Glycemic Control in Adult

Intensive Care PatientsJoshua 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

Neuman Systems Theory

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?

The Push for Intensive Glycemic Control

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

The Push for Intensive Glycemic Control

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)

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