Comparative Trial Between 3 Types of Insulin Infusion Protocols
Comparative Trial Between 3 Types of Insulin Infusion Protocols
Increasing evidence from observational studies in hospitalized patients with and without
 diabetes indicates that hyperglycemia is a predictor of poor outcome. Over the short-term,
 hyperglycemia can adversely affects fluid balance (through glycosuria and dehydration),
 impairs immunologic response to infection, and promotes inflammation and endothelial
 dysfunction. Blood glucose control with intensive insulin therapy in patients with acute
 critical illness reduces the risk of multiorgan failure and systemic infections, and
 decreases short- and long-term mortality .

 - Hypotheses: we hypothesize that management of inpatient hyperglycemia with a
 computer-guided intravenous infusion protocol (Glucommander) will facilitate a smoother
 glycemic control with a lower rate of hypoglycemic events than treatment following a standard
 insulin infusion algorithm or a simple calculated infusion protocol in critically ill
 patients in the medical and surgical ICU.
I. RESEARCH OBJECTIVES AND SPECIFIC AIMS

 A. Introduction:

 Increasing evidence from observational studies in hospitalized patients with and without
 diabetes indicates that hyperglycemia is a predictor of poor outcome. Over the short-term,
 hyperglycemia can adversely affects fluid balance (through glycosuria and dehydration),
 impairs immunologic response to infection, and promotes inflammation and endothelial
 dysfunction. Blood glucose control with intensive insulin therapy in patients with acute
 critical illness reduces the risk of multiorgan failure and systemic infections, and
 decreases short- and long-term mortality .

 The use of intravenous insulin infusion is the preferred route of insulin administration for
 the management of diabetic subjects with diabetic ketoacidosis and nonketotic hyperosmolar
 state, intraoperative and postoperative care, the postoperative period following heart
 surgery and organ transplantation, acute myocardial infarction, stroke, and critical care
 illness. Some of these settings may be characterized by, or associated with, severe or
 rapidly changing insulin requirements, generalized patient edema, impaired perfusion of
 subcutaneous sites, requirement for pressor support, and/or use of total parenteral
 nutrition. In these settings, the intravenous route for insulin administration has been
 considered superior to the subcutaneous injection of split-mixed regimen of intermediate and
 regular insulin with respect to rapidity of effect in controlling hyperglycemia, overall
 ability to achieve glycemic control, and most importantly, preventing hypoglycemic episodes.
 Recently, several insulin infusion protocols have been reported in the literature . In
 general, orders to "titrate drip" are given to achieve a target blood glucose range using an
 established algorithm or by the application of mathematical rules by nursing staff. These
 algorithms and formulas, however, may be confusing and difficult to follow and may increase
 the risk of dosing errors. To facilitate patient care, insulin algorithms could be placed on
 a computer and used at the patient bedside to direct the nursing staff administering the
 intravenous insulin. The Glucommander is one such computer-derived insulin infusion protocol
 which has been used successfully in over 5,802 patients with diabetes between 1984 and 1998.

 B. Hypotheses: we hypothesize that management of inpatient hyperglycemia with a
 computer-guided intravenous infusion protocol (Glucommander) will facilitate a smoother
 glycemic control with a lower rate of hypoglycemic events than treatment following a standard
 insulin infusion algorithm or a simple calculated infusion protocol in critically ill
 patients in the medical and surgical ICU.

 C. Specific Aim: to determine differences in glycemic control between treatment with
 computer-guided intravenous infusion protocol (Glucommander), a standard insulin infusion
 algorithm and a simple calculated infusion protocol in critically ill patients in the medical
 and surgical ICU.

 II. BACKGROUND AND CURRENT STATUS OF WORK IN THE FIELD.

 The result of several observational and interventional studies indicate that hyperglycemia is
 associated with poor hospital outcomes including prolonged hospital stay, infections,
 disability after hospital discharge, and death , and that improvement in outcomes can be
 achieved with improved glycemic control in patients with critical and surgical illness.
 Although there are still no proven mechanisms to explain the detrimental effects of
 hyperglycemia, there are increasing efforts worldwide to improve and maintain strict glycemic
 control in subjects with critical illness.

 In 2001, a large prospective, randomized controlled trial from Leuven, showed that near
 normalization of blood glucose levels using an intensive insulin protocol improved clinical
 outcomes in patients admitted to a surgical intensive care area . In that study, insulin
 administration to maintain blood glucose levels between 80-110 mg/dl, reduced ICU mortality
 by 34%, and reduced the risk of multiorgan failure, systemic infection, incidence of acute
 renal failure, and the need for blood transfusions and prolonged mechanical ventilatory
 support. Interventional studies in the setting of acute coronary events have shown that
 intensive insulin therapy resulted in decreased short- and long-term mortality. Similarly,
 attainment of targeted glucose control in the setting of cardiac surgery is associated with
 reduced mortality and with a significant reduction in deep sternal wound infections.
 Similarly, in the setting of acute neurological illness, stroke, and head injury extensive
 observational and interventional studies indicates that hyperglycemia is associated with
 increased mortality and with diminished neurological recovery . Based in these observational
 and interventional studies, aggressive control of blood glucose is recommended in patients
 with critical illness. A recent position statement of the American Association of Clinical
 Endocrinologists recommended glycemic targets for hospitalized patients in the intensive care
 unit between 80 - 110 mg/dL.

 The American College of Endocrinology position statement supports the following indications
 for intravenous insulin therapy in hospitalized patients with diabetes:

 -  Prolonged fasting (> 12 hours) in type 1 diabetes

 -  Critical illness

 -  Before major surgical procedures

 -  After organ transplantation

 -  Diabetic ketoacidosis

 -  Total parenteral nutrition therapy

 -  Labor and delivery

 -  Myocardial infarction

 -  Other illnesses requiring prompt glucose control.

 Institutions around the world use a variety of insulin infusion algorithms that can be
 implemented by nursing staff. These algorithms facilitate communication between physicians
 and nurses, achieve correction of hyperglycemia in a timely manner, provide a method to
 determine the insulin infusion rate required to maintain blood sugars within a defined target
 range, include a rule for making temporary corrective increments or decrements of insulin
 infusion rate without under- or overcompensation, and allow for adjustment of the maintenance
 rate as patient insulin sensitivity or carbohydrate intake changes. In most insulin infusion
 protocols, orders to "titrate drip" are given to achieve a target blood glucose range using
 an established algorithm or by the application of mathematical rules by nursing staff. These
 algorithms may be confusing and difficult to follow which may increase the risk of errors.

 To facilitate patient care, Drs. Davidson and Steed developed the Glucommander in 1984, a
 computer based system for glycemic control in hospitalized patients. This computer-guided
 insulin infusion system directs the administration of intravenous insulin in response to
 blood glucose measurement at the patient's bedside. Prior to starting the insulin infusion,
 the physician must specify the following parameters: the low end and high end of the target
 range for blood glucose, an initial factor or multiplier, and the maximum time interval
 between blood glucose measurements. During the infusion, the nurse enters blood glucose
 levels and the computer recommends the insulin infusion rate and a time to check the next
 blood glucose testing. The starting insulin infusion follows the formula: insulin / hour =
 multiplier x (BG - 60). The "multiplier" is a parameter that is automatically adjusted based
 on the glucose pattern and response to insulin. For most adults, the initial multiplier is
 0.02. The Glucommander is programmed to adjust the multiplier upwards or downwards if blood
 glucose levels are above or below target levels.

 This study will compare three methods of comparing how glucose is regulated with IV insulin.
 The first method uses a sliding scale of insulin based on glucoses drawn at set intervals.
 The second method uses an algorithm that uses the glucose drawn at a set interval and also
 how much that glucose changed from the last time the glucose was drawn to adjust the amount
 of insulin to be given. The algorithm takes into count how fast the glucose is changing and
 also how far the glucose is from the expected values to improve the accuracy of the amount of
 insulin to be given. The glucocommander is a handheld based algorithm that again takes in how
 fast the glucose has changed and how far the glucose is from where you want to be and adds
 another layer in that it tells the nurse when to draw the next glucose so that if the glucose
 is very far away from the expected value drawing glucose in a shorter time period will help
 get to the expected glucose faster. The comparison is does the method reach the expected
 glucose faster and how often is the glucose going to be to low. Methods that improve the way
 to get the glucose to the expected value are not better for the patient if they increase the
 chance of hypoglycemia. This study will compare three methods of regulating glucose with
 insulin.
Inclusion Criteria:

 -  Patients who are admitted to Medical or Surgical ICU.

 -  History of diabetes mellitus

 -  Newly diagnosed hyperglycemia (defined as a blood glucose greater than 140 mg/dl on ≥
 2 occasions)

 -  Subjects must have an admission blood glucose < 500 mg/dL, without laboratory evidence
 of diabetic ketoacidosis (serum bicarbonate < 18 mEq/L or positive serum or urinary
 ketones).

 Exclusion Criteria:

 -  Non-Diabetic patients

 -  Subjects with acute hyperglycemic crises such as diabetic ketoacidosis (DKA) and
 hyperosmolar hyperglycemic state.

 -  Patients with known HIV

 -  Patients with severely impaired renal function (serum creatinine ≥3.0 mg/dl).

 -  Patients with mental condition rendering the subject unable to understand the nature,
 scope, and possible consequences of the study.

 -  Female subjects who are pregnant or breast feeding at time of enrollment into the
 study