Glycemic Control in Adult ICU

Glycemic Control in Adult
Intensive Care Patients
Joshua Alderman
Adult-Gerontology Acute Care Nurse Practitioner Track
University of Connecticut

In adult medical/surgical
intensive care patients, what is
the effect of intensive vs.
conventional glycemic control
on mortality and the incidence
of hypoglycemic events?

Neuman Systems Theory
 Provides a holistic and system-based approach to
nursing, and states there is constant energy exchange
with the environment
 Examines how the patient-system responds to actual or
potential stressors; these responses can be used as a
guide as to how severe illness is
 Primary, secondary, and tertiary nursing
prevention/intervention is utilized to retain, attain, and
maintain patient-system wellness
 In acute care we focus on the secondary and tertiary
prevention/intervention

Prevalence of Hyperglycemia in ICU
 Australian study from 2013 found approximately 80% of the
1,000 patient’s developed hyperglycemia at some point
within the first 48 hours in the ICU (Farrokhi et al., 2013)
 Other studies have shown this percentage to be even higher

Major Causes of Hyperglycemia in the
ICU
 Critical illness and Stress Hyperglycemia
 Immobility
 IV fluids containing dextrose and feedings
 Drugs including: corticosteroids, catecholemines
(particularly epinephrine), beta blockers, octreotide
 History of Diabetes mellitus, and related disorders such as
DKA and HHNK

Critical Illness and Hyperglycemia
 Increased levels of counter-regulatory hormones and
cytokines cause insulin resistance
 This resistance results in impaired cellular glucose uptake
as well as hepatic glycogenesis/gluconeogenesis leading to
hyperglycemia
 These mechanisms are believed to be a way for the body to
provide more “fuel” for vital organs

Why is Glucose Control
Important in the ICU?

Deleterious Effects of
Hyperglycemia
 Impaired immune function
 Inflammation and Coagulopathy
 Oxidant Stress

Deleterious Effects of Hyperglycemia
These factors can lead to acute
complications including, but not
limited to:
 Poor wound healing
 Severe infections
 Kidney injury
 Critical illness polyneuropathy
 Hypovolemia
 Poor wound healing

Given these consequences, the question is
not whether to control glucose, but rather
what is the optimal level of glycemic
control during critical illness?

The Push for Intensive Glycemic Control
 AKA Intensive Insulin Therapy (IIT)
 In 2001, Van den Berghe G, et al. published their landmark
article “Intensive Insulin Therapy in Critically Ill Patients” in
the New England Journal of Medicine
 The study asked, in surgical ICU patients, how does
intensive glycemic control (80-110 mg/dl) compare to
conventional glycemic control (180-200 mg/dl) in reducing
mortality?

 12-month single center, non-blinded, randomized,
controlled trial with 1,548 mostly surgical ICU patients
 The trial found ICU mortality to be 4.6% in the intensive
group vs. 8% in the conventional group (p < 0.04)
 However, hypoglycemic events for the intensive group
were seen much more often than with the conventional
group (7% vs. 0.5%, respectively)
 The trial concluded that intensive glucose therapy at or
below 110 mg/dl reduced morbidity and mortality in the
surgical intensive care unit

 Quick Adoption of IIT throughout critical care
 However, as research progressed, a number of new trials
began to show that intensive glycemic control may not be
as beneficial as once thought

Follow-up Lueven Trial
 One of the major limitations of the Lueven Surgical Trial
was the lack of medical patients
 In 2006, the Lueven investigators published a follow-up
RCT to their 2001 study focusing on 1,200 medical
patients
 “Intensive insulin therapy significantly reduced
morbidity but not mortality among all patients in the
medical ICU.”
 First to contradict 2001 study

Further Data Against IIT
 In the years following, several other RCTs concluded
similar findings to the 2006 Lueven study
 The VISEP and Glucontrol trials were both terminated
early due to safety concerns related to the high
incidence of hypoglycemic events
 Both of these studies concluded mortality was not
significantly affected with IIT, and the risk of
hypoglycemia was significant

The NICE-SUGAR Trial
 This trial put the nail in the coffin of the research
supporting IIT
 In 2009, the “Normoglycemia in Intensive Care
Evaluation – Survival Using Glucose Algorithm
Regulation” was published
 This was a large, multi-center, parallel-group, RCT with
6,104 patients in medical/surgical 42 ICUs with the
hypothesis that IIT would decrease 90-day mortality

The NICE-SUGAR Trial
 Those expected to require 3 or more days in ICU were
randomly placed into an IIT group (81-108 mg/dl) or
conventional group (144-180 mg/dl)the two groups had
similar characteristics at baseline
 A total of 829 patients (27.5%) in the intensive-control
group and 751 (24.9%) in the conventional-control group
died (p = 0.02); no effect on ICU LOS, Hospital LOS, or days
of mechanical ventilation
 Severe hypoglycemia presented in 6.8% of the IIT vs. only
0.5% of the conventional group

Can computers help?
 In 2014, Kalfon et al. published the Computerized
Glucose Control in Critically Ill Patients trial
 Large, multi-center, RCT with 2,646 mixed ICU patients
 Used computerized glucose control with computer-aided
clinical decision making tool
 Found that IIT with computer-aided tech could not
significantly change 90-d mortality (32.3% IIT vs. 34.1%
conventional), and hypoglycemic risk was greater

Limitations Shared by the RCTs
 Inability to blind ICU staff
 Use of subjective inclusion criteria (expected ICU LOS >2 or
3 days)
 Inability to keep patients in the target glucose ranges

“Diabetes Paradox”
 Although the exact rationale remains unknown, it appears
the chronicity of higher glucose levels in diabetics actually
reduces the harm of hyperglycemia when critically ill
 The benefit of IIT in the 2001 Lueven trial was seen to be
greatest in the non-diabetic population (mortality rate 4.8%
in IIT group vs. 8.4% in the conventional group)

Hypoglycemia and Mortality
 Since the NICE-SUGAR trial, the Lueven Trial, NICE-
SUGAR, and CGAO-REA authors published post-hoc
analyses of their studies examining hypoglycemia and
it’s association with mortality
 All three studies determined that hypoglycemia is
independently associated with increased mortality
 In 2010, the Leuven investigators found that there is a
threefold increase in the risk of death associated with a
single severe hypoglycemic event (<40 mg/dl)

Hypoglycemia and Mortality
 NICE-SUGAR investigators supported that moderate (41-70
mg/dl) and severe hypoglycemia (<40 mg/dl) are associated
with increased mortality (particularly in those with
distributive shock)
 Mortality rate was 23.5% in those without hypoglycemic
event
 Morality rates for moderate vs. severe hypoglycemic events
were 28.5% and 35.4%, respectively

Summary
 IIT adult medical/surgical ICUs has the potential to
increase mortality
 IIT is strongly associated with greater incidence of
severe hypoglycemia (BG <40 mg/dl)
 Hypoglycemia is independently associated with
increased mortality and increased LOS
 Due to glucose variability, it is difficult to keep
glucose within target ranges

Recommendations for Practice
 Insulin therapy should be initiated when BG reaches >180
mg/dl
 The target range for blood glucose should be 140-180 mg/dl
 The best way to achieve target glucose levels and reduce
hypoglycemia is by reducing use of fluids with containing
dextrose and using insulin only when necessary
 Enteral feeding is the method of choice over parenteral
 How would Neuman’s System Theory be used in the
management of hyperglycemia?

1. Check BG level and
monitor S/Sx
hyperglycemia
2. Diagnosis of
treatable
hyperglycemia
>180 mg/dl
3. BG Target
Range of 140-
180 mg/dl
4. Determining
best treatment
plan to reduce
hyperglycemia
5. Restriction of
IVF containing
dextrose and
short-acting insulin
therapy;
continuous enteral
feedings
6. Continuously evaluating BG
and assessing patient’s core and
lines of defense after treatment

Current Practice
 Despite being recommended in several guidelines (e.g.
Surviving Sepsis), the best evidence on proper glycemic
control is not being practiced universally
 Not all ICU protocols have been updated to reflect current
evidence
 Practitioners do not always follow current guidelines or
their specific ICUs protocol
 How can the APRN increase awareness of evidence and best
incorporate it into standard practice?

APRN Role in Implementing the
Evidence
 LEADER
 COLLABORATER
 EDUCATER
 CLINICIAN
 ADVOCATE

Practice/Policy Change and Impact
 Patient/Family
 Community
 Nursing/Hospital
 Environment

Future Research
 Glucose variability effects and control
 More over, with the development and implementation of
better tech/glucose variability control, could intensive
glycemic control be viable?
 Should diabetics be managed differently?
 Certain populations should be examined further (e.g.
neurosurgical/trauma/on corticosteroids)

References
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References
Kalfon, P., Giraudeau, B., Ichai, C., Guerrini, A., Brechot, N., Cinotti, R., . . . Riou, B. (2014). Tight computerized versus
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Krinsley, J., Schultz, M. J., Spronk, P. E., Houckgeest, F. V., Sluijs, J. P., Mélot, C., & Preiser, J. (2011). Mild hypoglycemia
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References
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Glycemic Control in Adult ICU

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