Tight Glycemic Control: What do we really know, and what should we expect?

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By Stanley A. Nasraway, Jr., M.D., F.C.C.M   
Wednesday, 08 June 2011 05:17
Tight glycemic control in hospital patients has engendered large numbers of clinical investigations, with conflicting results. The world has largely embraced intensive insulin as a practice, but applies this with great variability in the manner of glucose control and measurement.  After numerous studies, what do we actually know with certainty, and what we can expect looking forward.

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This is what we know with certainty:

1. Hyperglycemia is bad.  Analysis of ICU patients has shown that hyperglycemia (glucose > 110 mg/) was associated with mortality independent of illness severity, type of ICU or length of stay.  Studies consistently indicate that ICU patients who are nondiabetic benefit more from insulin than do diabetics.

2. Hypoglycemia is bad.  An incidental and constant observation from many studies is that severe hypoglycemia (glucose < 40 mg/dL) in a population of patients by logistic regression is associated with a 6-fold increase in death.  It would not be surprising to find with additional study that even mild hypoglycemia has longlasting but subtle neurologic consequences that are not clinically evident or measured.

3. Critically ill patients typically sustain large swings in blood glucose, even with insulin administration.  Sustaining the blood glucose within a target range in a hypermetabolic patient with changing gluconeogenic drivers in a 24 hour day is enormously challenging, frequently outstripping the crude tools used at the bedside to measure blood glucose and respond to its variation in concentration.

4. Software-driven insulin dosing is better than paper-driven insulin protocols.  Software integrates all of the glucose measurements and all of the previous insulin adjustments to determine the next best insulin dose.  Software appears to reduce hypoglycemia, glucose variability and to sustain glucose within the target range for prolonged periods of time. There are now many software programs tested and/or available.

5. Handheld blood glucometers, originally intended for use by Type I diabetic outpatients in the 1980s, are not accurate enough in the ICU environment, and are very laborious to use.  In the USA, the Food and Drug Administration in March of 2010 hosted a public inquiry into glucose meters, after which it is redefining what it will accept in the way of accuracy by blood glucose measurement devices in the hospital setting going forward.  It has asked the international standards body to reset its limits for accuracy for glucometers.  Current generation handheld devices now in use will not make the cut.

6.    The more frequent the blood glucose measurement, even with handheld glucometers, the less hypoglycemia experienced by patients and the tighter the glycemic control.  Frequency is crucial, however laborious it may be.

What can we expect going forward?  

We can expect that the world will continue to use intensive insulin, but that the range that defines “tight” will be narrowed as it becomes more achievable.  We can expect that there will be more emphasis on defining hypoglycemia, and in avoiding it with greater rigor.  We can expect a movement towards insulin-dosing software, as the development of many programs appears to be simple, and competition will force down the cost of purchase and use.  Software-insulin dosing has hidden advantages:  it forces more blood glucose monitoring and also provides an instant database for analysis.  

We will someday be using glucometers that are engineered to be less invasive and more accurate, especially in the hypoglycemic range, avoiding pitfalls in today’s instruments due to chemical interferences and specific disease conditions.  Importantly, these devices will be continuous or near continuous, and by their nature will prevent dangerous glucose excursions by alerting the caregiver in real-time when an excursion has just occurred.  Frequent, real time readings will provide tracking and trending information that will allow for more precise and timely insulin dosing adjustments. The frequency of blood glucose measurements by these devices will dramatically make safer the continuous administration of insulin.  One company that understands the need for continuous glucose monitoring in the ICU environment is Echo Therapeutics.  Echo Therapeutics is currently developing its Symphony tCGM System, which has been tested here at Tufts Medical Center in Boston, as a non-invasive, wireless, transdermal continuous glucose monitoring system (tCGM) that may be used for both hospital patients and for outpatient diabetics.

Improving the accuracy of blood glucose measurements and increasing the frequency of measurements by using continuous monitors will begin to standardize insulin dosing with better methods will produce better quality research, synergizing global convergence on tight glycemic control, reduced glucose variability and better patient outcomes.

About the Author:

Stanley A. Nasraway, Jr., M.D., F.A.C.P., F.C.C.P., F.C.C.M., is the Director of the Surgical Intensive Care Units at Tufts Medical Center, and Professor of Surgery, Medicine and Anesthesiology at Tufts University School of Medicine in Boston, MA. He also is on the Scientific Advisory Board of Echo Therapeutics, Inc (OTCBB:ECTE).



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