
sepsis, and need for dialysis.
There was no significant difference found in any
primary outcome, and among secondary outcomes,
only severe hypoglycemia in the intensive group was
more common (relative risk = 4.9, 95% CI = 3.2–
7.5, NNH = 12). Notably, there was no significant dif-
ference found in any outcome between patients in
medical, surgical, or mixed ICUs.
CAVEATS
This meta-analysis is limited in several ways. There
was variation, in glucose targets, type of insulin, dose
and mode of administration, duration of follow-up,
and concomitant therapy. Additionally, not all trials
From the 1
Albert Einstein College of Medicine, Bronx, NY. 2
Department of Emergency Medicine, Albert Einstein College of Medicine, Bronx, NY.
Received April 7, 2019; revision received May 5, 2019; accepted May 7, 2019.
The authors have no relevant financial information or potential conflicts to disclose.
Both authors wrote and edited this manuscript based on a topic suggested by Dr. Zehtabchi. The authors obtained approval from Dr. Zehtabchi,
who also reviewed a draft of the manuscript before submission.
Supervising Editor: Shahriar Zehtabchi, MD.
Address for correspondence and reprints: John Conway; e-mail: john.conway@einsteinmed.org.
ACADEMIC EMERGENCY MEDICINE 2019;00:1–2.
© 2019 by the Society for Academic Emergency Medicine
doi: 10.1111/acem.13777
ISSN 1553-2712
1

2. reported on all outcomes of interest, and patient-level
data are not available, limiting secondary research.
The quality of evidence included in this meta-analy-
sis is high. For most outcomes, despite the clinical
heterogeneity noted above, there was little statistical
heterogeneity. The only outcome with significant
heterogeneity was severe hypoglycemia (I2
= 76.1%,
p < 0.001), suggesting that clinical variation between
studies affected this outcome.
Despite these flaws three additional, slightly less
recent reviews have pooled these data as well with sim-
ilar results despite differing numbers of trials, subjects,
and point estimates. This consistency across author
groups and approaches is reassuring.9–11
This meta-analysis also fails to address some ongoing
research that has identified subgroups of patients who
may stand to benefit from intensive glucose control. For
example, two recent studies from the surgical ICU set-
ting have found that among nondiabetic patients who
had undergone major cardiothoracic surgery, intensive
glucose control reduced morbidity.12,13
No similar bene-
fit was found for patients with a prior diagnosis of dia-
betes. Despite these interesting findings and ongoing
research, conventional glucose control currently remains
the standard of care in hospitalized patients.14
In summary, there was no benefit found with inten-
sive glucose control in critical care patients but there
was increased incidence of severe hypoglycemia. With
no benefits and increased harms, the most appropriate
color rating for intensive glucose control is black
(harms > benefits). Current ADA guidelines, citing
the findings of prior meta-analyses, recommend con-
ventional glucose control with targeted blood glucose
of 140 to 180 mg/dL in critically ill patients who
experience persistent hyperglycemia.4
References
1. Herring AA, Ginde AA, Fahimi J, et al. Increasing critical
care admissions from U.S. emergency departments, 2001-
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3. Finfer S, Chittock DR, Su SY, et al. Intensive versus con-
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4. American Diabetes Association. 14. Diabetes care in the
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critically ill patients: an updated meta-analysis. Endocr
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11. Ling Y, Li X, Gao X. Intensive versus conventional glu-
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12. Blaha J, Mraz M, Kopecky P, et al. Perioperative tight glu-
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13. Umpierrez G, Cardona S, Pasquel F, et al. Randomized
controlled trial of intensive versus conservative glucose
control in patients undergoing coronary artery bypass graft
surgery: GLUCO-CABG trial. Diabetes Care
2015;38:1665–72.
14. Galindo RJ, Fayfman M, Umpierrez GE. Perioperative
management of hyperglycemia and diabetes in cardiac sur-
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2 Conway et al. • INTENSIVE GLUCOSE CONTROL FOR CRITICALLY ILL PATIENTS